Chemically modified peptides and use thereof

Abstract

The present application relates to chemically modified peptides and uses thereof in treating certain diseases or disorders.

Description

Attorney Docket No.14794-016-228 / 336.WO1.PCT CHEMICALLY MODIFIED PEPTIDES AND USE THEREOF RELATED APPLICATION

[0001] This application claims priority to U.S. Provisional Application No.63 / 662,949, filed on June 21, 2024, the entirety of which is incorporated herein by reference. SEQUENCE LISTING

[0002] This application contains a computer readable Sequence Listing which has been submitted in XML file format with this application, the entire content of which is incorporated by reference herein in its entirety. The Sequence Listing XML file submitted with this application is entitled “14794-016-228_SEQ_LISTING.xml”, was created on June 12, 2025, and is 365,890 bytes in size. 1. FIELD

[0003] The present application relates to chemically modified peptides and uses thereof in treating certain diseases or disorders. 2. BACKGROUND

[0004] Metabolic syndrome, associated with obesity, hypertension, hyperglycemia and other serum irregularities, represents an increasingly prevalent and costly chronic disease. Obesity itself is often comorbid with a host of other disorders including type 2 diabetes, heart disease, stroke, and some forms of cancer. Typical treatments for this cluster of syndromes include changes to diet, increased exercise, and / or insulin-base therapies. Such treatments can be ineffective. As such, new therapeutic agents which address obesity, type 2 diabetes, and the impact of diseases associated with obesity are critically needed. 3. SUMMARY

[0005] In one aspect, provided herein are chemically modified peptides. 3.1 Formulae (I), (Ia), (Ib), (Ic), and (Id)

[0006] In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (I) (SEQ ID NO:8): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(I), 1 NAI-5000824421wherein: Rxis Gly; Ry is selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3is selected from Gln and Glu; R6 is selected from amF and Phe; R15is selected from Asp and Glu; R16 is selected from K*, Lys, amK, and Glu; R17is selected from Lys and Gln; R20 is selected from K* and Aib; R21is selected from Ala and Glu; R24 is selected from K*, Glu, and D-Glu; and R25is selected from amY and Tyr; and wherein: ; amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X; (OH)2;0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; q is 14-20; and one and only one K* is present in Formula (I). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (I) (SEQ ID NO:8).

[0007] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Ia) (SEQ ID NO:9). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ia) (SEQ ID NO:9): Tyr-Aib-R3-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-Tyr-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ia), 2 NAI-5000824421wherein: Rxis Gly; Ry is selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3is selected from Gln and Glu; R15 is selected from Asp and Glu; R16is selected from K*, Lys, amK, and Glu; R17 is selected from Lys and Gln; R20is selected from K* and Aib; R21 is selected from Ala and Glu; and R24is selected from K*, Glu, and D-Glu; and wherein: ; amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X;X is -CO2H or -P(O)(OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; q is 14-20; and one and only one K* is present in Formula (Ia). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ia) (SEQ ID NO:9).

[0008] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Ib) (SEQ ID NO:10). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ib) (SEQ ID NO:10): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-K*-R17-Ala-Gln-Aib-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ib), wherein: Rx is Gly; 3 NAI-5000824421Ry is selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3is selected from Gln and Glu; R6 is selected from amF and Phe; R15is selected from Asp and Glu; R17 is selected from Lys and Gln; R21is selected from Ala and Glu; R24 is selected from Glu and D-Glu; and R25is selected from amY and Tyr; and wherein: ; amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X; (OH)2;0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; and q is 14-20. In certain embodiments, provided herein is a pharmaceutically acceptable of a peptide comprising or consisting of an amino acid sequence of Formula (Ib) (SEQ ID NO:10).

[0009] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Ic) (SEQ ID NO:11). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ic) (SEQ ID NO:11): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-K*-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 (Ic), wherein: Rxis Gly; Ry is selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3is selected from Gln and Glu; R6 is selected from amF and Phe; 4 NAI-5000824421R15 is selected from Asp and Glu; R16is selected from Lys, amK and Glu; R17 is selected from Lys and Gln; R21is selected from Ala and Glu; R24 is selected from Glu and D-Glu; and R25is selected from amY and Tyr; and wherein: ; amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X;- or - (OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; and q is 14-20. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ic) (SEQ ID NO:11).

[0010] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Id) (SEQ ID NO:12). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Id) (SEQ ID NO:12): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-Aib-R21- Phe-Ile-K*-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Id), wherein: Rxis Gly; Ry is selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3is selected from Gln and Glu; R6 is selected from amF and Phe; R15is selected from Asp and Glu; R16 is selected from Lys, amK, and Glu; 5 NAI-5000824421R17 is selected from Lys and Gln; R21is selected from Ala and Glu; and R25 is selected from amY and Tyr; and wherein: ; amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X;- - (OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; and q is 14-20. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Id) (SEQ ID NO:12).

[0011] In certain embodiments, R16is K*. In certain embodiments, R16is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16 is Glu. In certain embodiments, R20 is K*. In certain embodiments, R20is Aib. In certain embodiments, R24is K*. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu.

[0012] In certain embodiments, Ryis Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ryis Gln. In certain embodiments, R3is Gln. In certain embodiments, R3 is Glu. In certain embodiments, R6 is Phe. In certain embodiments, R6 is amF. In certain embodiments, R15is Asp. In certain embodiments, R15is Glu. In certain embodiments, R17 is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R21 is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R25 is amY. In certain embodiments, R25is Tyr.

[0013] In certain embodiments, a is 0, b is 2, c is 1, d is 0. In certain embodiments, a is 0, b is 2, c is 2, d is 0. In certain embodiments, a is 0, b is 1, c is 1, d is 0. In certain embodiments, a is 2, b is 0, c is 1, d is 1. In certain embodiments, a is 0, b is 2, c is 1, d is 1. In certain embodiments, a is 1, b is 0, c is 1, d is 1. In certain embodiments, q is 14, 16, 18, or 20. In certain embodiments, q is 15, 17, or 19. 6 NAI-5000824421

[0014] In certain embodiments, Rz is -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c- (Trx)d-(CO)-(CH2)q-X. In certain embodiments, b is 1 or 2 and c is 1 or 2. In certain embodiments, Rz is (i) -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)-(CH2)18-CO2H; (ii) -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-(CO)-(CH2)18-CO2H; (iii) -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-(CO)-(CH2)18-CO2H; (iv) -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(Trx)-(CO)-(CH2)18-CO2H; or (v) -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)-(CH2)18-P(O)(OH)2.

[0015] In certain embodiments, Rz is -(eLys)a-(gGlu)c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, Rzis -(eLys)2-(gGlu)-(Trx)-(CO)-(CH2)18-CO2H. 3.2 Formulae (I’), (Ia’), (Ib’), (Ic’), and (Id’)

[0016] In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (I’) (SEQ ID NO:13): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2 (I’), wherein: Rx is Gly; Ryis selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3 is selected from Gln and Glu; R6is selected from amF and Phe; R15 is selected from Asp and Glu; R16is selected from K*, Lys, amK, and Glu; R17 is selected from Lys and Gln; R20is selected from K* and Aib; R21 is selected from Ala and Glu; R24is selected from K*, Glu, and D-Glu; R25 is selected from amY and Tyr; and R29is absent or Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18), or a fragment thereof; and wherein: 7 NAI-5000824421K* ; Rz 2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X; X is -CO2H or -P(O)(OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; q is 14-20; and one and only one K* is present in Formula (I’). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (I’) (SEQ ID NO:13).

[0017] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Ia’) (SEQ ID NO:14). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ia’) (SEQ ID NO:14): Tyr-Aib-R3-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-Tyr-Leu-Leu-Glu-Rx-Ry-R29-NH2(Ia’), wherein: Rx is Gly; Ryis selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3 is selected from Gln and Glu; R15is selected from Asp and Glu; R16 is selected from K*, Lys, amK, and Glu; R17 is selected from Lys and Gln; R20is selected from K* and Aib; R21 is selected from Ala and Glu; R24is selected from K*, Glu, and D-Glu; and R29 is absent or Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18), or a fragment thereof; and wherein: 8 NAI-5000824421K* ; Rz 2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X; X is -CO2H or -P(O)(OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; q is 14-20; and one and only one K* is present in Formula (Ia’). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ia’) (SEQ ID NO:14).

[0018] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid comprising or consisting of Formula (Ib’) (SEQ ID NO:15). In certain provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ib’) (SEQ ID NO:15): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-K*-R17-Ala-Gln-Aib-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2(Ib’), wherein: Rx is Gly; Ryis selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3 is selected from Gln and Glu; R6is selected from amF and Phe; R15 is selected from Asp and Glu; R17 is selected from Lys and Gln; R21is selected from Ala and Glu; R24 is selected from Glu and D-Glu; R25is selected from amY and Tyr; and R29 is absent or Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18), or a fragment thereof; and wherein: 9 NAI-5000824421K* ; Rz 2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X; X is -CO2H or -P(O)(OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; and q is 14-20. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ib’) (SEQ ID NO:15).

[0019] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Ic’) (SEQ ID NO:16). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ic’) (SEQ ID NO:16): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-K*-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2 (Ic’), wherein:Rxis Gly; Ry is selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3is selected from Gln and Glu; R6 is selected from amF and Phe; R15is selected from Asp and Glu; R16 is selected from Lys, amK and Glu; R17 is selected from Lys and Gln; R21is selected from Ala and Glu; R24 is selected from Glu and D-Glu; R25is selected from amY and Tyr; and R29 is absent or Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18), or a fragment thereof; and wherein: 10 NAI-5000824421; 2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X; )(OH)2; ependently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; and q is 14-20. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ic’) (SEQ ID NO:16).

[0020] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Id’) (SEQ ID NO:17). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Id’) (SEQ ID NO:17): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-Aib-R21- Phe-Ile-K*-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2 (Id’), wherein: Rxis Gly; Ry is selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3is selected from Gln and Glu; R6 is selected from amF and Phe; R15is selected from Asp and Glu; R16 is selected from Lys, amK, and Glu; R17 is selected from Lys and Gln; R21is selected from Ala and Glu; R25 is selected from amY and Tyr; and R29is absent or Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18), or a fragment thereof; and wherein: 11 NAI-5000824421K* ; Rz 2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X; X is -CO2H or -P(O)(OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; and q is 14-20. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Id’) (SEQ ID NO:17).

[0021] In certain embodiments, R16is K*. In certain embodiments, R16is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16 is Glu. In certain embodiments, R20 is K*. In certain embodiments, R20is Aib. In certain embodiments, R24is K*. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu.

[0022] In certain embodiments, Ryis Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ryis Gln. In certain embodiments, R3is Gln. In certain embodiments, R3 is Glu. In certain embodiments, R6 is Phe. In certain embodiments, R6 is amF. In certain embodiments, R15is Asp. In certain embodiments, R15is Glu. In certain embodiments, R17 is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R21 is Ala. In certain embodiments, R21is Glu. In certain embodiments, R25is amY. In certain embodiments, R25 is Tyr.

[0023] In certain embodiments, a is 0, b is 2, c is 1, d is 0. In certain embodiments, a is 0, b is 2, c is 2, d is 0. In certain embodiments, a is 0, b is 1, c is 1, d is 0. In certain embodiments, a is 2, b is 0, c is 1, d is 1. In certain embodiments, a is 0, b is 2, c is 1, d is 1. In certain embodiments, a is 1, b is 0, c is 1, d is 1. In certain embodiments, q is 14, 16, 18, or 20. In certain embodiments, q is 15, 17, or 19.

[0024] In certain embodiments, Rzis -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c- (Trx)d-(CO)-(CH2)q-X. In certain embodiments, b is 1 or 2 and c is 1 or 2. In certain embodiments, Rzis (i) -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)-(CH2)18-CO2H; 12 NAI-5000824421(ii) -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)2-(CO)-(CH2)18-CO2H; (iii) -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(gGlu)-(CO)-(CH2)18-CO2H; (iv) -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(Trx)-(CO)-(CH2)18-CO2H; or (v) -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)-(CH2)18-P(O)(OH)2.

[0025] In certain embodiments, Rz is -(eLys)a-(gGlu)c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, Rzis -(eLys)2-(gGlu)-(Trx)-(CO)-(CH2)18-CO2H.

[0026] In certain embodiments, R29 is absent. In certain embodiments, R29 is Gly-Gly- Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29is Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29is Gly-Gly- Pro-Ser-Ser-Gly-Ala-Pro (SEQ ID NO:21). In certain embodiments, R29 is Gly-Gly-Pro-Ser- Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29 is Gly-Gly-Pro-Ser (SEQ ID NO:25). In certain embodiments, R29 is Gly-Gly-Pro. In certain embodiments, R29is Gly-Gly. In certain embodiments, R29is Gly.

[0027] In certain embodiments, provided herein is a peptide represented by Formula (I), (Ia), (Ib), (Ic), or (Id). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide represented by Formula (I), (Ia), (Ib), (Ic), or (Id). In certain embodiments, provided herein is a peptide represented by Formula (I’), (Ia’), (Ib’), (Ic’), or (Id’). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide represented by Formula (I’), (Ia’), (Ib’), (Ic’), or (Id’).

[0028] In certain embodiments, provided herein is a peptide comprising the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, provided herein is a peptide consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, provided herein is a compound comprising a peptide described herein. 13 NAI-5000824421

[0029] In another aspect, provided herein are methods of treating a disease or disorder. In certain embodiments, provided herein is a method of treating a disease or disorder in a subject comprising administering to the subject a therapeutically effective amount of the peptide provided herein. In yet another aspect, provided herein are peptides for use in treating a disease or disorder. In yet another aspect, provided herein is use of the peptide provided herein in the manufacture of a medicament for treating a disease or disorder. In certain embodiments, the disease or disorder is selected from diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction– associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast 14 NAI-5000824421cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA). 4. BRIEF DESCRIPTION OF DRAWINGS

[0030] FIG.1 depicts the structure of exemplary peptide represented by SEQ ID NO:1.

[0031] FIG.2 depicts the structure of exemplary peptide represented by SEQ ID NO:2.

[0032] FIG.3 depicts the structure of exemplary peptide represented by SEQ ID NO:3.

[0033] FIG.4 depicts the structure of exemplary peptide represented by SEQ ID NO:4.

[0034] FIG.5 depicts the structure of exemplary peptide represented by SEQ ID NO:5.

[0035] FIG.6 depicts the structure of exemplary peptide represented by SEQ ID NO:6.

[0036] FIG.7 depicts the structure of exemplary peptide represented by SEQ ID NO:7.

[0037] FIG.8 depicts the results of a functional assay measuring the activity of human incretin receptors upon stimulation with reference peptides and exemplary peptides provided herein, in the presence of 0.1% casein. Bar plot shows the human GLP-1 receptor (GLP1R), the GIP receptor (GIPR) or the GCG receptor (GCGR) mediated agonist responses (EC50 (pM)).

[0038] FIG.9 depicts the results of a functional assay measuring the activity of human incretin receptors upon stimulation with reference peptides and exemplary peptides provided herein, in the presence of 0.1% BSA. Bar plot shows the human GLP-1 receptor (GLP1R), the GIP receptor (GIPR) or the GCG receptor (GCGR) mediated agonist responses (EC50 (pM)). 5. DETAILED DESCRIPTION

[0039] Provided herein are chemically modified peptides and related methods of treatments. In one aspect, provided herein are chemically modified peptides (e.g., the peptides as described in Section 5.2). In certain embodiments, the peptides provided herein comprises a fatty acid component (e.g., a fatty acid component as described in Section 5.2.3). In certain embodiments, the peptides provided herein have or exhibit certain advantageous characteristics (e.g., physical, chemical and / or biological characteristics and activities as described in Section 5.3). In another aspect, provided herein are methods of treating a disease or disorder (e.g., methods as described in Section 5.4.1). In yet another aspect, 15 NAI-5000824421provided herein are peptides for use in treating a disease or disorder (e.g., the peptides for use in treating a disease or disorder as described in Section 5.4.2). In yet another aspect, provided herein is use of a peptide provided herein in the manufacture of a medicament for treating a disease or disorder (e.g., the use as described in Section 5.4.3).

[0040] The peptides provided herein have a unique fatty acid component linked to the unique peptide chain at particular amino acid positions, and the peptides have been demonstrated to exhibit agonist activity at one or more of three different receptors: glucagon- like peptide-1 (GLP-1) receptor, glucose-dependent insulinotropic polypeptide (GIP; also known as gastric inhibitory peptide) receptor and glucagon (GCG) receptor. In certain embodiments, the peptides provided herein exhibit agonistic activity at two or more of: the GLP-1 receptor, the GIP receptor and the GCG receptor. In certain embodiments, the peptides provided herein exhibit agonistic activity at all three of: the GLP-1 receptor, the GIP receptor and the GCG receptor. In some embodiments, as described herein, for example in Section 7 (Examples), the peptides provided herein are shown to exhibit unique activity ratios between three receptors: the GLP-1 receptor, the GIP receptor and the GCG receptor. In certain embodiments, the peptides provided herein have superior results relative to reference peptides, such as the reference peptide represented by any one of SEQ ID NOs:42-48. Exemplary assays for demonstrating such superior results are provided in Section 5.3 and Section 7 (Examples).

[0041] In certain embodiments, such superior results include, but are not limited to, superior solubility, superior stability, superior relative activity profile against the GIP receptor, the GLP-1 receptor, and the GCG receptor (e.g., as expressed in ratios between potencies against the GIP receptor, GLP-1 receptor, and / or GCG receptor). In certain embodiments, the peptides provided herein show the superior results of reduced activity at the GCG receptor without affecting the potent activity at the GLP-1 receptor or the GIP receptor. Without being bound by the theory, in some cases, increasing levels of activity at the GCG receptor is associated with an increased heart rate and / or gastrointestinal side effects, such as nausea, diarrhea, stomach (abdominal) pain, vomiting, and / or constipation, in humans.

[0042] Many of the exemplary peptides provided herein demonstrate a lower GCG receptor activity, while retaining potent activity at the GLP-1 receptor and the GIP receptor as compared to one or more reference peptides (e.g., peptides represented by SEQ ID NOs:42- 48). Attenuating the relative GCG receptor activity of the exemplary peptides alleviates glucagon effects, such as elevated glucose, increased heart rate and / or gastrointestinal side effects, such as nausea and / or vomiting. 16 NAI-5000824421

[0043] Accordingly, in some aspects, the peptides provided herein with certain features are associated with a particular range of ratios of agonist activity at the GLP-1 receptor versus the GIP receptor and / or versus the GCG receptor, resulting in advantageous activity profiles. The superior activity profile, therefore, can lead to superior therapeutic effects and / or reduced glucagon effects. In certain embodiments, the peptides provided herein are demonstrated to have a more favorable activity ratio between the GLP-1 receptor, the GIP receptor and / or the GCG receptor as compared to one or more reference peptides (e.g., peptides represented by SEQ ID NOs: 42-48), for example, as described in the Examples below. In certain embodiments, the superior activity profile lead to superior therapeutic activities and / or safety profile. In certain embodiments, the superior therapeutic activities or safety profile can be demonstrated in animal models or clinical studies, such as the ones provided in Section 7. In certain embodiments, the provided peptides are also associated with superior chemical and physical properties, including superior solubility and superior stability, as demonstrated in Section 7 (Examples). 5.1 Definitions

[0044] The nomenclature of Schroder & Lubke, “The Peptides”, Academic Press (1965) is used to define the peptides disclosed herein, wherein, in accordance with conventional representation, the amino terminal group appears to the left and the carboxyl terminal group to the right. The standard 1-letter or 3-letter abbreviations are used to identify the alpha- amino acid residues, and where the amino acid residue has isomeric forms, it is the L-form of the amino acid residue that is represented unless otherwise expressly indicated, e.g., Ser=L- serine, Orn=L-ornithine, Aad=L-2-aminoadipic acid, and Nle=L-norleucine. The D-form of an amino acid residue can be indicated using formats such as D-[three-letter abbreviation], d([three-letter abbreviation]), or [lowercase one-letter abbreviation]. For example, the D- form of Glutamic acid (three-letter abbreviation: Glu; one-letter abbreviation: E) can be indicated as “D-Glu”, “d(Glu)”, or “e”.

[0045] Table 1 provides terms and structures used herein for exemplary moieties. Table 1: Exemplary terms and corresponding structures Term Structure17 NAI-5000824421Term Structure (S)-2-amino-2-methyl-3-phenylpropanoic acidTerm Structure (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)19 NAI-5000824421Term Structure

[0046] As used herein and unless otherwise indicated, the terms effective amount or “therapeutically effective amount” refer to an amount of a therapeutic (e.g., a composition provided herein) which is sufficient to treat, prevent, delay the onset of, reduce and / or ameliorate the severity and / or duration of a given condition, disorder or disease and / or a symptom related thereto. These terms also encompass an amount necessary for the reduction, slowing, or amelioration of the advancement or progression of a given disease, reduction, slowing, or amelioration of the recurrence, development or onset of a given disease, and / or to improve or enhance the prophylactic or therapeutic effect(s) of another therapy or to serve as a bridge to another therapy. In some embodiments, “effective amount” as used herein also refers to the amount of a composition described herein to achieve a specified result. As used herein, the terms “subject” and “patient” are used interchangeably.

[0047] As used herein and unless otherwise specified, the term “pharmaceutically acceptable salt” encompasses non-toxic acid and base addition salts of the peptide to which the term refers. Acceptable non-toxic acid addition salts include those derived from organic 20 NAI-5000824421and inorganic acids or bases know in the art, which include, for example, hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, methanesulfonic acid, acetic acid, tartaric acid, lactic acid, succinic acid, citric acid, malic acid, maleic acid, sorbic acid, aconitic acid, salicylic acid, phthalic acid, embolic acid, enanthic acid, and the like. In certain embodiments, the peptides provided herein are a free base. In certain embodiments, a pharmaceutically acceptable salt is sodium, potassium, or other cationic salts. In certain embodiments, a pharmaceutically accepted salt is a salt as described in Gupta et al. Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations. Molecules. 2018 Jul; 23(7): 1719, the disclosure of which is incorporated by reference in its entirety. In certain embodiments, a pharmaceutically accepted salt is a salt as described in Bharate, Modulation of biopharmaceutical properties of acidic drugs using cationic counterions: A critical analysis of FDA-approved pharmaceutical salts. International Journal of Pharmaceutics Volume 607, 25 September 2021, 120993, the disclosure of which is incorporated by reference in its entirety.

[0048] As used herein, and unless otherwise specified, the term “about” or “approximately” means an acceptable error for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined. In certain embodiments, the term “about” or “approximately” means within 1, 2, 3, or 4 standard deviations. In certain embodiments, the term “about” or “approximately” means within 50%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.05% of a given value or range.

[0049] The amino group (-NH2) as recited in the Formulae and amino acid sequences provided herein is the amino group of the respective amidated C-terminal amino acid residue. The structures shown in the figures provide examples showing that the amino group is the amino group of the respective amidated C-terminal amino acid residue. 5.2 Peptides

[0050] In one aspect, provided herein are chemically modified peptides. In certain embodiments, the peptides provided herein have activity (such as agonist activity) at each of the glucagon-like peptide-1 (GLP-l) receptor, the glucose-dependent insulinotropic polypeptide (GIP; also known as gastric inhibitory peptide) receptor, and the glucagon (GCG) receptor. In certain embodiments, the peptides provided herein have agonist activity on two or more of: the GLP-1 receptor, the GIP receptor, and the GCG receptor. In certain embodiments, the peptides provided herein have agonist activity on each (i.e., all three) of the 21 NAI-5000824421GLP-1 receptor, the GIP receptor, and the GCG receptor. In certain embodiments, the peptides provided herein can be used in the methods and uses provided in Section 5.3. In certain embodiments, the peptides provided herein can be made, evaluated or tested for their characteristics using the methods provided in Section 7. 5.2.1 Formulae (I), (Ia), (Ib), (Ic), and (Id), and sub-formulae thereof (i) Formulae (I), (Ia), (Ib), (Ic), and (Id)

[0051] In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (I) (SEQ ID NO:8): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 (I). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (I) (SEQ ID NO:8). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R3 is Gln. In certain embodiments, R3 is Glu. In certain embodiments, R6 is Phe. In certain embodiments, R6 is amF. In certain embodiments, R15 is Asp. In certain embodiments, R15 is Glu. In certain embodiments, R16 is K*. In certain embodiments, R16 is Lys. In certain embodiments, R16is amK. In certain embodiments, R16is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R20 is K*. In certain embodiments, R20is Aib. In certain embodiments, R21is Ala. In certain embodiments, R21is Glu. In certain embodiments, R24 is K*. In certain embodiments, R24 is Glu. In certain embodiments, R24is D-Glu. In certain embodiments, R24is D-Glu. In certain embodiments, R25 is amY. In certain embodiments, R25 is Tyr. In certain embodiments, K* is . In certain embodiments, Rzis -(Z)a-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X or -((CO)-(PEG)h-(CH2)2-NH)f-(gGlu)e-(CO)-(CH2)g- X. In certain embodiments, Z is independently Gly, Glu, gGlu, Lys, eLys, Ala, Gln, or His. In certain embodiments, Z is Gly. In certain embodiments, Z is Glu. In certain 22 NAI-5000824421embodiments, Z is gGlu. In certain embodiments, Z is Lys. In certain embodiments, Z is eLys. In certain embodiments, Z is Ala. In certain embodiments, Z is Gln. In certain embodiments, Z is His. In certain embodiments, the gGlu is D-gGlu. In other embodiments, the gGlu is L-gGlu. In certain embodiments, Rzis -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, d, and e are each independently 0, 1, 2, or 3. In certain embodiments, q and g are each independently 14-20. In certain embodiments, h is 2, 4, 6, 8, 10, 12, 14, or 16. In certain embodiments, f is 1, 2, 3, or 4. In certain embodiments, one and only one K* is present in Formula (I).

[0052] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Ia) (SEQ ID NO:9). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ia) (SEQ ID NO:9): Tyr-Aib-R3-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-Tyr-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ia). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ia) (SEQ ID NO:9). In certain embodiments, Rxis Gly. In certain embodiments, Ryis Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ryis Gln. In certain embodiments, R3is Gln. In certain embodiments, R3 is Glu. In certain embodiments, R15 is Asp. In certain embodiments, R15is Glu. In certain embodiments, R16is K*. In certain embodiments, R16is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16 is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17is Gln. In certain embodiments, R20is K*. In certain embodiments, R20 is Aib. In certain embodiments, R21 is Ala. In certain embodiments, R21is Glu. In certain embodiments, R24is K*. In certain embodiments, R24is Glu. In certain embodiments, R24 is D-Glu. In certain embodiments, R24 is D-Glu. In certain . In certain embodiments, Rzis -(eLys)a-(2-[2-(2-amino- ethoxy)-d-(CO)-(CH2)q-X. In certain embodiments, X is - 23 NAI-5000824421CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d, are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20. In certain embodiments, one and only one K* is present in Formula (Ia).

[0053] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Ib) (SEQ ID NO:10). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ib) (SEQ ID NO:10): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-K*-R17-Ala-Gln-Aib-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ib). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ib) (SEQ ID NO:10). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R3 is Gln. In certain embodiments, R3is Glu. In certain embodiments, R6is Phe. In certain embodiments, R6 is amF. In certain embodiments, R15 is Asp. In certain embodiments, R15 is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17is Gln. In certain embodiments, R21 is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R24 is Glu. In certain embodiments, R24is D-Glu. In certain embodiments, R25is amY. In certain embodiments, R25 is Tyr. In certain . In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino-c-(Trx)d-(CO)- (CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0054] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid comprising or consisting of sequence of Formula (Ic) (SEQ ID NO:11). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ic) (SEQ ID NO:11): 24 NAI-5000824421Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-K*-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ic). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising an amino acid sequence of Formula (Ic) (SEQ ID NO:11). In certain embodiments, Rxis Gly. In certain embodiments, Ryis Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ryis Gln. In certain embodiments, R3is Gln. In certain embodiments, R3 is Glu. In certain embodiments, R6 is Phe. In certain embodiments, R6is amF. In certain embodiments, R15is Asp. In certain embodiments, R15is Glu. In certain embodiments, R16 is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17is Gln. In certain embodiments, R21 is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu. In certain embodiments, R25is amY. In certain embodiments, R25is Tyr. In certain embodiments, K* is . In certain embodiments, Rzis -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]-c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d, are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0055] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Id) (SEQ ID NO:12). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Id) (SEQ ID NO:12): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-Aib-R21- Phe-Ile-K*-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 (Id). In certain embodiments, provided herein is a peptide comprising an amino acid sequence of Formula (Id) (SEQ ID NO:12). In certain embodiments, Rxis Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ry is Glu. In certain 25 NAI-5000824421embodiments, Ry is Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R3is Gln. In certain embodiments, R3is Glu. In certain embodiments, R6 is Phe. In certain embodiments, R6 is amF. In certain embodiments, R15 is Asp. In certain embodiments, R15is Glu. In certain embodiments, R16is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16 is Glu. In certain embodiments, R17 is Lys. In certain embodiments, R17is Gln. In certain embodiments, R21is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R25 is amY. In certain embodiments, R25 is Tyr. In certain . In certain embodiments, Rzis - (eLys)a-(2-[2-(2-amino- c-(Trx)d-(CO)-(CH2)q-X. In certainembodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d, are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20. (ii) Sub-formulae of Formulae (I), (Ia), (Ib), (Ic), and (Id)

[0056] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Ia-1) (SEQ ID NO:26). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ia-1) (SEQ ID NO:26): Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-Tyr-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ia-1). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ia-1) (SEQ ID NO:26). In certain embodiments, Rxis Gly. In certain embodiments, Ryis Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ryis Gln. In certain embodiments, R15is Asp. In certain embodiments, R15 is Glu. In certain embodiments, R16 is K*. In certain embodiments, R16is Lys. In certain embodiments, R16is amK. In certain embodiments, R16is Glu. In certain embodiments, R17 is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R20is K*. In certain embodiments, R20is Aib. In certain embodiments, R21is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R24 is K*. In certain 26 NAI-5000824421embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu. In certain embodiments, K* . In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]- d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certainis -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20. In certain embodiments, one and only one K* is present in Formula (Ia-1).

[0057] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Ia-2) (SEQ ID NO:27). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ia-2) (SEQ ID NO:27): Tyr-Aib-R3-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-Asp-R16-R17-Ala-Gln-Aib-R21- Phe-Ile-R24-Tyr-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 (Ia-2). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ia-2) (SEQ ID NO:27). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R3 is Gln. In certain embodiments, R3is Glu. In certain embodiments, R16is K*. In certain embodiments, R16 is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16 is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17is Gln. In certain embodiments, R21 is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R24 is K*. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu. In certain . In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino- ethoxy)-d-(CO)-(CH2)q-X. In certain embodiments, X is - 27 NAI-5000824421CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20. In certain embodiments, one and only one K* is present in Formula (Ia-2).

[0058] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Ib-1) (SEQ ID NO:28). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ib-1) (SEQ ID NO:28): Tyr-Aib-Gln-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-K*-R17-Ala-Gln-Aib-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ib-1). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ib-1) (SEQ ID NO:28). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R6 is Phe. In certain embodiments, R6is amF. In certain embodiments, R15is Asp. In certain embodiments, R15 is Glu. In certain embodiments, R17 is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R21is Ala. In certain embodiments, R21is Glu. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu. In certain embodiments, R25is amY. In certain embodiments, R25is Tyr. In certain embodiments, K* is . In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]-c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0059] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Ib-2) (SEQ ID NO:29). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ib-2) (SEQ ID NO:29): 28 NAI-5000824421Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-Asp-K*-Lys-Ala-Gln-Aib-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ib-2). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ib-2) (SEQ ID NO:29). In certain embodiments, Rxis Gly. In certain embodiments, Ryis Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ryis Gln. In certain embodiments, R3is Gln. In certain embodiments, R3 is Glu. In certain embodiments, R6 is Phe. In certain embodiments, R6is amF. In certain embodiments, R21is Ala. In certain embodiments, R21is Glu. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu. In certain embodiments, R25is amY. In certain embodiments, R25is Tyr. In certain embodiments, K* . In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]-d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0060] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Ic-1) (SEQ ID NO:30). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ic-1) (SEQ ID NO:30): Tyr-Aib-Gln-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-K*-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 (Ic-1). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ic-1) (SEQ ID NO:30). In certain embodiments, Rxis Gly. In certain embodiments, Ryis Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ryis Gln. In certain embodiments, R6is Phe. In certain embodiments, R6 is amF. In certain embodiments, R15 is Asp. In certain 29 NAI-5000824421embodiments, R15 is Glu. In certain embodiments, R16 is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R21 is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R24is Glu. In certain embodiments, R24is D-Glu. In certain embodiments, R25 is amY. In certain embodiments, R25 is Tyr. In certain embodiments, K* . In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]- d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certainis -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0061] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Ic-2) (SEQ ID NO:31). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ic-2) (SEQ ID NO:31): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-Asp-R16-Lys-Ala-Gln-K*-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ic-2). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ic-2) (SEQ ID NO:31). In certain embodiments, Rxis Gly. In certain embodiments, Ryis Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ryis Gln. In certain embodiments, R3is Gln. In certain embodiments, R3 is Glu. In certain embodiments, R6 is Phe. In certain embodiments, R6 is amF. In certain embodiments, R16 is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16is Glu. In certain embodiments, R21is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu. In certain embodiments, R25is amY. In certain embodiments, R25is Tyr. In certain 30 NAI-5000824421embodiments, K* is . In certain embodiments, Rzis -(eLys)a-(2-[2-(2-amino- ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is - CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0062] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Id-1) (SEQ ID NO:32). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Id-1) (SEQ ID NO:32): Tyr-Aib-Gln-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-Aib-R21- Phe-Ile-K*-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 (Id-1). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Id-1) (SEQ ID NO:32). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R6 is Phe. In certain embodiments, R6is amF. In certain embodiments, R15is Asp. In certain embodiments, R15 is Glu. In certain embodiments, R16 is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R21 is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R25is amY. In certain embodiments, R25is Tyr. In certain . In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino- ethoxy)-d-(CO)-(CH2)q-X. In certain embodiments, X is - CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are 31 NAI-5000824421each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0063] In certain embodiments, the amino acid sequence of Formula (I) is an amino acid sequence comprising or consisting of Formula (Id-2) (SEQ ID NO:33). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Id-2) (SEQ ID NO:33): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-Asp-R16-Lys-Ala-Gln-Aib-R21- Phe-Ile-K*-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Id-2). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Id-2) (SEQ ID NO:33). In certain embodiments, Rxis Gly. In certain embodiments, Ryis Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R3 is Gln. In certain embodiments, R3is Glu. In certain embodiments, R6is Phe. In certain embodiments, R6 is amF. In certain embodiments, R16 is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16is Glu. In certain embodiments, R21is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R25 is amY. In certain embodiments, R25 is Tyr. In certain In certain embodiments, Rz is - (eLys)a-(2-[2-(2-amino-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d, are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20. 5.2.2 Formulae (I’), (Ia’), (Ib’), (Ic’), and (Id’) and sub-formulae thereof (i) Formulae (I’), (Ia’), (Ib’), (Ic’), and (Id’)

[0064] In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (I’) (SEQ ID NO:13): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2 32 NAI-5000824421(I’). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (I’) (SEQ ID NO:13). In certain embodiments, Rxis Gly. In certain embodiments, Ryis Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ryis Gln. In certain embodiments, R3is Gln. In certain embodiments, R3 is Glu. In certain embodiments, R6 is Phe. In certain embodiments, R6is amF. In certain embodiments, R15is Asp. In certain embodiments, R15is Glu. In certain embodiments, R16 is K*. In certain embodiments, R16 is Lys. In certain embodiments, R16is amK. In certain embodiments, R16is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R20 is K*. In certain embodiments, R20is Aib. In certain embodiments, R21is Ala. In certain embodiments, R21is Glu. In certain embodiments, R24 is K*. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu. In certain embodiments, R25 is amY. In certain embodiments, R25is Tyr. In certain embodiments, R29is absent. In certain embodiments, R29is Gly-Gly- Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29 is Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29is Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29 is Gly-Gly- Pro-Ser-Ser-Gly-Ala-Pro (SEQ ID NO:21). In certain embodiments, R29is Gly-Gly-Pro-Ser- Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29 is Gly-Gly-Pro-Ser (SEQ ID NO:25). In certain embodiments, R29 is Gly-Gly-Pro. In certain embodiments, R29is Gly-Gly. In certain embodiments, R29is Gly. In certain certain embodiments, Rz is -(Z)a-(2-[2-(2- amino-ethoxy)-ethoxy]-(CH2)q-X or -((CO)-(PEG)h-(CH2)2- NH)f-(gGlu)e-(CO)-(CH2)g-X. In certain embodiments, Z is independently Gly, Glu, gGlu, Lys, eLys, Ala, Gln, or His. In certain embodiments, Z is Gly. In certain embodiments, Z is Glu. In certain embodiments, Z is gGlu. In certain embodiments, Z is Lys. In certain embodiments, Z is eLys. In certain embodiments, Z is Ala. In certain embodiments, Z is Gln. In certain embodiments, Z is His. In certain embodiments, the gGlu is D-gGlu. In 33 NAI-5000824421other embodiments, the gGlu is L-gGlu. In certain embodiments, Rz is -(eLys)a-(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, d, and e are each independently 0, 1, 2, or 3. In certain embodiments, q and g are each independently 14-20. In certain embodiments, h is 2, 4, 6, 8, 10, 12, 14, or 16. In certain embodiments, f is 1, 2, 3, or 4. In certain embodiments, one and only one K* is present in Formula (I’).

[0065] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Ia’) (SEQ ID NO:14). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ia’) (SEQ ID NO:14): Tyr-Aib-R3-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-Tyr-Leu-Leu-Glu-Rx-Ry-R29-NH2(Ia’). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ia’) (SEQ ID NO:14). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R3 is Gln. In certain embodiments, R3is Glu. In certain embodiments, R15is Asp. In certain embodiments, R15 is Glu. In certain embodiments, R16 is K*. In certain embodiments, R16 is Lys. In certain embodiments, R16is amK. In certain embodiments, R16is Glu. In certain embodiments, R17 is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R20 is K*. In certain embodiments, R20is Aib. In certain embodiments, R21is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R24 is K*. In certain embodiments, R24 is Glu. In certain embodiments, R24is D-Glu. In certain embodiments, R29is absent. In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro (SEQ ID NO:21). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29is Gly-Gly-Pro- Ser (SEQ ID NO:25). In certain embodiments, R29 is Gly-Gly-Pro. In certain embodiments, R29is Gly-Gly. In certain embodiments, R29is Gly. In certain embodiments, K* is 34 NAI-5000824421. In certain embodiments, Rzis -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]- )c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20. In certain embodiments, one and only one K* is present in Formula (Ia’).

[0066] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Ib’) (SEQ ID NO:15). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ib’) (SEQ ID NO:15): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-K*-R17-Ala-Gln-Aib-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2(Ib’). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ib’) (SEQ ID NO:15). In certain embodiments, Rx is Gly. In certain embodiments, Ryis Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ryis Gln. In certain embodiments, R3is Gln. In certain embodiments, R3is Glu. In certain embodiments, R6 is Phe. In certain embodiments, R6 is amF. In certain embodiments, R15is Asp. In certain embodiments, R15is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R21 is Ala. In certain embodiments, R21is Glu. In certain embodiments, R24is Glu. In certain embodiments, R24is D-Glu. In certain embodiments, R25 is amY. In certain embodiments, R25 is Tyr. In certain embodiments, R29 is absent. In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala- Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly- Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly- Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala- Pro (SEQ ID NO:21). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, 35 NAI-5000824421R29 is Gly-Gly-Pro-Ser (SEQ ID NO:25). In certain embodiments, R29 is Gly-Gly-Pro. In certain embodiments, R29is Gly-Gly. In certain embodiments, R29is Gly. In certain embodiments, R25is Tyr. In certain . In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino- c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0067] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Ic’) (SEQ ID NO:16). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ic’) (SEQ ID NO:16): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-K*-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2 (Ic’). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ic’) (SEQ ID NO:16). In certain embodiments, Rxis Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ry is Gln. In certain embodiments, R3 is Gln. In certain embodiments, R3 is Glu. In certain embodiments, R6is Phe. In certain embodiments, R6is amF. In certain embodiments, R15 is Asp. In certain embodiments, R15 is Glu. In certain embodiments, R16 is Lys. In certain embodiments, R16is amK. In certain embodiments, R16is Glu. In certain embodiments, R17 is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R21 is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R24 is Glu. In certain embodiments, R24is D-Glu. In certain embodiments, R25is amY. In certain embodiments, R25 is Tyr. In certain embodiments, R29 is absent. In certain embodiments, R29 is Gly-Gly- Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29is Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29is Gly-Gly- Pro-Ser-Ser-Gly-Ala-Pro (SEQ ID NO:21). In certain embodiments, R29 is Gly-Gly-Pro-Ser- 36 NAI-5000824421Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29 is Gly-Gly-Pro-Ser (SEQ ID NO:25). In certain embodiments, R29 is Gly-Gly-Pro. In certain embodiments, R29is Gly-Gly. In certain embodiments, R29is Gly. In certain . In certain embodiments, Rzis -(eLys)a-(2-[2- (2-amino-ethoxy)- d-(CO)-(CH2)q-X. In certain embodiments,X is -CO2H. In certain - (O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0068] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Id’) (SEQ ID NO:17). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Id’) (SEQ ID NO:17): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-Aib-R21- Phe-Ile-K*-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2 (Id’). In certain embodiments provided herein is a pharmaceutically acceptable salt of a peptide comprising an amino acid sequence of Formula (Id’) (SEQ ID NO:17). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R3 is Gln. In certain embodiments, R3is Glu. In certain embodiments, R6is Phe. In certain embodiments, R6 is amF. In certain embodiments, R15 is Asp. In certain embodiments, R15 is Glu. In certain embodiments, R16 is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17is Gln. In certain embodiments, R21 is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R25is amY. In certain embodiments, R25is Tyr. In certain embodiments, R29is absent. In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro 37 NAI-5000824421(SEQ ID NO:20). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro (SEQ ID NO:21). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29is Gly-Gly-Pro-Ser (SEQ ID NO:25). In certain embodiments, R29 is Gly-Gly-Pro. In certain embodiments, R29is Gly-Gly. In certain embodiments, R29is Gly. In certain embodiments, . In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino-ethoxy)- c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. InX is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20. (ii) Sub-formulae of Formulae (I’), (Ia’), (Ib’), (Ic’), and (Id’)

[0069] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Ia’-1) (SEQ ID NO:34). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ia’-1) (SEQ ID NO:34): Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-Tyr-Leu-Leu-Glu-Rx-Ry-R29-NH2 (Ia’-1). In certain embodiments provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ia’-1) (SEQ ID NO:34). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R15 is Asp. In certain embodiments, R15is Glu. In certain embodiments, R16is K*. In certain embodiments, R16 is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16 is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17is Gln. In certain embodiments, R20 is K*. In certain embodiments, R20 is Aib. In certain embodiments, R21 is Ala. In certain embodiments, R21is Glu. In certain embodiments, R24is K*. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu. In certain embodiments, 38 NAI-5000824421R29 is absent. In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro (SEQ ID NO:21). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29 is Gly-Gly-Pro-Ser (SEQ ID NO:25). In certain embodiments, R29is Gly-Gly-Pro. In certain embodiments, R29 is Gly-Gly. In certain embodiments, R29 is Gly. In certain embodiments, . In certain embodiments, Rzis -(eLys)a-(2-[2-(2-amino-ethoxy)- c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. Incertain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20. In certain embodiments, one and only one K* is present in Formula (Ia’-1).

[0070] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Ia’-2) (SEQ ID NO:35). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ia’-2) (SEQ ID NO:35): Tyr-Aib-R3-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-Asp-R16-R17-Ala-Gln-Aib-R21- Phe-Ile-R24-Tyr-Leu-Leu-Glu-Rx-Ry-R29-NH2 (Ia’-2). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ia’-2) (SEQ ID NO:35). In certain embodiments, Rxis Gly. In certain embodiments, Ryis Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ryis Gln. In certain embodiments, R3is Gln. In certain embodiments, R3 is Glu. In certain embodiments, R16 is K*. In certain embodiments, R16is Lys. In certain embodiments, R16is amK. In certain embodiments, R16is Glu. In certain embodiments, R17 is Lys. In certain embodiments, R17 is Gln. In certain 39 NAI-5000824421embodiments, R21 is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R24 is K*. In certain embodiments, R24is Glu. In certain embodiments, R24is D-Glu. In certain embodiments, R29 is absent. In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala- Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly- Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly- Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala- Pro (SEQ ID NO:21). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29is Gly-Gly-Pro-Ser (SEQ ID NO:25). In certain embodiments, R29is Gly-Gly-Pro. In certain embodiments, R29 is Gly-Gly. In certain embodiments, R29 is Gly. In certain . In certain embodiments, Rzis -(eLys)a-(2-[2-(2-amino- ethoxy)- d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20. In certain embodiments, one and only one K* is present in Formula (Ia’-2).

[0071] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Ib’-1) (SEQ ID NO:36). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ib’-1) (SEQ ID NO:36): Tyr-Aib-Gln-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-K*-R17-Ala-Gln-Aib-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2 (Ib’-1). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ib’-1) 9SEQ ID NO:36). In certain embodiments, Rxis Gly. In certain embodiments, Ryis Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ryis Gln. In certain embodiments, R6is Phe. In certain embodiments, R6 is amF. In certain embodiments, R15 is Asp. In certain 40 NAI-5000824421embodiments, R15 is Glu. In certain embodiments, R17 is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R21is Ala. In certain embodiments, R21is Glu. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu. In certain embodiments, R25is amY. In certain embodiments, R25is Tyr. In certain embodiments, R29is absent. In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro (SEQ ID NO:21). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29 is Gly-Gly-Pro- Ser (SEQ ID NO:25). In certain embodiments, R29is Gly-Gly-Pro. In certain embodiments, R29 is Gly-Gly. In certain embodiments, R29 is Gly. In certain embodiments, K* is In certain embodiments, Rzis -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0072] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Ib’-2) (SEQ ID NO:37). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ib’-2) (SEQ ID NO:37): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-Asp-K*-Lys-Ala-Gln-Aib-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2 (Ib’-2). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ib’-2) (SEQ ID NO:37). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R3 is 41 NAI-5000824421Gln. In certain embodiments, R3 is Glu. In certain embodiments, R6 is Phe. In certain embodiments, R6is amF. In certain embodiments, R21is Ala. In certain embodiments, R21is Glu. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu. In certain embodiments, R25is amY. In certain embodiments, R25is Tyr. In certain embodiments, R29is absent. In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro (SEQ ID NO:21). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29 is Gly-Gly-Pro-Ser (SEQ ID NO:25). In certain embodiments, R29is Gly-Gly-Pro. In certain embodiments, R29 is Gly-Gly. In certain embodiments, R29 is Gly. In certain embodiments, K* is . In certain embodiments, Rzis -(eLys)a-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0073] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Ic’-1) (SEQ ID NO:38). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ic’-1) (SEQ ID NO:38): Tyr-Aib-Gln-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-K*-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2 (Ic’-1). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ic’-1) (SEQ ID NO:38). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R6 is 42 NAI-5000824421Phe. In certain embodiments, R6 is amF. In certain embodiments, R15 is Asp. In certain embodiments, R15is Glu. In certain embodiments, R16is Lys. In certain embodiments, R16is amK. In certain embodiments, R16 is Glu. In certain embodiments, R17 is Lys. In certain embodiments, R17is Gln. In certain embodiments, R21is Ala. In certain embodiments, R21is Glu. In certain embodiments, R24 is Glu. In certain embodiments, R24 is D-Glu. In certain embodiments, R25is amY. In certain embodiments, R25is Tyr. In certain embodiments, R29is absent. In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro (SEQ ID NO:21). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29 is Gly-Gly-Pro-Ser (SEQ ID NO:25). In certain embodiments, R29 is Gly-Gly-Pro. In certain embodiments, R29is Gly-Gly. In certain embodiments, R29is Gly. In certain embodiments, K* is . In certain embodiments, Rzis -(eLys)a-(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0074] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Ic’-2) (SEQ ID NO:39). In certain embodiments provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Ic’-2) (SEQ ID NO:39): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-Asp-R16-Lys-Ala-Gln-K*-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2 (Ic’-2). In certain embodiments provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Ic’-2) (SEQ ID NO:39). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, 43 NAI-5000824421Ry is Lys. In certain embodiments, Ry is Glu. In certain embodiments, Ry is Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ryis Gln. In certain embodiments, R3is Gln. In certain embodiments, R3 is Glu. In certain embodiments, R6 is Phe. In certain embodiments, R6is amF. In certain embodiments, R16is Lys. In certain embodiments, R16is amK. In certain embodiments, R16 is Glu. In certain embodiments, R21 is Ala. In certain embodiments, R21is Glu. In certain embodiments, R24is Glu. In certain embodiments, R24is D-Glu. In certain embodiments, R25 is amY. In certain embodiments, R25 is Tyr. In certain embodiments, R29is absent. In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala- Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly- Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly- Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala- Pro (SEQ ID NO:21). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29is Gly-Gly-Pro-Ser (SEQ ID NO:25). In certain embodiments, R29is Gly-Gly-Pro. In certain embodiments, R29 is Gly-Gly. In certain embodiments, R29 is Gly. In certain . In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino- ethoxy)-d-(CO)-(CH2)q-X. In certain embodiments, X is - CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0075] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Id’-1) (SEQ ID NO:40). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Id’-1) (SEQ ID NO:40): Tyr-Aib-Gln-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-Aib-R21- Phe-Ile-K*-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2(Id’-1). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Id’-1) (SEQ ID NO:40). In certain embodiments, Rx is Gly. In 44 NAI-5000824421certain embodiments, Ry is Arg. In certain embodiments, Ry is Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ryis Gly. In certain embodiments, Ry is Gln. In certain embodiments, R6 is Phe. In certain embodiments, R6 is amF. In certain embodiments, R15is Asp. In certain embodiments, R15is Glu. In certain embodiments, R16 is Lys. In certain embodiments, R16 is amK. In certain embodiments, R16 is Glu. In certain embodiments, R17is Lys. In certain embodiments, R17is Gln. In certain embodiments, R21 is Ala. In certain embodiments, R21 is Glu. In certain embodiments, R25 is amY. In certain embodiments, R25is Tyr. In certain embodiments, R29is absent. In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro (SEQ ID NO:21). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29is Gly-Gly-Pro- Ser (SEQ ID NO:25). In certain embodiments, R29 is Gly-Gly-Pro. In certain embodiments, R29is Gly-Gly. In certain embodiments, R29is Gly. In certain embodiments, K* is In certain embodiments, Rzis -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]-d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20.

[0076] In certain embodiments, the amino acid sequence of Formula (I’) is an amino acid sequence comprising or consisting of Formula (Id’-2) (SEQ ID NO:41). In certain embodiments, provided herein is a peptide comprising or consisting of an amino acid sequence of Formula (Id’-2) (SEQ ID NO:41): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-Asp-R16-Lys-Ala-Gln-Aib-R21- Phe-Ile-K*-R25-Leu-Leu-Glu-Rx-Ry-R29-NH2 (Id’-2). 45 NAI-5000824421In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of an amino acid sequence of Formula (Id’-2) (SEQ ID NO:41). In certain embodiments, Rx is Gly. In certain embodiments, Ry is Arg. In certain embodiments, Ryis Lys. In certain embodiments, Ryis Glu. In certain embodiments, Ryis Aib. In certain embodiments, Ry is Gly. In certain embodiments, Ry is Gln. In certain embodiments, R3 is Gln. In certain embodiments, R3is Glu. In certain embodiments, R6is Phe. In certain embodiments, R6 is amF. In certain embodiments, R15 is Asp. In certain embodiments, R15 is Glu. In certain embodiments, R16is Lys. In certain embodiments, R16is amK. In certain embodiments, R16 is Glu. In certain embodiments, R17 is Lys. In certain embodiments, R17 is Gln. In certain embodiments, R21is Ala. In certain embodiments, R21is Glu. In certain embodiments, R25 is amY. In certain embodiments, R25 is Tyr. In certain embodiments, R29 is absent. In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO:18). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro (SEQ ID NO:19). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro (SEQ ID NO:20). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro (SEQ ID NO:21). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser-Gly-Ala (SEQ ID NO:22). In certain embodiments, R29is Gly-Gly-Pro-Ser-Ser-Gly (SEQ ID NO:23). In certain embodiments, R29 is Gly-Gly-Pro-Ser-Ser (SEQ ID NO:24). In certain embodiments, R29 is Gly-Gly-Pro-Ser (SEQ ID NO:25). In certain embodiments, R29is Gly-Gly-Pro. In certain embodiments, R29 is Gly-Gly. In certain embodiments, R29 is Gly. In certain embodiments, . In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino-ethoxy)-c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0. In certain embodiments, q is 14-20. 5.2.3 Fatty Acid Component

[0077] In one aspect, the peptide provided herein comprises a fatty acid component. In certain embodiments, the fatty acid component is connected to the peptide via a side chain of an amino acid residue. In certain embodiments, the fatty acid component is connected to the peptide via the side chain of lysine. In certain embodiments, the connection of the fatty acid 46 NAI-5000824421component to the peptide through the side chain of a lysine residue is represented by K* that is of the .

[0078] In Rzis -(Z)a-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d- - q- certain embodiments, Z is independently Gly, Glu, gGlu, Lys, eLys, Ala, Gln, or His. In certain embodiments, Z is Gly. In certain embodiments, Z is Glu. In certain embodiments, Z is gGlu. In certain embodiments, Z is Lys. In certain embodiments, Z is eLys. In certain embodiments, Z is Ala. In certain embodiments, Z is Gln. In certain embodiments, Z is His. In certain embodiments, the gGlu is D-gGlu. In other embodiments, the gGlu is L-gGlu. In certain embodiments, q is 14-20. In certain embodiments, q is 14, 16, 18, or 20. In certain embodiments, q is 15, 17, or 19. In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)- (CH2)q-X. In certain embodiments, the gGlu is D-gGlu. In other embodiments, the gGlu is L-gGlu. In certain embodiments, X is -P(O)(OH)2. In other embodiments, X is -CO2H. In certain embodiments, “-(CO)-(CH2)q-CO2H” is collectively referred to as a diacid. In certain embodiments, the diacid is a C16, C18, C20, or C22 diacid. In certain embodiments, a, b, c, and d are each independently 0, 1, 2, or 3. In certain embodiments, a and b are not both 0. In certain embodiments, a is 0, b is 2, c is 1, d is 0. In certain embodiments, a is 0, b is 2, c is 2, d is 0. In certain embodiments, a is 0, b is 1, c is 1, d is 0. In certain embodiments, a is 2, b is 0, c is 1, d is 1. In certain embodiments, a is 0, b is 2, c is 1, d is 1. In certain embodiments, a is 1, b is 0, c is 1, d is 1. In certain embodiments, q is 14-20. In certain embodiments, q is 14, 16, 18, or 20. In certain embodiments, q is 15, 17, or 19.

[0079] In certain embodiments, Rzis -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c- (Trx)d-(CO)-(CH2)q-X. In certain embodiments, b is 1 or 2 and c is 1 or 2.

[0080] In certain embodiments, Rz is -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)- (CO)-(CH2)18-CO2H. In certain embodiments, Rzis -(2-[2-(2-amino-ethoxy)-ethoxy]- acetyl)2-(gGlu)2-(CO)-(CH2)18-CO2H. In certain embodiments, Rz is -(2-[2-(2-amino- ethoxy)-ethoxy]-acetyl)-(gGlu)-(CO)-(CH2)18-CO2H. In certain embodiments, Rzis -(2-[2- (2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(Trx)-(CO)-(CH2)18-CO2H. In certain embodiments, Rzis -(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)-(CH2)18- 47 NAI-5000824421P(O)(OH)2. In certain embodiments, Rz is -(eLys)a-(gGlu)c-(Trx)d-(CO)-(CH2)q-X. In certain embodiments, Rzis -(eLys)2-(gGlu)-(Trx)-(CO)-(CH2)18-CO2H.

[0081] In certain embodiments, Rz comprises one or more PEG units. In certain embodiments, the PEG units in Rzare linked to each other via a linker. In certain embodiments, Rz is -(linker-(PEG)h-linker)f-(gGlu)e-(CO)-(CH2)g-X. In certain embodiments, the PEG units in Rzare linked to each other directly. In certain embodiments, Rz is –((PEG)h)f-(gGlu)e-(CO)-(CH2)g-X. In certain embodiments, the PEG unit is linked to the rest of the Rzmoiety directly. In certain embodiments, the PEG units are linked to the rest of the Rz moiety via a linker. In certain embodiments, Rz is -(linker-(PEG)h)f-linker- (gGlu)e-(CO)-(CH2)g-X, -linker-((PEG)h-linker)f-(gGlu)e-(CO)-(CH2)g-X, -linker-((PEG)h)f- (gGlu)e-(CO)-(CH2)g-X, or -((PEG)h)f-linker-(gGlu)e-(CO)-(CH2)g-X. In certain embodiments, the linker is a peptide bond (i.e., an amide group). In certain embodiments, the linker is an alkyl group.

[0082] In certain embodiments, Rz is -((CO)-(PEG)h-(CH2)2-NH)f-(gGlu)e-(CO)-(CH2)g- X. In certain embodiments, X is -CO2H. In certain embodiments, X is -P(O)(OH)2. In certain embodiments, h is 2, 4, 6, 8, 10, 12, 14, or 16. In certain embodiments, f is 1, 2, 3, or 4. In certain embodiments, e is 0, 1, 2, or 3. In certain embodiments, g is 14-20.

[0083] In certain embodiments, Rz is prepared using one or more PEG linkers known in the art. In certain embodiments, Rzis prepared using one or more PEG linkers such as alkyne PEG, amino PEG, aminooxy PEG, 3-arylpropiolonitrile (APN) PEG, bicyclo[6.1.0]nonyne (BCN)-PEG, benzyl-PEG, biotin PEG, bis-PEG-acid (PEG di(carboxylic acid)), bis-PEG- NHS, Boc-PEG (Boc-protected PEG linkers), branched PEG, bromo PEG, a cleavable linker (e.g., a disulfide linker, a enzymatically cleavable linker, a photocleavable linker, a photoreactive linker, a diazo linker), dibenzocyclooctyne (DBCO) PEG, diketone linker, 2,4- Dinitrophenol PEG (DNP-PEG), DOTA reagent (e.g., DOTA-PEG-amine, DOTA-PEG- azide, DOTA-(t-Butyl)3-PEG-azide, DOTA-PEG-DBCO, bromoacetamido-PEG-DOTA, DOTA(OtBu)3, fluorescein-triazole-PEG-DOTA, and DOTA-PEG-DSPE), a fluorescent reagent (e.g., Cy3-PEG-azide, Cy3-PEG-alkyne, Cy5-PEG-acid, Cy5-PEG-NHS ester, Cy5- PEG-alkyne, Cy5-PEG-amine, Cy5-PEG-azide, Cy5-PEG-biotin, Cy5-PEG-DBCO, Cy5- PEG-hydroxyl, Cy5-PEG-Maleimide, Cy7-PEG-azide, fluorescein-PEG, carboxyfluorescein- PEG, BDP FL-PEG, rhodamine-PEG, and pyrene-PEG), fluorine PEG, Fmoc PEG (e.g., Fmoc-NH-PEG8-CH2COOH), hybrid linker (bromoacetamido-PEG-aliphatic-acid, bromoacetamido-PEG-aliphatic-t-butyl ester, amine-PEG-aliphatic-t-butyl ester, azide-PEG- aliphatic-t-butyl ester, C18-PEG-acid, C18-PEG-azide, Palmitic acid-PEG-acid, palmitic 48 NAI-5000824421acid-PEG-NHS ester, palmitamide-PEG-amine, and diethylene glycol monopentyl ether), hydroxy PEG ((PEG alcohols), Iodo PEG, lipid PEG, m-PEG (Poly(ethylene glycol) monomethyl ether), a maleimide linker, methylamino-PEG, non-PEG linker, NOTA reagent, PEG acid, PEG aldehyde, PEG azide, PEG hydrazide, PEG NHS ester, PEG PFP ester, PEG phosphonate, PEG PNP carbonate, PEG silane, PEG sulfonic acid, PEG tosylate, PEG-X- PEG (e.g., PEG-NH-PEG, PEG-Boc-PEG, PEG-Mal-PEG, PEG-N-Me-PEG, PEG-N-OH- PEG, PEG-Fluorescein-PEG, PEG-Biotin-PEG, PEG-DBCO-PEG, PEG-Methyltetrazine- PEG, PEG-TCO-PEG, PEG-N-Benzyl-PEG, PEG-S-PEG, PEG-SO2-PEG), poly PEG (PEG polymer), propargyl PEG, a PROTAC linker, SPDP PEG, sugar PEG, TCO-PEG, tetrazine- PEG, and thiol PEG.

[0084] In certain embodiments, h is 2-16. In certain embodiments, h is 2, 4, 6, 8, 10, 12, 14, or 16. In certain embodiments, f is 1, 2, 3, or 4. In certain embodiments, the gGlu is D- gGlu. In certain embodiments, the gGlu is L-gGlu. In certain embodiments, X is - P(O)(OH)2. In other embodiments, X is -CO2H. In certain embodiments, Rz is –(CO)- (PEG)12-(CH2)2-NH-(gGlu)e-(CO)-(CH2)g-CO2H. In certain embodiments, e is 0, 1, 2, or 3. In certain embodiments, g is 14, 16, 18, or 20. In certain embodiments, g is 15, 17, or 19. In certain embodiments, e is 1 or 2. In certain embodiments, g is 16 or 18.

[0085] In certain embodiments, Rz is -((CO)-(PEG)h-(CH2)2-NH)f-(gGlu)e-(CO)-(CH2)g- X. In certain embodiments, h is 2-16. In certain embodiments, h is 2, 4, 6, 8, 10, 12, 14, or 16. In certain embodiments, f is 1, 2, 3, or 4. In certain embodiments, the gGlu is D-gGlu. In certain embodiments, the gGlu is L-gGlu. In certain embodiments, X is -P(O)(OH)2. In other embodiments, X is -CO2H. In certain embodiments, Rz is –(CO)-(PEG)12-(CH2)2-NH- (gGlu)e-(CO)-(CH2)g-CO2H. In certain embodiments, e is 0, 1, 2, or 3. In certain embodiments, g is 14, 16, 18, or 20. In certain embodiments, g is 15, 17, or 19. In certain embodiments, e is 1 or 2. In certain embodiments, g is 16 or 18.

[0086] In certain embodiments, Rz is the corresponding moiety as shown in any one of FIGs.1-7. In certain embodiments, Rzis the fatty acid component in the peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, Rz is the fatty acid component in the pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7.

[0087] In certain embodiments, Rz is -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)b- (gGlu)c-(Trx)d-(CO)-(CH2)q-X, wherein a is 0, b is 1, c is 1, d is 0, q is 18, and X is -CO2H. 49 NAI-5000824421In certain embodiments, Rz is . -acetyl)b-c- d- - q- X is -CO2H. In certain embodiments, Rz is or,.-ethoxy]-acetyl)b- (gGlu)c-(Trx)d-(CO)-(CH2)q-X, wherein a=2, b=0, c=1, d=1, q=18, Z is eLys, and X is - CO2H. In certain embodiments, Rz is ,.acetyl)b- (gGlu)c-(Trx)d-(CO)-(CH2)q-X, wherein a is 0, b is 2, c is 2, d is 0, q is 18, and X is -CO2H. In certain embodiments, Rz is ,50 NAI-5000824421. y]-acetyl)b- (gGlu)c-(Trx)d-(CO)-(CH2)q-X, wherein a is 0, b is 2, c is 1, d is 0, q is 18, and X is - P(O)(OH)2. In certain embodiments, Rz is . b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X, wherein a=0, b=2, c=1, d=1, q=18, and X is -CO2H. In certain embodiments, Rzis ’ g- g- g-

[0096] In certain embodiments, Rz is -((CO)-(PEG)h-(CH2)2-NH)f-(gGlu)e-(CO)-(CH2)g- X, wherein h=12, f=1, e=1, g=18, and X is -P(O)(OH)2. In certain embodiments, Rzis .Exemplary Rz= -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d- Variables (CO)-(CH2)q-X52 NAI-5000824421Exemplary Rz= -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d- Variables (CO)-(CH2)q-X53 NAI-5000824421Exemplary Rz= -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d- Variables (CO)-(CH2)q-X 254 NAI-5000824421Exemplary Rz= -(eLys)a-(2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d- Variables (CO)-(CH2)q-X

[0098] In certain embodiments, provided herein is a peptide of Formula (I), (Ia), (Ib), (Ic) or (Id), or sub-formulae thereof. In certain embodiments, provided herein is a peptide of Formula (I’), (Ia’), (Ib’), (Ic’) or (Id’), or sub-formulae thereof. In certain embodiments, the peptide comprises the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, the peptide consists of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, provided herein is a peptide comprising or consists of the amino acid sequence as depicted in FIGs.1-7.

[0099] In certain embodiments, provided herein is a peptide that comprises the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide comprising the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a peptide that consists of the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide consisting of the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a peptide that comprises or consists of the amino acid sequence of SEQ ID NO:1: Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser- Ile-amL-Leu-Asp-K*-Lys-Ala-Gln-Aib-Glu-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Arg-Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2; 55 NAI-5000824421wherein (2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)- (CH2)18 vided herein is a peptide as depicted in FIG.1 or a pharmaceu ca y accepab e sa ereo . In certain embodiments, provided herein is a peptide that comprises or consists of the structure of SEQ ID NO:1 as illustrated below:

[0100] In certain embodiments, provided herein is a peptide that comprises the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide comprising the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a peptide that consists of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide consisting of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a peptide that comprises or consists of the amino acid sequence of SEQ ID NO:2: Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser- Ile-amL-Leu-Asp-K*-Lys-Ala-Gln-Aib-Glu-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Lys-Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2; 56 NAI-5000824421wherein (2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)- (CH2)18 vided herein is a peptide as depicted in FIG.2 or a pharmaceu ca y accepab e sa ereo . In certain embodiments, provided herein is a peptide that comprises or consists of the structure of SEQ ID NO:2 as illustrated below:

[0101] In certain embodiments, provided herein is a peptide that comprises the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide comprising the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a peptide that consists of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide consisting of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a peptide that comprises or consists of the amino acid sequence of SEQ ID NO:3: Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser- Ile-amL-Leu-Asp-K*-Lys-Ala-Gln-Aib-Glu-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Glu-Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2; 57 NAI-5000824421wherein (2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)- (CH2)18 vided herein is a peptide as depicted in FIG.3 or a pharmaceu ca y accepab e sa ereo . In certain embodiments, provided herein is a peptide that comprises or consists of the structure of SEQ ID NO:3 as illustrated below:

[0102] In certain embodiments, provided herein is a peptide that comprises the amino acid sequence of SEQ ID NO:4. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide comprising the amino acid sequence of SEQ ID NO:4. In certain embodiments, provided herein is a peptide that consists of the amino acid sequence of SEQ ID NO:4. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide consisting of the amino acid sequence of SEQ ID NO:4. In certain embodiments, provided herein is a peptide that comprises or consists of the amino acid sequence of SEQ ID NO:4: Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser- Ile-amL-Leu-Asp-K*-Lys-Ala-Gln-Aib-Glu-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Aib-Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2; 58 NAI-5000824421wherein (2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)- (CH2)18 vided herein is a peptide as depicted in FIG.4 or a pharmaceu ca y accepab e sa ereo . In certain embodiments, provided herein is a peptide that comprises or consists of the structure of SEQ ID NO:4 as illustrated below:

[0103] In certain embodiments, provided herein is a peptide that comprises the amino acid sequence of SEQ ID NO:5. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide comprising the amino acid sequence of SEQ ID NO:5. In certain embodiments, provided herein is a peptide that consists of the amino acid sequence of SEQ ID NO:5. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide consisting of the amino acid sequence of SEQ ID NO:5. In certain embodiments, provided herein is a peptide that comprises or consists of the amino acid sequence of SEQ ID NO:5: Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser- Ile-amL-Leu-Asp-K*-Lys-Ala-Gln-Aib-Glu-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Gly-Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2; 59 NAI-5000824421wherein (2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)- (CH2)18 vided herein is a peptide as depicted in FIG.5 or a pharmaceu ca y accepab e sa ereo . In certain embodiments, provided herein is a peptide that comprises or consists of the structure of SEQ ID NO:5 as illustrated below:

[0104] In certain embodiments, provided herein is a peptide that consists of the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide consisting of the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a peptide that comprises the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide comprising the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a peptide that comprises or consists of the amino acid sequence of SEQ ID NO:6: Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile- amL-Leu-Asp-K*-Lys-Ala-Gln-Aib-Glu-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Gln-Gly-Gly- Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2; 60 NAI-5000824421wherein (2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)- (CH2)18 vided herein is a peptide as depicted in FIG.6 or a pharmaceu ca y accepab e sa ereo . In certain embodiments, provided herein is a peptide that comprises or consists of the structure of SEQ ID NO:6 as illustrated below:

[0105] In certain embodiments, provided herein is a peptide that comprises the amino acid sequence of SEQ ID NO:7. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide comprising the amino acid sequence of SEQ ID NO:7. In certain embodiments, provided herein is a peptide that consists of the amino acid sequence of SEQ ID NO:7. In certain embodiments, provided herein is a peptide that is a pharmaceutically acceptable salt of a peptide consisting of the amino acid sequence of SEQ ID NO:7. In certain embodiments, provided herein is a peptide that comprises or consists of the amino acid sequence of SEQ ID NO:7: Tyr-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser- Ile-amL-Leu-Glu-K*-Lys-Ala-Gln-Aib-Glu-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Arg-Gly- Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2; 61 NAI-5000824421wherein (2-amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)- (CH2)18 vided herein is a peptide as depicted in FIG.7 or a pharmaceu ca y accepab e sa ereo . In certain embodiments, provided herein is a peptide that comprises or consists of the structure of SEQ ID NO:7 as illustrated below:5.3 Characteristics of the Peptides

[0106] The peptides described in the present disclosure have characteristics that are beneficial for treating diseases and disorders in a subject, or for alleviating one or more symptoms or conditions, such as for reducing body fat, reducing body weight, and / or increasing weight loss in a subject; and / or have characteristics that are beneficial for producing a pharmaceutical composition comprising the peptides of the present disclosure, such as for producing a pharmaceutical composition or formulation with high solubility and / or high physical and / or chemical stability. Such characteristics include, but are not 62 NAI-5000824421limited to, superior solubility, superior physical stability, superior chemical stability and / or superior relative activity profile against the GIP receptor, the GLP-1 receptor, and the GCG receptor as compared to, for example, one or more reference peptides (e.g., peptides represented by SEQ ID NOs: 42-48).

[0107] In certain embodiments, the peptides described herein exhibit superior solubility. In certain embodiments, such superior solubility of the peptides described herein are advantageous for the generation of pharmaceutical compositions or formulations comprising the peptides, particularly if high concentrations of the peptides are needed.

[0108] In certain embodiments, the peptides described herein have a solubility of about 1 to about 100 mg / mL, or about 2 to about 50 mg / mL (e.g., about 2 to about 50 mg / mL, about 2 to about 49 mg / mL, about 2 to about 48 mg / mL, about 2 to about 47 mg / mL, about 2 to about 46 mg / mL, about 2 to about 45 mg / mL, about 2 to about 44 mg / mL, about 2 to about 43 mg / mL, about 2 to about 42 mg / mL, about 2 to about 41 mg / mL, about 2 to about 40 mg / mL, about 2 to about 39 mg / mL, about 2 to about 38 mg / mL, about 2 to about 37 mg / mL, about 2 to about 36 mg / mL, about 2 to about 35 mg / mL, about 2 to about 34 mg / mL, about 2 to about 33 mg / mL, about 2 to about 32 mg / mL, about 2 to about 31 mg / mL, about 2 to about 30 mg / mL, about 2 to about 29 mg / mL, about 2 to about 28 mg / mL, about 2 to about 27 mg / mL, about 2 to about 26 mg / mL, about 2 to about 25 mg / mL, about 2 to about 24 mg / mL, about 2 to about 23 mg / mL, about 2 to about 22 mg / mL, about 2 to about 21 mg / mL, about 2 to about 20 mg / mL, about 2 to about 19 mg / mL, about 2 to about 18 mg / mL, about 2 to about 17 mg / mL, about 2 to about 16 mg / mL, about 2 to about 15 mg / mL, about 2 to about 14 mg / mL, about 2 to about 13 mg / mL, about 2 to about 12 mg / mL, about 2 to about 11 mg / mL, about 2 to about 10 mg / mL, about 2 to about 9 mg / mL, about 2 to about 8 mg / mL, about 2 to about 7 mg / mL, about 2 to about 6 mg / mL, about 2 to about 5 mg / mL, about 2 to about 4 mg / mL, about 2 to about 3 mg / mL, about 2 to about 50 mg / mL, about 3 to about 50 mg / mL, about 4 to about 50 mg / mL, about 5 to about 50 mg / mL, about 6 to about 50 mg / mL, about 7 to about 50 mg / mL, about 8 to about 50 mg / mL, about 9 to about 50 mg / mL, about 10 to about 50 mg / mL, about 11 to about 50 mg / mL, about 12 to about 50 mg / mL, about 13 to about 50 mg / mL, about 14 to about 50 mg / mL, about 15 to about 50 mg / mL, about 16 to about 50 mg / mL, about 17 to about 50 mg / mL, about 18 to about 50 mg / mL, about 19 to about 50 mg / mL, about 20 to about 50 mg / mL, about 21 to about 50 mg / mL, about 22 to about 50 mg / mL, about 23 to about 50 mg / mL, about 24 to about 50 mg / mL, about 25 to about 50 mg / mL, about 26 to about 50 mg / mL, about 27 to about 50 mg / mL, about 28 to about 50 mg / mL, about 29 to about 50 mg / mL, about 30 to about 50 mg / mL, about 31 to about 50 63 NAI-5000824421mg / mL, about 32 to about 50 mg / mL, about 33 to about 50 mg / mL, about 34 to about 50 mg / mL, about 35 to about 50 mg / mL, about 36 to about 50 mg / mL, about 37 to about 50 mg / mL, about 38 to about 50 mg / mL, about 39 to about 50 mg / mL, about 40 to about 50 mg / mL, about 41 to about 50 mg / mL, about 42 to about 50 mg / mL, about 43 to about 50 mg / mL, about 44 to about 50 mg / mL, about 45 to about 50 mg / mL, about 46 to about 50 mg / mL, about 47 to about 50 mg / mL, about 48 to about 50 mg / mL, or about 49 to about 50 mg / mL). In certain embodiments, the peptides described herein have a solubility of about 10 to about 100 mg / mL, about 10 to about 50 mg / mL, about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL. In some embodiments, the peptides described herein have a solubility of about 1 mg / mL, about 2 mg / mL, about 3 mg / mL, about 4 mg / mL, about 5 mg / mL, about 6 mg / mL, about 7 mg / mL, about 8 mg / mL, about 9 mg / mL, about 10 mg / mL, about 11 mg / mL, about 12 mg / mL, about 13 mg / mL, about 14 mg / mL, about 15 mg / mL, about 16 mg / mL, about 17 mg / mL, about 18 mg / mL, about 19 mg / mL, about 20 mg / mL, about 21 mg / mL, about 22 mg / mL, about 23 mg / mL, about 24 mg / mL, about 25 mg / mL, about 26 mg / mL, about 27 mg / mL, about 28 mg / mL, about 29 mg / mL, about 30 mg / mL, about 31 mg / mL, about 32 mg / mL, about 33 mg / mL, about 34 mg / mL, about 35 mg / mL, about 36 mg / mL, about 37 mg / mL, about 38 mg / mL, about 39 mg / mL, about 40 mg / mL, about 41 mg / mL, about 42 mg / mL, about 43 mg / mL, about 44 mg / mL, about 45 mg / mL, about 46 mg / mL, about 47 mg / mL, about 48 mg / mL, about 49 mg / mL, or about 50 mg / mL. In some embodiments, the peptides described herein have a solubility of at least about 2 mg / mL. In some embodiments, the peptides described herein have a solubility of at least about 5 mg / mL. In some embodiments, the peptides described herein have a solubility of at least about 10 mg / mL. In some embodiments, the peptides described herein have a solubility of at least about 20 mg / mL. In some embodiments, the peptides described herein have a solubility of about 20 mg / mL.

[0109] In certain embodiments, the solubility of the peptides described herein is determined under certain pH conditions, such as at a pH between about 6.5 and about 8, such as at about pH 7.0 or about pH 7.5. In certain embodiments, the peptides described herein have a solubility of about 10 to about 100 mg / mL, about 10 to about 50 mg / mL, about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, or at least 2 mg / mL. In certain embodiments, the peptides described herein have a solubility of about 10 to about 100 mg / mL, about 10 to about 50 mg / mL, about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, or at least 2 mg / mL, at about pH 7.0 or about pH 7.5. In certain embodiments, the peptides described herein have a solubility of about 10 to about 100 mg / mL, about 10 to 64 NAI-5000824421about 50 mg / mL, about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, at about pH 7.0. In certain embodiments, the peptides described herein have a solubility of about 10 to about 100 mg / mL, about 10 to about 50 mg / mL, about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, at about pH 7.5. In certain embodiments, the peptides described herein have a solubility of about 10 to about 100 mg / mL, about 10 to about 50 mg / mL, about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, or at least 10 mg / mL. In certain embodiments, the peptides described herein have a solubility of about 10 to about 100 mg / mL, about 10 to about 50 mg / mL, about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, or at least 10 mg / mL, at about pH 7.0 or about pH 7.5. In certain embodiments, the peptides described herein have a solubility of about 10 to about 100 mg / mL, about 10 to about 50 mg / mL, about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, or at least 10 mg / mL, at about pH 7.0. In certain embodiments, the peptides described herein have a solubility of at least 10 mg / mL, at about pH 7.5. In certain embodiments, the peptides described herein have a solubility of about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, or at least 20 mg / mL. In certain embodiments, the peptides described herein have a solubility of about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, or at least 20 mg / mL, at about pH 7.0 or about pH 7.5. In certain embodiments, the peptides described herein have a solubility of about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, or at least 20 mg / mL, at about pH 7.0. In certain embodiments, the peptides described herein have a solubility of about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, or at least 20 mg / mL, at about pH 7.5.

[0110] In certain embodiments, the peptides represented by any one of SEQ ID NOs:1, 2, 3, 4, 5, 6, and 7, have a solubility of about 1 to about 100 mg / mL, about 2 to about 50 mg / mL, or about 20 to about 50 mg / mL (e.g., about 2 to about 50 mg / mL, about 2 to about 49 mg / mL, about 2 to about 48 mg / mL, about 2 to about 47 mg / mL, about 2 to about 46 mg / mL, about 2 to about 45 mg / mL, about 2 to about 44 mg / mL, about 2 to about 43 mg / mL, about 2 to about 42 mg / mL, about 2 to about 41 mg / mL, about 2 to about 40 mg / mL, about 2 to about 39 mg / mL, about 2 to about 38 mg / mL, about 2 to about 37 mg / mL, about 2 to about 36 mg / mL, about 2 to about 35 mg / mL, about 2 to about 34 mg / mL, about 2 to about 33 mg / mL, about 2 to about 32 mg / mL, about 2 to about 31 mg / mL, about 2 to about 30 mg / mL, about 2 to about 29 mg / mL, about 2 to about 28 mg / mL, about 2 to about 27 mg / mL, about 2 to about 26 mg / mL, about 2 to about 25 mg / mL, about 2 to about 24 mg / mL, about 2 to about 23 mg / mL, about 2 to about 22 mg / mL, about 2 to about 21 mg / mL, about 2 to about 20 mg / mL, about 2 to about 19 mg / mL, about 2 to about 18 mg / mL, about 2 to about 17 mg / mL, about 2 to about 16 mg / mL, about 2 to about 15 mg / mL, about 2 to about 14 mg / mL, about 2 to about 65 NAI-500082442113 mg / mL, about 2 to about 12 mg / mL, about 2 to about 11 mg / mL, about 2 to about 10 mg / mL, about 2 to about 9 mg / mL, about 2 to about 8 mg / mL, about 2 to about 7 mg / mL, about 2 to about 6 mg / mL, about 2 to about 5 mg / mL, about 2 to about 4 mg / mL, about 2 to about 3 mg / mL, about 2 to about 50 mg / mL, about 3 to about 50 mg / mL, about 4 to about 50 mg / mL, about 5 to about 50 mg / mL, about 6 to about 50 mg / mL, about 7 to about 50 mg / mL, about 8 to about 50 mg / mL, about 9 to about 50 mg / mL, about 10 to about 50 mg / mL, about 11 to about 50 mg / mL, about 12 to about 50 mg / mL, about 13 to about 50 mg / mL, about 14 to about 50 mg / mL, about 15 to about 50 mg / mL, about 16 to about 50 mg / mL, about 17 to about 50 mg / mL, about 18 to about 50 mg / mL, about 19 to about 50 mg / mL, about 20 to about 50 mg / mL, about 21 to about 50 mg / mL, about 22 to about 50 mg / mL, about 23 to about 50 mg / mL, about 24 to about 50 mg / mL, about 25 to about 50 mg / mL, about 26 to about 50 mg / mL, about 27 to about 50 mg / mL, about 28 to about 50 mg / mL, about 29 to about 50 mg / mL, about 30 to about 50 mg / mL, about 31 to about 50 mg / mL, about 32 to about 50 mg / mL, about 33 to about 50 mg / mL, about 34 to about 50 mg / mL, about 35 to about 50 mg / mL, about 36 to about 50 mg / mL, about 37 to about 50 mg / mL, about 38 to about 50 mg / mL, about 39 to about 50 mg / mL, about 40 to about 50 mg / mL, about 41 to about 50 mg / mL, about 42 to about 50 mg / mL, about 43 to about 50 mg / mL, about 44 to about 50 mg / mL, about 45 to about 50 mg / mL, about 46 to about 50 mg / mL, about 47 to about 50 mg / mL, about 48 to about 50 mg / mL, or about 49 to about 50 mg / mL). In certain embodiments, the peptides represented by any one of SEQ ID NOs:1, 2, 3, 4, 5, 6, and 7, have a solubility of about 1 mg / mL, about 2 mg / mL, about 3 mg / mL, about 4 mg / mL, about 5 mg / mL, about 6 mg / mL, about 7 mg / mL, about 8 mg / mL, about 9 mg / mL, about 10 mg / mL, about 11 mg / mL, about 12 mg / mL, about 13 mg / mL, about 14 mg / mL, about 15 mg / mL, about 16 mg / mL, about 17 mg / mL, about 18 mg / mL, about 19 mg / mL, about 20 mg / mL, about 21 mg / mL, about 22 mg / mL, about 23 mg / mL, about 24 mg / mL, about 25 mg / mL, about 26 mg / mL, about 27 mg / mL, about 28 mg / mL, about 29 mg / mL, about 30 mg / mL, about 31 mg / mL, about 32 mg / mL, about 33 mg / mL, about 34 mg / mL, about 35 mg / mL, about 36 mg / mL, about 37 mg / mL, about 38 mg / mL, about 39 mg / mL, about 40 mg / mL, about 41 mg / mL, about 42 mg / mL, about 43 mg / mL, about 44 mg / mL, about 45 mg / mL, about 46 mg / mL, about 47 mg / mL, about 48 mg / mL, about 49 mg / mL, or about 50 mg / mL. In certain embodiments, the peptides represented by any one of SEQ ID NOs:1, 2, 3, 4, 5, 6, and 7, have a solubility of about 10 to about 100 mg / mL, about 10 to about 50 mg / mL, about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, at about pH 7.0 or at about pH 7.5. In certain embodiments, the peptides represented by any one of SEQ ID NOs:1, 2, 3, 4, 5, 6, 66 NAI-5000824421and 7, have a solubility of about 10 to about 100 mg / mL, about 10 to about 50 mg / mL, about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, at about pH 7.0. In certain embodiments, the peptides represented by any one of SEQ ID NOs:1, 2, 3, 4, 5, 6, and 7, have a solubility of about 10 to about 100 mg / mL, about 10 to about 50 mg / mL, about 20 to about 100 mg / mL, or about 20 to about 50 mg / mL, at about pH 7.5.

[0111] In certain embodiments, the peptide represented by any one of SEQ ID NOs:1, 2, 3, 4, 5, 6, and 7 has a solubility of about 20 to about 50 mg / mL, at about pH 7.5.

[0112] In certain embodiments, the peptides described herein exhibit high physical stability, including a high level of physical stability even after storage for an extended time. In certain embodiments, such superior physical stability of the peptides described herein are advantageous for storing pharmaceutical compositions or formulations comprising the peptides, particularly if long-term storage or storage at particular conditions is needed.

[0113] In certain embodiments, the peptides described herein exhibit high physical stability as shown by low or undetectable aggregate formation, for example, as observed based on size exclusion chromatography (SEC) of a solution comprising the provided peptides. In certain embodiments, the peptides described herein have a % aggregation (as indicated by the area under the curve of peaks with estimated molecular weight of greater than 150,000 Da on SEC) of undetectable (about 0%, indicating high physical stability over time) to about 10% (e.g., about 0% to about 10%, about 0.1% to about 10%, about 0.25% to about 10%, about 0.5% to about 10%, about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 0% to about 0.1%, about 0% to about 0.25%, about 0% to about 0.5%, about 0% to about 1%, about 0% to about 2%, about 0% to about 3%, about 0% to about 4%, about 0% to about 5%, about 0% to about 6%, about 0% to about 7%, about 0% to about 8%, or about 0% to about 9%). In certain embodiments, the peptides described herein have a % aggregation of about 0%, about 0.1%, about 0.25%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%. In certain embodiments, the % aggregation of the peptides described herein is determined after storage of a solution comprising the peptides for a period of time, such as about 3 days, about 5 days, about 7 days, about 14 days, about 28 days, about 30 days, about 60 days, or about 90 days, for example, about 7 days or about 30 days.

[0114] In certain embodiments, the peptides described herein have % aggregation of less than about 0.1%, such as about 0%, after storage for about 7 days. In certain embodiments, 67 NAI-5000824421the peptides described herein have % aggregation of about 0% to about 10% (e.g., about 0% to about 10%, about 0.1% to about 10%, about 0.25% to about 10%, about 0.5% to about 10%, about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 0% to about 0.1%, about 0% to about 0.25%, about 0% to about 0.5%, about 0% to about 1%, about 0% to about 2%, about 0% to about 3%, about 0% to about 4%, about 0% to about 5%, about 0% to about 6%, about 0% to about 7%, about 0% to about 8%, or about 0% to about 9%, such as of about 0%, about 0.1%, about 0.25%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%, after storage for about 30 days. In certain embodiments, the peptides described herein have % aggregation of less than about 7%, such as about 6%, about 5%, about 4%, about 3%, about 2%, about 1% or about 0%, after storage for about 30 days.

[0115] In certain embodiments, the peptides represented by any one of SEQ ID NOs:1, 2, 3, 4, 5, 6, and 7, have a % aggregation of about 0%, after about 7 days.

[0116] In certain embodiments, the peptides represented by any one of SEQ ID NOs:1, 2, 3, 4, 5, 6, and 7, have a % aggregation of about 0%, after about 30 days.

[0117] In certain embodiments, the peptides described herein exhibit high chemical stability, including a high level of chemical stability even after storage for an extended time, at a higher temperature compared to typical storage conditions. In certain embodiments, such superior chemical stability of the peptides described herein are advantageous for storing pharmaceutical compositions or formulations comprising the peptides, particularly if long- term storage or storage at particular conditions such as high temperature is needed.

[0118] In certain embodiments, the chemical stability of the peptides described herein are advantageous for maintaining stability and bioavailability of the peptides over time when administered to a subject. In certain embodiments, the peptides described herein exhibit high chemical stability as shown by low or undetectable aggregate formation, for example, as observed based on reverse-phase high-performance liquid chromatography (RP-HPLC)- ultraviolet (UV) spectroscopy of a solution comprising the provided peptides. In certain embodiments, the peptides described herein have a % purity loss (as indicated by the difference in the area under the curve of the peak of the UV absorption trace at 220 nm based on RP-HPLC-UV, before storage of a solution comprising the peptides for a period of time (i.e., at day 0) and after storage (e.g., at day 7 or day 30)) of about 0% to about 10% (e.g., about 0% to about 10%, about 0.1% to about 10%, about 0.25% to about 10%, about 0.5% to 68 NAI-5000824421about 10%, about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 0% to about 0.1%, about 0% to about 0.25%, about 0% to about 0.5%, about 0% to about 1%, about 0% to about 2%, about 0% to about 3%, about 0% to about 4%, about 0% to about 5%, about 0% to about 6%, about 0% to about 7%, about 0% to about 8%, or about 0% to about 9%), or is undetectable (about 0%, indicating high chemical stability over time). In certain embodiments, the peptides described herein have a % purity loss of about 0%, about 0.1%, about 0.25%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%. In certain embodiments, the % purity loss of the peptides described herein is determined after storage of a solution comprising the peptides for a period of time, such as about 3 days, about 5 days, about 7 days, about 14 days, about 28 days, about 30 days, about 60 days, or about 90 days, for example, about 7 days or about 30 days. In certain embodiments, the % purity loss of the peptides described herein is determined after storage of a solution comprising the peptides at a physiological temperature or typical human body temperature, for example, about 34°C, about 35°C, about 36°C, about 37°C, about 38°C, or about 39°C, such as at about 37°C. In certain embodiments, the % purity loss of the peptides described herein is determined under agitating conditions, for example, agitating or shaking the solution at particular speeds, such as 300 revolutions per minute (rpm), 400 rpm, 500 rpm, 600 rpm or more. In certain embodiments, the peptides provided herein result in minimal purity loss despite exposure to high temperatures or agitating conditions.

[0119] In certain embodiments, the peptides described herein have % purity loss of about 0% to about 10% (e.g., about 0% to about 10%, about 0.1% to about 10%, about 0.25% to about 10%, about 0.5% to about 10%, about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 0% to about 0.1%, about 0% to about 0.25%, about 0% to about 0.5%, about 0% to about 1%, about 0% to about 2%, about 0% to about 3%, about 0% to about 4%, about 0% to about 5%, about 0% to about 6%, about 0% to about 7%, about 0% to about 8%, or about 0% to about 9%), such as about 0%, about 0.1%, about 0.25%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%, after storage for about 7 days, at about 37°C. In certain embodiments, the peptides described herein have % purity loss of about 0% to about 10% (e.g., about 0% to about 10%, about 0.1% to about 10%, about 0.25% to about 10%, about 0.5% to about 10%, about 1% to about 10%, about 2% to about 69 NAI-500082442110%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 0% to about 0.1%, about 0% to about 0.25%, about 0% to about 0.5%, about 0% to about 1%, about 0% to about 2%, about 0% to about 3%, about 0% to about 4%, about 0% to about 5%, about 0% to about 6%, about 0% to about 7%, about 0% to about 8%, or about 0% to about 9%), such as about 0%, about 0.1%, about 0.25%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%, after storage for about 30 days, at about 37°C.

[0120] In certain embodiments, the peptides represented by any one of SEQ ID NOs:1, 2, 3, 4, 5, 6, and 7, have a % purity loss of about 0% to about 10% (e.g., about 0% to about 10%, about 0.1% to about 10%, about 0.25% to about 10%, about 0.5% to about 10%, about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 0% to about 0.1%, about 0% to about 0.25%, about 0% to about 0.5%, about 0% to about 1%, about 0% to about 2%, about 0% to about 3%, about 0% to about 4%, about 0% to about 5%, about 0% to about 6%, about 0% to about 7%, about 0% to about 8%, or about 0% to about 9%), such as about 0%, about 0.1%, about 0.25%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%, after about 7 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:1 has a % purity loss of about 1%, after about 7 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:2 has a % purity loss of about 0%, after about 7 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:3 has a % purity loss of about 0%, after about 7 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:4 has a % purity loss of about 0%, after about 7 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:5 has a % purity loss of about 0%, after about 7 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:6 has a % purity loss of about 0%, after about 7 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:7 has a % purity loss of about 1%, after about 7 days at about 37°C.

[0121] In certain embodiments, the peptides represented by any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, and 7, have a % purity loss of about 0% to about 10% (e.g., about 0% to about 10%, about 0.1% to about 10%, about 0.25% to about 10%, about 0.5% to about 10%, about 1% to about 10%, about 2% to about 10%, about 3% to about 10%, about 4% to about 10%, 70 NAI-5000824421about 5% to about 10%, about 6% to about 10%, about 7% to about 10%, about 8% to about 10%, about 9% to about 10%, about 0% to about 0.1%, about 0% to about 0.25%, about 0% to about 0.5%, about 0% to about 1%, about 0% to about 2%, about 0% to about 3%, about 0% to about 4%, about 0% to about 5%, about 0% to about 6%, about 0% to about 7%, about 0% to about 8%, or about 0% to about 9%), such as about 0%, about 0.1%, about 0.25%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%, after about 30 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:1 has a % purity loss of about 3%, after about 30 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:2 has a % purity loss of about 5%, after about 30 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:3 has a % purity loss of about 3%, after about 30 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:4 has a % purity loss of about 3.5%, such as about 4%, after about 30 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:5 has a % purity loss of about 3.3%, such as about 3%, after about 30 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:6 has a % purity loss of about 3.8%, such as about 4%, after about 30 days at about 37°C. In certain embodiments, the peptide represented by SEQ ID NO:7 has a % purity loss of about 2%, after about 30 days at about 37°C.

[0122] In certain embodiments, the peptides described herein have characteristics that include an agonistic activity profile against the three different incretin receptors and the agonism ratio of two of the three receptors. In certain embodiments, the peptides provided herein have a superior activity profile against the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor, and additionally in some embodiments the glucagon (GCG) receptor. In certain embodiments, the peptides provided herein demonstrate reduced or absent activity at the glucagon receptor without affecting the potent activity at the GLP-1 receptor or the GIP receptor. In certain embodiments, the peptides provided herein do not have an increased levels of glucagon receptor activity, which is known to be associated with an increased heart rate in humans. In certain embodiments, the peptides of the present disclosure demonstrate a lower GCG receptor activity, while maintaining potent agonistic activity at the GLP-1 receptor or the GIP receptor. In certain embodiment, the potent activity at the GLP-1 receptor or the GIP receptor, together with lower (or absent) activity at the GCG receptor of the peptides described herein, are advantageous for reducing side effects, such as side effects associated with increased heart rate and / or gastrointestinal side effects, such as nausea, diarrhea, 71 NAI-5000824421stomach (abdominal) pain, vomiting, constipation, while maintaining therapeutic effects such as in body weight reduction, resulting in superior therapeutic activities, superior drug tolerability, and / or superior safety profile.

[0123] In certain embodiments, the peptides described herein exhibit potent agonistic activity at the glucagon-like peptide-1 (GLP-1) receptor (as indicated by low half maximal effective concentration (EC50) at the GLP-1 receptor), the glucagon (GCG) receptor (as indicated by low EC50 at the GCG receptor), and / or at the glucose-dependent insulinotropic polypeptide (GIP) receptor (as indicated by low EC50at the GIP receptor), for example as assessed using a cell-based assay. In certain embodiments, EC50 is determined using a cell- based assay, such as a cell engineered to stably express the human GLP-1 receptor, the human GCG receptor, or the human GIP receptor.

[0124] In certain embodiments, the EC50at the GLP-1 receptor, GCG receptor, or GIP receptor is determined in the presence of an agent that blocks nonspecific binding, such as casein.

[0125] In certain embodiments, the peptides described herein have an EC50at the GLP-1 receptor in the presence of casein of about 1 pM to about 30 pM, or about 1 pM to about 10 pM, or about 2 pM to about 5 pM (e.g., about 1 pM to about 10 pM, about 2 pM to about 10 pM, about 3 pM to about 10 pM, about 4 pM to about 10 pM, about 5 pM to about 10 pM, about 6 pM to about 10 pM, about 7 pM to about 10 pM, about 8 pM to about 10 pM, about 9 pM to about 10 pM, about 1 pM to about 10 pM, about 1 pM to about 9 pM, about 1 pM to about 8 pM, about 1 pM to about 7 pM, about 1 pM to about 6 pM, about 1 pM to about 5 pM, about 1 pM to about 4 pM, about 1 pM to about 3 pM, or about 1 pM to about 2 pM). In some embodiments, the peptides described herein have an EC50at the GLP-1 receptor in the presence of casein of about 15 pM, about 14 pM, about 13 pM, about 12 pM, about 11 pM, about 10 pM, about 9 pM, about 8 pM, about 7 pM, about 6 pM, about 5 pM, about 4 pM, about 3 pM, about 2 pM, about 1 pM, or about 1 pM or less.

[0126] In certain embodiments, the peptide represented by SEQ ID NO:1 has an EC50at the GLP-1 receptor of about 5.1 pM, such as about 5 pM in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:2 has an EC50 at the GLP-1 receptor of about 4.2 pM, such as about 4 pM in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:3 has an EC50 at the GLP-1 receptor of about 3.1 pM, such as about 3 pM in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:4 has an EC50 at the GLP-1 receptor of about 3.5 pM, such as about 3 pM or such as about 4 pM in the presence of casein. In certain embodiments, the peptide represented 72 NAI-5000824421by SEQ ID NO:5 has an EC50 at the GLP-1 receptor of about 3 pM in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:6 has an EC50at the GLP-1 receptor of about 2.6 pM, such as about 3 pM, in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:7 has an EC50at the GLP-1 receptor of about 3.2 pM, such as about 3 pM in the presence of casein.

[0127] In certain embodiments, the peptides described herein have an EC50at the GCG receptor in the presence of casein of about 30 pM to about 150,000 pM, or about 30 pM to about 10,000 pM, or about 30 pM to about 1,000 pM (e.g., about 30 pM to about 10,000 pM, about 40 pM to about 10,000 pM, about 50 pM to about 10,000 pM, about 60 pM to about 10,000 pM, about 70 pM to about 10,000 pM, about 80 pM to about 10,000 pM, about 90 pM to about 10,000 pM, about 100 pM to about 10,000 pM, about 200 pM to about 10,000 pM, about 300 pM to about 10,000 pM, about 400 pM to about 10,000 pM, about 500 pM to about 10,000 pM, about 600 pM to about 10,000 pM, about 800 pM to about 10,000 pM, about 1000 pM to about 10,000 pM, about 1500 pM to about 10,000 pM, about 2000 pM to about 10,000 pM, about 2500 pM to about 10,000 pM, about 3000 pM to about 10,000 pM, about 3500 pM to about 10,000 pM, about 4000 pM to about 10,000 pM, about 5000 pM to about 10,000 pM, about 6000 pM to about 10,000 pM, about 7000 pM to about 10,000 pM, about 8000 pM to about 10,000 pM, about 9000 pM to about 10,000 pM, about 30 pM to about 9000 pM, about 30 pM to about 8000 pM, about 30 pM to about 7000 pM, about 30 pM to about 6000 pM, about 30 pM to about 5000 pM, about 30 pM to about 4000 pM, about 30 pM to about 3500 pM, about 30 pM to about 3000 pM, 30 pM to about 2500 pM, 30 pM to about 2000 pM, 30 pM to about 1800 pM, 30 pM to about 1600 pM, 30 pM to about 1500 pM, 30 pM to about 1400 pM, 30 pM to about 1300 pM, 30 pM to about 1200 pM, 30 pM to about 1100 pM, 30 pM to about 1000 pM, 30 pM to about 900 pM, 30 pM to about 800 pM, 30 pM to about 700 pM, 30 pM to about 600 pM, 30 pM to about 500 pM, 30 pM to about 400 pM, 30 pM to about 300 pM, 30 pM to about 200 pM, 30 pM to about 100 pM, 30 pM to about 90 pM, 30 pM to about 80 pM, 30 pM to about 70 pM, 30 pM to about 60 pM, about 30 pM to about 50 pM, or about 30 pM to about 40 pM). In some embodiments, the peptides described herein have an EC50 at the GCG receptor in the presence of casein of about 30 pM, about 40 pM, about 50 pM, about 60 pM, about 70 pM, about 80 pM, about 90 pM, about 100 pM, about 200 pM, about 300 pM, about 400 pM, about 500 pM, about 600 pM, about 800 pM, about 1000 pM, about 1500 pM, about 2000 pM, about 2500 pM, about 3000 pM, about 3500 pM, about 4000 pM, about 5000 pM, about 6000 pM, about 7000 pM, about 8000 pM, about 9000 pM, or about 10,000 pM. 73 NAI-5000824421

[0128] In some embodiments, the peptides described herein have an EC50 at the GCG receptor in the presence of casein that is above the limit of detection (e.g., binding of a peptide to the GCG receptor is too weak for a given assay to detect) of the assay being used to measure the EC50; in certain embodiments, a peptide described herein is considered to be inactive at the GCG receptor in the presence of casein.

[0129] In certain embodiments, the peptide represented by SEQ ID NO:1 has an EC50at the GCG receptor in the presence of casein of about 1083.7 pM, such as about 1084 pM, such as about 1080 pM, such as about 1100 pM. In certain embodiments, the peptide represented by SEQ ID NO: 2 has an EC50 at the GCG receptor in the presence of casein of about 1293.3 pM, such as about 1293 pM, such as about 1290 pM, such as about 1300 pM. In certain embodiments, the peptide represented by SEQ ID NO: 3 has an EC50 at the GCG receptor in the presence of casein of about 368.4 pM, such as about 368 pM, such as about 370 pM, such as about 400 pM. In certain embodiments, the peptide represented by SEQ ID NO: 4 has an EC50 at the GCG receptor in the presence of casein of about 1172.1 pM, such as about 1172 pM, such as about 1170 pM, such as about 1200 pM. In certain embodiments, the peptide represented by SEQ ID NO: 5 has an EC50 at the GCG receptor in the presence of casein of about 387 pM, such as about 390 pM, such as about 400 pM. In certain embodiments, the peptide represented by SEQ ID NO: 6 has an EC50 at the GCG receptor in the presence of casein of about 803.6 pM, such as about 804 pM, such as about 800 pM. In certain embodiments, the peptide represented by SEQ ID NO: 7 has an EC50 at the GCG receptor in the presence of casein that is above the limit of detection (e.g., binding of a peptide to the GCG receptor is too weak for a given assay to detect) of the assay used to detect the EC50; in certain embodiments, the peptide represented by SEQ ID NO: 7 is considered to be inactive at the GCG receptor in the presence of casein.

[0130] In certain embodiments, the peptides described herein have an EC50at the GIP receptor in the presence of casein of about 2 pM to about 200 pM, or about 2 pM to about 20 pM, or about 2 pM to about 4 pM (e.g., about 2 pM to about 20 pM, about 3 pM to about 20 pM, about 4 pM to about 20 pM, about 5 pM to about 20 pM, about 6 pM to about 20 pM, about 7 pM to about 20 pM, about 8 pM to about 20 pM, about 9 pM to about 20 pM, about 10 pM to about 20 pM, about 11 pM to about 20 pM, about 12 pM to about 20 pM, about 13 pM to about 20 pM, about 14 pM to about 20 pM, about 15 pM to about 20 pM, about 16 pM to about 20 pM, about 17 pM to about 20 pM, about 18 pM to about 20 pM, about 19 pM to about 20 pM, about 2 pM to about 19 pM, about 2 pM to about 18 pM, about 2 pM to about 17 pM, about 2 pM to about 16 pM, about 2 pM to about 15 pM, about 2 pM to about 14 pM, 74 NAI-5000824421about 2 pM to about 13 pM, about 2 pM to about 12 pM, about 2 pM to about 11 pM, about 2 pM to about 10 pM, about 2 pM to about 9 pM, about 2 pM to about 8 pM, about 2 pM to about 7 pM, about 2 pM to about 6 pM, about 2 pM to about 5 pM, about 2 pM to about 4 pM, or about 2 pM to about 3 pM). In some embodiments, the peptides described herein have an EC50 at the GIP receptor in the presence of casein of about 2 pM, about 3 pM, about 4 pM, about 5 pM, about 6 pM, about 7 pM, about 8 pM, about 9 pM, about 10 pM, about 11 pM, about 12 pM, about 13 pM, about 14 pM, about 15 pM, about 16 pM, about 17 pM, about 18 pM, about 19 pM, or about 20 pM.

[0131] In certain embodiments, the peptide represented by SEQ ID NO:1 has an EC50 at the GIP receptor of about 2.9 pM, such as about 3 pM in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:2 has an EC50 at the GIP receptor of about 2.4 pM, such as about 2 pM in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:3 has an EC50 at the GIP receptor of about 2.0 pM, such as about 2 pM in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:4 has an EC50at the GIP receptor of about 2.1 pM, such as about 2 pM in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:5 has an EC50at the GIP receptor of about 2.2 pM, such as about 2 pM in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:6 has an EC50 at the GIP receptor of about 2.1 pM, such as about 2 pM in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:7 has an EC50 at the GIP receptor of about 3.7 pM, such as about 4 pM in the presence of casein.

[0132] In certain embodiments, the EC50 at the GLP-1 receptor, GCG receptor, or GIP receptor is determined in the presence of an agent, such as bovine serum albumin (BSA) that is capable of binding to a fatty acid-containing side chain, such as the K* side chain of the peptides disclosed herein. In some embodiments, a decrease in potency in the presence of BSA (e.g., an increase in EC50 in the presence of BSA as compared to the EC50 in the presence of casein (e.g., in the absence of BSA)) is indicative of a higher in vivo half-life for a fatty acid-containing peptide of the disclosure, as compared to a peptide that does not experience a comparable loss in potency in the presence of BSA.

[0133] In certain embodiments, the peptides described herein have an EC50 at the GLP-1 receptor in the presence of BSA of about 20 pM to about 1000 pM, or about 30 pM to about 600 pM (e.g.,about 30 pM to about 600 pM, about 40 pM to about 600 pM, about 50 pM to about 600 pM, about 60 pM to about 600 pM, about 70 pM to about 600 pM, about 80 pM to about 600 pM, about 90 pM to about 600 pM, about 100 pM to about 600 pM, about 120 pM 75 NAI-5000824421to about 600 pM, about 140 pM to about 600 pM, about 160 pM to about 600 pM, about 180 pM to about 600 pM, about 200 pM to about 600 pM, about 250 pM to about 600 pM, about 300 pM to about 600 pM, about 350 pM to about 600 pM, about 400 pM to about 600 pM, about 450 pM to about 600 pM, about 500 pM to about 600 pM, about 550 pM to about 600 pM, about 30 pM to about 600 pM, about 30 pM to about 550 pM, about 30 pM to about 500 pM, about 30 pM to about 450 pM, about 30 pM to about 400 pM, about 30 pM to about 350 pM, about 30 pM to about 300 pM, about 30 pM to about 250 pM, about 30 pM to about 200 pM, about 30 pM to about 180 pM, about 30 pM to about 160 pM, about 30 pM to about 140 pM, about 30 pM to about 120 pM, about 30 pM to about 100 pM, about 30 pM to about 90 pM, about 30 pM to about 80 pM, about 30 pM to about 70 pM, about 30 pM to about 60 pM, about 30 pM to about 50 pM, about 30 pM to about 40 pM). In some embodiments, the peptides described herein have an EC50at the GLP-1 receptor in the presence of BSA of about 80 pM, about 85 pM, about 90 pM, about 100 pM, about 110 pM, about 120 pM, about 130 pM, about 140 pM, about 150 pM, about 160 pM, about 170 pM, about 180 pM, about 190 pM, about 200 pM, about 250 pM, about 300 pM, about 350 pM, about 400 pM, about 450 pM, or about 500 pM.

[0134] In certain embodiments, the peptide represented by SEQ ID NO:1 has an EC50at the GLP-1 receptor of about 203.2 pM, such as about 200 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:2 has an EC50at the GLP-1 receptor of about 221.2 pM, such as about 220 pM, such as about 200 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:3 has an EC50at the GLP-1 receptor of about 512.2 pM, such as about 512 pM, such as about 510 pM, such as about 500 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:4 has an EC50 at the GLP-1 receptor of about 279.5 pM, such as about 280 pM, or such as about 300 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:5 has an EC50 at the GLP-1 receptor of about 230.6 pM, such as about 231 pM, such as about 230 pM, such as about 200 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:6 has an EC50 at the GLP-1 receptor of about 213.1 pM, such as about 213 pM, such as about 210 pM, such as about 200 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:7 has an EC50 at the GLP-1 receptor of about 207.9 pM, such as about 208 pM, such as about 200 pM in the presence of BSA.

[0135] In certain embodiments, the peptides described herein have an EC50 at the GCG receptor in the presence of BSA of about 700 pM to about 400,000 pM, or about 700 pM to 76 NAI-5000824421about 20,000 pM (e.g., about 700 pM to about 20000 pM, about 800 pM to about 20000 pM, about 900 pM to about 20000 pM, about 1000 pM to about 20000 pM, about 2000 pM to about 20000 pM, about 3000 pM to about 20000 pM, about 4000 pM to about 20000 pM, about 5000 pM to about 20000 pM, about 10000 pM to about 20000 pM, about 11000 pM to about 20000 pM, about 12000 pM to about 20000 pM, about 13000 pM to about 20000 pM, about 14000 pM to about 20000 pM, about 15000 pM to about 20000 pM, about 16000 pM to about 20000 pM, about 17000 pM to about 20000 pM, about 18000 pM to about 20000 pM, about 19000 pM to about 20000 pM, about 700 pM to about 20000 pM, about 700 pM to about 19000 pM, about 700 pM to about 18000 pM, about 700 pM to about 17000 pM, about 700 pM to about 16000 pM, about 700 pM to about 15000 pM, about 700 pM to about 14000 pM, about 700 pM to about 13000 pM, about 700 pM to about 12000 pM, about 700 pM to about 11000 pM, about 700 pM to about 10000 pM, about 700 pM to about 5000 pM, about 700 pM to about 4000 pM, about 700 pM to about 3000 pM, about 700 pM to about 2000 pM, about 700 pM to about 1000 pM, about 700 pM to about 900 pM, or about 700 pM to about 800 pM). In some embodiments, the peptides described herein have an EC50at the GCG receptor in the presence of BSA of about 700 pM, about 800 pM, about 900 pM, about 1000 pM, about 2000 pM, about 3000 pM, about 4000 pM, about 5000 pM, about 6000 pM, about 7000 pM, about 8000 pM, about 9000 pM, about 10,000 pM, about 11,000 pM, about 12,000 pM, about 13,000 pM, about 14,000 pM, about 15,000 pM, about 16,000 pM, about 17,000 pM, about 18,000 pM, about 19,000 pM, about 20,000 pM, about 30,000 pM, about 40,000 pM, about 50,000 pM, about 60,000 pM, about 70,000 pM, about 80,000 pM, about 90,000 pM, about 100,000 pM, about 110,000 pM, about 120,000 pM, about 130,000 pM, or about 140,000 pM.

[0136] In some embodiments, the peptides described herein have an EC50 at the GCG receptor in the presence of BSA that is above the limit of detection (e.g., binding of a peptide to the GCG receptor is too weak for a given assay to detect); in certain embodiments, peptides described herein are considered to be inactive at the GCG receptor in the presence of BSA.

[0137] In certain embodiments, the peptide represented by SEQ ID NO: 1 has an EC50 at the GCG receptor in the presence of BSA of about 16361 pM, such as about 16400 pM, such as about 16000 pM. In certain embodiments, the peptide represented by SEQ ID NO: 2 has an EC50at the GCG receptor in the presence of BSA of about 18383 pM, such as about 18400 pM, such as about 18000 pM. In certain embodiments, the peptide represented by SEQ ID NO: 3 has an EC50at the GCG receptor in the presence of BSA of about 8737 pM, such as 77 NAI-5000824421about 8740 pM, such as about 8700 pM, such as about 9000 pM. In certain embodiments, the peptide represented by SEQ ID NO: 4 has an EC50at the GCG receptor in the presence of BSA of about 19922 pM, such as about 19900 pM, such as about 20000 pM. In certain embodiments, the peptide represented by SEQ ID NO: 5 has an EC50at the GCG receptor in the presence of BSA of about 6512 pM, such as about 6510 pM, such as about 6500 pM, such as about 7000 pM. In certain embodiments, the peptide represented by SEQ ID NO: 6 has an EC50 at the GCG receptor in the presence of BSA of about 10716 pM, such as about 10700 pM, such as about 11000 pM. In some embodiments, the peptide represented by SEQ ID NO: 7 has an EC50 at the GCG receptor in the presence of BSA that is above the limit of detection (e.g., binding of a peptide to the GCG receptor is too weak for a given assay to detect). In some embodiments, the peptide represented by SEQ ID NO: 7 is considered to be inactive at the GCG receptor in the presence of BSA.

[0138] In certain embodiments, the peptides described herein have an EC50 at the GIP receptor in the presence of BSA of about 50 pM to about 2500 pM, or about 50 pM to about 1000 pM, or about 70 pM to about 150 pM (e.g., about 50 pM to about 1000 pM, about 60 pM to about 1000 pM, about 70 pM to about 1000 pM, about 80 pM to about 1000 pM, about 90 pM to about 1000 pM, about 100 pM to about 1000 pM, about 150 pM to about 1000 pM, about 200 pM to about 1000 pM, about 250 pM to about 1000 pM, about 300 pM to about 1000 pM, about 350 pM to about 1000 pM, about 400 pM to about 1000 pM, about 450 pM to about 1000 pM, about 500 pM to about 1000 pM, about 550 pM to about 1000 pM, about 600 pM to about 1000 pM, about 650 pM to about 1000 pM, about 700 pM to about 1000 pM, about 750 pM to about 1000 pM, about 800 pM to about 1000 pM, about 850 pM to about 1000 pM, about 900 pM to about 1000 pM, about 950 pM to about 1000 pM, about 50 pM to about 950 pM, about 50 pM to about 900 pM, about 50 pM to about 850 pM, about 50 pM to about 800 pM, about 50 pM to about 750 pM, about 50 pM to about 700 pM, about 50 pM to about 650 pM, about 50 pM to about 600 pM, about 50 pM to about 550 pM, about 50 pM to about 500 pM, about 50 pM to about 450 pM, about 50 pM to about 400 pM, about 50 pM to about 350 pM, about 50 pM to about 300 pM, about 50 pM to about 250 pM, about 50 pM to about 200 pM, about 50 pM to about 150 pM, about 50 pM to about 100 pM, about 50 pM to about 90 pM, about 50 pM to about 80 pM, about 50 pM to about 70 pM, or about 50 pM to about 60 pM). In some embodiments, the peptides described herein have an EC50 at the GIP receptor in the presence of BSA of about 50 pM, about 60 pM, about 70 pM, about 80 pM, about 90 pM, about 100 pM, about 150 pM, about 160 pM, about 170 pM, about 180 78 NAI-5000824421pM, about 190 pM, about 200 pM, about 250 pM, about 300 pM, about 350 pM, about 400 pM, about 450 pM, about 500 pM, or about 550 pM.

[0139] In certain embodiments, the peptide represented by SEQ ID NO:1 has an EC50 at the GIP receptor of about 73.8 pM, such as about 74 pM, such as about 70 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:2 has an EC50 at the GIP receptor of about 76 pM, such as about 80 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:3 has an EC50 at the GIP receptor of about 136 pM, such as about 140 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:4 has an EC50 at the GIP receptor of about 104.5 pM, such as about 106 pM, such as about 110 pM, such as about 100 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:5 has an EC50 at the GIP receptor of about 88 pM, such as about 90 pM, such as about 100 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:6 has an EC50 at the GIP receptor of about 75.7 pM, such as about 76 pM, such as about 80 pM, such as about 100 pM in the presence of BSA. In certain embodiments, the peptide represented by SEQ ID NO:7 has an EC50 at the GIP receptor of about 135 pM, such as about 130 pM, such as about 140 pM, such as about 100 pM in the presence of BSA.

[0140] In certain embodiments, the ratio of the EC50 at the GLP-1 receptor, GCG receptor, or GIP receptor in the presence of BSA to the corresponding EC50at the GLP-1 receptor, GCG receptor, or GIP receptor in the presence of casein (the “BSA shift”) is indicative of the degree to which the fatty acid-containing side chain in a peptide (e.g., the K* side chain) will bind serum albumin and thereby extend a peptide’s in vivo half-life in comparison to a comparable peptide lacking a fatty acid side chain. In some embodiments, a BSA shift of from about 10 to about 100, or about 10 to about 50, or about 10 to about 30 indicates potentially substantial half-life extension. In some embodiments, a BSA shift of about 50 to about 500, or about 100 to about 500, or greater than about 100 indicates potential loss of potency due to tight binding to BSA.

[0141] In some embodiments, the GLP-1 receptor BSA shift for the peptides disclosed herein is from about 5 to about 170, or about 10 to about 170 (e.g., about 10 to about170, about 20 to about170, about 30 to about170, about 40 to about170, about 50 to about170, about 60 to about170, about 70 to about170, about 80 to about170, about 90 to about170, about 100 to about170, about 110 to about170, about 120 to about170, about 130 to about170, about 140 to about170, about 150 to about 170, about 160 to about 170, about 10 to about 170, about 10 to about 160, about 10 to about 150, about 10 to about 140, about 10 79 NAI-5000824421to about 130, about 10 to about 120, about 10 to about 110, about 10 to about 100, about 10 to about 90, about 10 to about 80, about 10 to about 70, about 10 to about 60, about 10 to about 50, about 10 to about 40, about 10 to about 30, or about 10 to about 20). In some embodiments, the GLP-1 receptor BSA shift for the peptides disclosed herein is about 10, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120, about 130, about 140, about 150, about 160, or about 170.

[0142] In certain embodiments, the peptide represented by SEQ ID NO:1 has a GLP-1 receptor BSA shift of about 40. In certain embodiments, the peptide represented by SEQ ID NO:2 has a GLP-1 receptor BSA shift of about 53, such as about 50. In certain embodiments, the peptide represented by SEQ ID NO:3 has a GLP-1 receptor BSA shift of about about 165, such as about 160 or such as about 170. In certain embodiments, the peptide represented by SEQ ID NO:4 has a GLP-1 receptor BSA shift of about 80. In certain embodiments, the peptide represented by SEQ ID NO:5 has a GLP-1 receptor BSA shift of about 77, such as about 80. In certain embodiments, the peptide represented by SEQ ID NO:6 has a GLP-1 receptor BSA shift of about 82, such as about 80. In certain embodiments, the peptide represented by SEQ ID NO:7 has a GLP-1 receptor BSA shift of about 65, such as about 70, or such as about 60.

[0143] In some embodiments, the GCG receptor BSA shift for the peptides disclosed herein is from about 0 to about 130, or about 20 to about 50, or about 20 to about 30 (e.g., about 20 to about 100, about 25 to about 100, about 30 to about 100, about 35 to about 100, about 40 to about 100, about 45 to about 100, about 50 to about 100, about 55 to about 100, about 60 to about 100, about 65 to about 100, about 70 to about 100, about 75 to about 100, about 80 to about 100, about 85 to about 100, about 90 to about 100, about 95 to about 100, about 20 to about 95, about 20 to about 90, about 20 to about 85, about 20 to about 80, about 20 to about 75, about 20 to about 70, about 20 to about 65, about 20 to about 60, about 20 to about 55, about 20 to about 50, about 20 to about 45, about 20 to about 40, about 20 to about 35, about 20 to about 30, or about 20 to about 25). In some embodiments, the GCG receptor BSA shift for the peptides disclosed herein is about 100, about 95, about 90, about 85, about 80, about 75, about 70, about 65, about 60, about 55, about 50, about 45, about 40, about 35, about 30, about 25, or about 20. In some embodiments, the GCG receptor BSA shift for a peptide disclosed herein is not calculated because the peptide’s EC50 at the GCG receptor in the presence of casein and / or BSA is above the limit of detection of the assay used to measure it, and / or the peptide is considered inactive at the GCG receptor. 80 NAI-5000824421

[0144] In certain embodiments, the peptide represented by SEQ ID NO:1 has a GCG receptor BSA shift of about 15, such as about 20 or such as about 10. In certain embodiments, the peptide represented by SEQ ID NO:2 has a GCG receptor BSA shift of about 14, such as about 10. In certain embodiments, the peptide represented by SEQ ID NO:3 has a GCG receptor BSA shift of about about 24, such as about 20. In certain embodiments, the peptide represented by SEQ ID NO:4 has a GCG receptor BSA shift of about 17, such as about 20. In certain embodiments, the peptide represented by SEQ ID NO:5 has a GCG receptor BSA shift of about 17, such as about 20. In certain embodiments, the peptide represented by SEQ ID NO:6 has a GCG receptor BSA shift of about 13, such as about 10. In certain embodiments, the peptide represented by SEQ ID NOs: 7 has an uncalculated GCG receptor BSA shift because such peptide is considered inactive at the CGC receptor.

[0145] In some embodiments, the GIP receptor BSA shift for the peptides disclosed herein is from about 5 to about 100, or about 30 to about 100, or about 40 to about 90 (e.g., about 30 to about 100, about 35 to about 100, about 40 to about 100, about 45 to about 100, about 50 to about 100, about 55 to about 100, about 60 to about 100, about 65 to about 100, about 70 to about 100, about 75 to about 100, about 80 to about 100, about 85 to about 100, about 90 to about 100, about 95 to about 100, about 30 to about 95, about 30 to about 90, about 30 to about 85, about 30 to about 80, about 30 to about 75, about 30 to about 70, about 30 to about 65, about 30 to about 60, about 30 to about 55, about 30 to about 50, about 30 to about 45, about 30 to about 40, or about 30 to about 35). In some embodiments, the GIP receptor BSA shift for the peptides disclosed herein is about 100, about 95, about 90, about 85, about 80, about 75, about 70, about 65, about 60, about 55, about 50, about 45, about 40, about 35, or about 30.

[0146] In certain embodiments, the peptide represented by SEQ ID NO:1 has a GIP receptor BSA shift of about 25, such as about 30 or such as about 20. In certain embodiments, the peptide represented by SEQ ID NO:2 has a GIP receptor BSA shift of about 32, such as about 30. In certain embodiments, the peptide represented by SEQ ID NO:3 has a GIP receptor BSA shift of about 68, such as about 70. In certain embodiments, the peptide represented by SEQ ID NO:4 has a GIP receptor BSA shift of about 50. In certain embodiments, the peptide represented by SEQ ID NO:5 has a GIP receptor BSA shift of about 40. In certain embodiments, the peptide represented by SEQ ID NO:6 has a GIP receptor BSA shift of about 36, such as about 40. In certain embodiments, the peptide represented by SEQ ID NO:7 has a GIP receptor BSA shift of about 37, such as about 40. 81 NAI-5000824421

[0147] In certain embodiments, the peptides of the present disclosure demonstrate a lower GCG receptor activity (as indicated by high half maximal effective concentration (EC50) at the GCG receptor), while maintaining potent agonistic activity at the GLP-1 receptor (as indicated by low half maximal effective concentration (EC50) at the GLP-1 receptor), for example as assessed using a cell-based assay. In certain embodiments, the EC50 at the GLP-1 receptor, the GIP receptor, or the GCG receptor is determined in the presence of a blocking agent, such as a casein. In certain embodiments, the peptides described herein exhibit a high GCG receptor EC50 / GLP-1 receptor EC50ratio. In certain embodiments, the GCG receptor EC50 / GLP-1 receptor EC50 ratio is determined in a cell-based assay the presence of a blocking agent, such as a casein.

[0148] In certain embodiments, the peptides described herein have a GCG receptor EC50 / GLP-1 receptor EC50ratio in the presence of casein of about 1 to about 400, or about 100 to about 400 (e.g., about 100 to about 400, about 110 to about 400, about 120 to about 400, about 130 to about 400, about 140 to about 400, about 150 to about 400, about 160 to about 400, about 170 to about 400, about 180 to about 400, about 190 to about 400, about 200 to about 400, about 210 to about 400, about 220 to about 400, about 230 to about 400, about 240 to about 400, about 250 to about 400, about 260 to about 400, about 270 to about 400, about 280 to about 400, about 290 to about 400, about 300 to about 400, about 310 to about 400, about 320 to about 400, about 330 to about 400, about 340 to about 400, about 350 to about 400, about 360 to about 400, about 370 to about 400, about 380 to about 400, about 390 to about 400, about 100 to about 400, about 100 to about 390, about 100 to about 380, about 100 to about 370, about 100 to about 360, about 100 to about 350, about 100 to about 340, about 100 to about 330, about 100 to about 320, about 100 to about 310, about 100 to about 300, about 100 to about 290, about 100 to about 280, about 100 to about 270, about 100 to about 260, about 100 to about 250, about 100 to about 240, about 100 to about 230, about 100 to about 220, about 100 to about 210, about 100 to about 200, about 100 to about 190, about 100 to about 180, about 100 to about 170, about 100 to about 160, about 100 to about 150, about 100 to about 140, about 100 to about 130, about 100 to about 120, or about 100 to about 110). In some embodiments, the peptides described herein have a GCG receptorEC50 / GLP-1 receptor EC50 ratio in the presence of casein of about 1, about 2, about 4, about 6, about 8, about 10, about 12, about 15, about 20, about 25, about 30, about 35, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120, about 130, about 140, about 150, about 160, about 170, about 180, about 190, about 200, about 210, about 220, about 230, about 240, about 250, about 260, about 270, about 280, about 290, 82 NAI-5000824421about 300, about 310, about 320, about 330, about 340, about 350, about 360, about 370, about 380, about 390, or about 400.

[0149] In some embodiments, a peptide of the disclosure has a GCG receptor EC50 / GLP- 1 receptor EC50ratio in the presence of casein that is uncalculated (e.g., undefined) because the peptide is inactive at the GCG receptor (e.g., its EC50 at the GCG receptor is above the limit of detection of the assay being used to measure that EC50).

[0150] In certain embodiments, the peptide represented by SEQ ID NO:1 has a GCG receptor EC50 / GLP-1 receptor EC50ratio in the presence of casein of about 212, such as about 210, such as about 200. In certain embodiments, the peptide represented by SEQ ID NO: 2 has a GCG receptor EC50 / GLP-1 receptor EC50ratio in the presence of casein of about 308, such as about 310, such as about 300. In certain embodiments, the peptide represented by SEQ ID NO: 3 has a GCG receptor EC50 / GLP-1 receptor EC50ratio in the presence of casein of about 119, such as about 120, such as about 100. In certain embodiments, the peptide represented by SEQ ID NO: 4 has a GCG receptor EC50 / GLP-1 receptor EC50 ratio in the presence of casein of about 335, such as about 340, such as about 300. In certain embodiments, the peptide represented by SEQ ID NO: 5 has a GCG receptor EC50 / GLP-1 receptor EC50ratio in the presence of casein of about 129, such as about 130, such as about 100. In certain embodiments, the peptide represented by SEQ ID NO: 6 has a GCG receptor EC50 / GLP-1 receptor EC50ratio in the presence of casein of about 309, such as about 310, such as about 300. In certain embodiments, the peptide represented by SEQ ID NO: 7 has a GCG receptor EC50 / GLP-1 receptor EC50ratio in the presence of casein that is uncalculated (e.g., undefined) because the peptide is considered inactive at the GCG receptor (e.g., its EC50 at the GCG receptor is above the limit of detection of the assay being used to measure that EC50).

[0151] In certain embodiments, the peptides of the present disclosure demonstrate a lower GCG receptor activity (as indicated by high half maximal effective concentration (EC50) at the GCG receptor), while maintaining potent agonistic activity at the GIP receptor (as indicated by low half maximal effective concentration (EC50) at the GIP receptor), for example as assessed using a cell-based assay. In certain embodiments, the EC50 at the GLP-1 receptor, the GIP receptor, or the GCG receptor is determined in the presence of a blocking agent, such as a casein. In certain embodiments, the peptides described herein exhibit a high GCG receptor EC50 / GIP receptor EC50ratio. In certain embodiments, the GCG receptor EC50 / GIP receptor EC50 ratio is determined in a cell-based assay the presence of a blocking agent, such as a casein. 83 NAI-5000824421

[0152] In certain embodiments, the peptides described herein have a GCG receptor EC50 / GIP receptor EC50ratio in the presence of casein of about 10 to about 2500, or about 175 to about 600 (e.g., about 10 to about 2500, about 20 to about 2500, about 30 to about 2500, about 40 to about 2500, about 50 to about 2500, about 60 to about 2500, about 70 to about 2500, about 80 to about 2500, about 90 to about 2500, about 100 to about 2500, about 125 to about 2500, about 150 to about 2500, about 175 to about 2500, about 200 to about 2500, about 225 to about 2500, about 250 to about 2500, about 275 to about 2500, about 300 to about 2500, about 375 to about 2500, about 400 to about 2500, about 500 to about 2500, about 600 to about 2500, about 700 to about 2500, about 800 to about 2500, about 900 to about 2500, about 1000 to about 2500, about 1250 to about 2500, about 1500 to about 2500, about 1750 to about 2500, about 2000 to about 2500, about 2250 to about 2500, or about 10 to about 20, about 10 to about 30, about 10 to about 40, about 10 to about 50, about 10 to about 60, about 10 to about 70, about 10 to about 80, about 10 to about 90, about 10 to about 100, about 10 to about 125, about 10 to about 150, about 10 to about 175, about 10 to about 200, about 10 to about 225, about 10 to about 250, about 10 to about 275, about 10 to about 300, about 10 to about 375, about 10 to about 400, about 10 to about 500, about 10 to about 600, about 10 to about 700, about 10 to about 800, about 10 to about 900, about 10 to about 1000, about 10 to about 1250, about 10 to about 1500, about 10 to about 1750, about 10 to about 2000, about 10 to about 2250). In some embodiments, the peptides described herein have a GCG receptor EC50 / GIP receptor EC50 ratio in the presence of casein of about 10, about 20, about 25, about 27, about 30, about 32, about 35, about 37, about 40, about 42, about 45, about 48, about 50, about 52, about 55, about 57, about 59, about 60, about 65, about 70, about 75, about 80, about 90, about 100, about 125, about 130, about 132, about 135, about 140, about 150, about 165, about 175, about 185, about 200, about 225, about 230, about 235, about 240, about 250, about 255, about 260, about 265, about 270, about 275, about 280, about 285, about 300, about 310, about 320, about 323, about 325, about 330, about 335, about 338, about 340, about 350, about 375, about 400, about 500, about 550, about 560, about 570, about 600, about 700, about 730, about 735, about 750, about 800, about 850, about 900, about 1000, about 1100, about 1200, about 1250, about 1300, about 1400, about 1500, about 1750, about 2000, about 2250, or about 2500.

[0153] In some embodiments, a peptide of the disclosure has a GCG receptor EC50 / GIP receptor EC50ratio in the presence of casein that is uncalculated (e.g., undefined) because the peptide is inactive at the GCG receptor (e.g., its EC50 at the GCG receptor is above the limit of detection of the assay being used to measure that EC50). 84 NAI-5000824421

[0154] In certain embodiments, the peptide represented by SEQ ID NO:1 has a GCG receptor EC50 / GIP receptor EC50ratio of about 375, such as about 374, in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:2 has a GCG receptor EC50 / GIP receptor EC50ratio of about 550, such as about 539, in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:3 has a GCG receptor EC50 / GIP receptor EC50ratio of about 185, such as about 184, in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:4 has a GCG receptor EC50 / GIP receptor EC50ratio of about 560, such as about 558, in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:5 has a GCG receptor EC50 / GIP receptor EC50ratio of about 175, in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:6 has a GCG receptor EC50 / GIP receptor EC50 ratio of about 380, such as about 382, in the presence of casein.

[0155] In certain embodiments, the peptides of the present disclosure exhibit a GIP receptor EC50 / GLP-1 receptor EC50 ratio within a particular range. In certain embodiments, the GIP receptor EC50 / GLP-1 receptor EC50ratio is determined in a cell-based assay the presence of a blocking agent, such as a casein. In certain embodiments, the GIP receptor EC50 / GLP-1 receptor EC50ratio of the peptides described herein is indicative of the maintenance of potent agonistic activity both at the GIP receptor and the GLP-1 receptor.

[0156] In certain embodiments, the peptides described herein have a GIP receptor EC50 / GLP-1 receptor EC50 ratio in the presence of casein of about 0.2 to about 8, or about 0.2 to about 1 (e.g., about 0.2 to about 1.0, about 0.3 to about 1.0, about 0.4 to about 1.0, about 0.5 to about 1.0, about 0.6 to about 1.0, about 0.7 to about 1.0, about 0.8 to about 1.0, about 0.9 to about 1.0, about 0.2 to about 1.0, about 0.2 to about 0.9, about 0.2 to about 0.8, about 0.2 to about 0.7, about 0.2 to about 0.6, about 0.2 to about 0.5, about 0.2 to about 0.4, or about 0.2 to about 0.3). In certain embodiments, the peptides described herein have a GIP receptor EC50 / GLP-1 receptor EC50 ratio in the presence of casein of about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1.0, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, about 2.0, about 2.1, or about 2.2.

[0157] In certain embodiments, the peptide represented by SEQ ID NO:1 has a GIP receptor EC50 / GLP-1 receptor EC50 ratio of about 0.57, such as about 0.6 in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:2 has a GIP receptor EC50 / GLP-1 receptor EC50 ratio of about 0.57, such as about 0.6 in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:3 has a GIP receptor 85 NAI-5000824421EC50 / GLP-1 receptor EC50 ratio of about 0.65, such as about 0.7 in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:4 has a GIP receptor EC50 / GLP-1 receptor EC50 ratio of about 0.6 in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:5 has a GIP receptor EC50 / GLP-1 receptor EC50 ratio of about 0.73, such as about 0.7 in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:6 has a GIP receptor EC50 / GLP-1 receptor EC50 ratio of about 0.81, such as about 0.8 in the presence of casein. In certain embodiments, the peptide represented by SEQ ID NO:7 has a GIP receptor EC50 / GLP-1 receptor EC50 ratio of about 1.16, such as about 1.1, such as about 1 in the presence of casein.

[0158] In certain embodiments, when administered to a mouse, the peptides disclosed herein lead to a reduction in food intake and / or a reduction in body weight. In certain embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in food intake relative to vehicle (e.g., relative to a mouse not having been administered the peptide) or relative to baseline (e.g., relative to the subject mouse’s own food intake prior to administration of the peptide) that is measured one, two, or three days after administration of the peptide.

[0159] In some embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in food intake relative to vehicle (e.g., relative to a mouse not having been administered the peptide) or relative to baseline (e.g., relative to the subject mouse’s own food intake prior to administration of the peptide) of from about 45% to about 85%, or from about 48% to about 82% (e.g., about 45% to about 85%, about 50% to about 85%, about 55% to about 85%, about 60% to about 85%, about 65% to about 85%, about 70% to about 85%, about 75% to about 85%, about 80% to about 85%, about 45% to about 85%, about 45% to about 80%, about 45% to about 75%, about 45% to about 70%, about 45% to about 65%, about 45% to about 60%, about 45% to about 55%, or about 45% to about 50%). In some embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in food intake relative to vehicle (e.g., relative to a mouse not having been administered the peptide) or relative to baseline (e.g., relative to the subject mouse’s own food intake prior to administration of the peptide) of about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, or about 95%. In some embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in food intake relative to vehicle (e.g., relative to a mouse 86 NAI-5000824421not having been administered the peptide) or relative to baseline (e.g., relative to the subject mouse’s own food intake prior to administration of the peptide) measured one day after administration of the peptide.

[0160] In some embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in food intake relative to vehicle (e.g., relative to a mouse not having been administered the peptide) or relative to baseline (e.g., relative to the subject mouse’s own food intake prior to administration of the peptide) of from about 5% to about 60%, about 9% to about 55%(e.g., about 9% to about 60%, about 10% to about 60%, about 15% to about 60%, about 20% to about 60%, about 25% to about 60%, about 30% to about 60%, about 35% to about 60%, about 40% to about 60%, about 45% to about 60%, about 50% to about 60%, about 55% to about 60%, about 9% to about 60%, about 9% to about 55%, about 9% to about 50%, about 9% to about 45%, about 9% to about 40%, about 9% to about 35%, about 9% to about 30%, about 9% to about 25%, about 9% to about 20%, about 9% to about 15%, or about 9% to about 10%). In some embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in food intake relative to vehicle (e.g., relative to a mouse not having been administered the peptide) or relative to baseline (e.g., relative to the subject mouse’s own food intake prior to administration of the peptide) of about 9%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, or about 60%. In some embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in food intake relative to vehicle (e.g., relative to a mouse not having been administered the peptide) or relative to baseline (e.g., relative to the subject mouse’s own food intake prior to administration of the peptide) measured two days after administration of the peptide.

[0161] In certain embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in body weight relative to baseline (e.g., relative to the subject mouse’s own body weight prior to administration of the peptide) that is measured one, two, or three days after administration of the peptide.

[0162] In certain embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in body weight relative to baseline (e.g., relative to the subject mouse’s own body weight prior to administration of the peptide) of from about 5% to about 15%, or about 5% to about 10% (e.g., about 5% to about 15%, or about 6% to about 15%, or 87 NAI-5000824421about 7% to about 15%, or about 8% to about 15%, or about 9% to about 15%, or about 10% to about 15%, or about 11% to about 15%, or about 12% to about 15%, or about 13% to about 15%, or about 14% to about 15%, or 5% to about 14%, or about 5% to about 13%, or about 5% to about 12%, or about 5% to about 11%, or about 5% to about 10%, or about 5% to about 9%, or about 5% to about 8%, or about 5% to about 7%, or about 5% to about 6%) measured one or two days after administration. In some embodiments, administration of a peptide of the disclosure to a subject (e.g., a mouse) leads to a percent reduction in body weight relative to baseline (e.g., relative to the subject’s own body weight prior to administration of the peptide) of about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 13%, about 14%, or about 15% measured one or two days after administration. In certain embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in body weight relative to baseline (e.g., relative to the subject mouse’s own body weight prior to administration of the peptide) of from about 5% to about 15% measured one or two days after administration of the peptide. In certain embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in body weight relative to baseline (e.g., relative to the subject mouse’s own body weight prior to administration of the peptide) of from about 8% to about 13% measured one day after administration of the peptide. In certain embodiments, administration of a peptide of the disclosure to a mouse leads to a percent reduction in body weight relative to baseline (e.g., relative to the subject mouse’s own body weight prior to administration of the peptide) of from about 7% to about 14% measured two days after administration of the peptide.

[0163] In some embodiments, administration of the peptide represented by SEQ ID NO: 1 to a mouse leads to about an 82% and about a 49% food intake reduction relative to baseline, at day 1 and day 2 respectively; and about an 8% and about a 10% body weight reduction relative to baseline at day 1 and 2 respectively. In some embodiments, administration of the peptide represented by SEQ ID NO: 3 to a mouse leads to about a 48% and about a 9% food intake reduction relative to baseline, at day 1 and day 2 respectively; and about a 6% and about a 5% body weight reduction relative to baseline at day 1 and 2 respectively. In some embodiments, administration of the peptide represented by SEQ ID NO: 4 to a mouse leads to about an 68% and about a 49% food intake reduction relative to baseline, at day 1 and day 2 respectively; and about an 8% and about a 9% body weight reduction relative to baseline at day 1 and 2 respectively. 5.4 Methods of treatments and Use of the Peptides 88 NAI-5000824421

[0164] Provided herein are methods of treatment, e.g., including administering any of the peptides described herein, a compound comprising any of the peptides described herein, or a pharmaceutical composition comprising the same, to a subject in need thereof, such as a subject who is at risk of having a disease or disorder, or has a disease or disorder. In some aspects, also provided are methods that involve administering any of the peptides or pharmaceutical compositions to a subject in need thereof. The described peptides or pharmaceutical compositions are useful in treating a variety of diseases and disorders in the subject, or in alleviating one or more symptoms or conditions, such as in reducing body fat, reducing body weight, and / or increasing weight loss in the subject. Such methods and uses include therapeutic methods and uses or prophylactic methods and uses, for example, to prevent a disease, disorder or condition in a subject. In some embodiments, the peptides or pharmaceutical compositions, are administered in an effective amount to treat or prevent the disease, disorder or condition. Uses include uses of the peptides or pharmaceutical compositions, in such methods, treatments, prophylaxis and / or alleviating symptoms or conditions, and in the preparation of a medicament in order to carry out such methods, treatments, prophylaxis and / or alleviating symptoms or conditions. In some embodiments, the methods are carried out by administering the peptides or pharmaceutical compositions, to the subject having or suspected of having the disease, disorder or condition. In some embodiments, the methods thereby treat the disease, disorder or condition in the subject.

[0165] In one aspect, provided herein are methods of treating a disease or disorder. In certain embodiments, provided herein is a method of treating a disease or disorder in a subject comprising administering to the subject a therapeutically effective amount of a peptide provided herein (e.g., a peptide as described in Section 5.2) or a compound comprising a peptide provide herein. In another aspect, provided herein are peptides or compounds (e.g., a peptide as described in Section 5.2 or a compound comprising the same) for use in treating a disease or disorder. In certain embodiments, provided herein are peptides or compounds (e.g., a peptide as described in Section 5.2 or a compound comprising the same) for use in a therapy. In yet another aspect, provided herein is use of the peptide provided herein (e.g., a peptide as described in Section 5.2) or a compound comprising a peptide described herein in the manufacture of a medicament for treating a disease or disorder.

[0166] In certain embodiments, the disease or disorder is selected from diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader- 89 NAI-5000824421Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction- associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA). 5.4.1 Methods of treatments

[0167] In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including chronic weight management, reducing body 90 NAI-5000824421weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader- Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction- associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of Formula (I). In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including 91 NAI-5000824421chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of Formula (I). 92 NAI-5000824421

[0168] In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader- Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction- associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a peptide 93 NAI-5000824421comprising or consisting of the amino acid sequence of Formula (Ia). In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the 94 NAI-5000824421subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of Formula (Ia).

[0169] In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader- Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction- associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including 95 NAI-5000824421dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of Formula (Ib). In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine 96 NAI-5000824421withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of Formula (Ib).

[0170] In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader- Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction- associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine 97 NAI-5000824421cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of Formula (Ic). In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal 98 NAI-5000824421fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of Formula (Ic).

[0171] In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader- Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction- associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); 99 NAI-5000824421idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of Formula (Id). In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; 100 NAI-5000824421chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of Formula (Id).

[0172] In certain embodiments, provided herein is a method of treating a disease or disorder in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, provided herein is a method of treating a disease or disorder in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre- diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass 101 NAI-5000824421graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7. In certain embodiments, provided herein is a method of treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, 102 NAI-5000824421myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7.

[0173] In certain embodiments, provided herein is a method of treating obesity in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a method of treating obesity in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1.

[0174] In certain embodiments, provided herein is a method of treating obesity in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a method of treating obesity in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2. 103 NAI-5000824421

[0175] In certain embodiments, provided herein is a method of treating obesity in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a method of treating obesity in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3.

[0176] In certain embodiments, provided herein is a method of treating obesity in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a method of treating obesity in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6.

[0177] In certain embodiments, provided herein is a method of treating type 2 diabetes in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a method of treating type 2 diabetes in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1.

[0178] In certain embodiments, provided herein is a method of treating type 2 diabetes in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a method of treating type 2 diabetes in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2.

[0179] In certain embodiments, provided herein is a method of treating type 2 diabetes in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a method of treating type 2 diabetes in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically 104 NAI-5000824421acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3.

[0180] In certain embodiments, provided herein is a method of treating type 2 diabetes in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a method of treating type 2 diabetes in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6.

[0181] In certain embodiments, provided herein is a method of treating dyslipidemia in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a method of treating dyslipidemia in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1.

[0182] In certain embodiments, provided herein is a method of treating dyslipidemia in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a method of treating dyslipidemia in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2.

[0183] In certain embodiments, provided herein is a method of treating dyslipidemia in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a method of treating dyslipidemia in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3.

[0184] In certain embodiments, provided herein is a method of treating dyslipidemia in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a method of treating dyslipidemia in a subject comprising 105 NAI-5000824421administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6.

[0185] In certain embodiments, provided herein is a method of treating metabolic syndrome in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a method of treating metabolic syndrome in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1.

[0186] In certain embodiments, provided herein is a method of treating metabolic syndrome in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a method of treating metabolic syndrome in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2.

[0187] In certain embodiments, provided herein is a method of treating metabolic syndrome in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a method of treating metabolic syndrome in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3.

[0188] In certain embodiments, provided herein is a method of treating metabolic syndrome in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a method of treating metabolic syndrome in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6.

[0189] In certain embodiments, provided herein is a method of treating nonalcoholic fatty liver disease (NAFLD) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID 106 NAI-5000824421NO:1. In certain embodiments, provided herein is a method of treating nonalcoholic fatty liver disease (NAFLD) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1.

[0190] In certain embodiments, provided herein is a method of treating nonalcoholic fatty liver disease (NAFLD) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a method of treating nonalcoholic fatty liver disease (NAFLD) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2.

[0191] In certain embodiments, provided herein is a method of treating nonalcoholic fatty liver disease (NAFLD) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a method of treating nonalcoholic fatty liver disease (NAFLD) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3.

[0192] In certain embodiments, provided herein is a method of treating nonalcoholic fatty liver disease (NAFLD) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a method of treating nonalcoholic fatty liver disease (NAFLD) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6.

[0193] In certain embodiments, provided herein is a method of treating metabolic dysfunction-associated steatohepatitis (MASH) or nonalcoholic steatohepatitis (NASH) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a method of treating metabolic dysfunction-associated steatohepatitis (MASH) or nonalcoholic steatohepatitis (NASH) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1. 107 NAI-5000824421

[0194] In certain embodiments, provided herein is a method of treating metabolic dysfunction-associated steatohepatitis (MASH) or nonalcoholic steatohepatitis (NASH) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a method of treating metabolic dysfunction-associated steatohepatitis (MASH) or nonalcoholic steatohepatitis (NASH) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2.

[0195] In certain embodiments, provided herein is a method of treating metabolic dysfunction-associated steatohepatitis (MASH) or nonalcoholic steatohepatitis (NASH) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a method of treating metabolic dysfunction-associated steatohepatitis (MASH) or nonalcoholic steatohepatitis (NASH) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3.

[0196] In certain embodiments, provided herein is a method of treating metabolic dysfunction-associated steatohepatitis (MASH) or nonalcoholic steatohepatitis (NASH) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a method of treating metabolic dysfunction-associated steatohepatitis (MASH) or nonalcoholic steatohepatitis (NASH) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6.

[0197] In certain embodiments, provided herein is a method of treating cardiovascular diseases in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a method of treating cardiovascular diseases in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1. 108 NAI-5000824421

[0198] In certain embodiments, provided herein is a method of treating cardiovascular diseases in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a method of treating cardiovascular diseases in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2.

[0199] In certain embodiments, provided herein is a method of treating cardiovascular diseases in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a method of treating cardiovascular diseases in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3.

[0200] In certain embodiments, provided herein is a method of treating cardiovascular diseases in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a method of treating cardiovascular diseases in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6.

[0201] In certain embodiments, provided herein is a method of treating obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a method of treating obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1.

[0202] In certain embodiments, provided herein is a method of treating obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a method of treating obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount 109 NAI-5000824421of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2.

[0203] In certain embodiments, provided herein is a method of treating obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a method of treating obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3.

[0204] In certain embodiments, provided herein is a method of treating obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a method of treating obstructive sleep apnea (OSA) in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6.

[0205] In certain embodiments, provided herein is a method of treating chronic kidney disease in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a method of treating chronic kidney disease in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1.

[0206] In certain embodiments, provided herein is a method of treating chronic kidney disease in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a method of treating chronic kidney disease in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2.

[0207] In certain embodiments, provided herein is a method of treating chronic kidney disease in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a method of treating chronic kidney disease in a 110 NAI-5000824421subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3.

[0208] In certain embodiments, provided herein is a method of treating chronic kidney disease in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6. In certain embodiments, provided herein is a method of treating chronic kidney disease in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6.

[0209] In certain embodiments, provided herein is a method of treating Alzheimer’s disease in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1. In certain embodiments, provided herein is a method of treating Alzheimer’s disease in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1.

[0210] In certain embodiments, provided herein is a method of treating Alzheimer’s disease in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2. In certain embodiments, provided herein is a method of treating Alzheimer’s disease in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2.

[0211] In certain embodiments, provided herein is a method of treating Alzheimer’s disease in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3. In certain embodiments, provided herein is a method of treating Alzheimer’s disease in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3.

[0212] In certain embodiments, provided herein is a method of treating Alzheimer’s disease in a subject comprising administering to the subject a therapeutically effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6. 111 NAI-5000824421In certain embodiments, provided herein is a method of treating Alzheimer’s disease in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6. 5.4.2 Peptides for use

[0213] In another aspect, provided herein are peptides for use in treating a disease or disorder. In certain embodiments, provided herein are peptides for use in a therapy. In another aspect, provided herein are peptides (e.g., a peptide as described in Section 5.2) for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet- Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome 112 NAI-5000824421(PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA).

[0214] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of Formula (I), for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction– associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; 113 NAI-5000824421back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of Formula (I), for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; 114 NAI-5000824421back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA).

[0215] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of Formula (Ia), for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction– associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; 115 NAI-5000824421back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of Formula (Ia), for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; 116 NAI-5000824421back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA).

[0216] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of Formula (Ib), for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction– associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; 117 NAI-5000824421back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of Formula (Ib), for use in treating In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of Formula (Ia), for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; 118 NAI-5000824421gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA).

[0217] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of Formula (Ic), for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction– associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; 119 NAI-5000824421gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of Formula (Ic), for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; 120 NAI-5000824421gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA).

[0218] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of Formula (Id), for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction– associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; 121 NAI-5000824421gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of Formula (Id), for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; 122 NAI-5000824421gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA).

[0219] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7, for use in treating a disease or disorder. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7, for use in treating a disease or disorder. In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7, for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader- Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction- associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart 123 NAI-5000824421failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA). In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7, for use in treating diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader- Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction- associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events 124 NAI-5000824421(MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA).

[0220] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 for use in treating obesity. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 for use in treating obesity.

[0221] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2 for use in treating obesity. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2 for use in treating obesity.

[0222] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3 for use in treating obesity. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3 for use in treating obesity.

[0223] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6 for use in treating obesity. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6 for use in treating obesity. 125 NAI-5000824421

[0224] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 for use in treating type 2 diabetes. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 for use in treating type 2 diabetes.

[0225] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2 for use in treating type 2 diabetes. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2 for use in treating type 2 diabetes.

[0226] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3 for use in treating type 2 diabetes. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3 for use in treating type 2 diabetes.

[0227] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6 for use in treating type 2 diabetes. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6 for use in treating type 2 diabetes.

[0228] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 for use in treating dyslipidemia. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 for use in treating dyslipidemia.

[0229] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2 for use in treating dyslipidemia. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:2 for use in treating dyslipidemia.

[0230] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3 for use in treating dyslipidemia. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:3 for use in treating dyslipidemia.

[0231] In certain embodiments, provided herein is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6 for use in treating dyslipidemia. In certain embodiments, provided herein is a pharmaceutically acceptable salt of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:6 for use in treating dyslipidemia.

[0232] In certain embodiments, provided her...

Claims

WHAT IS CLAIMED:

1. A peptide comprising an amino acid sequence of Formula (I) (SEQ ID NO:8): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(I), wherein: Rx is Gly; Ry is selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3is selected from Gln and Glu; R6 is selected from amF and Phe; R15is selected from Asp and Glu; R16 is selected from K*, Lys, amK, and Glu; R17is selected from Lys and Gln; R20 is selected from K* and Aib; R21is selected from Ala and Glu; R24 is selected from K*, Glu and D-Glu; and R25is selected from amY and Tyr; and wherein: ;amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X; X is -CO2H or -P(O)(OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; q is 14-20; and one and only one K* is present in Formula (I); or a pharmaceutically acceptable salt thereof.

2. The peptide of claim 1, wherein the amino acid sequence of Formula (I) is amino acid sequence of Formula (Ia) (SEQ ID NO:9): 202 NAI-5000824421Tyr-Aib-R3-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-R20-R21- Phe-Ile-R24-Tyr-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ia), wherein: Rx is Gly; Ryis selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3 is selected from Gln and Glu; R15is selected from Asp and Glu; R16 is selected from K*, Lys, amK, and Glu; R17is selected from Lys and Gln; R20 is selected from K* and Aib; R21is selected from Ala and Glu; and R24 is selected from K*, Glu, and D-Glu; and wherein: ;amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X; X is -CO2H or -P(O)(OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; q is 14-20; and one and only one K* is present in Formula (Ia).

3. The peptide of claim 1, wherein the amino acid sequence of Formula (I) is amino acid sequence of Formula (Ib) (SEQ ID NO:10): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-K*-R17-Ala-Gln-Aib-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ib), wherein: Rx is Gly; 203 NAI-5000824421Ry is selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3is selected from Gln and Glu; R6 is selected from amF and Phe; R15is selected from Asp and Glu; R17 is selected from Lys and Gln; R21is selected from Ala and Glu; R24 is selected from Glu and D-Glu; and R25is selected from amY and Tyr; and wherein: ; amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X;- or - (OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; and q is 14-20.

4. The peptide of claim 1, wherein the amino acid sequence of Formula (I) is amino acid sequence of Formula (Ic) (SEQ ID NO:11): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-K*-R21- Phe-Ile-R24-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2(Ic), wherein: Rx is Gly; Ryis selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3 is selected from Gln and Glu; R6is selected from amF and Phe; R15 is selected from Asp and Glu; R16is selected from Lys, amK and Glu; R17 is selected from Lys and Gln; 204 NAI-5000824421R21 is selected from Ala and Glu; R24is selected from Glu and D-Glu; and R25 is selected from amY and Tyr; and wherein: ; amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X;- - (OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; and q is 14-20.

5. The peptide of claim 1, wherein the amino acid sequence of Formula (I) is amino acid sequence of Formula (Id) (SEQ ID NO:12): Tyr-Aib-R3-Gly-Thr-R6-Thr-Ser-Asp-Tyr-Ser-Ile-amL-Leu-R15-R16-R17-Ala-Gln-Aib-R21- Phe-Ile-K*-R25-Leu-Leu-Glu-Rx-Ry-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 (Id), wherein: Rxis Gly; Ry is selected from Arg, Lys, Glu, Aib, Gly, and Gln; R3is selected from Gln and Glu; R6 is selected from amF and Phe; R15is selected from Asp and Glu; R16 is selected from Lys, amK, and Glu; R17is selected from Lys and Gln; R21 is selected from Ala and Glu; and R25is selected from amY and Tyr; and wherein: 205 NAI-5000824421; (2-amino-ethoxy)-ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X; s -CO2 or - (O)(OH)2; a, b, c, and d are each independently 0, 1, 2, or 3, with the provisos that: when a is not 0, b is 0; and when b is not 0, a is 0; and q is 14-20.

6. The peptide of claim 1 or 2, wherein R16 is K*.

7. The peptide of any one of claims 1, 2, 4, and 5, wherein R16 is Lys.

8. The peptide of any one of claims 1, 2, 4, and 5, wherein R16 is amK.

9. The peptide of any one of claims 1, 2, 4, and 5, wherein R16 is Glu.

10. The peptide of claim 1 or 2, wherein R20is K*.

11. The peptide of any one of claims 1, 2, and 7 to 9, wherein R20is Aib.

12. The peptide of any one of claim 1 or 2, wherein R24is K*.

13. The peptide of any one of claims 1 to 4, and 6 to 11, wherein R24is Glu.

14. The peptide of any one of claims 1 to 4, and 6 to 11, wherein R24is D-Glu.

15. The peptide of any one of claims 1 to 14, wherein Ryis Arg.

16. The peptide of any one of claims 1 to 14, wherein Ryis Lys. 206 NAI-500082442117. The peptide of any one of claims 1 to 14, wherein Ry is Glu.

18. The peptide of any one of claims 1 to 14, wherein Ry is Aib.

19. The peptide of any one of claims 1 to 14, wherein Ry is Gly.

20. The peptide of any one of claims 1 to 14, wherein Ry is Gln.

21. The peptide of any one of claims 1 to 20, wherein R3 is Gln.

22. The peptide of any one of claims 1 to 20, wherein R3 is Glu.

23. The peptide of any one of claims 1 and 3 to 22, wherein R6 is Phe.

24. The peptide of any one of claims 1 and 3 to 22, wherein R6is amF.

25. The peptide of any one of claims 1 to 24, wherein R15is Asp.

26. The peptide of any one of claims 1 to 24, wherein R15is Glu.

27. The peptide of any one of claims 1 to 26, wherein R17is Lys.

28. The peptide of any one of claims 1 to 26, wherein R17is Gln.

29. The peptide of any one of claims 1 to 28, wherein R21is Ala.

30. The peptide of any one of claims 1 to 28, wherein R21is Glu.

31. The peptide of any one of claims 1 and 3 to 30, wherein R25 is amY.

32. The peptide of any one of claims 1 and 3 to 30, wherein R25 is Tyr.

33. The peptide of any one of claims 1 to 32, wherein: (i) a is 0, b is 2, c is 1, d is 0; 207 NAI-5000824421(ii) a is 0, b is 2, c is 2, d is 0; (iii) a is 0, b is 1, c is 1, d is 0; (iv) a is 2, b is 0, c is 1, d is 1; (v) a is 0, b is 2, c is 1, d is 1; or (vi) a is 1, b is 0, c is 1, d is 1.

34. The peptide of any one of claims 1 to 33, wherein q is 14, 16, 18, or 20.

35. The peptide of any one of claims 1 to 33, wherein q is 15, 17, or 19.

36. The peptide of any one of claims 1 to 35, wherein Rz is -(2-[2-(2-amino-ethoxy)- ethoxy]-acetyl)b-(gGlu)c-(Trx)d-(CO)-(CH2)q-X.

37. The peptide of claim 36, wherein b is 1 or 2 and c is 1 or 2.

38. The peptide of any one of claims 1 to 34, 36, and 37, wherein the Rz is -(2-[2-(2- amino-ethoxy)-ethoxy]-acetyl)2-(gGlu)-(CO)-(CH2)18-CO2H.

39. A peptide consisting of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:

7.

40. A peptide comprising the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:

7.

41. A compound comprising the peptide of any one of claims 1 to 40.

42. A pharmaceutically acceptable salt of the peptide of any one of claims 2 to 40 or the compound of claim 41.

43. A formulation comprising the peptide of any one of claims 1 to 40 or the compound of claim 41, in admixture with one or more pharmaceutically acceptable excipients.

44. A formulation comprising the pharmaceutically acceptable salt of claim 42, in admixture with one or more pharmaceutically acceptable excipients. 208 NAI-500082442145. A method of treating a disease or disorder in a subject comprising administering to the subject a therapeutically effective amount of the peptide of any one of claims 1 to 40, the compound of claim 41, the pharmaceutically acceptable salt of claim 42, or the formulation of claim 43 or 44.

46. The method of claim 45, wherein the disease or disorder is selected from: diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader- Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction- associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); 209 NAI-5000824421idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA).

47. The peptide of any one of claims 1 to 40, the compound of claim 41, the pharmaceutically acceptable salt of claim 42, or the formulation of claim 43 or 44 for use in treating a disease or disorder selected from: diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader-Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction-associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram-negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; 210 NAI-5000824421back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA).

48. Use of the peptide of any one of claims 1 to 40, the compound of claim 41, the pharmaceutically acceptable salt of claim 42, or the formulations of claim 43 or 44 in the manufacture of a medicament for treating a disease or disorder selected from: diseases associated with excess body weight including chronic weight management, reducing body weight, reducing food intake, and / or inducing satiety; obesity, hypothalamic obesity, Prader- Willi syndrome; rare genetic causes of obesity such as Bardet-Biedl syndrome (BBS); bulimia nervosa; type 2 diabetes including type 2 diabetes associated with insulin resistance; gestational diabetes mellitus (GDM); insulin resistance syndrome; pre-diabetes; non-insulin dependent diabetes; diabetic retinopathy; impaired glucose tolerance; reduction in HbA1C; hyperglycemia; improving glycemic control; insulin resistance syndrome; diabetic retinopathy; dyslipidemia; metabolic syndrome; nonalcoholic fatty liver disease (NAFLD); metabolic dysfunction–associated fatty liver disease (MAFLD); metabolic dysfunction- associated steatohepatitis (MASH); nonalcoholic steatohepatitis (NASH); liver fibrosis; primary sclerosing cholangitis; biliary fibrosis; primary biliary cirrhosis; cardiovascular diseases; atherosclerotic cardiovascular disease (ASCVD); heart failure (for example, HFpEF); peripheral artery disease; atherosclerosis; arteriosclerosis; hypertension; hyperlipidemia; dyslipidemia; hypercholesteremia (reducing LDL cholesterol and / or triglycerides); atrial fibrillation; coronary heart disease; stroke; major adverse cardiac events (MACE) including death, myocardial infarction, stroke, hospitalization because of heart failure, revascularization, percutaneous coronary intervention, and coronary artery bypass graft; atherosclerosis; atherosclerotic cardiovascular disease (ASCVD); rheumatologic or inflammatory disorders; skin inflammation; acute inflammatory response due to gram- negative bacteria in the colon; sarcopenia; gallbladder disease; diabetic kidney disease; chronic kidney disease (CKD); lipohypertrophy; neuroinflammations (for example, Wolfram Syndrome); rheumatoid arthritis; depression (alleviating depressive symptoms); fatigue; myalgic encephalomyelitis (chronic fatigue syndrome); anxiety; stress relief; Parkinson’s 211 NAI-5000824421Disease; Alzheimer’s disease; gastroesophageal reflux disease; inflammatory bowel disease (IBD); microbiome dysbiosis; male infertility; hypogonadism; polycystic ovary syndrome (PCOS); physical impairment; back pain; dyslipidemia; gall stones; gout; psoriasis; thrombosis; lung embolism; asthma; chronic obstructive pulmonary disease (COPD); idiopathic fibrosis; colon cancer; breast cancer; pancreatic cancer; acute pancreatitis; pancreatic fibrosis; kidney cancer; renal fibrosis; hepatic steatosis; prostate cancer; uterine cancer; esophageal cancer; urogenital infection and incontinence; increasing bone formation; osteoarthritis; addiction / nicotine withdrawal syndrome; alcohol use disorder (including dependence and binge drinking); sleep apnea; and obstructive sleep apnea (OSA).

49. A method of reducing body fat in a subject comprising administering to the subject an effective amount of the peptide of any one of claims 1 to 40, the compound of claim 41, the pharmaceutically acceptable salt of claim 42, or the formulation of claim 43 or 44.

50. A method of reducing body weight and / or increasing weight loss in a subject comprising administering to the subject an effective amount of the peptide of any one of claims 1 to 40, the compound of claim 41, the pharmaceutically acceptable salt of claim 42, or the formulation of claim 43 or 44.

51. The peptide of any one of claims 1 to 40, the compound of claim 41, the pharmaceutically acceptable salt of claim 42, or the formulation of claim 43 or 44 for use in reducing body fat in a subject.

52. The peptide of any one of claims 1 to 40, the compound of claim 41, the pharmaceutically acceptable salt of claim 42, or the formulation of claim 43 or 44 for use in reducing body weight and / or increasing weight loss in a subject.

53. Use of the peptide of any one of claims 1 to 40, the compound of claim 41, the pharmaceutically acceptable salt of claim 42, or the formulation of claim 43 or 44 in the manufacture of a medicament for reducing body fat in a subject.

54. Use of the peptide of any one of claims 1 to 40, the compound of claim 41, the pharmaceutically acceptable salt of claim 42, or the formulation of claim 43 or 44 in the 212 NAI-5000824421manufacture of a medicament for reducing body weight and / or increasing weight loss in a subject. 213 NAI-5000824421

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