Anti-PTK7 conjugates and uses thereof

Abstract

Provided herein is a conjugate of the Formula (XX): or a pharmaceutically acceptable salt thereof, wherein; L is a Targeting Unit, wherein the Targeting Unit is an anti-PTK7 antibody or an antigenbinding portion thereof, wherein the variables of Formula (XX) are as defined in the application. Such compounds can be useful as anti-cancer agents.

Description

WSGR Docket No.63125-715.601 CONJUGATES AND USES THEREOF CROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Patent Application No.63 / 636,041 filed on April 18, 2024, and U.S. Provisional Patent Application No.63 / 722,552 filed on November 19, 2024, the entire contents of each of which are incorporated herein by reference. BACKGROUND

[0002] Protein tyrosine kinase 7 (PTK7), also known as colon carcinoma kinase 4 (CCK4),is a receptor tyrosine kinase involved in non-canonical Wnt signaling and was first identified as a gene upregulated in colon cancer cells. PTK belongs to the Wnt ligand binding receptor family whose other members include receptor tyrosine kinase-like orphan receptors 1 (ROR1) and 2 (ROR2), and receptor tyrosine kinase RYK. Members of this receptor family are transmembrane proteins that are void of kinase activity. PTK7 plays roles in embryonic development, maintenance of tissue homeostasis, and stem cell signaling; however, expression of PTK7 is absent or minimal in differentiated healthy adult tissues. Overexpression of PTK7 has been reported in a variety of cancers including head and neck cancer, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), bladder cancer, and ovarian cancer. In this milieu, PTK7 promotes cell survival, migration, and invasion, and chemotherapy resistance.

[0003] PTK7 expression has been associated with poor prognosis and higher metastaticpotential in patients with various cancers, and thus represents a promising therapeutic target. In view of PTK7’s critical role in tumor progression, there is a need for new and improved cancer immunotherapies that target PTK7. SUMMARY OF THE INVENTION

[0004] The present disclosure provides antibody-drug conjugates that bind specifically toPTK7. Drug-linkers are conjugated to an anti-PTK7 antibody or an antigen-binding portion thereof to form antibody-drug conjugates that target PTK7 and ultimately release a payload of choice (e.g., exatecan) to treat a PTK7-positive cancer. To this end, the present invention provides novel antibody-drug conjugates that target PTK7-positive cancers. The disclosed anti- PTK7 antibody-drug conjugates can exert a clinically useful cytotoxic effect on PTK7 expressing tumor cells without exerting undesirable effects on non-PTK7 expressing cells.

[0005] In an aspect, the present disclosure provides a Drug-Linker of Formula (X):-1-WSGR Docket No.63125-715.601 Formula (X) or a pharmaceutically acceptable salt thereof, wherein; R40 is independently selected from hydrogen,D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; z is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- -2-WSGR Docket No.63125-715.601 C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, K2, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and -3-WSGR Docket No.63125-715.601 (iv) a polyether; wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12-membered heterocycle.

[0006] In an aspect, the present disclosure provides a Drug-Linker of Formula (I):Formula (I) or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; -4-WSGR Docket No.63125-715.601 T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - -5-WSGR Docket No.63125-715.601C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6 alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2; (iii) an oligosaccharide; and (iv) a polyether; wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - -6-WSGR Docket No.63125-715.601 N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle.

[0007] In an aspect, the present disclosure provides a Drug-Linker of Formula (Ia) orFormula (Ib):, or a pharmaceutically acceptable salt of any one thereof, wherein; D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino -7-WSGR Docket No.63125-715.601 acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from: -8-WSGR Docket No.63125-715.601 (i) a peptide unit, (ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2; (iii) an oligosaccharide; and (iv) a polyether; wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle.

[0008] In an aspect, the present disclosure provides a conjugate of the Formula (XX):Formula (XX) or a pharmaceutically acceptable salt thereof, wherein; -9-WSGR Docket No.63125-715.601 R40 is independently selected from hydrogen,D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; z is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; -10-WSGR Docket No.63125-715.601 S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6 alkynyl; L is a Targeting Unit, wherein the Targeting Unit is an anti-PTK7 antibody or an antigen- binding portion thereof; M2is a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; K2is selected from: (i) a peptide unit, -11-WSGR Docket No.63125-715.601 (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle.

[0009] In an aspect, the present disclosure provides a conjugate of the Formula (A):Formula (A) or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – -12-WSGR Docket No.63125-715.601 N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and -13-WSGR Docket No.63125-715.601 (iii) C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6 alkynyl; L is a Targeting Unit, wherein the Targeting Unit is an anti-PTK7 antibody or an antigen- binding portion thereof; M2is a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.

[0010] In an aspect the present disclosure provides a conjugate of the Formula (A#):-14-WSGR Docket No.63125-715.601Formula (A#) or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino -15-WSGR Docket No.63125-715.601 acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6alkynyl; L is a Targeting Unit, wherein the Targeting Unit is an anti-PTK7 antibody or an antigen- binding portion thereof; M2is a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; K2is selected from: -16-WSGR Docket No.63125-715.601 (i) a peptide unit, (ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.

[0011] In an aspect, the present disclosure provides a conjugate of the Formula (Aa) orFormula (Ab):, or or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; n is selected from 0 and 1; -17-WSGR Docket No.63125-715.601 m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from: -18-WSGR Docket No.63125-715.601 (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6alkynyl; L is a Targeting Unit, wherein the Targeting Unit is an anti-PTK7 antibody or an antigen- binding portion thereof; M2is a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted -19-WSGR Docket No.63125-715.601 with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12-membered heterocycle.

[0012] In an aspect, the present disclosure provides a method of treating a subject with adisease or disorder comprising administering to a subject in need thereof a Drug-Linker or salt of Formula (I), Formula (I-A), Formula (I-B), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), or Formula (II-B) (each of which further comprises a targeting unit), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), or Formula (A-4), or a pharmaceutical composition of any one thereof. INCORPORATION BY REFERENCE

[0013] All publications, patents, and patent applications mentioned in this specification areherein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The novel features of the invention are set forth with particularity in the appendedclaims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “figure” and “FIG.” herein), of which:

[0015] FIG. 1 illustrates the stability of different ADCs in mouse plasma;

[0016] FIG. 2 illustrates the stability of different ADCs in human plasma;

[0017] FIG. 3 illustrates the percentage of cellular binding of different ADCs;

[0018] FIG. 4 illustrates the median fluorescence intensity (MFI) of different ADCs;

[0019] FIG. 5 illustrates the percentage of inhibition of Jeko-1 cells of different ADCs;-20-WSGR Docket No.63125-715.601

[0020] FIG. 6 illustrates internalization of different ADCs;

[0021] FIG. 7 illustrates the release of exatecan from the ADCs;

[0022] FIG. 8 illustrates in vivo antitumor activity of ADCs in the Jeko-1 xenograft model;

[0023] FIG. 9 illustrates in vivo antitumor activity of ADCs in the H1975 xenograft model;

[0024] FIG. 10 illustrates Pharmacokinetic Parameters of various ADCs;

[0025] FIG. 11 illustrates the stability of different ADCs in mouse plasma;

[0026] FIG. 12 illustrates the stability of different ADCs in human plasma;

[0027] FIG. 13 illustrates the percentage of cellular binding of different ADCs;

[0028] FIG. 14 illustrates the median fluorescence intensity (MFI) of different ADCs;

[0029] FIG. 15 illustrates the percentage of inhibition of Jeko-1 cells of different ADCs;

[0030] FIG. 16 illustrates internalization of different ADCs;

[0031] FIG. 17 illustrates the release of exatecan from the ADCs;

[0032] FIG. 18 illustrates Pharmacokinetic Parameters of various ADCs.

[0033] FIG. 19 Chiral HPLC Chromatograms of Compound 37, Compound 107-S andCompound 118-R;

[0034] FIG. 20 illustrates the percentage of cellular binding of different ADC isomers inhuman plasma;

[0035] FIG. 21 illustrates the median fluorescence intensity of different ADC isomers;

[0036] FIG. 22 illustrates the quench internalization of different ADC isomers;

[0037] FIG. 23 illustrates the percentage of inhibition of Jeko-1 cells of different ADCisomers;

[0038] FIG. 24 illustrates the percentage of inhibition LCLC-103H cells of different ADCisomers;

[0039] FIG. 25 in vivo antitumor activity of ADCs in the LCLC-103H xenograft model;

[0040] FIG. 26 shows in vivo antitumor activity of ADCs for 12 PTK7 antibodies in theH1975 NSCLC model;

[0041] FIG. 27 shows in vivo antitumor activity of ADCs for 4 PTK7 antibodies in theH1975 NSCLC xenograft model;

[0042] FIG. 28 shows in vivo antitumor activity of ADCs in the Hep3B (liver) xenograftmodel;

[0043] FIG. 29 shows in vivo antitumor activity of ADCs in the Du145 (prostate) xenograftmodel;

[0044] FIG. 30 shows in vivo antitumor activity for ADC-29 and ADC-30 in the H1975NSCLC xenograft model; -21-WSGR Docket No.63125-715.601

[0045] FIG. 31 shows in vivo antitumor activity of ADCs with a chimeric PTK7 antibodyand a humanized PTK7 antibody in H520 NSCLC xenograft model;

[0046] FIG. 32 shows in vivo antitumor activity of ADCs with different payloads in theH520 NSCLC xenograft model;

[0047] FIG. 33 shows in vivo antitumor activity of ADCs with different linkers in the H520NSCLC xenograft model;

[0048] FIG. 34 shows in vivo antitumor activity of ADCs with different linkers in theLCLC-103H NSCLC xenograft model;

[0049] FIG. 35 shows dose titration in vivo antitumor activity of ADCs in the LCLC-103Hxenograft model;

[0050] FIG. 36 shows in vivo antitumor activity of ADCs with different DARs in theLCLC-103H xenograft model;

[0051] FIG. 37 shows replicate in vivo antitumor activity of ADCs with different DARs inthe LCLC-103H xenograft model;

[0052] FIG. 38 shows dose titration in vivo antitumor activity of ADC in the PA-1 (ovarian)xenograft model;

[0053] FIG. 39 shows dose titration in vivo antitumor activity of ADC in the LCLC-103Hxenograft model;

[0054] FIG. 40 shows dose titration in vivo antitumor activity of ADC in the TNBC PDXxenograft model; and

[0055] FIG. 41 shows dose titration in vivo antitumor activity of ADC in the SCLC PDXxenograft model. DETAILED DESCRIPTION OF THE INVENTION

[0056] The following description sets forth numerous exemplary configurations, methods,parameters, and the like. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure, but is instead provided as a description of exemplary embodiments.

[0057] In the following description, certain specific details are set forth in order to provide athorough understanding of various embodiments of the disclosure. However, one skilled in the art will understand that the disclosure may be practiced without these details. Definitions

[0058] Unless defined otherwise, all technical and scientific terms used herein have the samemeaning as is commonly understood by one of skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference. -22-WSGR Docket No.63125-715.601

[0059] "Alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely ofcarbon and hydrogen atoms, containing no unsaturation, and preferably having from one to fifteen carbon atoms (i.e., C1-C15alkyl). In certain embodiments, an alkyl comprises one to thirteen carbon atoms (i.e., C1-C13 alkyl). In certain embodiments, an alkyl comprises one to eight carbon atoms (i.e., C1-C8 alkyl). In other embodiments, an alkyl comprises one to five carbon atoms (i.e., C1-C5alkyl). In other embodiments, an alkyl comprises one to four carbon atoms (i.e., C1-C4 alkyl). In other embodiments, an alkyl comprises one to three carbon atoms (i.e., C1-C3 alkyl). In other embodiments, an alkyl comprises one to two carbon atoms (i.e., C1- C2alkyl). In other embodiments, an alkyl comprises one carbon atom (i.e., C1alkyl). In other embodiments, an alkyl comprises five to fifteen carbon atoms (i.e., C5-C15 alkyl). In other embodiments, an alkyl comprises five to eight carbon atoms (i.e., C5-C8 alkyl). In other embodiments, an alkyl comprises two to five carbon atoms (i.e., C2-C5alkyl). In other embodiments, an alkyl comprises three to five carbon atoms (i.e., C3-C5alkyl). In certain embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl). The alkyl is attached to the rest of the molecule by a single bond.

[0060] The term “Cx-y” or “Cx-Cy” when used in conjunction with a chemical moiety, suchas alkyl, alkenyl, or alkynyl is meant to include groups that contain from x to y carbons in the chain. For example, the term “C1-6alkyl” refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain alkyl and branched-chain alkyl groups that contain from 1 to 6 carbons. The term –Cx-yalkylene- refers to a substituted or unsubstituted alkylene chain with from x to y carbons in the alkylene chain. For example –C1-6alkylene- may be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any one of which is optionally substituted.

[0061] "Alkoxy" refers to a radical bonded through an oxygen atom of the formula –O-alkyl,where alkyl is an alkyl chain as defined above.

[0062] "Alkenyl" refers to a straight or branched hydrocarbon chain radical group consistingsolely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms (i.e., C2-C12 alkenyl). In certain embodiments, an alkenyl comprises two to eight carbon atoms (i.e., C2-C8 alkenyl). In certain embodiments, an alkenyl comprises two to six carbon atoms (i.e., C2-C6alkenyl). In other embodiments, an alkenyl comprises two to four carbon atoms (i.e., C2-C4alkenyl). The alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like. -23-WSGR Docket No.63125-715.601

[0063] "Alkynyl" refers to a straight or branched hydrocarbon chain radical group consistingsolely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms (i.e., C2-C12alkynyl). In certain embodiments, an alkynyl comprises two to eight carbon atoms (i.e., C2-C8 alkynyl). In other embodiments, an alkynyl comprises two to six carbon atoms (i.e., C2-C6 alkynyl). In other embodiments, an alkynyl comprises two to four carbon atoms (i.e., C2-C4alkynyl). The alkynyl is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0064] The terms “Cx-yalkenyl” and “Cx-yalkynyl” refer to substituted or unsubstitutedunsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond, respectively. The term –Cx-yalkenylene- refers to a substituted or unsubstituted alkenylene chain with from x to y carbons in the alkenylene chain. For example, –C2-6alkenylene- may be selected from ethenylene, propenylene, butenylene, pentenylene, and hexenylene, any one of which is optionally substituted. An alkenylene chain may have one double bond or more than one double bond in the alkenylene chain. The term –Cx-yalkynylene- refers to a substituted or unsubstituted alkynylene chain with from x to y carbons in the alkenylene chain. For example, –C2- 6alkenylene- may be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, any one of which is optionally substituted. An alkynylene chain may have one triple bond or more than one triple bond in the alkynylene chain.

[0065] "Alkylene" or "alkylene chain" refers to a straight or branched divalent hydrocarbonchain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturation, and preferably having from one to twelve carbon atoms, for example, methylene, ethylene, propylene, n-butylene, and the like. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain. In certain embodiments, an alkylene comprises one to ten carbon atoms (i.e., C1-C8 alkylene). In certain embodiments, an alkylene comprises one to eight carbon atoms (i.e., C1-C8alkylene). In other embodiments, an alkylene comprises one to five carbon atoms (i.e., C1-C5 alkylene). In other embodiments, an alkylene comprises one to four carbon atoms (i.e., C1-C4 alkylene). In other embodiments, an alkylene comprises one to three carbon atoms (i.e., C1-C3alkylene). In other embodiments, an alkylene comprises one to two carbon atoms (i.e., C1-C2alkylene). In other embodiments, an alkylene comprises one carbon atom (i.e., C1 alkylene). In other embodiments, an alkylene comprises five to eight carbon atoms (i.e., C5-C8 alkylene). In other embodiments, an alkylene -24-WSGR Docket No.63125-715.601 comprises two to five carbon atoms (i.e., C2-C5 alkylene). In other embodiments, an alkylene comprises three to five carbon atoms (i.e., C3-C5alkylene).

[0066] "Alkenylene" or "alkenylene chain" refers to a straight or branched divalenthydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkenylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain. In certain embodiments, an alkenylene comprises two to ten carbon atoms (i.e., C2-C10 alkenylene). In certain embodiments, an alkenylene comprises two to eight carbon atoms (i.e., C2-C8 alkenylene). In other embodiments, an alkenylene comprises two to five carbon atoms (i.e., C2-C5alkenylene). In other embodiments, an alkenylene comprises two to four carbon atoms (i.e., C2-C4alkenylene). In other embodiments, an alkenylene comprises two to three carbon atoms (i.e., C2-C3 alkenylene). In other embodiments, an alkenylene comprises two carbon atom (i.e., C2 alkenylene). In other embodiments, an alkenylene comprises five to eight carbon atoms (i.e., C5-C8alkenylene). In other embodiments, an alkenylene comprises three to five carbon atoms (i.e., C3-C5 alkenylene).

[0067] "Alkynylene" or "alkynylene chain" refers to a straight or branched divalenthydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkynylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain. In certain embodiments, an alkynylene comprises two to ten carbon atoms (i.e., C2-C10 alkynylene). In certain embodiments, an alkynylene comprises two to eight carbon atoms (i.e., C2-C8alkynylene). In other embodiments, an alkynylene comprises two to five carbon atoms (i.e., C2-C5 alkynylene). In other embodiments, an alkynylene comprises two to four carbon atoms (i.e., C2-C4 alkynylene). In other embodiments, an alkynylene comprises two to three carbon atoms (i.e., C2-C3alkynylene). In other embodiments, an alkynylene comprises two carbon atom (i.e., C2 alkynylene). In other embodiments, an alkynylene comprises five to eight carbon atoms (i.e., C5-C8 alkynylene). In other embodiments, an alkynylene comprises three to five carbon atoms (i.e., C3-C5alkynylene).

[0068] "Aryl" refers to a radical derived from an aromatic monocyclic or aromaticmulticyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or aromatic multicyclic hydrocarbon ring system contains only -25-WSGR Docket No.63125-715.601 hydrogen and carbon and from five to eighteen carbon atoms, where at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) ^–electron system in accordance with the Hückel theory. The ring system from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin and naphthalene.

[0069] "Aralkyl" refers to a radical of the formula -Rc-aryl where Rc is an alkylene chain asdefined above, for example, methylene, ethylene, and the like.

[0070] "Aralkenyl" refers to a radical of the formula –Rd-aryl where Rd is an alkenylenechain as defined above. "Aralkynyl" refers to a radical of the formula -Re-aryl, where Reis an alkynylene chain as defined above.

[0071] “Activated group” refers to a cyclic alkyne which is highly reactive due to ringstrain towards azide group to form a triazole.

[0072] "Activated disulfide group” refers to a disulfide which is capable to react with a thiolto form a new disulfide bond.

[0073] “Carbocycle” refers to a saturated, unsaturated or aromatic rings in which each atomof the ring is carbon. Carbocycle may include 3- to 10-membered monocyclic rings, 6- to 12- membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic carbocycle may be selected from saturated, unsaturated, and aromatic rings. An aromatic ring, e.g., phenyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated and aromatic bicyclic rings, as valence permits, are included in the definition of carbocyclic. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Bicyclic carbocycles may be fused, bridged or spiro-ring systems. In some cases, spiro-ring carbocycles have at least two molecular rings with only one common atom.

[0074] “Carbocyclene” refers to a divalent carbocycle linking the rest of the molecule to aradical group.

[0075] The term “unsaturated carbocycle” refers to carbocycles with at least one degree ofunsaturation and excluding aromatic carbocycles. Examples of unsaturated carbocycles include cyclohexadiene, cyclohexene, and cyclopentene.

[0076] "Cycloalkyl" refers to a fully saturated monocyclic or polycyclic hydrocarbon radicalconsisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, and preferably having from three to twelve carbon atoms. In certain embodiments, a cycloalkyl comprises three to ten carbon atoms. In other embodiments, a cycloalkyl comprises five to seven carbon atoms. The cycloalkyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, -26-WSGR Docket No.63125-715.601 cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like.

[0077] "Cycloalkenyl" refers to an unsaturated non-aromatic monocyclic or polycyclichydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, preferably having from three to twelve carbon atoms and comprising at least one double bond. In certain embodiments, a cycloalkenyl comprises three to ten carbon atoms. In other embodiments, a cycloalkenyl comprises five to seven carbon atoms. The cycloalkenyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyls includes, e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.

[0078] "Cycloalkylalkyl" refers to a radical of the formula –Rc-cycloalkyl where Rc is analkylene chain as described above.

[0079] "Cycloalkylalkoxy" refers to a radical bonded through an oxygen atom of the formula–O-Rc-cycloalkyl where Rcis an alkylene chain as described above.

[0080] "Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro andiodo substituents.

[0081] As used herein, the term "haloalkyl" or “haloalkane” refers to an alkyl radical, asdefined above, that is substituted by one or more halogen radicals, for example, trifluoromethyl,dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like. In some embodiments, the alkyl part of the fluoroalkyl radical is optionally further substituted. Examples of halogen substituted alkanes (“haloalkanes”) include halomethane (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di-and trihalomethane (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2- haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combinations of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F, I, etc.). When an alkyl group is substituted with more than one halogen radicals, each halogen may be independently selected e.g., 1-chloro,2-fluoroethane.

[0082] "Fluoroalkyl" refers to an alkyl radical, as defined above, that is substituted by one ormore fluoro radicals, for example, trifluoromethyl, difluoromethyl, fluoromethyl,2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like.

[0083] "Aminoalkyl" refers to an alkyl radical, as defined above, that is substituted by one ormore amine radicals, for example, propan-2-amine, butane-1,2-diamine, pentane-1,2,4-triamineand the like. -27-WSGR Docket No.63125-715.601

[0084] "Hydroxyalkyl" refers to an alkyl radical, as defined above, that is substituted by oneor more hydroxy radicals, for example, propan-1-ol, butane-1,4-diol, pentane-1,2,4-triol, and thelike.

[0085] "Alkoxyalkyl" refers to an alkyl radical, as defined above, that is substituted by oneor more alkoxy radicals, for example, methoxymethane, 1,3-dimethoxybutane, 1-methoxypropane, 2-ethoxypentane, and the like.

[0086] "Cyanoalkyl" as used herein refers to an alkyl radical, as defined above, that issubstituted by one or more cyano radicals, for example, acetonitrile, 2-ethyl-3-methylsuccinonitrile, butyronitrile, and the like.

[0087] “Heterocycle” refers to a saturated or unsaturated or aromatic ring comprising one ormore heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12- membered bridged rings. Each ring of a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings. Bicyclic heterocycles may be fused, bridged or spiro-ring systems. In some cases, spiro-ring heterocycles have at least two molecular rings with only one common atom. The spiro-ring heterocycle includes at least one heteroatom.

[0088] “Heterocyclene” refers to a divalent heterocycle linking the rest of the molecule to aradical group.

[0089] "Heteroaryl" or “aromatic heterocycle” refers to a radical derived from aheteroaromatic ring radical that comprises one to eleven carbon atoms and at least one heteroatom wherein each heteroatom may be selected from N, O, and S. As used herein, the heteroaryl ring may be selected from monocyclic or bicyclic and fused or bridged ring systems rings wherein at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) ^–electron system in accordance with the Hückel theory. The heteroatom(s) in the heteroaryl radical may be optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl may be attached to the rest of the molecule through any atom of the heteroaryl, valence permitting, such as a carbon or nitrogen atom of the heteroaryl. Examples of heteroaryls include, but are not limited to, pyridine, pyrimidine, oxazole, furan, pyran, thiophene, isoxazole, benzimidazole, benzthiazole, and imidazopyridine.

[0090] An “X-membered heteroaryl” refers to the number of endocylic atoms, i.e., X, in thering. For example, a 5-membered heteroaryl ring or 5-membered aromatic heterocycle has 5 endocyclic atoms, e.g., triazole, oxazole, thiophene, etc.

[0091] The term “unsaturated heterocycle” refers to heterocycles with at least one degree ofunsaturation and excluding aromatic heterocycles. Examples of unsaturated heterocycles include -28-WSGR Docket No.63125-715.601 dihydropyrrole, dihydrofuran, oxazoline, pyrazoline, and dihydropyridine. Heterocycles may be optionally substituted by one or more substituents such as those substituents described herein.

[0092] The term “substituted” refers to moieties having substituents replacing a hydrogen onone or more carbons or substitutable heteroatoms, e.g., NH, of the structure. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, i.e., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. In certain embodiments, substituted refers to moieties having substituents replacing two hydrogen atoms on the same carbon atom, such as substituting the two hydrogen atoms on a single carbon with an oxo, imino or thioxo group.

[0093] As used herein, the term “substituted” is contemplated to include all permissiblesubstituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non- aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms such as nitrogen may have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. In some embodiments, substituents may include any substituents described herein, for example: halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N- H), oximo (=N-OH), hydrazino (=N- NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, - Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2), and -Rb-S(O)tN(Ra)2 (where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, and heterocycle, any of which may be optionally substituted by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazine (=N- NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb- N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2(where t is 1 or 2); wherein each Rais independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each Ra, valence permitting, may be optionally substituted with alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, -29-WSGR Docket No.63125-715.601 haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazine (=N- NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb- N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2(where t is 1 or 2); and wherein each Rbis independently selected from a direct bond or a straight or branched alkylene, alkenylene, or alkynylene chain, and each Rcis astraight or branched alkylene, alkenylene or alkynylene chain.

[0094] As used in the specification and claims, the singular form “a”, “an” and “the”includes plural references unless the context clearly dictates otherwise.

[0095] The term “salt” or “pharmaceutically acceptable salt” refers to salts derived from avariety of organic and inorganic counter ions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like, specifically such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, the pharmaceutically acceptable base addition salt is chosen from ammonium, potassium, sodium, calcium, and magnesium salts.

[0096] The phrases “parenteral administration” and “administered parenterally” as usedherein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

[0097] The phrase “pharmaceutically acceptable” is employed herein to refer to thosecompounds, materials, compositions, and / or dosage forms which are, within the scope of sound -30-WSGR Docket No.63125-715.601 medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0098] The phrase “pharmaceutically acceptable excipient” or “pharmaceutically acceptablecarrier” as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen- free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations.

[0099] In certain embodiments, the term “prevent” or “preventing” as related to a disease ordisorder may refer to a compound that, in a statistical sample, reduces the occurrence of the disorder or condition in the treated sample relative to an untreated control sample, or delays the onset or reduces the severity of one or more symptoms of the disorder or condition relative to the untreated control sample.

[0100] The terms “treat,” “treating” or “treatment,” as used herein, may include alleviating,abating or ameliorating a disease or condition symptoms, preventing additional symptoms, ameliorating or preventing the underlying causes of symptoms, inhibiting the disease or condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a condition caused by the disease or condition, or stopping the symptoms of the disease or condition either prophylactically and / or therapeutically.

[0101] The term "ligand" generally refers to a macromolecular compound capable ofrecognizing and binding to an antigen or receptor associated with a target cell. The ligand can be used to bring the drug to the target cell population that binds to the ligand, including but not limited to protein hormones, lectins, growth factors, antibodies, or others that can bind to cells, -31-WSGR Docket No.63125-715.601 receptors and / or antigens molecule. The ligand can be an antibody. The ligand can be an antigen binding fragment.

[0102] The term “targeting moiety” or “Targeting Unit” refers to a structure that has aselective affinity for a target molecule relative to other non-target molecules. The targeting moiety binds to a target molecule. A Targeting Unit may include, for example, an antibody, a peptide, a ligand, a receptor, or a binding portion thereof. The target biological molecule may be a biological receptor or other structure of a cell such as a tumor antigen.

[0103] The term “antibody” means whole antibodies and any antigen binding fragment (i.e.,“antigen-binding portion”) or single chain variants thereof. A whole antibody is a protein comprising at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds. Each heavy chain comprises a heavy chain variable region (VH) and a heavy chain constant region comprising three domains, CH1, CH2 and CH3. Each light chain comprises a light chain variable region (VL or Vk) and a light chain constant region comprising one single domain, CL. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with more conserved framework regions (FRs). Each VH and VL comprises three CDRs (HCDR herein designates a CDR from the heavy chain; and LCDR herein designates a CDR from the light chain) and four FRs, arranged from amino- to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The variable regions contain a binding domain that interacts with an antigen. The constant regions may mediate the binding of the antibody to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system.

[0104] The assignment of amino acid numbers, and of FR and CDR regions, in the heavy orlight chain may be in accordance with IMGT®definitions (Lefranc et al., Dev Comp Immunol. (2003) 27(1):55-77); or the definitions of Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, MD (1987 and 1991)); Chothia & Lesk, J Mol Biol. (1987) 196:901-17; Chothia et al., Nature (1989) 342:878-83; Abhinandan et al., Molecular Immunology (2008) 45(14):3832-39; MacCallum et al., J Mol Biol. (1996) 262:732- 45; or Honegger and Plückthun, J Mol Biol. (2001) 309(3):657-70. The CDR boundaries of various schemes are illustrated in Table Z, where the amino acid numbers are Kabat numbers unless otherwise indicated. Table Z. CDR Delineations According to Various Schemes-32-WSGR Docket No.63125-715.601

[0105] An antibody is said to “specifically bind” to an antigen X if the antibody binds toantigen X with a KD of 5×10−8M or less, more preferably 1×10−8M or less, more preferably 6×10−9M or less, more preferably 3×10−9M or less, even more preferably 2×10−9M or less. The antibody can be chimeric, humanized, or, preferably, human. The heavy chain constant region can be engineered to affect glycosylation type or extent, to extend antibody half-life, to enhance or reduce inter-actions with effector cells or the complement system, or to modulate some other property. The engineering can be accomplished by replacement, addition, or deletion of one or more amino acids or by replacement of a domain with a domain from another immunoglobulin type, or a combination of the foregoing.

[0106] The term “antigen binding fragment” and “antigen binding portion” of an antibody(or simply “antibody portion” or “antibody fragment”) mean one or more fragments of an antibody that retain the ability to specifically bind to an antigen. It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody, such as (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab’)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fab’ fragment, which is essentially an Fab with part of the hinge region (see, for example, Abbas et al., Cellular and Molecular Immunology, 6th Ed., Saunders Elsevier 2007); (iv) a Fd fragment consisting of the VH and CH1 domains; (v) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (vi) a dAb fragment (Ward et al., (1989) Nature 341:544-546), which consists of a VH domain; (vii) an isolated complementarity determining region (CDR); and (viii) a nanobody, a heavy chain variable region containing a single variable domain and two constant domains. Preferred antigen binding fragments are Fab, F(ab’)2, Fab’, Fv, and Fd fragments. Furthermore, although the two domains of the Fv fragment, VL and VH, are encoded by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv, or scFv); see, e.g., Bird et al. (1988) Science 242:423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). Such single chain antibodies are also encompassed within the term “antigen-binding portion” of an antibody. -33-WSGR Docket No.63125-715.601

[0107] Antibody portions, such as Fab and F(ab’)2 fragments, can be prepared from wholeantibodies using conventional techniques, such as papain or pepsin digestion of whole antibodies. Moreover, antibodies, antibody portions and immunoadhesin molecules can be obtained using standard recombinant DNA techniques, e.g., as described herein.

[0108] In some embodiments, antibodies may originate from non-human sources and havebeen humanized to reduce anti-antibody immune responses. The term “humanize” refers to the fact that where an antibody is wholly or partially of non-human origin (for example, a murine or chicken antibody obtained from immunization of mice or chickens, respectively, with an antigen of interest, or a chimeric antibody based on such a murine or chicken antibody), it is possible to replace certain amino acids, in particular in the framework regions and constant regions of the heavy and light chains, in order to avoid or minimize an immune response in humans. Although it is not possible to precisely predict the immunogenicity, and thereby the human anti-antibody response, of a particular antibody, non-human antibodies tend to be more immunogenic in humans than human antibodies. Antibodies of non-human origin thus can be humanized to reduce the risk of a human anti-antibody response.

[0109] Humanization typically involves modification of the framework regions of thevariable domain sequences. Amino acid residues that are part of complementarity determining regions (CDRs) most often will not be altered in connection with humanization, although in certain cases it may be desirable to alter individual CDR amino acid residues, for example to remove a glycosylation site, a deamidation site, an aspartate isomerization site or an undesired cysteine or methionine residue. N-linked glycosylation occurs by attachment of an oligosaccharide chain to an asparagine residue in the tripeptide sequence Asn-X-Ser or Asn-X- Thr, where X may be any amino acid except Pro. Removal of an N-glycosylation site may be achieved by mutating either the Asn or the Ser / Thr residue to a different residue, preferably by way of conservative substitution. Deamidation of asparagine and glutamine residues can occur depending on factors such as pH and surface exposure. Asparagine residues are particularly susceptible to deamidation, primarily when present in the sequence Asn-Gly, and to a lesser extent in other dipeptide sequences such as Asn-Ser, Asn-Thr, and Asn-Ala. When such a deamidation site, in particular Asn-Gly, is present in a CDR sequence, it may therefore be desirable to remove the site, typically by conservative substitution to remove one of the implicated residues.

[0110] The term “isolated antibody” means an antibody that is substantially free of otherantibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds antigen X is substantially free of antibodies that specifically bind antigens other than antigen X). An isolated antibody that specifically binds antigen X may, however, have cross- -34-WSGR Docket No.63125-715.601 reactivity to other antigens, such as antigen X molecules from other species. In certain embodiments, an isolated antibody specifically binds to human antigen X and does not cross- react with other (non-human) antigen X antigens. Moreover, an isolated antibody may be substantially free of other cellular material and / or chemicals.

[0111] The term “monoclonal antibody” or “monoclonal antibody composition” means apreparation of antibody molecules of single molecular composition, which displays a single binding specificity and affinity for a particular epitope.

[0112] The term “human antibody” means an antibody having variable regions in whichboth the framework and CDR regions (and the constant region, if present) are derived from human germline immunoglobulin sequences. Human antibodies may include later modifications, including natural or synthetic modifications. Human antibodies may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo). However, “human antibody” does not include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences.

[0113] The term “human monoclonal antibody” means an antibody displaying a singlebinding specificity, which has variable regions in which both the framework and CDR regions are derived from human germline immunoglobulin sequences. In one embodiment, human monoclonal antibodies are produced by a hybridoma that includes a B cell obtained from a transgenic nonhuman animal, e.g., a transgenic mouse, having a genome comprising a human heavy chain transgene and a light chain transgene fused to an immortalized cell.

[0114] The term "epitope" refers to the amino acids conventionally bound by animmunoglobulin VH / VL pair, such as the antibodies, antigen binding portions thereof and other binding agents described herein. Other binding agents comprise non-antibody scaffolds. An epitope can be formed on a polypeptide from contiguous amino acids or noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained on exposure to denaturing solvents, whereas epitopes formed by tertiary folding are typically lost on treatment with denaturing solvents. An epitope typically includes at least 3, and more usually, at least 5, about 9, or about 8-10 amino acids in a unique spatial conformation. An epitope defines the minimum binding site for an antibody, antigen binding portions thereof and other binding agent, and thus represents the target of specificity of an antibody, antigen binding portion thereof or other immunoglobulin-based binding agent. In the case of a single domain antibody, an epitope represents the unit of structure bound by a variable domain in isolation. -35-WSGR Docket No.63125-715.601

[0115] A “variant” antibody or antigen-binding portion has amino acid substitutions (whichmay be conservative or non-conservative) from a reference antibody or antigen-binding portion, but does not have substantially altered biologic activity from the reference antibody or antigen- binding portion. For example, the variant antibody or antigen-binding portion may retain at least 50%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% of the binding affinity of the reference antibody or antigen-binding portion, or may exceed the binding affinity of the reference antibody or antigen-binding portion.

[0116] The term “specifically binds” refers to the ability of a molecule (e.g., an antibody orantigen binding portion thereof or non-antibody scaffold) described herein to bind to a target with a KD of 10-5M (10000 nM) or less, e.g., 10-6M, 10-7M, 10-8M, 10-9M, 10-10M, 10-11M, 10-12M, or less. Specific binding can be influenced by, for example, the affinity and avidity of the antibody, antigen binding portion or other binding agent and the concentration of target polypeptide.

[0117] As used herein, the term “approximately” or “about” as applied to one or more valuesof interest refers to a value that is similar to a stated reference value. In certain embodiments, the term refers to a range of values that fall within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context.

[0118] The term “cleavable unit” refers to a chemical group that may be cleaved by action ofan internal or external, preferably external, stimulus. The stimulus triggering the cleavage of the cleavable unit may be for instance pH or temperature conditions, or the presence of an enzyme. Cleavage of the cleavable unit preferably triggers self-immolation of the phenyl-comprising linker of the compounds of the invention, and release of the active agent D.

[0119] The term “cleavable sugar unit” or “sugar cleavable unit” can refer to a sugar moiety,preferably a glucuronide or a galactoside.

[0120] The term “peptide cleavable unit” can refer to a polypeptide, preferably a dipeptideor a tripeptide. Linkers, Drug-Linkers and Conjugates of the Disclosure

[0121] In an aspect, the present disclosure provides a Drug-Linker of Formula (X):Formula (X) -36-WSGR Docket No.63125-715.601 or a pharmaceutically acceptable salt thereof, wherein; R40 is independently selected from hydrogen,D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; z is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; -37-WSGR Docket No.63125-715.601 S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, K2, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6 alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – -38-WSGR Docket No.63125-715.601 C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12-memberedheterocycle.

[0122] In some embodiments, Formula (X) is represented byFormula (XI) orFormula (XII) or a pharmaceutically acceptable salt thereof.

[0123] In some embodiments, Formula (X) is represented byFormula (XIII) or a pharmaceutically acceptable salt thereof. -39-WSGR Docket No.63125-715.601

[0124] In some embodiments, Formula (X) or Formula (XIII) is represented byFormula (I) or a pharmaceutically acceptable salt thereof.

[0125] In an aspect, the present disclosure provides a Drug-Linker of Formula (I):Formula (I) or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; -40-WSGR Docket No.63125-715.601 S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6 alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from: (i) a peptide unit, -41-WSGR Docket No.63125-715.601 (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle.

[0126] In an aspect, the present disclosure provides a Drug-Linker of Formula (Ia) orFormula (Ib):Formula (Ia) -42-WSGR Docket No.63125-715.601Formula (Ib) or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino -43-WSGR Docket No.63125-715.601 acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines; K2is selected from: (i) a peptide unit, -44-WSGR Docket No.63125-715.601 (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle.

[0127] In an aspect, the present disclosure provides a conjugate of the Formula (XX):Formula (XX) or a pharmaceutically acceptable salt thereof, wherein; L is a Targeting Unit, wherein the Targeting Unit is an anti-PTK7 antibody or an antigen- binding portion thereof; R40 is independently selected from hydrogen,D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; -45-WSGR Docket No.63125-715.601 z is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4are independently selected at each occurrence from: -46-WSGR Docket No.63125-715.601 (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6alkynyl; M2is a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and -47-WSGR Docket No.63125-715.601 each R30is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12-membered heterocycle.

[0128] In some embodiments, Formula (XX) is represented byFormula (XX), or a pharmaceutically acceptable salt thereof, wherein DAR is selected from about 1 to about 8.

[0129] In some embodiments, for a conjugate or salt of Formula (XX), L is an anti-PTK7antibody or an antigen-binding portion thereof. In some cases, the anti-PTK7 antibody is selected from PTK7-1; PTK7-1EL; PTK7-2; L is PTK7-3; L is PTK7-4; PTK7-5; PTK7-6; PTK7-7; PTK7-8; PTK7-9; PTK7-9EL; PTK7-10; PTK7-11; PTK7-12; PTK7-13; and PTK7- 14.

[0130] In some embodiments, for a conjugate or salt of Formula (XX), when X is CH, D isexatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines.

[0131] In an aspect, the present disclosure provides a conjugate of the Formula (XX):Formula (XX) or a pharmaceutically acceptable salt thereof, wherein; R40 is independently selected from hydrogen,-48-WSGR Docket No.63125-715.601 D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; z is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – -49-WSGR Docket No.63125-715.601 N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6 alkynyl; L is a Targeting Unit, wherein the Targeting Unit is an anti-PTK7 antibody or an antigen- binding portion thereof; M2is a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and -50-WSGR Docket No.63125-715.601 (iv) a polyether; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12-membered heterocycle.

[0132] In an aspect, the present disclosure provides a conjugate of the Formula (A):Formula (A) or a pharmaceutically acceptable salt thereof, wherein; L is a Targeting Unit, wherein the Targeting Unit is an anti-PTK7 antibody or an antigen- binding portion thereof; D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- -51-WSGR Docket No.63125-715.601 C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, --52-WSGR Docket No.63125-715.601S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6alkynyl; M2is a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle.

[0133] In some embodiments, Formula (A) is represented by-53-WSGR Docket No.63125-715.601Formula (A), or a pharmaceutically acceptable salt thereof, wherein DAR is selected from about 1 to about 8.

[0134] In some embodiments, for a conjugate or salt of Formula (A), wherein when X isCH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines.

[0135] In some embodiments, for a conjugate or salt of Formula (A), the Targeting Unit isan anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, L is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the anti-PTK7 antibody is selected from PTK7-1; PTK7-1EL; PTK7-2; PTK7-3; PTK7-4; PTK7-5; PTK7-6; PTK7-7; PTK7-8; PTK7-9; PTK7-9EL; PTK7-10; PTK7-11; PTK7-12; PTK7-13; and PTK7-14.

[0136] In an aspect, the present disclosure provides a conjugate of the Formula (Aa) orFormula (Ab):, or or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; -54-WSGR Docket No.63125-715.601 p is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from: -55-WSGR Docket No.63125-715.601 (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6alkynyl; L is a Targeting Unit, wherein the Targeting Unit is an anti-PTK7 antibody or an antigen- binding portion thereof; M2is a connector unit; K1is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - -56-WSGR Docket No.63125-715.601 N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12-membered heterocycle.

[0137] In some embodiments, Formula (Aa) or Formula (Ab) are represented byor a pharmaceutically acceptable salt thereof, wherein each DAR is selected from about 1 to about 8.

[0138] In some embodiments, for a conjugate or salt of Formula (Aa) or Formula (Ab):when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines.

[0139] In some embodiments, for a conjugate or salt of Formula (Aa) or Formula (Ab), theTargeting Unit is an anti-PTK7 antibody or an antigen-binding portion thereof.

[0140] In some embodiments, for a conjugate or salt of Formula (Aa) or Formula (Ab), theTargeting Unit is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, L is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the anti-PTK7 antibody is selected from PTK7-1; PTK7-1EL; PTK7-2; PTK7-3; PTK7-4; PTK7-5; PTK7-6; PTK7-7; PTK7-8; PTK7-9; PTK7-9EL; PTK7-10; PTK7-11; PTK7-12; PTK7-13; and PTK7- 14. -57-WSGR Docket No.63125-715.601

[0141] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (Ia), Formula (Ib), Formula (X), Formula (XIII) or conjugate of Formula (A), Formula (Aa), Formula (Ab), Formula (XX), or Formula (XXIII), n is 0. In some cases, n is 1.

[0142] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (Ia), Formula (Ib), Formula (X), Formula (XIII) or conjugate of Formula (A), Formula (Aa), Formula (Ab), Formula (XX), or Formula (XXIII), p is 0. In some cases, p is 1.

[0143] In some embodiments, Formula (I) is represented byFormula (I-AA) or a pharmaceutically acceptable salt thereof.

[0144] In some embodiments, Formula (I) or Formula (Ia) is represented byFormula (I-AAa) or a pharmaceutically acceptable salt thereof.

[0145] In some embodiments, Formula (I) or Formula (Ib) is represented byFormula (I-AAb) or a pharmaceutically acceptable salt thereof.

[0146] In some embodiments, Formula (I) is represented by-58-WSGR Docket No.63125-715.601or a pharmaceutically acceptable salt thereof.

[0147] In some embodiments, Formula (I) or Formula (Ia) is represented byor a pharmaceutically acceptable salt thereof.

[0148] In some embodiments, Formula (I) or Formula (Ib) is represented by-59-WSGR Docket No.63125-715.601or a pharmaceutically acceptable salt thereof.

[0149] In some embodiments, Formula (I) is represented byFormula (I-A) or a pharmaceutically acceptable salt thereof.

[0150] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-D), Formula (II-G), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), or Formula (A-4), S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, – N(R20)S(O)2–, –S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or – P(O)(R20)2–. In some cases, S1is selected from: (i) an optionally substituted C6-C10alkylene wherein one or more alkylene units of the C6-C10alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, or –C(O)–. In some cases, S1is an optionally substituted C1alkylene. In some cases, S1is an optionally substituted C2alkylene. In some cases, S1is an optionally substituted C3alkylene. In some cases, S1is an optionally substituted C4 alkylene. In some cases, S1is an optionally substituted C5 alkylene. In some cases, S1is an optionally substituted C6 alkylene. In some cases, S1is an optionally substituted -60-WSGR Docket No.63125-715.601 C7 alkylene. In some cases, S1is an optionally substituted C8 alkylene. In some cases, S1is an optionally substituted C9alkylene. In some cases, S1is an optionally substituted C10alkylene. In some cases, S1is an optionally substituted C11alkylene. In some cases, S1is an optionally substituted C12 alkylene. In some cases, S1is an optionally substituted C13 alkylene. In some cases, S1is an optionally substituted C14 alkylene. In some cases, S1is an optionally substituted C15alkylene. In some cases, S1is an optionally substituted C16alkylene. In some cases, S1is an optionally substituted C17 alkylene. In some cases, S1is an optionally substituted C18 alkylene. In some cases, S1is an optionally substituted C19 alkylene. In some cases, S1is an optionally substituted C20alkylene. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, – N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or – P(O)(R20)2–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, or –C(O)–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –N(R20)–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –N(R20)C(O)–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –C(O)N(R20)–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –C(O)–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –O–. In some cases, if an alkylene unit of the alkylene is replaced, the alkylene may be referred to as a resulting alkylene. In some cases, if two or more of the alkylene units of S1are replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if two or more of the alkylene units of S1are replaced, the adjacent alkylene units of the resulting alkylene are not replaced. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene has no repeating heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene has no repeating of the same heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene unit has no -N-N- or -O-O-. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene unit is a stable alkylene. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene unit is an unreactive alkylene. In some cases, the resulting alkylene has only 1 heteroatom. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are different from each other. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 3 heteroatoms, wherein the 3 heteroatoms are not adjacent to -61-WSGR Docket No.63125-715.601 each other. In some cases, the alkylene has 0 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 2 replaced units. In some cases, the alkylene has 3 replaced units. In some cases, the alkylene has 4 replaced units. In some cases, the alkylene has 5 replaced units. In some cases, the alkylene has 6 replaced units. In some cases, no adjacent alkylene units of the alkylene are replaced. In some cases, no adjacent alkylene units resulting in two or more adjacent heteroatoms are present in the resulting alkylene (e.g., adjacent – N(R20)S(O)2– and –N(R20)– are not allowed, but the singular –N(R20)S(O)2– is allowed). In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, a resulting alkylene has two heteroatoms, the two heteroatoms are from a singular replaced alkylene unit. In some cases, there are two heteroatoms in a resulting alkylene if they result from a singular replacement of an alkylene unit. In some cases, the optional substituents on S1are independently selected at eachoccurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituentsindependently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, the optional substituents on S1are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN. In some cases, the optional substituents on S1are independently selected at each occurrence from: halogen, -OR30, - N(R30)2, =O, and -CN. In some cases, the optional substituents on S1are independently selected at each occurrence from: =O.

[0151] In some embodiments, for a Drug-Linker or salt of Formula (I), Formula (X),Formula (XIII), X is CH; S1is selected from-62-WSGR Docket No.63125-715.601n is 0; m is 1; Y is selected from a cleavable sugar and cleavable peptide (e.g., dipeptide); K1is selected from a peptide unit and oligosaccharide; and.

[00152] In some embodiments, for a Drug-Linker or salt of Formula (Ia), Formula (Ib),Formula (I-AAa), or Formula (I-AAb), X is CH:n is 0; -63-WSGR Docket No.63125-715.601 m is 1; Y is selected from a cleavable sugar and cleavable peptide (e.g., dipeptide); K1is selected from a peptide unit and oligosaccharide; and.

[0153] In some embodiments, for a Drug-Linker or salt of Formula (I), Formula (X),Formula (XIII), X is CH;-64-WSGR Docket No.63125-715.601

[0154] In some embodiments, for a Drug-Linker or salt of Formula (I), Formula (X),Formula (XIII), X is CH;-65-WSGR Docket No.63125-715.601 n is 0;-66-WSGR Docket No.63125-715.601.

[0155] In some embodiments, for a Drug-Linker or salt of Formula (Ia), Formula (Ib),X is CH;-67-WSGR Docket No.63125-715.601

[0156] In some embodiments, for a Drug-Linker or salt of Formula (I-AAa), or Formula (I-Aab), -68-WSGR Docket No.63125-715.601, -69-WSGR Docket No.63125-715.601

[0157] In some embodiments, for a Drug-Linker or salt of Formula (I), Formula (X),Formula (XIII), X is N; S1is selected from-70-WSGR Docket No.63125-715.601-71-WSGR Docket No.63125-715.601.

[00158] In some embodiments, for a Drug-Linker or salt of Formula (I), Formula (X),Formula (XIII), X is N;-72-WSGR Docket No.63125-715.601.

[0159] In some embodiments, for a Drug-Linker or salt of Formula (Ia), Formula (Ib),Formula (I-AAa), or Formula (I-AAb), -73-WSGR Docket No.63125-715.601 X is N;, -74-WSGR Docket No.63125-715.601

[0160] In some embodiments, for a Drug-Linker or salt of Formula (I), Formula (X),Formula (XIII), X is CH;n is 1; -75-WSGR Docket No.63125-715.601 m is 0; p is 1;Y is selected from a cleavable sugar and cleavable peptide (e.g., dipeptide); K2is selected from a peptide unit and oligosaccharide; and.

[00161] In some embodiments, for a Drug-Linker or salt of Formula (Ia), Formula (Ib),Formula (I-AAa), or Formula (I-AAb), X is CH;Y is selected from a cleavable sugar and cleavable peptide (e.g., dipeptide); K2is selected from a peptide unit and oligosaccharide; and -76-WSGR Docket No.63125-715.601.

[00162] In some embodiments, for a Drug-Linker or salt of Formula (I), Formula (X),Formula (XIII), X is CH;-77-WSGR Docket No.63125-715.601.

[00163] In some embodiments, for a Drug-Linker or salt of Formula (I), Formula (X),Formula (XIII), X is CH;n is 1; m is 0; p is 1; -78-WSGR Docket No.63125-715.601-79-WSGR Docket No.63125-715.601.

[00164] In some embodiments, for a Drug-Linker or salt of Formula (Ia), Formula (Ib),Formula (I-AAa), or Formula (I-AAb), X is CH;-80-WSGR Docket No.63125-715.601.

[00165] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I- AAa), Formula (Ib), Formula (I-AAb), Formula (II-C), Formula (I-CA), or Formula (II-D), Formula (X), Formula (XI), Formula (XII), Formula (XIII) or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), Formula (A-4), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S1is a branched alkylene.

[00166] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I- AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), Formula (II-C), Formula -81-WSGR Docket No.63125-715.601 (II-CA), Formula (II-D), Formula (X), Formula (XI), Formula (XII), Formula (XIII) or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (XX),Formula (XXI), Formula (XXII), or Formula (XXIII), S1 is selected from.

[0167] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I- AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-D), Formula (X), Formula (XI), Formula (XII), Formula (XIII) or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S1is represented

[0168] In some embodiments, for a Drug-Linker or salt of Formula (I), S1-K1 is represented

[0169] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I- AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-CA), Formula (II-D), Formula (II-G), Formula (X), Formula (XI), Formula (XII), Formula (XIII) or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), Formula (A-4), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S2is selected from: (i) an optionally substituted C8-C12alkylene wherein one or more alkylene units of the C8-C12alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –O–, and –C(O)–. In some cases, S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, – N(R20)S(O)2–, –S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or – P(O)(R20)2–. In some cases, S2is selected from: (i) an optionally substituted C6-C10 alkylene wherein one or more alkylene units of the C6-C10alkylene are optionally and independently -82-WSGR Docket No.63125-715.601 replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, or –C(O)–. In some cases, S2is an optionally substituted C1alkylene. In some cases, S2is an optionally substituted C2alkylene. In some cases, S2is an optionally substituted C3alkylene. In some cases, S2is an optionally substituted C4 alkylene. In some cases, S2is an optionally substituted C5 alkylene. In some cases, S2is an optionally substituted C6 alkylene. In some cases, S2is an optionally substituted C7alkylene. In some cases, S2is an optionally substituted C8alkylene. In some cases, S2is an optionally substituted C9 alkylene. In some cases, S2is an optionally substituted C10 alkylene. In some cases, S2is an optionally substituted C11 alkylene. In some cases, S2is an optionally substituted C12alkylene. In some cases, S2is an optionally substituted C13alkylene. In some cases, S2is an optionally substituted C14 alkylene. In some cases, S2is an optionally substituted C15 alkylene. In some cases, S2is an optionally substituted C16 alkylene. In some cases, S2is an optionally substituted C17alkylene. In some cases, S2is an optionally substituted C18alkylene. In some cases, S2is an optionally substituted C19alkylene. In some cases, S2is an optionally substituted C20 alkylene. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, – N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or – P(O)(R20)2–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, or –C(O)–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –N(R20)–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –N(R20)C(O)–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –C(O)N(R20)–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –C(O)–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –O–. In some cases, if an alkylene unit of the alkylene is replaced, the alkylene may be referred to as a resulting alkylene. In some cases, if two or more of the alkylene units of S2are replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if two or more of the alkylene units of S2are replaced, the adjacent alkylene units of the resulting alkylene are not replaced. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene has no repeating heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene has no repeating of the same heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene unit has no -N-N- or -O-O-. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene unit is a stable alkylene. In some cases, if two or more of the alkylene units of -83-WSGR Docket No.63125-715.601 S2are replaced, the resulting alkylene unit is an unreactive alkylene. In some cases, the resulting alkylene has only 1 heteroatom. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are different from each other. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 3 heteroatoms, wherein the 3 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 4 heteroatoms, wherein the 4 heteroatoms are not adjacent to each other. In some cases, the alkylene has 0 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 2 replaced units. In some cases, the alkylene has 3 replaced units. In some cases, the alkylene has 4 replaced units. In some cases, the alkylene has 5 replaced units. In some cases, the optional substituents on S2, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30,-O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituentsindependently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, the optional substituents on S2, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN. In some cases, the optional substituents on S2, are independently selected at each occurrence from: halogen, -OR30, -N(R30)2, =O, and -CN. In some cases, the optional substituents on S2, are independently selected at each occurrence from: =O. In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, a resulting alkylene has two heteroatoms, the two heteroatoms are from a singular replaced alkylene unit. In some cases, there are two heteroatoms in a resulting alkylene if they result from a singular replacement of an alkylene unit.

[0170] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), or Formula (II-B), Formula (II-C), Formula (II-D), Formula (II-G), Formula (X), Formula (XI), Formula (XII), Formula (XIII) or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), Formula (A-4), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S2is a linear alkylene. -84-WSGR Docket No.63125-715.601

[0171] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), Formula (X), Formula (XI), Formula (XII), Formula (XIII) or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), Formula (A-4), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S2is.

[0172] In some embodiments, Formula (I) or Formula (I-A) is represented byFormula (I-B) or a pharmaceutically acceptable salt thereof.

[0173] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (Ia), Formula (Ib), Formula (I-A), or Formula (I-B), Formula (X), Formula (XIII) or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (XX), or Formula (XXIII), X is CH. -85-WSGR Docket No.63125-715.601

[0174] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (Ia), Formula (Ib), Formula (I-A), or Formula (I-B), Formula (X), Formula (XIII) or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (XX), or Formula (XXIII), X is N.

[0175] In some embodiments, Formula (I) is represented byFormula (II-A) or a pharmaceutically acceptable salt thereof.

[0176] In some embodiments, Formula (I) is represented byFormula (II-B) or a pharmaceutically acceptable salt thereof.

[0177] In some embodiments, Formula (X) is represented byFormula (II-G) or a pharmaceutically acceptable salt thereof.

[0178] In some embodiments, Formula (I) is represented byFormula (II-C) or a pharmaceutically acceptable salt thereof.

[0179] In some embodiments, Formula (I) is represented by-86-WSGR Docket No.63125-715.601Formula (II-D) or a pharmaceutically acceptable salt thereof.

[0180] In some embodiments, Formula (I) is represented byor a pharmaceutically acceptable salt thereof.

[0181] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I- AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-CA), Formula (II-D), Formula (II-G), Formula (X), Formula (XI), Formula (XII), Formula (XIII) or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), Formula (A-4), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S1is selected from: (i) an optionally substituted C4-C10alkylene wherein one or more alkylene units of the C4-C10 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, or –C(O)–.

[0182] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), or Formula (A-4), S1is selected from: (i) an optionally substituted C1-C3alkylene wherein one or more alkylene units of the C1-C3alkylene are optionally and independently replaced by –N(R20)–. In some cases, S1is selected from: (i) an optionally substituted C1-C2alkylene wherein one or more alkylene units of the C1-C2alkylene are optionally and independently replaced by –N(R20)–. In some cases, S1is selected from: (i) an -87-WSGR Docket No.63125-715.601 optionally substituted C2-C3 alkylene wherein one or more alkylene units of the C2-C3 alkylene are optionally and independently replaced by –N(R20)–. In some cases, S1is selected from. In some cases, S1is represented by.

[0183] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), or Formula (A-4), S1is selected from. some cases, S1is represented

[0184] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-CA), Formula (II-D), Formula (II- G), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), or Formula (A-4), S2is selected from: (i) an optionally substituted C8-C12 alkylene wherein one or more alkylene units of the C8-C12 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –O–, and –C(O)–. In some cases, S2is selected from.

[0185] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-CA), Formula (II-D), Formula (II- G), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula -88-WSGR Docket No.63125-715.601 (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), or Formula (A-4), S2is selected from: (i) an optionally substituted C8-C12alkylene wherein one or more alkylene units of the C8-C12alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –O–, and –C(O)–. In some cases, S2is selected from.

[0186] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I- AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), or Formula (A-4), S2is a linear alkylene.

[0187] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-AA), Formula (I- AB), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-CA), Formula (II-D), Formula (II-G), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), or Formula -89-WSGR Docket No.63125-715.601.

[0188] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), or Formula (A-4), S1-S2is represented by.

[0189] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (II-A), Formula (II-B), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), or Formula (A-4), S1-S2-M1is represented by, wherein S3is absent.

[0190] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (I-AA), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-D), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), or Formula (A-4), S3is present and is a phenylene.

[0191] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (I), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I- -90-WSGR Docket No.63125-715.601 AA), Formula (I-A), Formula (I-B), Formula (II-A), Formula (II-B), Formula (II-C), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), or Formula (A-4), S3is absent.

[0192] In some embodiments, a Drug-Linker or salt of Formula (I), is represented byFormula (II-E). In some cases, p is 1.

[0193] In some embodiments, a Drug-Linker or salt of Formula (I), is represented byFormula (II-F). In some cases, p is 1.

[0194] In some embodiments, the conjugate is represented byFormula (XX), wherein the DAR is a drug to Targeting Unit (L) ratio. In some cases, the DAR is a drug to antibody ratio. In some cases, the DAR is about 4. In some cases, the DAR is about 8.

[0195] In some embodiments, the conjugate of Formula (XX) is represented byFormula (A), -91-WSGR Docket No.63125-715.601 wherein the DAR is a drug to Targeting Unit (L) ratio. In some cases, the DAR is a drug to antibody ratio. In some cases, the DAR is about 4. In some cases, the DAR is about 8.

[0196] In some embodiments, the conjugate of Formula (XX) is represented byFormula (A-1), wherein the DAR is a drug to Targeting Unit (L) ratio. In some cases, the DAR is a drug to antibody ratio. In some cases, the DAR is about 4. In some cases, the DAR is about 8. In some cases, X is CH. In some cases, X is N.

[0197] In some embodiments, for a conjugate or salt of Formula (A),, wherein L is an anti-PTK7 antibody or an antigen-binding portion thereof; and DAR is a drug to Targeting Unit (L) ratio wherein K1is selected from a peptide unit; wherein the amino acids of K1is selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β-Alanine;.Y-92-WSGR Docket No.63125-715.601some cases, DAR is about 8. In some cases, K1is selected from,, -93-WSGR Docket No.63125-715.601-94-WSGR Docket No.63125-715.601. In some cases,. In some cases, K1isome cases, L is selected from -95-WSGR Docket No.63125-715.601 PTK7-1; PTK7-1EL; PTK7-2; L is PTK7-3; L is PTK7-4; PTK7-5; PTK7-6; PTK7-7; PTK7-8; PTK7-9; PTK7-9EL; PTK7-10; PTK7-11; PTK7-12; PTK7-13; and PTK7-14. In some cases, L is PTK7-1.

[0198] In some cases, L is PTK7-1EL. In some cases, L is PTK7-2. In some cases, L isPTK7-3. In some cases, L is PTK7-4. In some cases, L is PTK7-5. In some cases, L is PTK7-6. In some cases, L is PTK7-7. In some cases, L is PTK7-8. In some cases, L is PTK7-9. In some cases, L is PTK7-10

[0199] In some cases, L is PTK7-11. In some cases, L is PTK7-12. In some cases, L isPTK7-13. In some cases, L is PTK7-14.

[0200] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-CA), Formula (I- A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II- A), Formula (II-B), Formula (II-C), Formula (II-CA), Formula (II-D), Formula (II-E), Formula (II-F), or for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the sugar cleavable unit of T1includes a sugar. In some cases, the sugar is glucuronide. In some cases, the sugar is selected from fructose, galactose, glucose, xylose and ribose. In some cases, the sugar is a monosaccharide. In some cases, the sugar is a disaccharide. In some cases, the β-glucuronidase enzyme in lysosomes or the tumor interstitium cleaves the drug-linker between the sugar and the oxygen bond, releasing the drug.

[0201] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I- A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II- A), Formula (II-B), Formula (II-C), Formula (II-CA), Formula (II-D), Formula (II-E), Formula (II-F), or for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (

[0202] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XIII), Formula (I), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (I-B), Formula (II- A), Formula (II-B), Formula (II-C), Formula (II-CA),Formula (II-D), Formula (II-E), Formula -96-WSGR Docket No.63125-715.601 (II-F), or for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the peptide unit of T2includes one or more amino acids selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine. In some cases, the peptide unit of T2includes one or more amino acids selected from a group consisting of alanine, arginine, asparagine, aspartic acid, glutamine, glycine, lysine, methionine, phenylalanine, proline, serine, valine, citrulline, and β-Alanine. In some cases, the peptide unit of T2includes a dipeptide or tripeptide. In some cases, the peptide unit of T2includes a dipeptide. In some cases, the dipeptide is selected from Val-Cit, Val-Ala and Phe- Lys. In some cases, Cathepsin B is a lysosomal cysteine protease that is highly up-regulated in malignant cells. In some cases, the peptide cleavable unit is cleaved by Cathepsin B.

[0203] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XIII), Formula (I), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (I-B), Formula (II- A), Formula (II-B), Formula (II-C), Formula (II-A), Formula (II-D), Formula (II-E), Formula (II-F), or for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the peptide unit of T2includes a capping moiety. In some cases, the capping moiety is a moiety capable of reacting with an amine of the peptide to form an amide, carbamate or sulfonamide. In some cases, the capping moiety is a moiety which results from reacting with an amine to form an amide, carbamate or sulfonamide. In some cases, the capping moiety is a moiety which results from reacting with an amine to form an amide. In some cases, the capping moiety is a moiety which caps the end of an peptide / amino acid. In some cases, the capping moiety i.

[0204] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-7), or Formula (A-8), K1is not a polysarcosine. In some cases, K1does not include adjacent sarcosines. In some cases, when K1includes a sarcosine, there is at least one other amino acid -97-WSGR Docket No.63125-715.601 present. In some cases, when a peptide unit includes a sarcosine, there is at least one other amino acid present.

[0205] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-7), or Formula (A-8), K1includes PASylation. In some cases, PASylation is a peptide comprising proline, alanine, and serine. In some cases, PASylation is a peptide consisting of only proline, alanine, and serine. In some cases, K1includes PASylation of less than PAS100. For example, PAS100 refers to a peptide having 100 amino acids, wherein the amino acids are selected from proline, alanine, and serine. In some cases, K1includes PASylation of less than PAS50. In some cases, K1includes PASylation of less than PAS25. In some cases, K1includes PASylation of more than PAS5. In some cases, K1includes PASylation of more than PAS9. In some cases, K1includes PASylation of more than PAS15. In some cases, K1includes PASylation of PAS5 to PAS25. In some cases, K1includes PASylation of PAS10 to PAS20. In some cases, K1includes PASylation of PAS10. In some cases, K1includes PASylation of PAS20. In some cases, K1includes a beta-alanine that links the PASylation to the drug-linker. In some cases, PASylation is used to extend the plasma half-life. In some cases, PASylation is used to increase solubility. In some cases, PASylation is used to increase solubility without generating secondary structures. In some cases, PASylation is.

[0206] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-7), or Formula (A-8), K1is not a polysarcosine. In some cases, K1includes adjacent sarcosines. In some cases, when K1includes a sarcosine, there is at least one other amino acid present. In some cases, when K1includes adjacent sarcosines, there is at least one other amino acid present. In -98-WSGR Docket No.63125-715.601 some cases, when a peptide unit includes a sarcosine, there is at least one other amino acid present. In some cases, when a peptide unit includes adjacent sarcosines, there is at least one other amino acid present. In some cases, K1includes a glycine and two adjacent sarcosines. In some cases, K1includes a glycine and three adjacent sarcosines. In some cases, K1includes a glycine and four adjacent sarcosines. In some cases, K1is a peptide unit selected from a glycine and two adjacent sarcosines. In some cases K1is a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, K1is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, K1includes 2 glycines and 8 sarcosines. In some cases, K1includes 3 glycines and 8 sarcosines. In some cases, K1includes 4 glycines and 7 sarcosines. In some cases, K1includes 3 glycines and 7 sarcosines. In some cases, K1includes 3 glycines and 6 sarcosines. In some cases, K1includes 3 glycines and 5 sarcosines. In some cases, K1includes 3 glycines and 4 sarcosines. In some cases, K1includes 3 glycines and 3 sarcosines. In some cases, K1includes 3 glycines and 9 sarcosines. In some cases, K1includes 3 glycines and 10 sarcosines. In some cases, K1includes 5 glycines and 5 sarcosines. In some cases, K1includes 4 glycines and 4 sarcosines. In some cases, K1includes 4 glycines and 5 sarcosines. In some cases, K1includes 5 glycines and 4 sarcosines. In some cases, K1has at most 9 sarcosines. In some cases, K1has at most 8 sarcosines. In some cases, K1has at most 7 sarcosines. In some cases, K1has at most 6 sarcosines. In some cases, K1has at most 5 sarcosines. In some cases, K1has at most 4 sarcosines. In some cases, K1has at most 3 sarcosines. In some cases, K1has at most 2 sarcosines. In some cases, K1has at most 1 sarcosine. In some cases, K1has at most 9 glycines. In some cases, K1has at most 8 glycines. In some cases, K1has at most 7 glycines. In some cases, K1has at most 6 glycines. In some cases, K1has at most 5 glycines. In some cases, K1has at most 4 glycines. In some cases, K1has at most 3 glycines. In some cases, K1has at most 2 glycines. In some cases, K1has at most 1 glycine.

[0207] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-7), or Formula (A-8), each K1is selected from a peptide unit. In some cases, the peptide unit of K1has 1 to 50 amino acids. In some cases, the peptide unit of K1has 1 to 20 amino acids. In some cases, the peptide unit of K1has 1 to 10 amino acids. In some cases, the peptide unit of K1has 2 to 50 amino acids. In some cases, the peptide unit of K1has 2 to 40 amino acids. In some cases, the peptide unit of K1has 2 to 30 amino acids. In some cases, the peptide unit of K1has 2 to 20 amino acids. In some cases, -99-WSGR Docket No.63125-715.601 the peptide unit of K1has 2 to 10 amino acids. In some cases, the peptide unit of K1has 5 to 10 amino acids. In some cases, the peptide unit of K1has at least 1 amino acids. In some cases, the peptide unit of K1has 1 amino acid. In some cases, the peptide unit of K1has at least 2 amino acids. In some cases, the peptide unit of K1has at least 5 amino acids. In some cases, the peptide unit of K1has at least 8 amino acids. In some cases, the peptide unit of K1has at least 10 amino acids. In some cases, the peptide unit of K1has at most 10 amino acids. In some cases, the peptide unit of K1has 10 amino acids. In some cases, the peptide unit of K1has at least 12 amino acids. In some cases, the peptide unit of K1has at most 12 amino acids. In some cases, the peptide unit of K1has at least 20 amino acids. In some cases, the peptide unit of K1has at most 20 amino acids. In some cases, the peptide unit of K1has 20 amino acids. In some cases, the peptide unit of K1has at most 30 amino acids. In some cases, the peptide unit of K1has at least 30 amino acids. In some cases, the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K1includes at least one glycine and at least one other amino acid. In some cases, the amino acids of K1includes at least one glycine and at least one sarcosine. In some cases, the amino acids of K1includes at least one glycine and at least one other amino acid selected from proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, proline, serine, alanine, and β- Alanine. In some cases, K1includes at least one glycine. In some cases, K1includes at least one proline. In some cases, K1includes at least one serine. In some cases, K1includes at least one alanine. In some cases, K1includes at least one β-Alanine.

[0208] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (Ia), -100-WSGR Docket No.63125-715.601 Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-7), or Formula (A-8), each K1is selected from a peptide unit. In some cases, the peptide unit of K1has 1 to 50 amino acids. In some cases, the peptide unit of K1has 1 to 20 amino acids. In some cases, the peptide unit of K1has 1 to 10 amino acids. In some cases, the peptide unit of K1has 2 to 50 amino acids. In some cases, the peptide unit of K1has 2 to 40 amino acids. In some cases, the peptide unit of K1has 2 to 30 amino acids. In some cases, the peptide unit of K1has 2 to 20 amino acids. In some cases, the peptide unit of K1has 2 to 10 amino acids. In some cases, the peptide unit of K1has 5 to 10 amino acids. In some cases, the peptide unit of K1has at least 1 amino acids. In some cases, the peptide unit of K1has 1 amino acid. In some cases, the peptide unit of K1has at least 2 amino acids. In some cases, the peptide unit of K1has at least 5 amino acids. In some cases, the peptide unit of K1has at least 8 amino acids. In some cases, the peptide unit of K1has at least 10 amino acids. In some cases, the peptide unit of K1has at most 10 amino acids. In some cases, the peptide unit of K1has 10 amino acids. In some cases, the peptide unit of K1has at least 12 amino acids. In some cases, the peptide unit of K1has at most 12 amino acids. In some cases, the peptide unit of K1has at least 20 amino acids. In some cases, the peptide unit of K1has at most 20 amino acids. In some cases, the peptide unit of K1has 20 amino acids. In some cases, the peptide unit of K1has at most 30 amino acids. In some cases, the peptide unit of K1has at least 30 amino acids. In some cases, K1is a peptide unit selected from a glycine and two adjacent sarcosines. In some cases K1is a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, K1is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, when a peptide unit includes adjacent sarcosines, there is at least one other amino acid present. In some cases, K1includes a glycine and two adjacent sarcosines. In some cases, K1includes a glycine and three adjacent sarcosines. In some cases, K1includes a glycine and four adjacent sarcosines. In some cases, K1is a peptide unit selected from a glycine and two adjacent sarcosines. In some cases K1is a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, K1is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, K1includes 2 glycines and 8 sarcosines. In some cases, K1includes 3 glycines and 8 sarcosines. In some cases, K1includes 4 glycines and 7 sarcosines. In some cases, K1includes 3 glycines and 7 sarcosines. In some cases, K1includes 3 glycines and 6 sarcosines. In some cases, K1includes 3 glycines and 5 sarcosines. In some cases, K1includes 3 glycines and 4 sarcosines. In some cases, K1includes 3 glycines and 3 sarcosines. In some cases, K1includes 3 glycines and 9 sarcosines. In some cases, K1includes 3 glycines and 10 -101-WSGR Docket No.63125-715.601 sarcosines. In some cases, K1includes 5 glycines and 5 sarcosines. In some cases, K1includes 4 glycines and 4 sarcosines. In some cases, K1includes 4 glycines and 5 sarcosines. In some cases, K1includes 5 glycines and 4 sarcosines. In some cases, K1has at most 9 sarcosines. In some cases, K1has at most 8 sarcosines. In some cases, K1has at most 7 sarcosines. In some cases, K1has at most 6 sarcosines. In some cases, K1has at most 5 sarcosines. In some cases, K1has at most 4 sarcosines. In some cases, K1has at most 3 sarcosines. In some cases, K1has at most 2 sarcosines. In some cases, K1has at most 1 sarcosine. In some cases, K1has at most 9 glycines. In some cases, K1has at most 8 glycines. In some cases, K1has at most 7 glycines. In some cases, K1has at most 6 glycines. In some cases, K1has at most 5 glycines. In some cases, K1has at most 4 glycines. In some cases, K1has at most 3 glycines. In some cases, K1has at most 2 glycines. In some cases, K1has at most 1 glycine. In some cases, the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β- Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K1includes at least one glycine and at least one other amino acid. In some cases, the amino acids of K1includes at least one glycine and at least one sarcosine. In some cases, the amino acids of K1includes at least one glycine and at least one other amino acid selected from proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, K1includes at least one glycine. In some cases, K1includes at least one proline. In some cases, K1includes at least one serine. In some cases, K1includes at least one alanine. In some cases, K1includes at least one β- Alanine.

[0209] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), -102-WSGR Docket No.63125-715.601 Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-7), or Formula (A-8), K1is selected from a peptide unit. wherein the peptide unit has a terminal -NH2. In some cases, K1is selected from a peptide unit. wherein the peptide unit has a terminal -OH. In some cases, K1is selected from a peptide. wherein the peptide has a terminal -NH2. In some cases, K1is selected from a peptide, wherein the peptide has a terminal -OH.

[0210] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-7), or Formula (A-8), the peptide unit, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some, -103-WSGR Docket No.63125-715.601, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, R6is selected from -OH, -NH2, and . In some cases, R6is -OH. In some cases, R6is -NH2. In some cases, R6is.

[0211] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-7), or Formula (A-8), K1is selected, -104-WSGR Docket No.63125-715.601some cases, K1is selected from. In some cases, K1is selected from. some cases, K1is selected from. some cases, K1is selected from.

[0212] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), or Formula (A-2), the peptide unit of K1has a terminus unit. In -105-WSGR Docket No.63125-715.601 some cases, K1is selected from, ,, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O--106-WSGR Docket No.63125-715.601S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, R6is selected from -OH, -NH2, and . In some cases, R6is -OH. In some cases, R6is -NH2. In some cases, R6is.

[0213] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-7), or Formula (A-8), K1is selected-107-WSGR Docket No.63125-715.601some cases, K1is selected from. In some cases, K1is selected fromsome cases, K1is selected fromsome cases, K1is selected from. In some cases, K1is selected from.-108-WSGR Docket No.63125-715.601.cases, K1 is selected fromsome cases, K1is selected from. In some cases, K1is selected from -109-WSGR Docket No.63125-715.601. cases, K1is selected from.

[0214] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-7), or Formula (A-8), the peptide unit of K1has a terminus unit. In some cases, K1is selected from,, -110-WSGR Docket No.63125-715.601, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some-111-WSGR Docket No.63125-715.601, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, R6is selected from -OH, -NH2, and . In some cases, R6is -OH. In some cases, R6is -NH2. In some cases, R6is.

[0215] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-D), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), or Formula (A-8), each K1is selected from: an oligosaccharide. In some cases, -112-WSGR Docket No.63125-715.601 each K1is selected from:, wherein k is selected from 2 to 10. In some cases, each K1is selected from:, wherein k is selected from 2 to 10. In some cases, k is 2. In some cases, k is 3. In some cases, k is 4. In some cases, k is 5. In some cases, k is 6. In some cases, each K1is selected from:.

[0216] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), or Formula (A-2), S1is represented by -113-WSGR Docket No.63125-715.601.

[0217] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XIII), Formula (I), Formula (Ia), Formula (Ib), Formula (II-A), Formula (II-B), Formula (II-E), Formula (II-F), or for a conjugate or salt of Formula (XX), -114-WSGR Docket No.63125-715.601 Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), K2is selected from a peptide unit. In some cases, the peptide unit is a residue. In some cases, the peptide unit of K2has 1 to 50 amino acids. In some cases, the peptide unit of K2has 1 to 20 amino acids. In some cases, the peptide unit of K2has 1 to 10 amino acids. In some cases, the peptide unit of K2has 2 to 50 amino acids. In some cases, the peptide unit of K2has 2 to 40 amino acids. In some cases, the peptide unit of K2has 2 to 30 amino acids. In some cases, the peptide unit of K2has 2 to 20 amino acids. In some cases, the peptide unit of K2has 2 to 10 amino acids. In some cases, the peptide unit of K2has 5 to 10 amino acids. In some cases, the peptide unit of K2has at least 1 amino acid. In some cases, the peptide unit of K2has 1 amino acid. In some cases, the peptide unit of K2has at least 2 amino acids. In some cases, the peptide unit of K2has at least 5 amino acids. In some cases, the peptide unit of K2has at least 8 amino acids. In some cases, the peptide unit of K2has at least 10 amino acids. In some cases, the peptide unit of K2has at most 10 amino acids. In some cases, the peptide unit of K2has 10 amino acids. In some cases, the peptide unit of K2has at least 12 amino acids. In some cases, the peptide unit of K2has at most 12 amino acids. In some cases, the peptide unit of K2has at least 20 amino acids. In some cases, the peptide unit of K2has at most 20 amino acids. In some cases, the peptide unit of K2has 20 amino acids. In some cases, the peptide unit of K2has at most 30 amino acids. In some cases, the peptide unit of K2has at least 30 amino acids. In some cases, the amino acids of K2are selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine. In some cases, the amino acids of K2are selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine. In some cases, the amino acids of K2are selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine. In some cases, the amino acids of K2are selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K2are selected from a group consisting of sarcosine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K2are selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K2are selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, K2includes at least one glycine. In some cases, K2includes at least one proline. In some cases, K2includes at least -115-WSGR Docket No.63125-715.601 one serine. In some cases, K2includes at least one alanine. In some cases, K2includes at least one β-Alanine. In some cases, K2is a polysarcosine. In some cases, K2is a polysarcosine with ten repeating sarcosine units. In some cases, the amino acids of K2includes at least one glycine and at least one amino acid. In some cases, the amino acids of K2includes at least one glycine and at least one amino acid selected from sarcosine, proline, serine, alanine, and β-Alanine.

[0218] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (I-AB), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-C), Formula (II-CA), Formula (II-D), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), or Formula (A-2), K2K2is not a polysarcosine. In some cases, K2includes adjacent sarcosines. In some cases, when K2includes a sarcosine, there is at least one other amino acid present. In some cases, when K2includes adjacent sarcosines, there is at least one other amino acid present. In some cases, when a peptide unit includes a sarcosine, there is at least one other amino acid present. In some cases, when a peptide unit includes adjacent sarcosines, there is at least one other amino acid present. In some cases, K2includes a glycine and two adjacent sarcosines. In some cases, K2includes a glycine and three adjacent sarcosines. In some cases, K2includes a glycine and four adjacent sarcosines. In some cases, K2is a peptide unit selected from a glycine and two adjacent sarcosines. In some cases K2is a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, K2is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, K2includes 2 glycines and 8 sarcosines. In some cases, K2includes 3 glycines and 8 sarcosines. In some cases, K2includes 4 glycines and 7 sarcosines. In some cases, K2includes 3 glycines and 7 sarcosines. In some cases, K2includes 3 glycines and 6 sarcosines. In some cases, K2includes 3 glycines and 5 sarcosines. In some cases, K2includes 3 glycines and 4 sarcosines. In some cases, K2includes 3 glycines and 3 sarcosines. In some cases, K2includes 3 glycines and 9 sarcosines. In some cases, K2includes 3 glycines and 10 sarcosines. In some cases, K2includes 5 glycines and 5 sarcosines. In some cases, K2includes 4 glycines and 4 sarcosines. In some cases, K2includes 4 glycines and 5 sarcosines. In some cases, K2includes 5 glycines and 4 sarcosines. In some cases, K2has at most 9 sarcosines. In some cases, K2has at most 8 sarcosines. In some cases, K2has at most 7 sarcosines. In some cases, K2has at most 6 sarcosines. In some cases, K2has at most 5 sarcosines. In some cases, K2has at most 4 sarcosines. In some cases, K2has at most 3 sarcosines. In some cases, K2has at most 2 sarcosines. In some cases, K2has at most 1 sarcosine. In some cases, K2has at most 9 glycines. In some cases, K2has at most 8 glycines. In some cases, K2has at most 7 glycines. In some cases, K2has at most 6 glycines. In some cases, K2has at most 5 glycines. In some cases, K2has at most 4 glycines. In some cases, K2has at -116-WSGR Docket No.63125-715.601 most 3 glycines. In some cases, K2has at most 2 glycines. In some cases, K2has at most 1 glycine.

[0219] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XIII), Formula (I), Formula (Ia), Formula (Ib), Formula (II-A), Formula (II-B), Formula (II-E), Formula (II-F), or for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab),Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), the peptide unit of K2has a terminus unit. In some cases, K2is, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - -117-WSGR Docket No.63125-715.601C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, R6is selected from -OH, -NH2, and . In some cases, R6is -OH. In some cases, R6is -NH2. In some cases, R6is.

[0220] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XIII), Formula (I), Formula (Ia), Formula (Ib), Formula (II-A), Formula (II-B), Formula (II-E), Formula (II-F), or for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab),Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), the peptide unit of K2has a terminus unit. In some cases, K2is, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, K2is selected, -118-WSGR Docket No.63125-715.601, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, R6is selected from -OH, -NH2, and . In some cases, R6is -OH. In some cases, R6is -NH2. In some cases, R6is.

[0221] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XIII), Formula (I), Formula (Ia), Formula (Ib), Formula (II-A), Formula (II-B), Formula (II-E), Formula (II-F), or for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), K2is selected from,, -119-WSGR Docket No.63125-715.601some cases, K2is selected from. In some cases, K2is selected from. In some cases, K2is selected fromsome cases, K2is selected from.

[0222] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XIII), Formula (I), Formula (Ia), Formula (Ib), Formula (II-A), -120-WSGR Docket No.63125-715.601 Formula (II-B), Formula (II-E), Formula (II-F), or for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4),, -121-WSGR Docket No.63125-715.601some cases, K2is selected from. In some cases, K2is selected from. In some cases, K2issome cases, K2is selected from-122-WSGR Docket No.63125-715.601. In some cases, K2is selected from-123-WSGR Docket No.63125-715.601

[0223] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XIII), Formula (I), Formula (Ia), Formula (Ib), Formula (II-A), Formula (II-B), Formula (II-E), Formula (II-F), or for a conjugate or salt of Formula (X), Formula (XIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), each K2is selected from: an oligosaccharide. In some cases, each K2is selected from:, wherein k is selected from 2 to 10. In some cases, k is 2. In some cases, k is 3. In some cases, k is 4. In some cases, k is 5. In some cases, k is 6. In some cases, each K2is selected from:. In some cases, each K2is selected from:.

[0224] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-AA), Formula (II- A), Formula (II-B), Formula (II-C), or Formula (II-D), M1is a group which can react with a Targeting Unit to form a connector unit. In some cases, a group that can react with a Targeting Unit to form a connector unit refers to any chemical moiety that is being reactive for covalently binding a Targeting Unit (e.g., antibody, ligand, antigen-binding fragment). In some cases, it may react with a thiol group present on a Targeting Unit. In some cases, it may react with a thiol group present on an antibody or antigen-binding fragment thereof. In some cases, it may react with a thiol group present on a ligand. In some cases, the chemical moieties that are being reactive for covalently binding a ligand includes: carboxylic acid; primary amine; secondary amine; tertiary amine; hydroxyl; halogen; activated ester such as N-hydroxysuccinimide ester, perfluorinated esters, nitrophenyl esters, aza-benzotriazole and benzotriazole activated ester, -124-WSGR Docket No.63125-715.601 acylureas; alkynyl; alkenyl; azide; isocyanate; isothiocyanate; aldehyde; thiol- reactive moieties such as maleimide, halomaleimides, haloacetyls, pyridyl disulfides; thiol; acrylate; mesylate; tosylate; triflate, hydroxylamine; chlorosulfonyl; boronic acid - B(OR’)2derivatives wherein R’ is hydrogen or alkyl group. In some cases, M1is selected from maleimide, halogen, COOH,, , , g p , , OH, SH, activated disulfide group, NH2, and -ONH2.

[0225] In some cases, M1 is maleimide. In some cases, M1 is halogen. In some cases, M1 isCOOH. In some cases,some cases, M1 is azide. In some cases, M1 is. In some cases, the activated group of M1is selected from,cases,. some cases, M1is OH. In some cases, M1is SH. In some cases, the activated disulfide group of M1is selected from. , . In some cases, M1is NH2. In some cases, M1is -ONH2. In some cases, M1is suitable for click reaction (eg., cyclic alkyne, azide)

[0226] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (XI),Formula (XII), Formula (XIII), Formula (I), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-AA), Formula (I-AB), Formula (I-B), Formula (II- A), Formula (II-B), Formula (II-C), Formula (II-CA), Formula (II-D), Formula (II-E), Formula (II-F), Formula (II-G), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula -125-WSGR Docket No.63125-715.601 (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), K1is a hydrophilic spacer. In some cases, K1is selected from polyethylene glycol units, cyclodextrin units, polyamides, hydrophilic peptides, polysaccharides and dendrimers. In some cases, K1is selected from polyamides, hydrophilic peptides, and polysaccharides. In some cases, K1is selected from hydrophilic peptides and polysaccharides. In some cases, K1is selected from hydrophilic peptides. In some cases, K1is selected from polysaccharides. In some cases, cases K1is a half-life promoting substituent. In some cases, the half-life promoting substituent increases the half-life of the drug. In some cases, the half-life promoting substituent increases the half-life of the conjugate.

[0227] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (XIII),Formula (I), Formula (Ia), Formula (Ib), Formula (II-A), Formula (II-B), Formula (II-E), Formula (II-F), or for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), K2is a hydrophilic spacer. In some cases, K2is selected from polyethylene glycol units, cyclodextrin units, polyamides, hydrophilic peptides, polysaccharides and dendrimers. In some cases, K2is selected from polyamides, hydrophilic peptides, and polysaccharides. In some cases, K2is selected from hydrophilic peptides and polysaccharides. In some cases, K2is selected from hydrophilic peptides. In some cases, K2is selected from polysaccharides. In some cases, cases K2is a half-life promoting substituent. In some cases, the half-life promoting substituent increases the half-life of the drug. In some cases, the half-life promoting substituent increases the half-life of the conjugate. In some cases, p is 1.

[0228] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (XIII),Formula (I), Formula (Ia), Formula (Ib), Formula (II-A), Formula (II-B), Formula (II-E), Formula (II-F), or for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), K2includes PASylation. In some cases, PASylation is a peptide comprising proline, alanine, and serine. In some cases, PASylation is a peptide consisting of only proline, alanine, and serine. In some cases, K2includes PASylation of less than PAS100. For example, PAS100 refers to a peptide having 100 amino acids, wherein the amino acids are selected from proline, alanine, and serine. In some cases, K2includes PASylation of less than PAS50. In some cases, K2includes PASylation of less than PAS25. In some cases, K2includes PASylation of more than PAS5. In some cases, K2includes PASylation of more than PAS9. In some cases, K2includes PASylation of more than PAS15. In some cases, K2includes PASylation of PAS5 to PAS25. In some cases, K2includes PASylation of PAS10 to PAS20. In some cases, K2includes PASylation of PAS10. -126-WSGR Docket No.63125-715.601 In some cases, K2includes PASylation of PAS20. In some cases, K2includes a beta-alanine that links the PASylation to the drug-linker. In some cases, PASylation is used to extend the plasma half-life. In some cases, PASylation is used to increase solubility. In some cases, PASylation is used to increase solubility without generating secondary structures. In some cases, PASylation is.

[0229] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (XI),Formula (XII), Formula (XIII), Formula (I), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb),Formula (I-B), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-D), Formula (II-E), or Formula (II-F), Formula (II-G), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), D is drug unit. In some cases, D includes a spacer. In some cases, the spacer is a divalent moiety that covalently attaches the drug to the linker. In some cases, the spacer is a divalent moiety that covalently attaches the drug to the rest of the molecule. In some cases, D does not include a spacer. In some cases, the spacer can be selected from the group consisting of –C1-C10 alkylene-, –C1-C10 heteroalkylene-, -C3- C8carbocyclo-, -O-(C1C8alkyl)-, -arylene-, –C1-C10alkylene-arylene-, -arylene-C1- C10 alkylene-, –C1-C10 alkylene-(C3-C8 carbocyclo)-, -(C3-C8 carbocyclo)-C1-C10 alkylene-, -C3- C8 heterocyclo-, –C1-C10 alkylene-(C3-C8 heterocyclo)-, -(C3-C8 heterocyclo)–C1-C10 alkylene-, –C1-C10alkylene-C(=O)-, –C1-C10heteroalkylene-C(=O)-, -C3-C8carbocyclo-C(=O)-, -O-(C1- C8alkyl)-C(=O)-, -arylene-C(=O)-, -C1-C10alkylene-arylene-C(=O)-, -arylene-C1-C10alkylene- C(=O)-, -C1- C10 alkylene-(C3-C8carbocyclo)-C(=O)-, -(C3-C8 carbocyclo)-C1-C10 alkylene- C(=O)-, - C3-C8heterocyclo-C(=O)-, -C1-C10alkylene-(C3-C8heterocyclo)-C(=O)-, -(C3- C8heterocyclo)-C1-C10alkylene-C(=O)-, -C1-C10alkylene-NH-, -C1-C10heteroalkylene-NH-, - C3-C8 carbocyclo-NH-, -O-(C1-C8 alkyl)-NH-, -arylene-NH-, -C1-C10 alkylene- arylene-NH-, - arylene-C1-C10 alkylene-NH-, -C1-C10 alkylene-(C3-C8 carbocyclo)-NH-, - (C3-C8 carbocyclo)- C1-C10alkylene-NH-, -C3-C8heterocyclo-NH-, -C1-C10alkylene-(C3- C8heterocyclo)-NH-, -(C3- C8 heterocyclo)-C1-C10 alkylene-NH-, -C1-C10 alkylene-S-, - C1-C10 heteroalkylene-S -, -C3- C8carbocyclo-S -, -O-(C1-C8 alkyl)-)-S-, -arylene-S-, -C1- C10 alkylene-arylene-S-, -arylene-C1- C10alkylene-S-, -C1-C10alkylene-(C3- C8carbocyclo)-S-, -(C3-C8carbocyclo)-C1-C10alkylene- -127-WSGR Docket No.63125-715.601 S-, -C3-C8 heterocyclo-S-, -C1- C10 alkylene-(C3-C8 heterocyclo)-S-, -(C3-C8 heterocyclo)-C1- C10alkylene-S-, –C1-C10alkylene-O-C(=O)-, -C3-C8carbocyclo-O-C(=O)-, -O-(C1-C8alkyl)-O- C(=O)-, -arylene- O-C(=O)-, -C1-C10alkylene-arylene-O-C(=O)-, -arylene-C1-C10alkylene-O- C(=O)-, -C1- C10 alkylene-(C3-C8carbocyclo)-O-C(=O)-,-(C3-C8 carbocyclo)-C1-C10 alkylene-O- C(=O)-, -C3-C8 heterocyclo-O-C(=O)-, -C1-C10 alkylene-(C3-C8heterocyclo)-O-C(=O)-, and - (C3-C8heterocyclo)-C1-C10alkylene-O-C(=O)-. In some cases, the spacer can be selected from the group consisting of –C1-C10 alkylene-, and -C1-C10 alkylene-NH-. In some cases, the drug unit is only a drug.

[0230] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (XI),Formula (XII), Formula (XIII), Formula (I), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb),Formula (I-B), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-D), Formula (II-E), or Formula (II-F), Formula (II-G), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), D is selected from a Drug unit. In some cases, the Drug unit comprises a drug. In some cases, the Drug unit is a drug. In some cases, the Drug unit is a drug and a spacer. In some cases, D is selected from a drug. In some cases, D is a selected from a cytotoxic agent, an immune modulatory agent, a nucleic acid, a growth inhibitory agent, a PROTAC, a toxin, a radioactive isotope and a chelating ligand. In some cases, D is a selected from a cytotoxic agent, and an immune modulatory agent. In some cases, D is selected from exatecan and monomethyl auristatin E (MMAE). In some cases, D is asome cases, D is SN-38. In some cases, D is selected from MMAF and MMAE. In some cases, the cytotoxic agent is selected from the group consisting of an auristatin, a maytansinoid, a camptothecin, a duocarmycin, and a calicheamicin. In some cases, a cytotoxic agent is an agent that has a cytotoxic effect on a cell. In some cases, cytotoxic agents include, for example, tubulin disrupting agents, topoisomerase inhibitors, DNA minor groove binders, and DNA alkylating agents. In some cases, tubulin disrupting agents include, for example, auristatins, dolastatins, tubulysins, colchicines, vinca alkaloids, taxanes, cryptophycins, maytansinoids, hemiasterlins, as well as other tubulin disrupting agents. In some cases, auristatins are -128-WSGR Docket No.63125-715.601 derivatives of the natural product dolastatin 10. In some cases, auristatins are selected from MMAE (N-methylvaline-valine-dolaisoleuine-dolaproine-norephedrine), MMAF (N- methylvaline-valine-dolaisoleuine-dolaproine-phenylalanine) and AFP. In some cases, a cytotoxic agent can be a topoisomerase inhibitor. In some cases, a drug is an immune modulatory agent, such as a TLR7 and / or TLR8 agonist. In some cases, an immune modulatory agent is a STING agonist. In some cases, a drug is a radioactive atom. In some cases, a drug is a proteolysis targeted chimera (PROTAC).

[00231] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (XI),Formula (XII), Formula (XIII), Formula (I), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb),Formula (I-B), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-D), Formula (II-E), or Formula (II-F), Formula (II-G), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), D is selected from a Drug unit. In some cases, the Drug unit comprises a drug. In some cases, the Drug unit is a drug. In some cases, the Drug unit is a drug and a spacer. In some cases, D is selected from a drug. In some cases, D is a selected from a cytotoxic agent, an immune modulatory agent, a nucleic acid, a growth inhibitory agent, a PROTAC, a toxin, a radioactive isotope and a chelating ligand. In some cases-129-WSGR Docket No.63125-715.601. ,-130-WSGR Docket No.63125-715.601.

[00232] In some embodiments, for a Linker or salt of Formula (III) or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-AA), Formula (I-B), Formula (II-A), Formula (II-B), Formula (II-C), or a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), or Formula (A-4), S3is selected from a spacer. In some cases, the spacer is a divalent moiety that covalently binds two components of the conjugate or Drug-Linker. In some cases, S3is present. In some cases, S3is absent. In some cases, the spacer is selected from: alkylene, heteroalkylene (an alkylene having one or more alkylene units replaced by at least one heteroatom selected from Si, N, O and S, with the appropriate valency); polyether such as polyalkylene glycol and typically polyethylene glycol; one or more natural or non-natural aminoacids such as glycine, alanine, proline, valine, N- methylglycine; C3-C8 heterocyclo; C3-C8 carbocyclo; arylene, and any combination thereof. In some cases, a spacer is a divalent linear alkylene group. In some cases, the spacer can be selected from the group consisting of –C1-C10 alkylene-, –C1-C10 heteroalkylene-, -C3- C8 carbocyclo-, -O-(C1 C8 alkyl)-, -arylene-, –C1-C10 alkylene-arylene-, -arylene-C1- C10alkylene-, –C1-C10alkylene-(C3-C8carbocyclo)-, -(C3-C8carbocyclo)-C1-C10alkylene-, -C3- C8 heterocyclo-, –C1-C10 alkylene-(C3-C8 heterocyclo)-, -(C3-C8 heterocyclo)–C1-C10 alkylene-, –C1-C10 alkylene-C(=O)-, –C1- C10 heteroalkylene-C(=O)-, -C3-C8 carbocyclo-C(=O)-, -O-(C1- -131-WSGR Docket No.63125-715.601 C8 alkyl)-C(=O)-, -arylene-C(=O)-, -C1-C10 alkylene-arylene-C(=O)-, -arylene-C1-C10 alkylene- C(=O)-, -C1- C10alkylene-(C3-C8carbocyclo)-C(=O)-, -(C3-C8carbocyclo)-C1-C10alkylene- C(=O)-, - C3-C8heterocyclo-C(=O)-, -C1-C10alkylene-(C3-C8heterocyclo)-C(=O)-, -(C3- C8 heterocyclo)-C1-C10 alkylene-C(=O)-, -C1-C10 alkylene-NH-, -C1-C10 heteroalkylene-NH-, - C3-C8 carbocyclo-NH-, -O-(C1-C8 alkyl)-NH-, -arylene-NH-, -C1-C10 alkylene- arylene-NH-, - arylene-C1-C10alkylene-NH-, -C1-C10alkylene-(C3-C8carbocyclo)-NH-, -(C3-C8carbocyclo)- C1-C10 alkylene-NH-, -C3-C8heterocyclo-NH-, -C1-C10 alkylene-(C3- C8 heterocyclo)-NH-, -(C3- C8 heterocyclo)-C1-C10 alkylene-NH-, -C1-C10 alkylene-S-, - C1-C10 heteroalkylene-S -, -C3- C8carbocyclo-S -, -O-(C1-C8alkyl)-)-S -, -arylene-S-, -C1- C10alkylene-arylene-S-, -arylene-C1- C10 alkylene-S-, -C1-C10 alkylene-(C3- C8 carbocyclo)-S-, -(C3-C8 carbocyclo)-C1-C10 alkylene- S-, -C3-C8 heterocyclo-S-, -C1- C10 alkylene-(C3-C8 heterocyclo)-S-, -(C3-C8 heterocyclo)-C1- C10alkylene-S-, –C1-C10alkylene-O-C(=O)-, -C3-C8carbocyclo-O-C(=O)-, -O-(C1-C8alkyl)-O- C(=O)-, -arylene- O-C(=O)-, -C1-C10alkylene-arylene-O-C(=O)-, -arylene-C1-C10alkylene-O- C(=O)-, -C1- C10 alkylene-(C3-C8carbocyclo)-O-C(=O)-,-(C3-C8 carbocyclo)-C1-C10 alkylene-O- C(=O)-, -C3-C8 heterocyclo-O-C(=O)-, -C1-C10 alkylene-(C3-C8heterocyclo)-O-C(=O)-, and - (C3-C8heterocyclo)-C1-C10alkylene-O-C(=O)-. In some cases, S3is optionally substituted with one or more of the substituents selected from (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -O-S(O)2R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituentsindependently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected fromhalogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl. In some cases, S3is optionally substituted with one or more of the substituents selected from (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -O-S(O)2R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN. In some cases, S3is unsubstituted. In some cases, S3is substituted. In some cases, S3is a phenylene. In some cases,. -132-WSGR Docket No.63125-715.601

[0233] In some embodiments, for a Linker or salt of Formula (III) or for a Drug-Linker orsalt of Formula (X), Formula (XIII), Formula (I), Formula (Ia), Formula (Ib), Formula (II-A), Formula (II-B), Formula (II-E), Formula (II-F), Formula (II-G), or a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), S4is selected from (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, – N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–. In some cases, S4is selected from (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –O–, – C(O)–. In some cases, S4is selected from (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by – N(R20)–, –O–, and –C(O)–. In some cases, S4is selected from: (i) an optionally substituted C8- C12 alkylene wherein one or more alkylene units of the C8-C12 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –O–, and –C(O)–. In some cases, S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–. In some cases, S4is selected from: (i) an optionally substituted C6-C10 alkylene wherein one or more alkylene units of the C6-C10 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, or – C(O)–. In some cases, S4is an optionally substituted C1alkylene. In some cases, S4is an optionally substituted C2 alkylene. In some cases, S4is an optionally substituted C3 alkylene. In some cases, S4is an optionally substituted C4 alkylene. In some cases, S4is an optionally substituted C5alkylene. In some cases, S4is an optionally substituted C6alkylene. In some cases, S4is an optionally substituted C7 alkylene. In some cases, S4is an optionally substituted C8 alkylene. In some cases, S4is an optionally substituted C9 alkylene. In some cases, S4is an optionally substituted C10alkylene. In some cases, S4is an optionally substituted C11alkylene. In some cases, S4is an optionally substituted C12 alkylene. In some cases, S4is an optionally substituted C13 alkylene. In some cases, S4is an optionally substituted C14 alkylene. In some cases, S4is an optionally substituted C15alkylene. In some cases, S4is an optionally substituted C16alkylene. In some cases, S4is an optionally substituted C17alkylene. In some cases, S4is an optionally substituted C18 alkylene. In some cases, S4is an optionally substituted C19 alkylene. In some cases, S4is an optionally substituted C20 alkylene. In some cases, the one or more -133-WSGR Docket No.63125-715.601 alkylene units of the alkylene of S4are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, or –C(O)–. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by –N(R20)–. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by –N(R20)C(O)–. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by –C(O)N(R20)–. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by –C(O)–. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by –O–. In some cases, if an alkylene unit of the alkylene is replaced, the alkylene may be referred to as a resulting alkylene. In some cases, if two or more of the alkylene units of S4are replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if two or more of the alkylene units of S4are replaced, the adjacent alkylene units of the resulting alkylene are not replaced. In some cases, if two or more of the alkylene units of S4are replaced, the resulting alkylene has no repeating heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S4are replaced, the resulting alkylene has no repeating of the same heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S4are replaced, the resulting alkylene unit has no -N-N- or -O-O-. In some cases, if two or more of the alkylene units of S4are replaced, the resulting alkylene unit is a stable alkylene. In some cases, if two or more of the alkylene units of S4are replaced, the resulting alkylene unit is an unreactive alkylene. In some cases, the resulting alkylene has only 1 heteroatom. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are different from each other. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 3 heteroatoms, wherein the 3 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 4 heteroatoms, wherein the 4 heteroatoms are not adjacent to each other. In some cases, the alkylene has 0 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 2 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 3 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 4 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 5 replaced units. In some cases, the optional substituents on S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O--134-WSGR Docket No.63125-715.601 S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituentsindependently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, the optional substituents on S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN. In some cases, the optional substituents on S4, are independently selected at each occurrence from: halogen, -OR30, -N(R30)2, =O, and -CN. In some cases, the optional substituents on S4, are independently selected at each occurrence from: =O. In some cases, S4is selected from, , and. In some cases, S4is. In some cases, S4is. In some cases,.

[0234] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker orsalt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-A), Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-AA), Formula (I-B), Formula (II-A), Formula (II-B), Formula (II-C), Formula (II-D), or Formula (II-G), further includes attaching a Targeting Unit to M1to form a conjugate, wherein M1of the Drug-Linker reacts and forms a covalent bond to the Targeting Unit. In some cases, the Targeting unit is selected from an antibody or an antigen-binding portion thereof. In some cases, the conjugate has an average ratio of Drug-Linker to Targeting unit of about 1 to 10. In some cases, the Targeting unit is selected from an antibody or an antigen-binding portion thereof. In some cases, the conjugate has an average ratio of Drug-Linker to Targeting unit of about 1 to 8. In some cases, the conjugate has an average ratio of Drug-Linker to Targeting unit of about 1 to 5. In some cases, the conjugate has an average ratio of Drug-Linker to Targeting unit of about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10.

[0235] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI),Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-3), Formula (A-4), or Formula (A-7), M2is a connector unit. In some cases, the connector unit refers to a component that connects different parts of the conjugate together. In -135-WSGR Docket No.63125-715.601 some cases, the connector unit can connect the Targeting Unit to S3(if present) or to S2. In some cases, the connector unit forms a bond with a sulfur atom of a Targeting unit. In some cases, the connector unit forms a bond with a sulfur atom of a Targeting unit via a maleimide group. In some cases, the sulfur atom can be derived from, for example, a sulfhydryl group of a Targetingunit (e.g., a thiol group of an interchain disulfide bond). In some cases,cases, M2is -CH2-C(O)NH-. In some cases, M2is linked to the Targeting unit via a disulfide bond between a sulfur atom of M2and a sulfur atom of the Targeting unit. In some cases, M2is . In some cases, the connector unit forms a bond with a primary or secondary amino group of a Targeting unit. In some cases, M2is selected from.

[0236] In an aspect, the present disclosure provides a Linker of Formula (III):-136-WSGR Docket No.63125-715.601Formula (III) or a pharmaceutically acceptable salt thereof, wherein; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; -137-WSGR Docket No.63125-715.601 S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from: (iv) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6 alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from: (iv) a peptide unit,(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; K2is selected from: (iv) a peptide unit,(ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – -138-WSGR Docket No.63125-715.601 C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and R50is selected from a substituent capable of reacting with a nucleophilic group on a Drug unit.

[0237] In some embodiments, for a linker of Formula (III), R50 is selected from a substituentcapable of reacting with a nucleophilic group on a Drug. In some cases, the nucleophilic group on the Drug contains a nitrogen. In some cases, the nucleophilic group on the Drug contains an oxygen.

[0238] In some embodiments, for a linker of Formula (III), R50 is selected from . Insome cases, R50is selected from -OH. In some cases, R50is selected fromCl. In somecases, R50 is selected from.

[0239] In some embodiments, a Drug-Linker of Formula (X) is selected from:-139-WSGR Docket No.63125-715.601-140-WSGR Docket No.63125-715.601-141-WSGR Docket No.63125-715.601-142-WSGR Docket No.63125-715.601; -143-WSGR Docket No.63125-715.601-144-WSGR Docket No.63125-715.601-145-WSGR Docket No.63125-715.601-146-WSGR Docket No.63125-715.601.

[0240] In some embodiments, a conjugate of Formula (A), is represented by:-147-WSGR Docket No.63125-715.601antibody or an antigen-binding portion thereof, wherein the antibody or portion thereof optionally without the C-terminal lysine, K1is as described elsewhere herein, and DAR is selected from about 1 to about 8. In some cases, PTK7 is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the DAR is about 8. In some cases, the DAR is as described elsewhere herein. In some cases, PTK7 is selected from an antibody from Table 8. In some cases, the PTK7 antibody is bound to the drug-linker via a sulfur atom.

[0241] In some embodiments, a conjugate of Formula (A), is represented by:antigen-binding portion thereof, wherein the antibody or portion thereof optionally without the C-terminal lysine, K1is as described elsewhere herein, and DAR is selected from about 1 to about 8. In some cases, PTK7 is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the DAR is about 8. In some cases, the DAR is as described elsewhere herein. In some cases, PTK7 is selected from an antibody from Table 8. In some cases, the PTK7 antibody is bound to the drug-linker via a sulfur atom.

[0242] In some embodiments, a conjugate of Formula (A), is represented by:-148-WSGR Docket No.63125-715.601antibody or an antigen-binding portion thereof, wherein the antibody or portion thereof optionally without the C-terminal lysine, K1is as described elsewhere herein, and DAR is selected from about 1 to about 8. In some cases, PTK7 is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the DAR is about 8. In some cases, the DAR is as described elsewhere herein. In some cases, the PTK7 is selected from an antibody from Table 8. In some cases, the PTK7 antibody is bound to the drug-linker via a sulfur atom.

[0243] In some embodiments, a conjugate of Formula (A), is represented by:antibody or an antigen-binding portion thereof, wherein the antibody or portion thereof optionally without the C-terminal lysine, K1is as described elsewhere herein, and DAR is selected from about 1 to about 8. In some cases, PTK7 is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the DAR is about 8. In some cases, the DAR is as described elsewhere herein. In some cases, PTK7 is selected from an antibody from Table 8. In some cases, the PTK7 antibody is bound to the drug-linker via a sulfur atom. In some cases, L is a PTK7 antibody. In some cases, the PTK7 antibody is selected from Table 8.

[0244] In some embodiments, a conjugate of Formula (A), is represented by:-149-WSGR Docket No.63125-715.601antibody or an antigen-binding portion thereof, wherein the antibody or portion thereof optionally without the C-terminal lysine, K1is as described elsewhere herein, and DAR is selected from about 1 to about 8. In some cases, PTK7 is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the DAR is about 8. In some cases, the DAR is as described elsewhere herein. In some cases, PTK7 is selected from an antibody from Table 8.

[0245] In some embodiments, a conjugate of Formula (A), is represented by:antibody or an antigen-binding portion thereof, wherein the antibody or portion thereof optionally without the C-terminal lysine, K1is as described elsewhere herein, and DAR is selected from about 1 to about 8. In some cases, PTK7 is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the DAR is about 8. In some cases, the DAR is as described elsewhere herein. In some cases, PTK7 is selected from an antibody from Table 8. In some cases, the PTK7 antibody is bound to the drug-linker via a sulfur atom.

[0246] In some embodiments, a conjugate of Formula (A), is represented by:-150-WSGR Docket No.63125-715.601-151-WSGR Docket No.63125-715.601;-152-WSGR Docket No.63125-715.601; wherein each L is aTargeting Unit; and each DAR is a drug to antibody ratio. In some cases, a conjugate of Formula (A), is represented by:wherein each L is a Targeting Unit; and each DAR is a drug to antibody ratio. In some cases, a conjugate of Formula (A), is represented by: -153-WSGR Docket No.63125-715.601wherein each L is a Targeting Unit; and each DAR is a drug to antibody ratio. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, the Targeting Unit is bound to the drug-linker via a sulfur atom. In some cases, L is a PTK7 antibody. In some cases, the PTK7 antibody is selected from Table 8.

[0247] In some embodiments, a conjugate of Formula (A), is represented by:-154-WSGR Docket No.63125-715.601-155-WSGR Docket No.63125-715.601;;-156-WSGR Docket No.63125-715.601-157-WSGR Docket No.63125-715.601wherein each L is a Targeting Unit; and each DAR is a drug to antibody ratio. In some cases, a conjugate of Formula (A), is represented by: -158-WSGR Docket No.63125-715.601wherein each L is a Targeting Unit; and each DAR is a drug to antibody ratio. In some cases, a conjugate of Formula (A), is represented by:wherein each L is a Targeting Unit; and each DAR is a drug to antibody ratio. In some cases, a conjugate of Formula (A), is represented by: -159-WSGR Docket No.63125-715.601wherein each L is a Targeting Unit; and each DAR is a drug to antibody ratio. In some cases, a conjugate of Formula (A), is represented by:wherein each L is a Targeting Unit; and each DAR is a drug to antibody ratio. In some cases, a conjugate of Formula (A), is represented by:wherein each L is a Targeting Unit; and each DAR is a drug to antibody ratio. In some cases, a conjugate of Formula (A), is represented by: -160-WSGR Docket No.63125-715.601wherein each L is a Targeting Unit; and each DAR is a drug to antibody ratio. In some cases, a conjugate of Formula (A), is represented by:wherein each L is a Targeting Unit; and each DAR is a drug to antibody ratio. In some cases, a conjugate of Formula (A), is represented by:wherein each L is a Targeting Unit; and each DAR is a drug to antibody ratio. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as -161-WSGR Docket No.63125-715.601 in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, the Targeting Unit is bound to the drug-linker via a sulfur atom. In some cases, L is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the anti- PTK7 antibody is selected from PTK7-1; PTK7-1EL; PTK7-2; L is PTK7-3; L is PTK7-4; PTK7-5; PTK7-6; PTK7-7; PTK7-8; PTK7-9; PTK7-9EL; PTK7-10; PTK7-11; PTK7-12; PTK7-13; and PTK7-14.

[0248] In some embodiments, the conjugate or salt of Formula (Aa) is represented by:in some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, DAR is a drug (D) to antibody (L) ratio. In some cases, the drug of the DAR is exatecan. In some cases, the drug of the DAR is exatecan. In some cases, the antibody is UC-961. In some cases, the Targeting Unit is bound to the drug-linker via a sulfur -162-WSGR Docket No.63125-715.601 atom. In some cases, the antibody is an anti-PTK7 antibody. In some cases, the anti-PTK7 antibody is selected from PTK7-1; PTK7-1EL; PTK7-2; L is PTK7-3; L is PTK7-4; PTK7-5; PTK7-6; PTK7-7; PTK7-8; PTK7-9; PTK7-9EL; PTK7-10; PTK7-11; PTK7-12; PTK7-13; and PTK7-14.

[0249] In some embodiments, the conjugate or salt of Formula (Ab) is represented by:, wherein L is the Targeting Unit; and DAR is a drug to antibody ratio. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, DAR is a drug (D) to antibody (L) ratio. In some cases, the drug of the DAR is exatecan. In some cases, the drug of the DAR is exatecan. In some cases, the antibody is UC-961. In some cases, L is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the anti-PTK7 antibody is selected from PTK7-1; PTK7-1EL; PTK7-2; L is PTK7- 3; L is PTK7-4; PTK7-5; PTK7-6; PTK7-7; PTK7-8; PTK7-9; PTK7-9EL; PTK7-10; PTK7-11; PTK7-12; PTK7-13; and PTK7-14.

[0250] In some embodiments, the conjugate or salt of Formula (A) or Formula (Aa) isrepresented by: -163-WSGR Docket No.63125-715.601wherein L is the Targeting Unit; and DAR is a drug to antibody ratio. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, DAR is a drug (D) to antibody (L) ratio. In some cases, the drug of the DAR is exatecan. In some cases, the drug of the DAR is exatecan. In some cases, the antibody is UC-961. In some cases, the antibody is PTK7. In some cases, L is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the anti-PTK7 antibody is selected from PTK7- 1; PTK7-1EL; PTK7-2; L is PTK7-3; L is PTK7-4; PTK7-5; PTK7-6; PTK7-7; PTK7-8; PTK7- 9; PTK7-9EL; PTK7-10; PTK7-11; PTK7-12; PTK7-13; and PTK7-14.

[0251] In some embodiments, the conjugate or salt of Formula (A) or Formula (Ab) isrepresented by: -164-WSGR Docket No.63125-715.601, wherein L is the Targeting Unit; and DAR is a drug to antibody ratio. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, DAR is a drug (D) to antibody (L) ratio. In some cases, the drug of the DAR is exatecan. In some cases, the drug of the DAR is exatecan. In some cases, the antibody is UC-961. In some cases, the antibody is PTK7. In some cases, L is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the anti-PTK7 antibody is selected from PTK7- 1; PTK7-1EL; PTK7-2; L is PTK7-3; L is PTK7-4; PTK7-5; PTK7-6; PTK7-7; PTK7-8; PTK7- 9; PTK7-9EL; PTK7-10; PTK7-11; PTK7-12; PTK7-13; and PTK7-14.

[0252] In some embodiments, the conjugate or salt of Formula (Ab) is represented by:-165-WSGR Docket No.63125-715.601, wherein L is the Targeting Unit; and DAR is a drug to antibody ratio. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, DAR is a drug (D) to antibody (L) ratio. In some cases, the drug of the DAR is exatecan. In some cases, the drug of the DAR is exatecan. In some cases, the Targeting Unit (L) is an antibody. In some cases, the antibody is UC-961. In some cases, the antibody is PTK7. In some cases, L is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, the anti-PTK7 antibody is selected from PTK7-1; PTK7-1EL; PTK7-2; L is PTK7-3; L is PTK7-4; PTK7-5; PTK7-6; PTK7-7; PTK7-8; PTK7-9; PTK7-9EL; PTK7-10; PTK7-11; PTK7- 12; PTK7-13; and PTK7-14.

[0253] In some embodiments, the conjugate or salt of Formula (XX) or Formula (A) isrepresented by: -166-WSGR Docket No.63125-715.601; -167-WSGR Docket No.63125-715.601; -168-WSGR Docket No.63125-715.601 ;-169-WSGR Docket No.63125-715.601-170-WSGR Docket No.63125-715.601; -171-WSGR Docket No.63125-715.601 ; ;-172-WSGR Docket No.63125-715.601 ;; -173-WSGR Docket No.63125-715.601-174-WSGR Docket No.63125-715.601 ;-175-WSGR Docket No.63125-715.601; -176-WSGR Docket No.63125-715.601; -177-WSGR Docket No.63125-715.601-178-WSGR Docket No.63125-715.601; -179-WSGR Docket No.63125-715.601 (; -180-WSGR Docket No.63125-715.601 ;; -181-WSGR Docket No.63125-715.601; -182-WSGR Docket No.63125-715.601 ;; -183-WSGR Docket No.63125-715.601; -184-WSGR Docket No.63125-715.601 ;; -185-WSGR Docket No.63125-715.601 ;; -186-WSGR Docket No.63125-715.601; ; -187-WSGR Docket No.63125-715.601-188-WSGR Docket No.63125-715.601-189-WSGR Docket No.63125-715.601-190-WSGR Docket No.63125-715.601, wherein (PTK7) is a PTK7 antibody or a PTK7 antigen-binding fragment thereof; and each DAR is a drug to antibody ratio. In some cases, the PTK7 antibody is selected from Table 8. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to -191-WSGR Docket No.63125-715.601 about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, the PTK7 antibody is bound to the drug-linker via a sulfur atom.

[0254] In some embodiments, the conjugate or salt of Formula (XX) or Formula (A) is; -192-WSGR Docket No.63125-715.601; -193-WSGR Docket No.63125-715.601 ;-194-WSGR Docket No.63125-715.601-195-WSGR Docket No.63125-715.601; -196-WSGR Docket No.63125-715.601 ; ;-197-WSGR Docket No.63125-715.601 ;; -198-WSGR Docket No.63125-715.601; -199-WSGR Docket No.63125-715.601; -200-WSGR Docket No.63125-715.601-201-WSGR Docket No.63125-715.601; -202-WSGR Docket No.63125-715.601 (; -203-WSGR Docket No.63125-715.601 ;; -204-WSGR Docket No.63125-715.601wherein (PTK7) is a PTK7 antibody or a PTK7 antigen-binding fragment thereof; and each DAR is a drug to antibody ratio. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, the PTK7 antibody is bound to the drug-linker via a sulfur atom.

[0255] In some embodiments, the conjugate or salt of Formula (XX) or Formula (A) isrepresented by: -205-WSGR Docket No.63125-715.601; -206-WSGR Docket No.63125-715.601-207-WSGR Docket No.63125-715.601-208-WSGR Docket No.63125-715.601-209-WSGR Docket No.63125-715.601; ; -210-WSGR Docket No.63125-715.601; -211-WSGR Docket No.63125-715.601-212-WSGR Docket No.63125-715.601, wherein (PTK7) is a PTK7 antibody or antigen-binding fragment thereof; and each DAR is a drug to antibody ratio. In some cases, the PTK7 antibody is selected from Table 8. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP- HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, the PTK7 antibody is bound to the drug-linker via a sulfur atom.

[0256] In some embodiments, the conjugate or salt of Formula (XX) or Formula (A) isrepresented by: -213-WSGR Docket No.63125-715.601 ;; -214-WSGR Docket No.63125-715.601 ;; -215-WSGR Docket No.63125-715.601, wherein (PTK7) is a PTK7 antibody or antigen-binding fragment thereof; and each DAR is a drug to antibody ratio. In some cases, the PTK7 antibody is selected from Table 8. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP- HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the -216-WSGR Docket No.63125-715.601 DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, the PTK7 antibody is bound to the drug-linker via a sulfur atom.

[0257] In some embodiments, the conjugate or salt of Formula (XX) or Formula (A) isrepresented by:; -217-WSGR Docket No.63125-715.601-218-WSGR Docket No.63125-715.601 ;-219-WSGR Docket No.63125-715.601-220-WSGR Docket No.63125-715.601 (; -221-WSGR Docket No.63125-715.601 ;; -222-WSGR Docket No.63125-715.601wherein (PTK7) is a PTK7 antibody or antigen-binding fragment thereof; and each DAR is a drug to antibody ratio. In some cases, the PTK7 antibody is selected from Table 8. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP- HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In -223-WSGR Docket No.63125-715.601 some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, the PTK7 antibody is bound to the drug-linker via a sulfur atom.

[0258] In some embodiments, the conjugate or salt of Formula (XX) or Formula (A) isrepresented by: ;; -224-WSGR Docket No.63125-715.601 ;; -225-WSGR Docket No.63125-715.601; -226-WSGR Docket No.63125-715.601; -227-WSGR Docket No.63125-715.601-228-WSGR Docket No.63125-715.601; ; -229-WSGR Docket No.63125-715.601, wherein (PTK7) is a PTK7 antibody or an antigen-binding fragment thereof; and each DAR is a drug to antibody ratio. In some cases, the PTK7 antibody is selected from Table 8. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP- -230-WSGR Docket No.63125-715.601 HPLC as in example 40. In some cases, the DAR is at most about 16. In some cases, the DAR is about 8. In some cases, the DAR is most about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is at most about 8. In some cases, the DAR is from about 1 to about 16. In some cases, the DAR is from about 4 to about 12. In some cases, the DAR is from about 6 to about 10. In some cases, the DAR is from about 7 to about 9. In some cases, the DAR is from about 8 to about 10. In some cases, the DAR is from about 6 to about 8. In some cases, the PTK7 antibody is bound to the drug-linker via a sulfur atom. Table A: Specific Conjugates of the Disclosure-231-WSGR Docket No.63125-715.601-232-WSGR Docket No.63125-715.601-233-WSGR Docket No.63125-715.601-234-WSGR Docket No.63125-715.601-235-WSGR Docket No.63125-715.601-236-WSGR Docket No.63125-715.601-237-WSGR Docket No.63125-715.601-238-WSGR Docket No.63125-715.601-239-WSGR Docket No.63125-715.601-240-WSGR Docket No.63125-715.601-241-WSGR Docket No.63125-715.601-242-WSGR Docket No.63125-715.601-243-WSGR Docket No.63125-715.601-244-WSGR Docket No.63125-715.601-245-WSGR Docket No.63125-715.601-246-WSGR Docket No.63125-715.601-247-WSGR Docket No.63125-715.601-248-WSGR Docket No.63125-715.601-249-WSGR Docket No.63125-715.601-250-WSGR Docket No.63125-715.601-251-WSGR Docket No.63125-715.601-252-WSGR Docket No.63125-715.601-253-WSGR Docket No.63125-715.601-254-WSGR Docket No.63125-715.601-255-WSGR Docket No.63125-715.601-256-WSGR Docket No.63125-715.601-257-WSGR Docket No.63125-715.601-258-WSGR Docket No.63125-715.601-259-WSGR Docket No.63125-715.601-260-WSGR Docket No.63125-715.601-261-WSGR Docket No.63125-715.601-262-WSGR Docket No.63125-715.601-263-WSGR Docket No.63125-715.601-264-WSGR Docket No.63125-715.601-265-WSGR Docket No.63125-715.601-266-WSGR Docket No.63125-715.601

[0259] In alternative embodiments, the specific conjugates of Table A are also envisionedwith no stereochemistry defined. Table A-R: Specific Conjugates of the Disclosure-267-WSGR Docket No.63125-715.601-268-WSGR Docket No.63125-715.601-269-WSGR Docket No.63125-715.601-270-WSGR Docket No.63125-715.601-271-WSGR Docket No.63125-715.601-272-WSGR Docket No.63125-715.601-273-WSGR Docket No.63125-715.601-274-WSGR Docket No.63125-715.601-275-WSGR Docket No.63125-715.601-276-WSGR Docket No.63125-715.601-277-WSGR Docket No.63125-715.601-278-WSGR Docket No.63125-715.601-279-WSGR Docket No.63125-715.601-280-WSGR Docket No.63125-715.601-281-WSGR Docket No.63125-715.601-282-WSGR Docket No.63125-715.601-283-WSGR Docket No.63125-715.601-284-WSGR Docket No.63125-715.601-285-WSGR Docket No.63125-715.601-286-WSGR Docket No.63125-715.601-287-WSGR Docket No.63125-715.601-288-WSGR Docket No.63125-715.601-289-WSGR Docket No.63125-715.601-290-WSGR Docket No.63125-715.601-291-WSGR Docket No.63125-715.601-292-WSGR Docket No.63125-715.601-293-WSGR Docket No.63125-715.601-294-WSGR Docket No.63125-715.601-295-WSGR Docket No.63125-715.601-296-WSGR Docket No.63125-715.601-297-WSGR Docket No.63125-715.601-298-WSGR Docket No.63125-715.601-299-WSGR Docket No.63125-715.601-300-WSGR Docket No.63125-715.601-301-WSGR Docket No.63125-715.601-302-WSGR Docket No.63125-715.601-303-WSGR Docket No.63125-715.601-304-WSGR Docket No.63125-715.601-305-WSGR Docket No.63125-715.601-306-WSGR Docket No.63125-715.601-307-WSGR Docket No.63125-715.601-308-WSGR Docket No.63125-715.601-309-WSGR Docket No.63125-715.601-310-WSGR Docket No.63125-715.601Table A-S: Specific Conjugates of the Disclosure-311-WSGR Docket No.63125-715.601-312-WSGR Docket No.63125-715.601-313-WSGR Docket No.63125-715.601-314-WSGR Docket No.63125-715.601-315-WSGR Docket No.63125-715.601-316-WSGR Docket No.63125-715.601-317-WSGR Docket No.63125-715.601-318-WSGR Docket No.63125-715.601-319-WSGR Docket No.63125-715.601-320-WSGR Docket No.63125-715.601-321-WSGR Docket No.63125-715.601-322-WSGR Docket No.63125-715.601-323-WSGR Docket No.63125-715.601-324-WSGR Docket No.63125-715.601-325-WSGR Docket No.63125-715.601-326-WSGR Docket No.63125-715.601-327-WSGR Docket No.63125-715.601-328-WSGR Docket No.63125-715.601-329-WSGR Docket No.63125-715.601-330-WSGR Docket No.63125-715.601-331-WSGR Docket No.63125-715.601-332-WSGR Docket No.63125-715.601-333-WSGR Docket No.63125-715.601-334-WSGR Docket No.63125-715.601-335-WSGR Docket No.63125-715.601-336-WSGR Docket No.63125-715.601-337-WSGR Docket No.63125-715.601-338-WSGR Docket No.63125-715.601-339-WSGR Docket No.63125-715.601-340-WSGR Docket No.63125-715.601-341-WSGR Docket No.63125-715.601-342-WSGR Docket No.63125-715.601-343-WSGR Docket No.63125-715.601-344-WSGR Docket No.63125-715.601-345-WSGR Docket No.63125-715.601-346-WSGR Docket No.63125-715.601-347-WSGR Docket No.63125-715.601-348-WSGR Docket No.63125-715.601-349-WSGR Docket No.63125-715.601-350-WSGR Docket No.63125-715.601-351-WSGR Docket No.63125-715.601-352-WSGR Docket No.63125-715.601-353-WSGR Docket No.63125-715.601-354-WSGR Docket No.63125-715.601-355-WSGR Docket No.63125-715.601

[0260] Conjugates of Table A, Table A-S, and Table A-R, each independently have a DARof about 1 to about 8. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 2 to about 8. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 2. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 3. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 4. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 5. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 6. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 7. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 8. -356-WSGR Docket No.63125-715.601 Table B: Specific Conjugates of the Disclosure-357-WSGR Docket No.63125-715.601-358-WSGR Docket No.63125-715.601-359-WSGR Docket No.63125-715.601-360-WSGR Docket No.63125-715.601-361-WSGR Docket No.63125-715.601-362-WSGR Docket No.63125-715.601-363-WSGR Docket No.63125-715.601-364-WSGR Docket No.63125-715.601-365-WSGR Docket No.63125-715.601-366-WSGR Docket No.63125-715.601-367-WSGR Docket No.63125-715.601-368-WSGR Docket No.63125-715.601-369-WSGR Docket No.63125-715.601-370-WSGR Docket No.63125-715.601-371-WSGR Docket No.63125-715.601-372-WSGR Docket No.63125-715.601-373-WSGR Docket No.63125-715.601-374-WSGR Docket No.63125-715.601-375-WSGR Docket No.63125-715.601-376-WSGR Docket No.63125-715.601-377-WSGR Docket No.63125-715.601-378-WSGR Docket No.63125-715.601-379-WSGR Docket No.63125-715.601-380-WSGR Docket No.63125-715.601-381-WSGR Docket No.63125-715.601-382-WSGR Docket No.63125-715.601-383-WSGR Docket No.63125-715.601-384-WSGR Docket No.63125-715.601-385-WSGR Docket No.63125-715.601-386-WSGR Docket No.63125-715.601-387-WSGR Docket No.63125-715.601-388-WSGR Docket No.63125-715.601-389-WSGR Docket No.63125-715.601-390-WSGR Docket No.63125-715.601-391-WSGR Docket No.63125-715.601-392-WSGR Docket No.63125-715.601-393-WSGR Docket No.63125-715.601

[0261] In alternative embodiments, specific conjugates of Table B are also envisioned withno stereochemistry. Table B-R: Specific Conjugates of the Disclosure-394-WSGR Docket No.63125-715.601-395-WSGR Docket No.63125-715.601-396-WSGR Docket No.63125-715.601-397-WSGR Docket No.63125-715.601-398-WSGR Docket No.63125-715.601-399-WSGR Docket No.63125-715.601-400-WSGR Docket No.63125-715.601-401-WSGR Docket No.63125-715.601-402-WSGR Docket No.63125-715.601-403-WSGR Docket No.63125-715.601-404-WSGR Docket No.63125-715.601-405-WSGR Docket No.63125-715.601-406-WSGR Docket No.63125-715.601-407-WSGR Docket No.63125-715.601-408-WSGR Docket No.63125-715.601-409-WSGR Docket No.63125-715.601-410-WSGR Docket No.63125-715.601-411-WSGR Docket No.63125-715.601-412-WSGR Docket No.63125-715.601-413-WSGR Docket No.63125-715.601-414-WSGR Docket No.63125-715.601-415-WSGR Docket No.63125-715.601-416-WSGR Docket No.63125-715.601-417-WSGR Docket No.63125-715.601-418-WSGR Docket No.63125-715.601-419-WSGR Docket No.63125-715.601-420-WSGR Docket No.63125-715.601-421-WSGR Docket No.63125-715.601-422-WSGR Docket No.63125-715.601-423-WSGR Docket No.63125-715.601-424-WSGR Docket No.63125-715.601-425-WSGR Docket No.63125-715.601-426-WSGR Docket No.63125-715.601-427-WSGR Docket No.63125-715.601-428-WSGR Docket No.63125-715.601-429-WSGR Docket No.63125-715.601-430-WSGR Docket No.63125-715.601-431-WSGR Docket No.63125-715.601-432-WSGR Docket No.63125-715.601-433-WSGR Docket No.63125-715.601Table B-S: Specific Conjugates of the Disclosure-434-WSGR Docket No.63125-715.601-435-WSGR Docket No.63125-715.601-436-WSGR Docket No.63125-715.601-437-WSGR Docket No.63125-715.601-438-WSGR Docket No.63125-715.601-439-WSGR Docket No.63125-715.601-440-WSGR Docket No.63125-715.601-441-WSGR Docket No.63125-715.601-442-WSGR Docket No.63125-715.601-443-WSGR Docket No.63125-715.601-444-WSGR Docket No.63125-715.601-445-WSGR Docket No.63125-715.601-446-WSGR Docket No.63125-715.601-447-WSGR Docket No.63125-715.601-448-WSGR Docket No.63125-715.601-449-WSGR Docket No.63125-715.601-450-WSGR Docket No.63125-715.601-451-WSGR Docket No.63125-715.601-452-WSGR Docket No.63125-715.601-453-WSGR Docket No.63125-715.601-454-WSGR Docket No.63125-715.601-455-WSGR Docket No.63125-715.601-456-WSGR Docket No.63125-715.601-457-WSGR Docket No.63125-715.601-458-WSGR Docket No.63125-715.601-459-WSGR Docket No.63125-715.601-460-WSGR Docket No.63125-715.601-461-WSGR Docket No.63125-715.601-462-WSGR Docket No.63125-715.601-463-WSGR Docket No.63125-715.601-464-WSGR Docket No.63125-715.601-465-WSGR Docket No.63125-715.601-466-WSGR Docket No.63125-715.601-467-WSGR Docket No.63125-715.601-468-WSGR Docket No.63125-715.601-469-WSGR Docket No.63125-715.601-470-WSGR Docket No.63125-715.601-471-WSGR Docket No.63125-715.601-472-WSGR Docket No.63125-715.601-473-WSGR Docket No.63125-715.601

[0262] Conjugates of Table B, Table B-S, and Table B-R, each independently have a DARof about 1 to about 8. Conjugates of Table B, Table B-S, and Table B-R, each independently have a DAR of about 2 to about 8. Conjugates of Table B, Table B-S, and Table B-R, each independently have a DAR of about 2. Conjugates of Table B, Table B-S, and Table B-R, each independently have a DAR of about 3. Conjugates of Table B, Table B-S, and Table B-R, each independently have a DAR of about 4. Conjugates of Table B, Table B-S, and Table B-R, each independently have a DAR of about 5. Conjugates of Table B, Table B-S, and Table B-R, each independently have a DAR of about 6. Conjugates of Table B, Table B-S, and Table B-R, each independently have a DAR of about 7. Conjugates of Table B, Table B-S, and Table B-R, each independently have a DAR of about 8.

[0263] Included in the present disclosure are salts, particularly pharmaceutically acceptablesalts, of the compounds described herein. The compounds of the present invention that possess a sufficiently acidic, a sufficiently basic, or both functional groups, can react with any of a number of inorganic bases, and inorganic and organic acids, to form a salt. Alternatively, compounds that are inherently charged, such as those with a quaternary nitrogen, can form a salt with an appropriate counterion, e.g., a halide such as bromide, chloride, or fluoride, particularly bromide.

[0264] Chemical entities having carbon-carbon double bonds or carbon-nitrogen doublebonds may exist in Z- or E- form (or cis- or trans- form). Furthermore, some chemical entities may exist in various tautomeric forms. Unless otherwise specified, compounds described herein are intended to include all Z-, E- and tautomeric forms as well.

[0265] A “tautomer” refers to a molecule wherein a proton shift from one atom of amolecule to another atom of the same molecule is possible. The compounds presented herein, in -474-WSGR Docket No.63125-715.601 certain embodiments, exist as tautomers. In circumstances where tautomerization is possible, a chemical equilibrium of the tautomers will exist. The exact ratio of the tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric equilibrium include:.

[0266] The compounds disclosed herein, in some embodiments, are used in differentenriched isotopic forms, e.g., enriched in the content of2H,3H,11C,13C and / or14C. In one particular embodiment, the compound is deuterated in at least one position. Such deuterated forms can be made by the procedure described in U.S. Patent Nos.5,846,514 and 6,334,997. As described in U.S. Patent Nos.5,846,514 and 6,334,997, deuteration can improve the metabolic stability and or efficacy, thus increasing the duration of action of drugs.

[0267] Unless otherwise stated, compounds described herein are intended to includecompounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by13C- or14C-enriched carbon are within the scope of the present disclosure.

[0268] The compounds of the present disclosure optionally contain unnatural proportions ofatomic isotopes at one or more atoms that constitute such compounds. For example, the compounds may be labeled with isotopes, such as for example, deuterium (2H), tritium (3H), iodine-125 (125I) or carbon-14 (14C). Isotopic substitution with2H,11C,13C,14C,15C,12N,13N,15N,16N,16O,17O,14F,15F,16F,17F,18F,33S,34S,35S,36S,35Cl,37Cl,79Br,81Br, and125I are all contemplated. All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention. -475-WSGR Docket No.63125-715.601

[0269] In certain embodiments, the compounds disclosed herein have some or all of the 1Hatoms replaced with2H atoms. The methods of synthesis for deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthetic methods.

[0270] Deuterium substituted compounds are synthesized using various methods such asdescribed in: Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0271] Deuterated starting materials are readily available and are subjected to the syntheticmethods described herein to provide for the synthesis of deuterium-containing compounds. Large numbers of deuterium-containing reagents and building blocks are available commercially from chemical vendors, such as Aldrich Chemical Co.

[0272] Compounds of the present invention also include crystalline and amorphous forms ofthose compounds, pharmaceutically acceptable salts, and active metabolites of these compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, as well as mixtures thereof.

[0273] The compounds described herein may in some cases exist as diastereomers,enantiomers, or other stereoisomeric forms. Where absolute stereochemistry is not specified, the compounds presented herein include all diastereomeric, enantiomeric, and epimeric forms as well as the appropriate mixtures thereof. Separation of stereoisomers may be performed by chromatography or by forming diastereomers and separating by recrystallization, or chromatography, or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions”, John Wiley And Sons, Inc., 1981, herein incorporated by reference for this disclosure). Stereoisomers may also be obtained by stereoselective synthesis.

[0274] The methods and compositions described herein include the use of amorphous formsas well as crystalline forms (also known as polymorphs). The compounds described herein may be in the form of pharmaceutically acceptable salts. As well, in some embodiments, active metabolites of these compounds having the same type of activity are included in the scope of the present disclosure. In addition, the compounds described herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. -476-WSGR Docket No.63125-715.601 The solvated forms of the compounds presented herein are also considered to be disclosed herein.

[0275] In certain embodiments, compounds or salts of the compounds may be prodrugs, e.g.,wherein a hydroxyl in the parent compound is presented as an ester or a carbonate, or carboxylic acid present in the parent compound is presented as an ester. The term “prodrug” is intended to encompass compounds which, under physiologic conditions, are converted into pharmaceutical agents of the present disclosure. One method for making a prodrug is to include one or more selected moieties which are hydrolyzed under physiologic conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by an enzymatic activity of the host animal such as specific target cells in the host animal. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids and esters of phosphonic acids) are preferred prodrugs of the present disclosure.

[0276] Prodrug forms of the herein described compounds, wherein the prodrug ismetabolized in vivo to produce a compound as set forth herein are included within the scope ofthe claims. In some cases, some of the herein-described compounds may be a prodrug for another derivative or active compound.

[0277] Prodrugs are often useful because, in some situations, they may be easier toadminister than the parent drug. They may, for instance, be bioavailable by oral administration whereas the parent is not. Prodrugs may help enhance the cell permeability of a compound relative to the parent drug. The prodrug may also have improved solubility in pharmaceutical compositions over the parent drug. Prodrugs may be designed as reversible drug derivatives, for use as modifiers to enhance drug transport to site-specific tissues or to increase drug residence inside of a cell.

[0278] In some embodiments, the design of a prodrug increases the lipophilicity of thepharmaceutical agent. In some embodiments, the design of a prodrug increases the effectivewater solubility. See, e.g., Fedorak et al., Am. J. Physiol., 269:G210-218 (1995); McLoed et al.,Gastroenterol, 106:405-413 (1994); Hochhaus et al., Biomed. Chrom., 6:283-286 (1992); J. Larsen and H. Bundgaard, Int. J. Pharmaceutics, 37, 87 (1987); J. Larsen et al., Int. J. Pharmaceutics, 47, 103 (1988); Sinkula et al., J. Pharm. Sci., 64:181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol.14 of the A.C.S. Symposium Series; and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, all incorporated herein for such disclosure). According to another embodiment, the present disclosure provides methods of producing the above-defined compounds. The compounds may be synthesized using conventional techniques. -477-WSGR Docket No.63125-715.601 Advantageously, these compounds are conveniently synthesized from readily available starting materials.

[0279] Synthetic chemistry transformations and methodologies useful in synthesizing thecompounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989); T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2d. Ed. (1991); L. Fieser and M. Fieser, Fieser and Fieser’s Reagents for Organic Synthesis (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995). Targeting Unit (L)

[0280] In some embodiments, for a Drug-Linker or salt of Formula (I), Formula (I-A),Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-AA), Formula (I- AB), Formula (I-B), Formula (II-A), Formula (II-B) (each of which further comprises a targeting unit), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6) Formula (A-7), or Formula (A-8), the Targeting Unit is selected from an antibody or an antigen-binding fragment thereof. In some cases, the Targeting Unit is selected from a group consisting of chimeric antibodies, humanized antibodies, and human antibodies. In some cases, the Targeting Unit, performs a targeting function. In some cases, a Targeting unit specifically binds to a target molecule. In some cases, specifically binds refers to the ability of a Targeting unit (e.g., an antibody or portion thereof) described herein to bind to a target with a KD 10-5M (10000 nM) or less, e.g., 10-6M, 10-7M, 10-8M, 10-9M, 10-10M, 10-11M, 10-12M, or less. In some cases, a Targeting unit is said to specifically bind to its target when it preferentially recognizes its target in a complex mixture of proteins and / or macromolecules.

[0281] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the Targeting unit is an antibody or antigen binding portion thereof is a bispecific or multispecific binding agent. Bispecific and multi-specific antibodies include the following: an scFv1-ScFv2, an ScFv12-Fc-scFv22, an IgG-scFv, a DVD-Ig, a triomab / quadroma, a two-in-one IgG, a scFv2-Fc, a TandAb, and an scFv-HSA-scFv. In some embodiments, an IgG-scFv is an IgG (H) -scFv, scFv-(H) IgG, IgG (L) -scFv, svFc- (L) IgG, 2scFV-IgG or IgG-2scFv.

[0282] In some embodiments, for a Drug-Linker or salt of Formula (I), Formula (I-A),Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-A), Formula (II-B), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6) Formula -478-WSGR Docket No.63125-715.601 (A-7), or Formula (A-8), the Targeting unit is UC-961. In some cases, L is UC-961. In some cases, the Targeting unit is PTK7. In some cases, L is PTK7.

[0283] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6) Formula (A-7), or Formula (A-8), L is an antibody that binds to human protein tyrosine kinase 7 (PTK7).

[0284] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6) Formula (A-7), or Formula (A-8), the Targeting unit is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, L is an anti-PTK7 antibody. In some cases, the anti-PTK7 antibody comprises 8 sulfur atoms that each can independently form a bond with about eight separate drug-linkers via M2.

[0285] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6) Formula (A-7), or Formula (A-8), the Targeting unit is an anti-PTK7 antibody or an antigen-binding portion thereof. In some cases, L is an anti-PTK7 antibody. In some cases, the PTK7 antibody is modified with a group capable of reacting to form M2(e.g., to formsome cases, the PTK7 antibody is modified with a group capable of a click reaction to form M2(e.g., to form).

[0286] In some embodiments, for a Drug-Linker or salt of Formula (I), Formula (I-A),Formula (Ia), Formula (I-AAa), Formula (Ib), Formula (I-AAb), Formula (I-B), Formula (II-A), Formula (II-B), or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6) Formula (A-7), or Formula (A-8), the Targeting unit is a cancer associated antigen such as CD19, CD20, CD30, CD33, CD38, CA125, MUC-1, prostate-specific membrane antigen (PSMA), CD44 surface adhesion molecule, mesothelin (MLSN), carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR), EGFRvIII, vascular endothelial growth factor receptor-2 -479-WSGR Docket No.63125-715.601 (VEGFR2) , high molecular weight-melanoma associated antigen (HMW-MAA) , MAGE-A1, IL-13R-a2, GD2, 1p19q, ABL1, AKT1, ALK, APC, AR, ATM, BRAF, BRCA1, BRCA2, cKIT, cMET, CSF1R, CTNNB1, FGFR1, FGFR2, FLT3, GNA11, GNAQ, GNAS, HRAS, IDH1, IDH2, JAK2, KDR (VEGFR2) , KRAS, MGMT, MGMT-Me, MLH1, MPL, NOTCH1, NRAS, PDGFRA, Pgp, PIK3CA, PR, PTEN, RET, RRM1, SMO, SPARC, TLE3, TOP2A, TOPO1, TP53, TS, TUBB3, VHL, CDH1, ERBB4, FBXW7, HNF1A, JAK3, NPM1, PTPN11, RB1, SMAD4, SMARCB1, STK1, MLH1, MSH2, MSH6, PMS2, ROS1, ERCC1, 5T4 (TPBG) , B7- H3, CCR7, CD105, CD22, CD46, CD47, CD56, CD70, CD71, CD79b, CDH6, CLDN6, CLDN18.2, CLEC12A, DLL3, DR5, ERBB3 (HER3) , EPCAM, FOLR1, IGF1R, IL2RA (CD25) , IL3RA, ITGB6, LIV-1, LRRC15, mesothelin (MSLN) , NaPi2b (SLC34A2) , nectin-4, PTK7, ROR1, SEZ6, SLC44A4, SLITRK6, Tissue Factor (TF) , TROP2 or B7-H4.

[0287] In some embodiments, a Targeting unit specifically binds to a target such as CD19,CD20, CD30, CD33, CD70, LIV-1 or EGFRv3.

[0288] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), L of the disclosed antibody-drug conjugate can be any PTK7-binding antibody. In some cases, the antibody is a chimeric, CDR-grafted, humanized, or a recombinant human antibody, or PTK7-binding fragment thereof. In some cases, the antibody is an internalizing antibody and / or a neutralizing antibody. In some cases, the PTK7 antibody, or antigen-binding fragment thereof, includes one or more CDR(s) of the antibody (such as one, two, three, four, five, or all six CDRs). In some cases, the CDRs are as described elsewhere herein.

[0289] In some embodiments, a human PTK7 polypeptide sequence is available underUniProt Accession No. Q13308 (PTK7_HUMAN) and is shown below: MGAARGSPAR PRRLPLLSVL LLPLLGGTQT AIVFIKQPSS QDALQGRRAL LRCEVEAPGP VHVYWLLDGA PVQDTERRFA QGSSLSFAAV DRLQDSGTFQ CVARDDVTGE EARSANASFN IKWIEAGPVV LKHPASEAEI QPQTQVTLRC HIDGHPRPTY QWFRDGTPLS DGQSNHTVSS KERNLTLRPA GPEHSGLYSC CAHSAFGQAC SSQNFTLSIA DESFARVVLA PQDVVVARYE EAMFHCQFSA QPPPSLQWLF EDETPITNRS RPPHLRRATV FANGSLLLTQ VRPRNAGIYR CIGQGQRGPP IILEATLHLA EIEDMPLFEP RVFTAGSEER VTCLPPKGLP EPSVWWEHAG VRLPTHGRVY QKGHELVLAN IAESDAGVYT CHAANLAGQR RQDVNITVAT VPSWLKKPQD SQLEEGKPGY LDCLTQATPK PTVVWYRNQM LISEDSRFEV FKNGTLRINS VEVYDGTWYR CMSSTPAGSI EAQARVQVLE KLKFTPPPQP QQCMEFDKEA TVPCSATGRE KPTIKWERAD GSSLPEWVTD NAGTLHFARV TRDDAGNYTC IASNGPQGQI RAHVQLTVAV FITFKVEPER TTVYQGHTAL LQCEAQGDPK PLIQWKGKDR ILDPTKLGPR MHIFQNGSLV IHDVAPEDSG RYTCIAGNSC NIKHTEAPLY VVDKPVPEES EGPGSPPPYK MIQTIGLSVG AAVAYIIAVL GLMFYCKKRC KAKRLQKQPE GEEPEMECLN GGPLQNGQPS AEIQEEVALT SLGSGPAATN KRHSTSDKMH FPRSSLQPIT TLGKSEFGEV FLAKAQGLEE GVAETLVLVK SLQSKDEQQQ LDFRRELEMF GKLNHANVVR LLGLCREAEP HYMVLEYVDL GDLKQFLRIS KSKDEKLKSQ -480-WSGR Docket No.63125-715.601 PLSTKQKVAL CTQVALGMEH LSNNRFVHKD LAARNCLVSA QRQVKVSALG LSKDVYNSEY YHFRQAWVPL RWMSPEAILE GDFSTKSDVW AFGVLMWEVF THGEMPHGGQ ADDEVLADLQ AGKARLPQPE GCPSKLYRLM QRCWALSPKD RPSFSEIASA LGDSTVDSKP (SEQ ID NO:198) In the above sequence, amino acids 1-30 correspond to the signal sequence; amino acids 31-704 correspond to the extracellular domain (ECD); amino acids 705-725 correspond to the transmembrane domain; and amino acids 726-1070 correspond to the intracellular domain. The PTK7 binders of the conjugates described herein bind to the ECD of PTK7.

[0290] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the conjugate is conjugated to an anti-PTK7 antibody or an antigen-binding portion thereof that competes or cross-competes for binding to human PTK7 with, or binds to the same epitope of human PTK7 as, any one of SLX-1040, Z12, Z23, Z31, SLX-1042, or SLX-1059.

[0291] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the conjugate is conjugated to an anti-PTK7 antibody or an antigen-binding portion thereof that competes or cross-competes for binding to human PTK7 with, or binds to the same epitope of human PTK7 as, an antibody comprising: a) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:76 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:75; b) a VH comprising the amino acid sequence of SEQ ID NO:178 and a VL comprising the amino acid sequence of SEQ ID NO:188; c) a VHcomprising the amino acid sequence of SEQ ID NO:193 and a VLcomprising the amino acid sequence of SEQ ID NO:188; d) a VH comprising the amino acid sequence of SEQ ID NO:173 and a VL comprising the amino acid sequence of SEQ ID NO:188; e) a VH comprising the amino acid sequence of SEQ ID NO:112 and a VL comprising the amino acid sequence of SEQ ID NO:111; or f) a VHcomprising the amino acid sequence of SEQ ID NO:128 and a VLcomprising the amino acid sequence of SEQ ID NO:127.

[0292] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody or antigen-binding portion comprises the HCDR1-3 and LCDR1-3 amino acid sequences of any one of the antibodies -481-WSGR Docket No.63125-715.601 exemplified herein. The assignment of CDR regions may be in accordance with any method known in the art, such as IMGT®, Kabat, Chothia, Martin, Contact, or AHo definitions, or any combination of any of these definitions (Kabat plus Chothia, for example). Examples of CDR definitions under different methods are shown below for SLX-1040 (SEQ: SEQ ID NO): SLX-1040 HCDRsSLX-1040 LCDRsThus, for example, the SLX-1040 IMGT®-defined HCDR1-3 and LCDR1-3 sequences of SEQ ID NOs:151, 157, 161, 164, 167, and 170, respectively, may be replaced in any embodiment described herein by SEQ ID NOs:149, 155, 160, 163, 166, and 170, respectively; SEQ ID NOs:150, 156, 160, 163, 166, and 170, respectively; SEQ ID NOs:152, 158, 161, 163, 168, and 170, respectively; or SEQ ID NOs:153, 159, 162, 165, 169, and 171, respectively. Also contemplated is a set of SLX-1040 CDRs wherein each of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 may individually be specified according to any of the methods for defining SLX-1040 CDRs as shown above (e.g., HCDR1 specified by the Kabat definition, HCDR2 specified by the Chothia definition, etc.). The same means for defining SLX-1040 CDRs are contemplated for any of the exemplified antibodies herein.

[0293] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula -482-WSGR Docket No.63125-715.601 (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody or antigen-binding portion thereof has: - an HCDR1 selected from SEQ ID NOs: 149-154; - an HCDR2 selected from SEQ ID NOs: 155-159; - an HCDR3 selected from SEQ ID NOs: 160-162; - an LCDR1 selected from SEQ ID NOs: 163-165; - an LCDR2 selected from SEQ ID NOs: 166-169; and - an LCDR3 selected from SEQ ID NOs: 170 and 171.

[0294] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody or antigen-binding portion thereof has HCDR1-3 and LCDR1-3 comprising SEQ ID NOs:151, 157, 161, 164, 167, and 170, respectively. In some embodiments, the anti-PTK7 antibody or antigen-binding portion has HCDR1-3 and LCDR1-3 comprising SEQ ID NOs:154, 155, 161, 163, 166, and 170, respectively.

[0295] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody or antigen-binding portion has HCDR1-3 and LCDR1-3 comprising SEQ ID NOs:204, 209, 213, 216, 219, and 222, respectively.

[0296] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody or antigen-binding portion has HCDR1-3 and LCDR1-3 comprising SEQ ID NOs:226, 231, 235, 238, 241, and 244, respectively.

[0297] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody comprises an HC amino acid sequence comprising SEQ ID NOs:76 and 201, optionally without the C-terminal lysine, and an LC amino acid sequence comprising SEQ ID NOs:75 and 199.

[0298] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody comprises an HC amino acid sequence comprising SEQ ID NOs:178 and 201, optionally without the C-terminal lysine, and an LC amino acid sequence comprising SEQ ID NOs:188 and 199. -483-WSGR Docket No.63125-715.601

[0299] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody comprises an HC amino acid sequence comprising SEQ ID NOs:193 and 201, optionally without the C-terminal lysine, and an LC amino acid sequence comprising SEQ ID NOs:188 and 199.

[0300] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody comprises an HC amino acid sequence comprising SEQ ID NOs:173 and 201, optionally without the C-terminal lysine, and an LC amino acid sequence comprising SEQ ID NOs:188 and 199.

[0301] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody comprises an HC amino acid sequence comprising SEQ ID NOs:112 and 201, optionally without the C-terminal lysine, and an LC amino acid sequence comprising SEQ ID NOs:111 and 199.

[0302] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody comprises an HC amino acid sequence comprising SEQ ID NOs:128 and 201, optionally without the C-terminal lysine, and an LC amino acid sequence comprising SEQ ID NOs:127 and 199.

[0303] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula(Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the anti-PTK7 antibody of the present disclosure can be an IgG, an IgM, an IgE, an IgA, or an IgD molecule, but is typically of the IgG isotype, e.g., of IgG subclass IgG1, IgG2, IgG3 or IgG4. In some embodiments, the antibody is of the isotype subclass IgG1. Making of PTK7-Binding Proteins (e.g., anti-PTK7 antibodies and proteins comprising the antibodies or antigen-binding portions thereof)

[0304] The PTK7-binding protein of the present disclosure may be produced recombinantlyusing isolated nucleic acid molecules such as expression constructs. The coding sequences for each polypeptide chain may be cloned into a single vector or cloned into separate vectors (e.g., a pair or set of vectors). The proteins may be produced in host cells, e.g., mammalian host cells, using appropriate expression constructs. Mammalian cell lines available as hosts for expression include, without limitation, Chinese hamster ovary (CHO) cells, NS0 cells, SP2 cells, HEK- 293T cells, 293 Freestyle cells (Invitrogen), NIH-3T3 cells, HeLa cells, baby hamster kidney -484-WSGR Docket No.63125-715.601 (BHK) cells, African green monkey kidney cells (COS), human hepatocellular carcinoma cells (e.g., Hep G2), and A549 cells. Other cell lines that may be used are insect cell lines, such as Sf9 or Sf21 cells, and yeast cell lines. In certain embodiments, the cell lines are not derived from a human embryo. Cell lines may be selected based on their expression levels.

[0305] Host cells used to produce the PTK7-binding proteins are “recombinant host cells.”A “recombinant host cell” (or simply “host cell”), as used herein, means a cell into which a recombinant expression construct has been introduced. By definition, a recombinant host cell does not occur in nature. A protein produced from a recombinant host cell is a recombinant protein.

[0306] The PTK7-binding protein may be isolated and purified from the host cell cultureusing well known methods, such as centrifugation; ultracentrifugation; protein A, protein G, protein A / G, or protein L purification; and / or ion exchange chromatography. Pharmaceutical Formulations

[0307] Provided herein, in certain embodiments, are pharmaceutical compositionscomprising a therapeutically effective amount of a Drug-Linker or salt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-A), Formula (Ia), Formula (I- AAa), Formula (Ib), Formula (I-AAb), Formula (I-AA), Formula (I-AB), Formula (I-B), Formula (II-A), Formula (II-B), or a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-1), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8) (also referred to herein as “a pharmaceutical agent”).

[0308] Pharmaceutical compositions may be formulated using one or more physiologicallyacceptable carriers including excipients and auxiliaries which facilitate processing of the pharmaceutical agent into preparations which are used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. A summary of pharmaceutical compositions is found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa., Mack Publishing Company, 1995); Hoover, John E., Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins, 1999).

[0309] The compositions and methods of the present disclosure may be utilized to treat anindividual in need thereof. In certain embodiments, the individual is a mammal such as a human, or a non-human mammal. When administered to an animal, such as a human, the composition or the pharmaceutical agent, is preferably administered as a pharmaceutical composition -485-WSGR Docket No.63125-715.601 comprising, for example, a pharmaceutical agent and a pharmaceutically acceptable carrier or excipient. Pharmaceutically acceptable carriers are well known in the art and includ...

Claims

WSGR Docket No.63125-715.601 CLAIMS WHAT IS CLAIMED IS:

1. A conjugate of the Formula (XX):Formula (XX) or a pharmaceutically acceptable salt thereof, wherein; L is a Targeting Unit, wherein the Targeting Unit is an anti-PTK7 antibody or an antigen- binding portion thereof; R40 is independently selected from hydrogen,D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; z is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino -594-WSGR Docket No.63125-715.601 acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6alkynyl; M2is a connector unit; K1is selected from: -595-WSGR Docket No.63125-715.601 (i) a peptide unit, (ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle.

2. The conjugate or salt of claim 1, wherein when X is CH, D is exatecan or MMAE, m is1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines.

3. The conjugate or salt of claims 1 or 2, wherein Formula (XX) is represented byFormula (XXI) or -596-WSGR Docket No.63125-715.601Formula (XXII) or a pharmaceutically acceptable salt thereof.

4. The conjugate or salt of any one of claims 1 to 3, wherein Formula (XX) is representedbyFormula (XXIII) or a pharmaceutically acceptable salt thereof.

5. The conjugate or salt of any one of claims 1 to 3, wherein Formula (XX) is representedbyFormula (A) or a pharmaceutically acceptable salt thereof.

6. The conjugate or salt of any one of claims 1 to 3, wherein Formula (A) is represented byFormula (A-1) or a pharmaceutically acceptable salt thereof.

7. The conjugate or salt of any one of claims 1 to 6, wherein S1 is selected from: (i) anoptionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, – -597-WSGR Docket No.63125-715.601 N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or – P(O)(R20)2–.

8. The conjugate or salt of any one of claims 1 to 7, where S1 is selected from: (i) anoptionally substituted C6-C10 alkylene wherein one or more alkylene units of the C6-C10 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, or – C(O)–.

9. The conjugate or salt of any one of claims 1 to 8, wherein S1 is a branched alkylene.

10. The conjugate or salt of any one of claims 1 to 9, wherein S1 is represented by. eor salt of any one of claims 1 to 10, wherein S1 is represented by.

12. The conjugate or salt of any one of claims 1 to 11, wherein S2 is selected from: (i) anoptionally substituted C8-C12 alkylene wherein one or more alkylene units of the C8-C12 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –O–, and –C(O)–.

13. The conjugate or salt of any one of claims 1 to 12, wherein S2 is a linear alkylene.

14. The conjugate or salt of any one of claims 1 to 13, wherein S2 is represented by. -598-WSGR Docket No.63125-715.60115. The conjugate or salt of any one of claims 1 to 14, wherein S2 is represented by.

16. The conjugate or salt of any one of claims 1 to 15, wherein M2 is selected from17. The conjugate or salt of any one of claims 1 to 16, wherein M2 is selected from18. The conjugate or salt of any one of claims 1 to 17, wherein.

19. The conjugate or salt of any one of claims 1 to 17, wherein.

20. The conjugate or salt of any one of claims 1 to 17, wherein.

21. The conjugate or salt of claim 18, wherein Formula (A) is represented by-599-WSGR Docket No.63125-715.601Formula (A-2) or a pharmaceutically acceptable salt thereof.

22. The conjugate or salt of any one of claims 1 to 21, wherein X is CH.

23. The conjugate or salt of any one of claims 1 to 21, wherein X is N.

24. The conjugate or salt of any one of claims 1 to 23, wherein S3 is present and is aphenylene.

25. The conjugate or salt of any one of claims 1 to 23, wherein S3 is absent.

26. The conjugate or salt of any one of claims 1 to 25, wherein Formula (A) is representedbyFormula (A-7) wherein DAR is a drug to antibody ratio, or a pharmaceutically acceptable salt thereof.

27. The conjugate or salt of any one of claims 1 to 26, wherein Formula (A) is representedby -600-WSGR Docket No.63125-715.601Formula (A-8), wherein DAR is a drug to antibody ratio, or a pharmaceutically acceptable salt thereof.

28. The conjugate or salt of any one of claims 1 to 27, wherein each K1 is selected from apeptide unit.

29. The conjugate or salt of any one of claims 1 to 28, wherein the peptide unit of K1 has 1 to50 amino acids.

30. The conjugate or salt of any one of claims 1 to 29, wherein the amino acids of K1 isselected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine.

31. The conjugate or salt of any one of claims 1 to 30, wherein the amino acids of K1 isselected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β-Alanine.

32. The conjugate or salt of any one of claims 1 to 31, wherein the peptide unit of K1 has aterminus unit.

33. The conjugate or salt of any one of claims 1 to 32, wherein K1 is selected from, -601-WSGR Docket No.63125-715.601, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30.

34. The conjugate or salt of any one of claims 1 to 33, wherein K1 is selected from, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30.

35. The conjugate or salt of any one of claims 1 to 33, wherein K1 is selected from, -602-WSGR Docket No.63125-715.601, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30.

36. The conjugate or salt of any one of claims 1 to 35, wherein K1 is selected from.

37. The conjugate or salt of any one of claims 1 to 33, 35, or 36, wherein K1 is selected fromor salt of any one of claims 1 to 33, or 37, wherein K1 is selected from, w erein j is selected from 5 to 15.

39. The conjugate or salt of any one of claims 1 to 33, or 37, wherein K1 is selected from, wherein j is selected from 3 to 8. -603-WSGR Docket No.63125-715.60140. The conjugate or salt of any one of claims 1 to 33, or 37, wherein K1 is selected from, wherein j is selected from 3 to 8.

41. The conjugate or salt of any one of claims 33 to 40, wherein R6 is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected fromhalogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S,=N(R30), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle.

42. The conjugate or salt of any one of claims 33 to 41, wherein R6 is selected from -OH, -43. The conjugate or salt of any one of claims 33 to 41, wherein R6 is -OH.

44. The conjugate or salt of any one of claims 33 to 36, wherein R6 is -NH2.

45. The conjugate or salt of any one of claims 33 to 36, wherein R6 is.

46. The conjugate or salt of any one of claims 1 to 32, wherein K1 is selected from, -604-WSGR Docket No.63125-715.601, -605-WSGR Docket No.63125-715.

601.

48. The conjugate or salt of any one of claims 1 to 32, wherein K1 is selected from, -606-WSGR Docket No.63125-715.601-607-WSGR Docket No.63125-715.601.

50. The conjugate or salt of any one of claims 1 to 32, wherein K1 is.

51. The conjugate or salt of any one of claims 1 to 32, wherein K1 is selected from.

52. The conjugate or salt of any one of claims 1 to 32, wherein K1 is.

53. The conjugate or salt of any one of claims 1 to 32, wherein K1 is.

54. The conjugate or salt of any one of claims 1 to 32, wherein K1 is selected from.

55. The conjugate or salt of any one of claims 1 to 32, wherein K1 is.-608-WSGR Docket No.63125-715.60156. The conjugate or salt of any one of claims 1 to 32, wherein K1 is.

57. The conjugate or salt of any one of claims 1 to 32, wherein K1 is selected from.

58. The conjugate or salt of any one of claims 1 to 32, wherein.

59. The conjugate or salt of any one of claims 1 to 32, wherein.

60. The conjugate or salt of any one of claims 1 to 32, wherein.

61. The conjugate or salt of any one of claims 1 to 32, wherein K1 is.

62. The conjugate or salt of any one of claims 1 to 32, wherein K1 is.

63. The conjugate or salt of any one of claims 1 to 32, wherein K1 is.

64. The conjugate or salt of any one of claims 1 to 32, wherein K1 is. -609-WSGR Docket No.63125-715.60165. The conjugate or salt of any one of claims 1 to 10, wherein S1 is represented by.

66. The conjugate or salt of claim 65, wherein each K1 is selected from: an oligosaccharide.

67. The conjugate or salt of claim 66, wherein each K1 is selected from:.

68. The conjugate or salt of claim 1, wherein Formula (A) is represented byFormula (A-3) or a pharmaceutically acceptable salt thereof.

69. The conjugate or salt of claim 1, wherein Formula (A) is represented byFormula (A-4) or a pharmaceutically acceptable salt thereof.

70. The conjugate or salt of any one of claims 68 to 69, wherein S1 is selected from: (i) anoptionally substituted C1-C2 alkylene wherein one or more alkylene units of the C1-C2 alkylene are optionally and independently replaced by –N(R20)–.

71. The conjugate or salt of any one of claims 68 to 70, wherein S1 is represented by. -610-WSGR Docket No.63125-715.60172. The conjugate or salt of any one of claims 68 to 71, wherein S2 is selected from: (i) anoptionally substituted C8-C12alkylene wherein one or more alkylene units of the C8-C12alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –O–, and –C(O)–.

73. The conjugate or salt of any one of claims 68 to 72, wherein S2 is a linear alkylene.

74. The conjugate or salt of any one of claims 68 to 73, wherein S2 is represented by.

75. The conjugate or salt of any one of claims 68 to 74, wherein S1-S2 is represented by.

76. The conjugate or salt of any one of claims 68 to 75, wherein S3 is present and is aphenylene.

77. The conjugate or salt of any one of claims 68 to 75, wherein S3 is absent.

78. The conjugate or salt of any one of claims 68 to 77, wherein M2 is selected from79. The conjugate or salt of any one of claims 68 to 78, wherein M2 is selected from. -611-WSGR Docket No.63125-715.60180. The conjugate or salt of any one of claims 68 to 78, wherein M2 is selected from81. The conjugate or salt of any one of claims 68 to 78, wherein.

82. The conjugate or salt of any one of claims 68 to 78, wherein.

83. The conjugate or salt of any one of claims 68 to 78, wherein.

84. The conjugate or salt of any one of claims 68 to 81, wherein S1-S2-M2-L is represented, wherein S3is absent.

85. The conjugate or salt of any one of claims 68 to 81, wherein Formula (A) is representedbyFormula (A-5) or a pharmaceutically acceptable salt thereof.

86. The conjugate or salt of any one of claims 68 to 81, wherein Formula (A) is represented-612-WSGR Docket No.63125-715.601Formula (A-6) or a pharmaceutically acceptable salt thereof.

87. The conjugate or salt of any one of claims 68 to 86, wherein p is 1.

88. The conjugate or salt of any one of claims 68 to 87, wherein S4 is selected from: (i) anoptionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –O–, or –C(O)–.

89. The conjugate or salt of any one of claims 68 to 88, wherein S4 is selected from: (i) anoptionally substituted C1-C5alkylene wherein one or more alkylene units of the C1-C5alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –O–, or –C(O)–.

90. The conjugate or salt of any one of claims 68 to 89, wherein S4 is selected from: (i) anoptionally substituted C1-C3 alkylene wherein one or more alkylene units of the C1-C5 alkylene are optionally and independently replaced by –N(H)–, –N(CH3)–, –O–, or –C(O)–.

91. The conjugate or salt of any one of claims 68 to 90, wherein S4 is selected from,92. The conjugate or salt of any one of claims 68 to 90, wherein S4 i.

93. The conjugate or salt of any one of claims 68 to 90, wherein S4 i.

94. The conjugate or salt of any one of claims 68 to 90, wherein S4 i.

95. The conjugate or salt of any one of claims 68 to 94, wherein each K2 is selected from apeptide unit.

96. The conjugate or salt of any one of claims 68 to 95, wherein the peptide unit of K2 has 1to 50 amino acids.

97. The conjugate or salt of claim 96, wherein the amino acids of K2 is selected from a groupconsisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, -613-WSGR Docket No.63125-715.601 glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine.

98. The conjugate or salt of claim 89, wherein the amino acids of K2 is selected from a groupconsisting of glycine, sarcosine, proline, serine, alanine, and β-Alanine.

99. The conjugate or salt of any one of claims 68 to 98, wherein the peptide unit of K2 has aterminus unit.

100. The conjugate or salt of any one of claims 68 to 99, wherein K2 is selected from.

101. The conjugate or salt of any one of claims 68 to 99, wherein K2 is selected from, -614-WSGR Docket No.63125-715.601, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30.

102. The conjugate or salt of any one of claims 68 to 98, wherein K2 is selected from, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30.

103. The conjugate or salt of any one of claims 100 to 102, wherein R6 is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S,=N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle.

104. The conjugate or salt of any one of claims 100 to 103, wherein R6 is selected from -OH, -105. The conjugate or salt of any one of claims 100 to 104, wherein R6 is -OH.

106. The conjugate or salt of any one of claims 100 to 104, wherein R6 is -NH2.-615-WSGR Docket No.63125-715.601 107. The conjugate or salt of any one of claims 100 to 104, wherein R6 is .

108. The conjugate or salt of any one of claims 68 to 99, wherein K2 is selected from, -616-WSGR Docket No.63125-715.

601.

109. The conjugate or salt of any one of claims 68 to 99, wherein K2 is selected from110. The conjugate or salt of any one of claims 68 to 99, wherein K2 is selected from, -617-WSGR Docket No.63125-715.601111. The conjugate or salt of any one of claims 68 to 99, wherein K2 is.

112. The conjugate or salt of any one of claims 68 to 99, wherein K2 is selected from.

113. The conjugate or salt of any one of claims 68 to 99, wherein K2 is.

115. The conjugate or salt of any one of claims 68 to 99, wherein K2 is selected from.

116. The conjugate or salt of any one of claims 68 to 99, wherein K2 is.-618-WSGR Docket No.63125-715.601117. The conjugate or salt of any one of claims 68 to 99, wherein K2 is.

118. The conjugate or salt of any one of claims 68 to 99, wherein K2 is selected from.

119. The conjugate or salt of any one of claims 68 to 99, wherein.

120. The conjugate or salt of any one of claims 68 to 99, wherein.

121. The conjugate or salt of any one of claims 68 to 99, wherein.

122. The conjugate or salt of any one of claims 68 to 99, wherein K2 is.

123. The conjugate or salt of any one of claims 68 to 99, wherein K2 is.

124. The conjugate or salt of any one of claims 68 to 99, wherein K2 is.

125. The conjugate or salt of any one of claims 68 to 99, wherein K2 is-619-WSGR Docket No.63125-715.601126. The conjugate or salt of any one of claims 68 to 99, wherein K2 is selected from: anoligosaccharide.

127. The conjugate or salt of claim 126, wherein each K2 is selected from:, wherein k is selected from 2 to 10.

128. The conjugate or salt of claim 127, wherein each K2 is selected from:.

129. The conjugate or salt of any one of claims 1 to 128, wherein the sugar cleavable unit ofT1includes a sugar.

130. The conjugate or salt of claim 129, wherein the sugar is glucuronide.

131. The conjugate or salt of any one of claims 1 to 130, wherein.

132. The conjugate or salt of any one of claims 1 to 128, wherein the peptide unit of T2includes one or more amino acids selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-Alanine.

133. The conjugate or salt of claim 132, wherein the peptide unit of T2 includes a dipeptide ortripeptide.

134. The conjugate or salt of claim 133, wherein the peptide unit of T2 includes a dipeptide.

135. The conjugate or salt of any one of claims 132 to 134, wherein the dipeptide is selectedfrom Val-Cit, Val-Ala and Phe-Lys. -620-WSGR Docket No.63125-715.601136. The conjugate or salt of any one of claims 132 to 135, wherein the peptide unit of T2includes a capping moiety.

137. The conjugate or salt of claim 136, wherein the capping moiety is.

138. The conjugate or salt of any one of claims 1 to 128, or 132 to 137, wherein Y is.

139. The conjugate or salt of any one of claims 1 to 138, wherein D is a selected from acytotoxic agent, an immune modulatory agent, a nucleic acid, a growth inhibitory agent, a PROTAC, a toxin, a radioactive isotope and a chelating ligand.

140. The conjugate or salt of any one of claims 1 to 138, wherein D is selected from acytotoxic agent, camptothecin derivative, and an immune modulatory agent.

141. The conjugate or salt of any one of claims 1 to 138, wherein D is a selected from acytotoxic agent, and an immune modulatory agent.

142. The conjugate or salt of any one of claims 1 to 138, wherein D is selected from exatecan,SN-38, and monomethyl auristatin E (MMAE).

143. The conjugate or salt of any one of claims 1 to 138, wherein D is selected from exatecanand monomethyl auristatin E (MMAE).

144. The conjugate or salt of any one of claims 1 to 138, wherein D is MMAE.

145. The conjugate or salt of any one of claims 1 to 138, wherein D is exatecan.

146. The conjugate or salt of any one of claims 1 to 138, wherein D is.

147. The conjugate or salt of any one of claims 1 to 146, having a DAR (drug to antibodyratio) of about 1 to about 10.

148. The conjugate or salt of any one of claims 1 to 147, having a DAR of about 2 to about 8.

149. The conjugate or salt of any one of claims 1 to 148, having a DAR of about 4 to about 8.

150. The conjugate or salt of any one of claims 1 to 149, having a DAR of about 4 or about 8.

151. The conjugate or salt of any one of claims 1 to 150, having a DAR of about 4.

152. The conjugate or salt of any one of claims 1 to 150, having a DAR of about 8.-621-WSGR Docket No.63125-715.601153. A conjugate represented by the Formula (Aa) or Formula (Ab):, or or a pharmaceutically acceptable salt thereof, wherein; L is an anti-PTK7 antibody or an antigen-binding portion thereof; D is selected from a Drug unit; n is selected from 0 and 1; m is selected from 0 and 1; wherein at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30 alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; -622-WSGR Docket No.63125-715.601 S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and (iii) C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30, -C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6 alkyl, C2-6 alkenyl,and C2-6 alkynyl; M2is a connector unit; K1is selected from: (i) a peptide unit, -623-WSGR Docket No.63125-715.601 (ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1- C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; K2is selected from: (i) a peptide unit, (ii) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1- C30 alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) an oligosaccharide; and (iv) a polyether; each R20is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, oxo, C3-12 carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.

154. The conjugate or salt of claim 153, wherein when X is CH, D is exatecan or MMAE, mis 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines;155. The conjugate or salt of claim 153, wherein the conjugate is represented by-624-WSGR Docket No.63125-715.601, wherein L is an anti-PTK7 antibody or an antigen-binding portion thereof; and DAR is a drug to antibody ratio.

156. The conjugate or salt of claim 153, wherein the conjugate is represented by, wherein L is an anti-PTK7 antibody or an antigen-binding portion thereof; and DAR is a drug to Targeting Unit (L) ratio.

157. The conjugate or salt of any one of claims 153 to 156, having a DAR of about 1 to 10.

158. The conjugate or salt of any one of claims 153 to 156, having a DAR of about 2 to 8.

159. The conjugate or salt of any one of claims 153 to 156, having a DAR about 8.

160. The conjugate or salt of any one of claims 1 to 159, wherein the antibody or portionthereof comprises a heavy chain CDR (HCDR) 1-3 and a light chain CDR (LCDR) 1-3 comprising SEQ ID NOs:151, 157, 161, 164, 167, and 170, respectively. -625-WSGR Docket No.63125-715.601161. The conjugate or salt of claim 160, wherein the antibody or portion thereof comprises aheavy chain variable domain (VH) and a light chain variable domain (VL) comprising SEQ ID NOs:76 and 75, respectively.

162. The conjugate or salt of claim 160, wherein the antibody or portion thereof comprises aVH comprising SEQ ID NOs:154, 155, and 161, and a VL comprising SEQ ID NOs:163, 166, and 170.

163. The conjugate or salt of claim 162, wherein the antibody or portion thereof is humanized.

164. The conjugate or salt of claim 163, wherein the VH comprises framework regions derivedfrom a human IGHV1-46*01 germline gene.

165. The conjugate or salt of claim 164, wherein the VH comprises one or more backmutations selected from Y91F, R71V, V78A, M48I, M69L, and V20L, wherein the numbering is according to SEQ ID NO:172.

166. The conjugate or salt of claim 163, wherein the VL comprises framework regions derivedfrom a human IGKV1D-16*01 germline gene.

167. The conjugate or salt of claim 166, wherein the VL comprises one or more backmutations selected from I21L, Y36L, A43T, S46R, G66R, T69S, and F71Y, wherein the numbering is according to SEQ ID NO:183.

168. The conjugate or salt of claim 163, whereina) the VHcomprises any one of SEQ ID NOs:172-182, 193, 196, and 197, or an amino acid sequence at least 95% identical thereto; b) the VL comprises any one of SEQ ID NOs:183-192, 194, and 195, or an amino acid sequence at least 95% identical thereto; or c) a) and b).

169. The conjugate or salt of claim 168, wherein the VH and the VL compriseSEQ ID NOs:178 and 188, respectively, SEQ ID NOs:193 and 188, respectively, or SEQ ID NOs:173 and 188, respectively.

170. The conjugate or salt of any one of claims 160 to 169, wherein the antibody comprises ahuman IgG1constant region.

171. The conjugate or salt of claim 170, wherein the human IgG1 constant region comprisesSEQ ID NO:201, optionally without the C-terminal lysine.

172. The conjugate or salt of any one of claims 160 to 170, wherein the antibody comprises ahuman light chain constant region that comprises SEQ ID NO:199.

173. The conjugate or salt of any one of claims 1 to 159, wherein the antibody or portionthereof comprising a heavy chain that comprises the amino acid sequences of SEQ ID NOs:193 -626-WSGR Docket No.63125-715.601 and 201, optionally without the C-terminal lysine, and a light chain that comprises the amino acid sequences of SEQ ID NOs:188 and 199.

174. The conjugate or salt of any one of claims 1 to 159, wherein the antibody or portionthereof comprises a) HCDR1-3 and LCDR1-3 comprising SEQ ID NOs:204, 209, 213, 216, 219, and 222, respectively; b) VH and VL comprising SEQ ID NOs:112 and 111, respectively; or c) an HC comprising SEQ ID NOs:112 and 201, optionally without the C-terminal lysine, and an LC comprising SEQ ID NOs:111 and 199.

175. The conjugate or salt of any one of claims 1 to 159, wherein the antibody or portionthereof comprises a) HCDR1-3 and LCDR1-3 comprising SEQ ID NOs:226, 231, 235, 238, 241, and 244, respectively; b) VH and VL comprising SEQ ID NOs:128 and 127, respectively; or c) an HC comprising SEQ ID NOs:128 and 201, optionally without the C-terminal lysine, and an LC comprising SEQ ID NOs:127 and 199.

176. The conjugate or salt of any one of claims 1 to 159, wherein the antibody or portionthereof comprises a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VHand the VLcomprise: SEQ ID NOs:148 and 147, respectively; SEQ ID NOs:24 and 23, respectively; SEQ ID NOs:36 and 35, respectively; SEQ ID NOs:4 and 3, respectively; SEQ ID NOs:10 and 9, respectively; SEQ ID NOs:16 and 15, respectively; SEQ ID NOs:18 and 17, respectively; SEQ ID NOs:20 and 19, respectively; SEQ ID NOs:22 and 21, respectively; SEQ ID NOs:26 and 25, respectively; SEQ ID NOs:28 and 27, respectively; SEQ ID NOs:30 and 29, respectively; SEQ ID NOs:32 and 31, respectively; SEQ ID NOs:34 and 33, respectively; SEQ ID NOs:38 and 37, respectively; SEQ ID NOs:40 and 39, respectively; -627-WSGR Docket No.63125-715.601 SEQ ID NOs:2 and 1, respectively; SEQ ID NOs:6 and 5, respectively; SEQ ID NOs:8 and 7, respectively; SEQ ID NOs:12 and 11, respectively; SEQ ID NOs:14 and 13, respectively; SEQ ID NOs:42 and 41, respectively; SEQ ID NOs:44 and 43, respectively; SEQ ID NOs:52 and 51, respectively; SEQ ID NOs:54 and 53, respectively; SEQ ID NOs:56 and 55, respectively; SEQ ID NOs:46 and 45, respectively; SEQ ID NOs:48 and 47, respectively; SEQ ID NOs:50 and 49, respectively; SEQ ID NOs:82 and 81, respectively; SEQ ID NOs:80 and 79, respectively; SEQ ID NOs:58 and 57, respectively; SEQ ID NOs:60 and 59, respectively; SEQ ID NOs:62 and 61, respectively; SEQ ID NOs:64 and 63, respectively; SEQ ID NOs:66 and 65, respectively; SEQ ID NOs:68 and 67, respectively; SEQ ID NOs:70 and 69, respectively; SEQ ID NOs:72 and 71, respectively; SEQ ID NOs:74 and 73, respectively; SEQ ID NOs:76 and 75, respectively; SEQ ID NOs:78 and 77, respectively; SEQ ID NOs:112 and 111, respectively; SEQ ID NOs:102 and 101, respectively; SEQ ID NOs:104 and 103, respectively; SEQ ID NOs:106 and 105, respectively; SEQ ID NOs:108 and 107, respectively; SEQ ID NOs:110 and 109, respectively; SEQ ID NOs:84 and 83, respectively; SEQ ID NOs:86 and 85, respectively; SEQ ID NOs:88 and 87, respectively; -628-WSGR Docket No.63125-715.601 SEQ ID NOs:90 and 89, respectively; SEQ ID NOs:92 and 91, respectively; SEQ ID NOs:94 and 93, respectively; SEQ ID NOs:96 and 95, respectively; SEQ ID NOs:98 and 97, respectively; SEQ ID NOs:100 and 99, respectively; SEQ ID NOs:114 and 113, respectively; SEQ ID NOs:120 and 119, respectively; SEQ ID NOs:128 and 127, respectively; SEQ ID NOs:130 and 129, respectively; SEQ ID NOs:132 and 131, respectively; SEQ ID NOs:134 and 133, respectively; SEQ ID NOs:136 and 135, respectively; SEQ ID NOs:138 and 137, respectively; SEQ ID NOs:140 and 139, respectively; SEQ ID NOs:142 and 141, respectively; SEQ ID NOs:144 and 143, respectively; SEQ ID NOs:146 and 145, respectively; SEQ ID NOs:116 and 115, respectively; SEQ ID NOs:118 and 117, respectively; SEQ ID NOs:122 and 121, respectively; SEQ ID NOs:124 and 123, respectively; SEQ ID NOs:126 and 125, respectively; or SEQ ID NOs:193 and 188, respectively.

177. The conjugate or salt of any one of claims 1 to 159, wherein the antibody or portionthereof comprises a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH and the VL comprise: SEQ ID NOs:148 and 147, respectively; SEQ ID NOs:10 and 9, respectively; SEQ ID NOs:16 and 15, respectively; SEQ ID NOs:18 and 17, respectively; SEQ ID NOs:20 and 19, respectively; SEQ ID NOs:26 and 25, respectively; SEQ ID NOs:30 and 29, respectively; SEQ ID NOs:112 and 111, respectively; -629-WSGR Docket No.63125-715.601 SEQ ID NOs:110 and 109, respectively; SEQ ID NOs:86 and 85, respectively; SEQ ID NOs:128 and 127, respectively; SEQ ID NOs:122 and 121, respectively; or SEQ ID NOs:193 and 188, respectively.

178. The conjugate or salt of any one of claims 176 to 177, wherein the antibody comprises ahuman IgG1 constant region.

179. The conjugate or salt of any one of claims 176 to 178, wherein the human IgG1 constantregion comprises SEQ ID NO:201, optionally without the C-terminal lysine.

180. The conjugate or salt of any one of claims 176 to 178, wherein the antibody comprises ahuman light chain constant region that comprises SEQ ID NO:199.

181. The conjugate or salt of any one of claims 1 to 177, wherein the PTK7 antibody isoptionally without the C-terminal lysine.

182. A pharmaceutical composition comprising a conjugate of any one of claims 1 to 181 anda pharmaceutically acceptable excipient.

183. A method of treating a subject with a disease or disorder, comprising administering tothe subject in need thereof a conjugate of any one of claims 1 to 180 or a pharmaceutical composition of claim 181.

184. The method of claim 182, wherein the disease or disorder is a cancer.

185. A method of treating a subject with a cancer, comprising administering to the subject inneed thereof a conjugate of any one of claims 1 to 181 or a pharmaceutical composition of claim 182.

186. A method of treating a subject with a PTK7-positive cancer, comprising administering tothe subject in need thereof a conjugate of any one of claims 1 to 181 or a pharmaceutical composition of claim 182.

187. The method of any one of claims 184 to 186, wherein the cancer is selected from:melanoma, skin basal cell cancer, glioblastoma, glioma, gliosarcoma, astrocytoma, meningioma, neuroblastoma, adrenocortical cancer, head and neck cancer (e.g., cancer of the head, neck, nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx, and / or salivary glands, and paragangliomas), oral cancer, salivary gland cancer, nasopharyngeal cancer, breast cancer (e.g., triple negative breast cancer), lung cancer (e.g., non-small cell lung cancer (NSCLC), small cell lung cancer, or squamous cell lung cancer), esophageal cancer, gastroesophageal junction cancer, gastric cancer, gastrointestinal cancer, primary peritoneal cancer, liver cancer, hepatocellular carcinoma, gallbladder cancer, biliary tract cancer, cholangiocarcinoma, colon cancer, rectal cancer, colorectal carcinoma, ovarian cancer, fallopian -630-WSGR Docket No.63125-715.601 tube cancer, bladder cancer, upper urinary tract cancer, urothelial cancer, renal cell carcinoma, kidney cancer, genitourinary cancer, cervical cancer, testicular cancer, prostate cancer, fibrosarcoma, liposarcoma, rhabdomyosarcoma (e.g., embryonal rhabdomyosarcoma), leiomyosarcoma, neurofibrosarcoma, synovial sarcoma, liposarcoma, alveolar soft part sarcoma, osteosarcoma, histiocytoma (e.g., malignant fibrous histiocytoma), pancreatic cancer, endometrial cancer, cancer of the appendix, thyroid cancer, advanced Merkel cell cancer, multiple myeloma, sarcomas, choriocarcinoma, leukemia (e.g., erythroleukemia, acute lymphoblastic leukemia, acute monocytic leukemia, acute promyelocytic leukemia, acute myeloid leukemia, acute myelogenous leukemia, chronic myeloid leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, or mast cell leukemia), lymphoma (e.g., small lymphocytic lymphoma, Burkitt’s lymphoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, diffuse large B cell lymphoma, lymphoplasmacytoid lymphoma, mucosa-associated lymphoid tissue lymphoma, mantle cell lymphoma, T-cell anaplastic large cell lymphoma, follicular lymphoma, monocytic lymphoma, or HTLV- associated T cell leukemia / lymphoma), or mesothelioma. In certain embodiments, the cancer is selected from the group consisting of head and neck cancer, bone cancer (e.g., osteosarcoma), Ewing sarcoma, squamous cell carcinoma, lung cancer (e.g., non-small cell lung cancer or small cell lung cancer), kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, cervical cancer, pancreatic cancer, breast cancer (e.g., triple negative breast cancer), melanoma, liver cancer, bladder cancer, stomach cancer, esophageal cancer, and chronic myelogenous leukemia. In particular embodiments, the cancer is selected from the group consisting of head and neck cancer, non-small cell lung cancer, esophageal cancer, gastric cancer, hepatic cancer, pancreatic cancer, colorectal cancer, breast cancer, endometrial cancer, ovarian cancer, soft-tissue sarcoma, bladder cancer, prostate cancer, renal cancer, and melanoma.

188. The method of any one of claims 184 to 186, wherein the cancer is selected from celllymphoma, non-small cell lung cancer, large-cell lung cancer, breast cancer, and small-cell lung cancer.

189. The method of any one of claims 184 to 186, wherein the cancer is cell lymphoma.

190. The method of any one of claims 184 to 186, wherein the cancer is non-small cell lungcancer.

191. The method of any one of claims 184 to 186, wherein the cancer is large-cell lungcancer.

192. The method of any one of claims 184 to 186, wherein the cancer is breast cancer.-631-WSGR Docket No.63125-715.601193. The method of any one of claims 184 to 186, wherein the cancer is small-cell lungcancer.

194. Use of a conjugate, for treating a subject with a disease or disorder, comprisingadministering to the subject in need thereof a conjugate of any one of claims 1 to 181 or a pharmaceutical composition of claim 182.

195. The use of claim 194, wherein the disease or disorder is cancer.

196. A conjugate selected from Table A, Table A-R, Table A-S, Table B, Table B-R, andTable B-S, or a pharmaceutically acceptable salt thereof.

197. A conjugate selected from Table A or a pharmaceutically acceptable salt thereof.

198. A conjugate selected from Table A-R or a pharmaceutically acceptable salt thereof.

199. A conjugate selected from Table A-S, or a pharmaceutically acceptable salt thereof.

200. A pharmaceutical composition comprising a conjugate of any one of claims 196 to 199and a pharmaceutically acceptable excipient.

201. A method of treating a subject with a disease or disorder, comprising administering tothe subject in need thereof a conjugate of any one of claims 196 to 199 or a pharmaceutical composition of claim 200.

202. The method of claim 201, wherein the disease or disorder is a cancer.

203. The method of claim 202, wherein the cancer is selected from: melanoma, skin basal cellcancer, glioblastoma, glioma, gliosarcoma, astrocytoma, meningioma, neuroblastoma, adrenocortical cancer, head and neck cancer (e.g., cancer of the head, neck, nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx, and / or salivary glands, and paragangliomas), oral cancer, salivary gland cancer, nasopharyngeal cancer, breast cancer (e.g., triple negative breast cancer), lung cancer (e.g., non-small cell lung cancer (NSCLC), small cell lung cancer, or squamous cell lung cancer), esophageal cancer, gastroesophageal junction cancer, gastric cancer, gastrointestinal cancer, primary peritoneal cancer, liver cancer, hepatocellular carcinoma, gallbladder cancer, biliary tract cancer, cholangiocarcinoma, colon cancer, rectal cancer, colorectal carcinoma, ovarian cancer, fallopian tube cancer, bladder cancer, upper urinary tract cancer, urothelial cancer, renal cell carcinoma, kidney cancer, genitourinary cancer, cervical cancer, testicular cancer, prostate cancer, fibrosarcoma, liposarcoma, rhabdomyosarcoma (e.g., embryonal rhabdomyosarcoma), leiomyosarcoma, neurofibrosarcoma, synovial sarcoma, liposarcoma, alveolar soft part sarcoma, osteosarcoma, histiocytoma (e.g., malignant fibrous histiocytoma), pancreatic cancer, endometrial cancer, cancer of the appendix, thyroid cancer, advanced Merkel cell cancer, multiple myeloma, sarcomas, choriocarcinoma, leukemia (e.g., erythroleukemia, acute lymphoblastic leukemia, acute monocytic leukemia, acute promyelocytic leukemia, acute -632-WSGR Docket No.63125-715.601 myeloid leukemia, acute myelogenous leukemia, chronic myeloid leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, or mast cell leukemia), lymphoma (e.g., small lymphocytic lymphoma, Burkitt’s lymphoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, diffuse large B cell lymphoma, lymphoplasmacytoid lymphoma, mucosa-associated lymphoid tissue lymphoma, mantle cell lymphoma, T-cell anaplastic large cell lymphoma, follicular lymphoma, monocytic lymphoma, or HTLV- associated T cell leukemia / lymphoma), or mesothelioma. In certain embodiments, the cancer is selected from the group consisting of head and neck cancer, bone cancer (e.g., osteosarcoma), Ewing sarcoma, squamous cell carcinoma, lung cancer (e.g., non-small cell lung cancer or small cell lung cancer), kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, cervical cancer, pancreatic cancer, breast cancer (e.g., triple negative breast cancer), melanoma, liver cancer, bladder cancer, stomach cancer, esophageal cancer, and chronic myelogenous leukemia. In particular embodiments, the cancer is selected from the group consisting of head and neck cancer, non-small cell lung cancer, esophageal cancer, gastric cancer, hepatic cancer, pancreatic cancer, colorectal cancer, breast cancer, endometrial cancer, ovarian cancer, soft-tissue sarcoma, bladder cancer, prostate cancer, renal cancer, and melanoma.

204. A conjugate represented by, or a pharmaceutically acceptable salt thereof, wherein L is an anti-PTK7 antibody or an antigen-binding portion thereof; and DAR is a drug to antibody ratio.

205. A conjugate represented by-633-WSGR Docket No.63125-715.601, or a pharmaceutically acceptable salt thereof, wherein L is an anti-PTK7 antibody or an antigen-binding portion thereof; and DAR is a drug to antibody ratio.

206. A conjugate represented by, or a pharmaceutically acceptable salt thereof, wherein L is an anti-PTK7 antibody or an antigen-binding portion thereof; and DAR is a drug to Targeting Unit (L) ratio.

207. A conjugate represented by-634-WSGR Docket No.63125-715.601, or a pharmaceutically acceptable salt thereof, wherein L is an anti-PTK7 antibody or an antigen-binding portion thereof; and DAR is a drug to antibody ratio.

208. A conjugate represented by, or a pharmaceutically acceptable salt thereof, wherein L is an anti-PTK7 antibody or an antigen-binding portion thereof; and DAR is a drug to antibody ratio.

209. A conjugate represented by-635-WSGR Docket No.63125-715.601, or a pharmaceutically acceptable salt thereof, wherein L is an anti-PTK7 antibody or an antigen-binding portion thereof; and DAR is a drug to Targeting Unit (L) ratio.

210. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isselected from PTK7-1; PTK7-1EL; PTK7-2; L is PTK7-3; L is PTK7-4; PTK7-5; PTK7-6; PTK7-7; PTK7-8; PTK7-9; PTK7-9EL; PTK7-10; PTK7-11; PTK7-12; PTK7-13; and PTK7- 14.

211. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-1.

212. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-1EL.

213. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-2.

214. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isL is PTK7-3.

215. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isL is PTK7-4.

216. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-5.

217. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-6.

218. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-7. -636-WSGR Docket No.63125-715.601219. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-8. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody is PTK7-9.

220. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-9EL.

221. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-10.

222. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-11.

223. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-12.

224. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-13.

225. The conjugate or salt of any one of claims 204 to 209, wherein the anti-PTK7 antibody isPTK7-14.

226. The conjugate or salt of any one of claims 204 to 209, wherein the antibody or portionthereof comprises a heavy chain CDR (HCDR) 1-3 and a light chain CDR (LCDR) 1-3 comprising SEQ ID NOs:151, 157, 161, 164, 167, and 170, respectively.

227. The conjugate or salt of claim 226, wherein the antibody or portion thereof comprises aheavy chain variable domain (VH) and a light chain variable domain (VL) comprising SEQ ID NOs:76 and 75, respectively.

228. The conjugate or salt of claim 226, wherein the antibody or portion thereof comprises aVH comprising SEQ ID NOs:154, 155, and 161, and a VL comprising SEQ ID NOs:163, 166, and 170.

229. The conjugate or salt of claim 228, wherein the antibody or portion thereof is humanized.

230. The conjugate or salt of claim 229, wherein the VH comprises framework regions derivedfrom a human IGHV1-46*01 germline gene.

231. The conjugate or salt of claim 230, wherein the VH comprises one or more backmutations selected from Y91F, R71V, V78A, M48I, M69L, and V20L, wherein the numbering is according to SEQ ID NO:172.

232. The conjugate or salt of claim 229, wherein the VL comprises framework regions derivedfrom a human IGKV1D-16*01 germline gene.

233. The conjugate or salt of claim 232, wherein the VL comprises one or more backmutations selected from I21L, Y36L, A43T, S46R, G66R, T69S, and F71Y, wherein the numbering is according to SEQ ID NO:

183. -637-WSGR Docket No.63125-715.601234. The conjugate or salt of claim 229, whereina) the VHcomprises any one of SEQ ID NOs:172-182, 193, 196, and 197, or an amino acid sequence at least 95% identical thereto; b) the VL comprises any one of SEQ ID NOs:183-192, 194, and 195, or an amino acid sequence at least 95% identical thereto; or c) a) and b).

235. The conjugate or salt of claim 234, wherein the VH and the VL compriseSEQ ID NOs:178 and 188, respectively, SEQ ID NOs:193 and 188, respectively, or SEQ ID NOs:173 and 188, respectively.

236. The conjugate or salt of any one of claims 226 to 235, wherein the antibody comprises ahuman IgG1constant region.

237. The conjugate or salt of claim 236, wherein the human IgG1 constant region comprisesSEQ ID NO:201, optionally without the C-terminal lysine.

238. The conjugate or salt of any one of claims 226 to 237, wherein the antibody comprises ahuman light chain constant region that comprises SEQ ID NO:199.

239. The conjugate or salt of any one of claims 226 to 238, wherein the antibody or portionthereof comprising a heavy chain that comprises the amino acid sequences of SEQ ID NOs:193 and 201, optionally without the C-terminal lysine, and a light chain that comprises the amino acid sequences of SEQ ID NOs:188 and 199.

240. The conjugate or salt of any one of claims 226 to 239, wherein the antibody or portionthereof comprises a) HCDR1-3 and LCDR1-3 comprising SEQ ID NOs:204, 209, 213, 216, 219, and 222, respectively; b) VH and VL comprising SEQ ID NOs:112 and 111, respectively; or c) an HC comprising SEQ ID NOs:112 and 201, optionally without the C-terminal lysine, and an LC comprising SEQ ID NOs:111 and 199.

241. The conjugate or salt of any one of claims 226 to 240, wherein the antibody or portionthereof comprises a) HCDR1-3 and LCDR1-3 comprising SEQ ID NOs:226, 231, 235, 238, 241, and 244, respectively; b) VHand VLcomprising SEQ ID NOs:128 and 127, respectively; or c) an HC comprising SEQ ID NOs:128 and 201, optionally without the C-terminal lysine, and an LC comprising SEQ ID NOs:127 and 199. -638-WSGR Docket No.63125-715.601242. The conjugate or salt of any one of claims 226 to 241, wherein the antibody or portionthereof comprises a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VHand the VLcomprise: SEQ ID NOs:148 and 147, respectively; SEQ ID NOs:24 and 23, respectively; SEQ ID NOs:36 and 35, respectively; SEQ ID NOs:4 and 3, respectively; SEQ ID NOs:10 and 9, respectively; SEQ ID NOs:16 and 15, respectively; SEQ ID NOs:18 and 17, respectively; SEQ ID NOs:20 and 19, respectively; SEQ ID NOs:22 and 21, respectively; SEQ ID NOs:26 and 25, respectively; SEQ ID NOs:28 and 27, respectively; SEQ ID NOs:30 and 29, respectively; SEQ ID NOs:32 and 31, respectively; SEQ ID NOs:34 and 33, respectively; SEQ ID NOs:38 and 37, respectively; SEQ ID NOs:40 and 39, respectively; SEQ ID NOs:2 and 1, respectively; SEQ ID NOs:6 and 5, respectively; SEQ ID NOs:8 and 7, respectively; SEQ ID NOs:12 and 11, respectively; SEQ ID NOs:14 and 13, respectively; SEQ ID NOs:42 and 41, respectively; SEQ ID NOs:44 and 43, respectively; SEQ ID NOs:52 and 51, respectively; SEQ ID NOs:54 and 53, respectively; SEQ ID NOs:56 and 55, respectively; SEQ ID NOs:46 and 45, respectively; SEQ ID NOs:48 and 47, respectively; SEQ ID NOs:50 and 49, respectively; SEQ ID NOs:82 and 81, respectively; SEQ ID NOs:80 and 79, respectively; SEQ ID NOs:58 and 57, respectively; -639-WSGR Docket No.63125-715.601 SEQ ID NOs:60 and 59, respectively; SEQ ID NOs:62 and 61, respectively; SEQ ID NOs:64 and 63, respectively; SEQ ID NOs:66 and 65, respectively; SEQ ID NOs:68 and 67, respectively; SEQ ID NOs:70 and 69, respectively; SEQ ID NOs:72 and 71, respectively; SEQ ID NOs:74 and 73, respectively; SEQ ID NOs:76 and 75, respectively; SEQ ID NOs:78 and 77, respectively; SEQ ID NOs:112 and 111, respectively; SEQ ID NOs:102 and 101, respectively; SEQ ID NOs:104 and 103, respectively; SEQ ID NOs:106 and 105, respectively; SEQ ID NOs:108 and 107, respectively; SEQ ID NOs:110 and 109, respectively; SEQ ID NOs:84 and 83, respectively; SEQ ID NOs:86 and 85, respectively; SEQ ID NOs:88 and 87, respectively; SEQ ID NOs:90 and 89, respectively; SEQ ID NOs:92 and 91, respectively; SEQ ID NOs:94 and 93, respectively; SEQ ID NOs:96 and 95, respectively; SEQ ID NOs:98 and 97, respectively; SEQ ID NOs:100 and 99, respectively; SEQ ID NOs:114 and 113, respectively; SEQ ID NOs:120 and 119, respectively; SEQ ID NOs:128 and 127, respectively; SEQ ID NOs:130 and 129, respectively; SEQ ID NOs:132 and 131, respectively; SEQ ID NOs:134 and 133, respectively; SEQ ID NOs:136 and 135, respectively; SEQ ID NOs:138 and 137, respectively; SEQ ID NOs:140 and 139, respectively; SEQ ID NOs:142 and 141, respectively; -640-WSGR Docket No.63125-715.601 SEQ ID NOs:144 and 143, respectively; SEQ ID NOs:146 and 145, respectively; SEQ ID NOs:116 and 115, respectively; SEQ ID NOs:118 and 117, respectively; SEQ ID NOs:122 and 121, respectively; SEQ ID NOs:124 and 123, respectively; SEQ ID NOs:126 and 125, respectively; or SEQ ID NOs:193 and 188, respectively.

243. The conjugate or salt of any one of claims 226 to 242, wherein the antibody or portionthereof comprises a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH and the VL comprise: SEQ ID NOs:148 and 147, respectively; SEQ ID NOs:10 and 9, respectively; SEQ ID NOs:16 and 15, respectively; SEQ ID NOs:18 and 17, respectively; SEQ ID NOs:20 and 19, respectively; SEQ ID NOs:26 and 25, respectively; SEQ ID NOs:30 and 29, respectively; SEQ ID NOs:112 and 111, respectively; SEQ ID NOs:110 and 109, respectively; SEQ ID NOs:86 and 85, respectively; SEQ ID NOs:128 and 127, respectively; SEQ ID NOs:122 and 121, respectively; or SEQ ID NOs:193 and 188, respectively.

244. The conjugate or salt of any one of claims 242 to 243, wherein the antibody comprises ahuman IgG1 constant region.

245. The conjugate or salt of any one of claims 242 to 244, wherein the human IgG1 constantregion comprises SEQ ID NO:201, optionally without the C-terminal lysine.

246. The conjugate or salt of any one of claims 242 to 245, wherein the antibody comprises ahuman light chain constant region that comprises SEQ ID NO:199.

247. The conjugate or salt of any one of claims 242 to 246, wherein the PTK7 antibody isoptionally without the C-terminal lysine.

248. The conjugate or salt of any one of claims 204 to 247, wherein the DAR is selected fromabout 1 to about 8.

249. The conjugate or salt of any one of claims 204 to 247, wherein the DAR is about 8.-641-WSGR Docket No.63125-715.601250. A pharmaceutical composition comprising a conjugate of any one of claims 204 to 249and a pharmaceutically acceptable excipient.

251. A method of treating a subject with a disease or disorder, comprising administering tothe subject in need thereof a conjugate of any one of claims 204 to 249 or a pharmaceutical composition of claim 250.

252. The method of claim 251, wherein the disease or disorder is a cancer.

253. A method of treating a subject with a cancer, comprising administering to the subject inneed thereof a conjugate of any one of claims 204 to 249 or a pharmaceutical composition of claim 250.

254. A method of treating a subject with a PTK7-positive cancer, comprising administering tothe subject in need thereof a conjugate of any one of claims 204 to 249 or a pharmaceutical composition of claim 250.

255. The method of any one of claims 252 to 254, wherein the cancer is selected from:melanoma, skin basal cell cancer, glioblastoma, glioma, gliosarcoma, astrocytoma, meningioma, neuroblastoma, adrenocortical cancer, head and neck cancer (e.g., cancer of the head, neck, nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx, and / or salivary glands, and paragangliomas), oral cancer, salivary gland cancer, nasopharyngeal cancer, breast cancer (e.g., triple negative breast cancer), lung cancer (e.g., non-small cell lung cancer (NSCLC), small cell lung cancer, or squamous cell lung cancer), esophageal cancer, gastroesophageal junction cancer, gastric cancer, gastrointestinal cancer, primary peritoneal cancer, liver cancer, hepatocellular carcinoma, gallbladder cancer, biliary tract cancer, cholangiocarcinoma, colon cancer, rectal cancer, colorectal carcinoma, ovarian cancer, fallopian tube cancer, bladder cancer, upper urinary tract cancer, urothelial cancer, renal cell carcinoma, kidney cancer, genitourinary cancer, cervical cancer, testicular cancer, prostate cancer, fibrosarcoma, liposarcoma, rhabdomyosarcoma (e.g., embryonal rhabdomyosarcoma), leiomyosarcoma, neurofibrosarcoma, synovial sarcoma, liposarcoma, alveolar soft part sarcoma, osteosarcoma, histiocytoma (e.g., malignant fibrous histiocytoma), pancreatic cancer, endometrial cancer, cancer of the appendix, thyroid cancer, advanced Merkel cell cancer, multiple myeloma, sarcomas, choriocarcinoma, leukemia (e.g., erythroleukemia, acute lymphoblastic leukemia, acute monocytic leukemia, acute promyelocytic leukemia, acute myeloid leukemia, acute myelogenous leukemia, chronic myeloid leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, or mast cell leukemia), lymphoma (e.g., small lymphocytic lymphoma, Burkitt’s lymphoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, diffuse large B cell lymphoma, lymphoplasmacytoid lymphoma, mucosa-associated lymphoid tissue lymphoma, mantle cell lymphoma, T-cell -642-WSGR Docket No.63125-715.601 anaplastic large cell lymphoma, follicular lymphoma, monocytic lymphoma, or HTLV- associated T cell leukemia / lymphoma), or mesothelioma. In certain embodiments, the cancer is selected from the group consisting of head and neck cancer, bone cancer (e.g., osteosarcoma), Ewing sarcoma, squamous cell carcinoma, lung cancer (e.g., non-small cell lung cancer or small cell lung cancer), kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, cervical cancer, pancreatic cancer, breast cancer (e.g., triple negative breast cancer), melanoma, liver cancer, bladder cancer, stomach cancer, esophageal cancer, and chronic myelogenous leukemia. In particular embodiments, the cancer is selected from the group consisting of head and neck cancer, non-small cell lung cancer, esophageal cancer, gastric cancer, hepatic cancer, pancreatic cancer, colorectal cancer, breast cancer, endometrial cancer, ovarian cancer, soft-tissue sarcoma, bladder cancer, prostate cancer, renal cancer, and melanoma.

256. The method of any one of claims 252 to 254, wherein the cancer is selected from celllymphoma, non-small cell lung cancer, large-cell lung cancer, breast cancer, and small-cell lung cancer.

257. The method of any one of claims 252 to 254, wherein the cancer is cell lymphoma.

258. The method of any one of claims 252 to 254, wherein the cancer is non-small cell lungcancer.

259. The method of any one of claims 252 to 254, wherein the cancer is large-cell lungcancer.

260. The method of any one of claims 252 to 254, wherein the cancer is breast cancer.

261. The method of any one of claims 252 to 254, wherein the cancer is small-cell lungcancer.

262. Use of a conjugate, for treating a subject with a disease or disorder, comprisingadministering to the subject in need thereof a conjugate of any one of claims 204 to 249 or a pharmaceutical composition of claim 250.

263. The use of claim 262, wherein the disease or disorder is cancer.-643-

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