FGF23 degrader conjugates

Abstract

The present invention relates to a conjugate or a pharmaceutically acceptable salt thereof comprising at least one moiety -D, which is conjugated via at least one moiety -L1(-L2)a- to at least one moiety -Z, wherein -L1- is conjugated to -D, and wherein -D is a drug moiety comprising at least one receptor-binding moiety -RB and at least one target-binding moiety -TB binding to FGF23; -L1- is a linker moiety that is covalently and reversibly conjugated to -D; -L2- is a spacer moiety; a is 1 or 0; and -Z is a polymeric moiety. It also relates to pharmaceutical compositions comprising such conjugated, to their use and related aspects.

Description

[0001] Ascendis Pharma A / S CPX75237PC 12 January 2026 FGF23 Degrader Conjugates

[0002] The present invention relates to a conjugate or a pharmaceutically acceptable salt thereof comprising at least one moiety -D, which is conjugated via at least one moiety -LJ(-L2)a- to at least one moiety -Z, wherein -L1- is conjugated to -D, and wherein -D is a drug moiety comprising at least one receptor-binding moiety -RB and at least one target-binding moiety -TB binding to FGF23; -L1- is a linker moiety that is covalently and reversibly conjugated to -D; -L2- is a spacer moiety; a is 1 or 0; and -Z is a polymeric moiety. It also relates to pharmaceutical compositions comprising such conjugated, to their use and related aspects.

[0003] Conventional protein-directed therapeutics may be used to treat diseases by modulating protein function or recruiting immune effectors to a target site. However, many potential therapeutic targets have molecular functions that are either incompletely understood or not readily inhibited, and thus are not druggable by conventional therapeutic approaches. Targeted protein degradation (TPD) is an approach for treating disease involving disease-causing proteins, peptides or hormones by selectively degrading the target rather than inhibiting its function, such as through traditional chemical or biological inhibition. TPD can be used to modulate targets considered undruggable by conventional modalities as well as improve on efficacy compared to conventional drugs by rapid effect, higher efficacy, lack of drug resistance and high specific! ty(Wells, J.A.et al., Nat Rev Drug Discov 23, 126-140 (2024)).

[0004] More recently, several approaches have been described to target the degradation of extracellular targets with bifunctional molecules. Such bifunctional molecules comprise a first moiety capable of binding to an extracellular target and a second moiety capable of binding to a membrane-bound receptor associated with a degradation pathway.

[0005] One example of a receptor associated with a degradation pathway is the asialoglycoprotein receptor (ASGPR), which is a Ca2+-dependent lectin that is primarily expressed in parenchymal hepatocyte cells. The main role of ASGPR is to help regulate serum glycoprotein levels by mediating endocytosis of desialylated glycoproteins, which are also referred to as asialoglycoproteins. ASGPR binds ligands with a terminal galactose or N-acetylgalactosamine. Asialoglycoproteins bind to ASGPRs and are then cleared by receptor-mediated endocytosis. The receptor and the protein are dissociated in the acidic endosomal compartment and the protein is eventually degraded by lysosomes.Ascendis Pharma A / S CPX75237PC 12 January 2026

[0006] Receptor-mediated degradation via ASGPR has been proven efficient at rapidly removing targets from circulation or the cell surface. However, current bifunctional molecules degrading a target via ASGPR are limited by this rapid mode of action as not only the target but also the bifunctional molecule is degraded rapidly. Consequently, current bifunctional molecules suffer from a short half-life. The short half-life of current bifunctional molecules is previously documented in W02014023709A1, where an ASGPR targeted antibody degrading IFNa was not detected at any timepoint monitored after subcutaneous injection in plasma samples despite having a Fc domain, due to the fast internalization into liver cells. Similarly smaller molecular weight degrader constructs have very short half-lives of less than 1 hour in serum (see for example Caianiello, et al., Nat Chem Biol 17, 947-953 (2021)) prohibiting their application in several diseases and against targets where sustained degradation is required.

[0007] Fibroblast growth factor 23 (FGF23) is a protein belonging to the family of fibroblast growth factors, which participates in the regulation of phosphate in plasma and vitamin D metabolism. FGF23 decreases reabsorption of phosphate in the kidney, which means phosphate is excreted in urine. FGF23 is secreted by osteocytes in response to increased calcitriol and phosphate. FGF23 acts on the kidneys by decreasing the expression of NPT2, a sodium-phosphate cotransporter in the proximal tube.

[0008] Increased FGF23 activity can result in rickets, such as X-linked hypophosphatemia (XLH). XLH can cause bone deformity including short stature and genu varum, and is associated with mutation in the PHEX gene. Conventional therapy consists of medications such as oral phosphate and calcitriol and unwanted effects of this therapy include secondary hypoparathyroidism, nephrocalcinosis, kidney stones and cardiovascular abnormalities. In 2018 a monoclonal antibody directed against FGF23 called burosumab was approved. Administration is once every two weeks via subcutaneous administration.

[0009] However, improvements in treatments of XLH are desirable and it is therefore an object of the present invention to at least partially overcome the above-mentioned limitations.

[0010] This object is achieved with a conjugate or a pharmaceutically acceptable salt thereof comprising at least one moiety -D, which is conjugated via at least one moiety -LJ(-L2)a- to at least one moiety -Z, wherein -L1- is conjugated to -D, and whereinAscendis Pharma A / S CPX75237PC 12 January 2026 -D is a drug moiety comprising at least one receptor-binding moiety -RB and at least one target-binding moiety -TB binding to FGF23;

[0011] -L1- is a linker moiety that is covalently and reversibly conjugated to -D;

[0012] -L2- is a spacer moiety;

[0013] a is 1 or 0; and

[0014] -Z is a polymeric moiety.

[0015] The conjugates of the present invention release the respective drug in a sustained manner.

[0016] The present invention relates to conjugates that release a drug comprising at least one receptorbinding moiety -RB and at least one target-binding moiety -TB binding to FGF23 useful for the degradation of FGF23 in a sustained manner.

[0017] Within the present invention the terms are used having the meaning as follows.

[0018] As used herein, the term “drug” refers to a substance used in the treatment, cure, prevention or diagnosis of a disease or used to otherwise enhance physical or mental well-being of a patient. If a drug is conjugated to another moiety, the moiety of the resulting product that originated from the drug is referred to as “drug moiety”. A drug comprising at least one receptor-binding moiety -RB and at least one target-binding moiety -TB may also be referred to as “bifunctional drug”.

[0019] As used herein, the term “receptor-binding moiety” or “RB” refers to a moiety that binds to at least one cell surface receptor associated with a degradation pathway, such as receptor-mediated endocytosis or lysosomal degradation.

[0020] As used herein, the term “target-binding moiety” or “TB” refers to a moiety that binds to fibroblast growth factor 23 (“FGF23”), which is an extracellular target.

[0021] As used herein, the term "extracellular target" in general refers to a molecule that is present in the space outside the plasma membrane of a cell, such as FGF23. An extracellular target may be a protein or a non-protein entity. An extracellular target may be any molecule outside a cell which is desired for targeted degradation via at least one cell surface receptor associated with a degradation pathway. It is understood that it is sufficient that at least one part of such moleculeAscendis Pharma A / S CPX75237PC 12 January 2026 is present in the space outside the plasma membrane of a cell, for example when the extracellular target is a cell surface molecule.

[0022] As used herein, the term "cell surface molecule" refers to a molecule associated with a cell membrane, for example because the molecule has a domain that inserts into or spans a cell membrane, such as a cell membrane-tethering domain or a transmembrane domain. The cell surface molecule may be any cell surface molecule which is desired for targeted degradation via at least one cell surface receptor associated with a degradation pathway.

[0023] As used herein, the term "ectodomain" refers to the domain of a cell surface molecule that extends into the space outside the plasma membrane of a cell.

[0024] As used herein, the term "reduction of the extracellular level" refers to decreasing the concentration and / or the activity of an extracellular target, such as FGF23, with a bifunctional drug, such as a bifunctional drug released from a conjugate of the present invention, compared to its concentration and / or activity in the absence of the bifunctional drugs of the conjugates described herein.

[0025] As used herein, the term "biomolecule" refers to a molecule produced by cells and living organisms. Biomolecules have a wide range of sizes and structures and perform a vast array of functions. The major types of biomolecules are carbohydrates, lipids, nucleic acids, proteins and small molecules, such as vitamins and hormones. However, many biomolecules comprise moieties of different types, such as proteoglycans and glycoproteins, which are proteins comprising carbohydrate moieties.

[0026] As used herein, the terms "mannose-6-phosphate receptor" and "M6PR" interchangeably refer to the Cation-Dependent Mannose-6-Phosphate Receptor (CD-M6PR) protein and include any of its naturally occurring forms, homologs, mutants, functional fragments or variants that maintain the activity of CD-M6PR.

[0027] As used herein, the terms "insulin-like growth factor 2 receptor" and "IGF2R" interchangeably refer to the Insulin Like Growth Factor 2 Receptor (IGF2R) protein, which is also referred to as the Cation-Independent Mannose-6-Phosphate Receptor (CI-M6PR), and include any of theAscendis Pharma A / S CPX75237PC 12 January 2026 IGF2R naturally occurring forms, homologs, mutants, functional fragments or variants that maintain the activity of IGF2R.

[0028] As used herein, the terms "asialoglycoprotein receptor" and “ASGPR” interchangeably refer to the protein ASGPR and include any of the ASGPR naturally occurring forms, homologs, mutants, functional fragments, or variants that maintain the activity of ASGPR. ASGPR is also known as the Ashwell Morell receptor. ASGPR is a transmembrane glycoprotein receptor found primarily in hepatocytes which plays an important role in serum glycoprotein homeostasis by mediating the endocytosis and lysosomal degradation of glycoproteins with exposed terminal galactose or N-acetylgalactosamine (GalNAc) residues. ASGPR cycles between endosomes and the cell surface.

[0029] As used herein, the term "antibody" refers to a tetrameric immunoglobulin protein comprising two light chain polypeptides (about 25 kDa each) and two heavy chain polypeptides (about 50 to 70 kDa each).

[0030] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of homogenous or substantially homogeneous antibodies. The term "monoclonal" is not limited to any particular method for making the antibody. Generally, a population of monoclonal antibodies may be generated by cells, a population of cells, or a cell line.

[0031] As used herein, the term "full-length antibody" refers to an antibody in its substantially intact form comprising two light chain polypeptides (about 25 kDa each) and two heavy chain polypeptides (about 50 to 70 kDa each).

[0032] "Antibody fragments" comprise one or more parts of a full-length antibody, wherein the antibody fragment retains at least one, two, three and as many as most or all of the functions associated with this part when present in a full-length antibody. Antibody fragments suitable for use in the conjugates of this disclosure include, for example, Fv fragments, Fab fragments, F(ab’)2 fragments, Fab’ fragments, scFv (sFv) fragments, tandem bispecific scFvs and scFv-Fc fragments.

[0033] As used herein, the terms "light chain" (LC) or "immunoglobulin light chain" refers to a polypeptide comprising, from amino terminus (N-terminus) to carboxyl terminus (C -terminus),Ascendis Pharma A / S CPX75237PC 12 January 2026 a single immunoglobulin light chain variable region (VL) and a single immunoglobulin light chain constant domain (CL). The immunoglobulin light chain constant domain (CL) can be a human kappa (x) or human lambda (k) constant domain.

[0034] As used herein, the terms "heavy chain" (HC) or "immunoglobulin heavy chain" interchangeably refer to a polypeptide comprising, from amino terminus (N-terminus) to carboxyl terminus (C-terminus), a single immunoglobulin heavy chain variable region (VH), an immunoglobulin heavy chain constant domain 1 (CHI), an immunoglobulin hinge region, an immunoglobulin heavy chain constant domain 2 (CH2), an immunoglobulin heavy chain constant domain 3 (CH3) and optionally an immunoglobulin heavy chain constant domain 4 (CH4). Heavy chains are classified as mu (micro), delta (5), gamma (y), alpha (a) and epsilon (a), and define the antibody's isotype as IgM, IgD, IgG, IgA and IgE, respectively. The IgG-class and IgA-class antibodies are further divided into subclasses, namely, IgGl, IgG2, IgG3 and IgG4 and IgAl and IgA2, respectively. The heavy chains in IgG, IgA and IgD antibodies have three constant domains (CHI, CH2 and CH3), whereas the heavy chains in IgM and IgE antibodies have four constant domains (CHI, CH2, CH3 and CH4). The immunoglobulin heavy chain constant domains can be from any immunoglobulin isotype, including subtypes. The antibody chains are linked together via inter-polypeptide disulfide bonds between the CL domain and the CHI domain, such as between the light and heavy chain, and between the hinge regions of the two antibody heavy chains.

[0035] Variable regions of immunoglobulin chains generally exhibit the same overall structure, comprising relatively conserved framework regions (FR) joined by three hypervariable regions, more often called "complementarity determining regions" or “CDRs”. The CDRs from the two chains of each heavy chain and light chain pair typically are aligned by the framework regions to form a structure that binds specifically to a specific epitope on the target protein. From N-terminus to C-terminus, naturally occurring light and heavy chain variable regions both typically conform with the following order of these elements: FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. Various numbering systems have been devised for assigning numbers to amino acids that occupy positions in each of these elements, such as Kabat (Wu et al., (1910) J Exp Med 132: 211-250), Chothia (Chothia et al., (1987) J Mol Biol 196: 901-17), IMGT (Lefranc et al., (2003) Dev Comp Immunol 27: 55-77) and AbM (Martin and Thornton (1996) J Bmol Biol 263: 800-815). Unless otherwise explicitly stated, amino acid positions in the variable regions of immunoglobulin chains are indicated using the Kabat numbering system, hereinAscendis Pharma A / S CPX75237PC 12 January 2026 referred to as “Kabat numbering”. The CDRs and FRs of a given antibody or fragment thereof may be identified using this system.

[0036] Papain digestion of antibodies produces two identical antigen-binding proteins, called "Fab" fragments, each with a single antigen-binding site, and a residual "Fc" fragment which contains all but the first domain of the immunoglobulin heavy chain constant region. The Fab fragment contains the variable domains from the light and heavy chains, as well as the constant domain of the light chain and the first constant domain (CHI) of the heavy chain. Thus, a "Fab fragment" comprises one immunoglobulin light chain (light chain variable region (VL) and constant region (CL)) and the CHI domain and variable region (VH) of one immunoglobulin heavy chain. The heavy chain of a Fab molecule cannot form a disulfide bond with another heavy chain molecule. The "Fd fragment" comprises the VH and CHI domains from an immunoglobulin heavy chain. The Fd fragment represents the heavy chain component of the Fab fragment.

[0037] As used herein, a "Fc fragment" or "Fc region" of an immunoglobulin generally comprises two constant domains, a CH2 domain and a CH3 domain and optionally comprises a CH4 domain. The Fc region may be an Fc region from an IgGl, IgG2, IgG3 or IgG4 immunoglobulin. In certain embodiments the Fc region comprises CH2 and CH3 domains from a human IgGl or human IgG2 immunoglobulin. The Fc region may retain effector function, such as Clq binding, complement dependent cytotoxicity (CDC), Fc receptor binding, antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis. The Fc region may be further modified to reduce or eliminate effector function.

[0038] As used herein, the term "F(ab')2 fragment" refers to a bivalent fragment including two Fab' fragments linked by a disulfide bridge between the heavy chains at the hinge region.

[0039] As used herein, the term "Fv" fragment refers to the minimum fragment that contains a complete antigen recognition and binding site from an antibody. This fragment consists of a dimer of one immunoglobulin heavy chain variable region (VH) and one immunoglobulin light chain variable region (VL) in tight, non-covalent association. It is in this configuration that the three CDRs of each variable region interact to define an antigen binding site on the surface of the VH-VL dimer. A single light chain or heavy chain variable region or half of an Fv fragmentAscendis Pharma A / S CPX75237PC 12 January 2026 comprising only three CDRs specific for an antigen has the ability to recognize and bind to an antigen, although at a lower affinity than the entire binding site comprising both VH and VL.

[0040] As used herein, the term "single-chain variable fragment" or "scFv fragment" refers to an antibody fragment that comprises the VH and VL regions of an antibody, wherein these regions are present in a single polypeptide chain, and optionally comprising a peptide linker between the VH and VL regions that enables the Fv to form the desired structure for antigen binding.

[0041] As used herein, the term “tandem bispecific scFv” comprises two single-chain variable fragments (scFvs) which are connected by a peptide linker.

[0042] As used herein, the terms "polynucleotide" or "nucleic acid" are used interchangeably herein and refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Examples are a gene, a gene fragment, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, ribozymes, copy DNA (cDNA), recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, control regions, isolated RNA of any sequence, nucleic acid probes and primers. The nucleic acid molecule may be linear, branched or circular. The nucleotides may be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase or by a synthetic reaction. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and their analogs. The nucleic acid may be an aptamer.

[0043] As used herein, the term “therapeutically effective amount” means an amount sufficient to cure, alleviate or partially arrest the clinical manifestations of a given disease and its complications. Effective amounts for each purpose will depend on various factors, such as the severity of the disease or injury as well as the weight and general state of the subject.

[0044] Any reference to a biologic drug herein, i.e., to a drug manufactured in, extracted from or semisynthesized from biological sources, such as a protein drug, also covers biosimilar versions of said drug.

[0045] It is understood that the conjugates of the present invention are prodrugs.Ascendis Pharma A / S CPX75237PC 12 January 2026 As used herein, the term “prodrug” refers to a drug moiety reversibly and covalently connected to a specialized protective group through a reversible prodrug linker moiety which is a linker moiety comprising a reversible linkage with the drug moiety and wherein the specialized protective group alters or eliminates undesirable properties in the parent molecule. This also includes the enhancement of desirable properties in the drug and the suppression of undesirable properties. The specialized non-toxic protective group may also be referred to as “carrier”, such as for example -Z. A prodrug releases the reversibly and covalently bound drug moiety in the form of its corresponding drug in free form or in the form of a drug comprising a moiety originating from the linker moiety, for example. In other words, a prodrug is a conjugate comprising a drug moiety, which is covalently and reversibly conjugated to a carrier moiety via a reversible linker moiety, such as for example -L which covalent and reversible conjugation of the carrier to the reversible linker moiety is either directly or through a spacer, such as for example -L2-. The reversible linker may also be referred to as “reversible prodrug linker”. If the conjugate releases the formerly conjugated drug moiety in the form of a free drug, the reversible linker or reversible prodrug linker is also referred to as a “traceless linker”.

[0046] A “reversible linkage” is a linkage that is degradable, i.e., cleavable, in the absence of enzymes under physiological conditions (aqueous buffer at pH 7.4, 37°C) with a half-life ranging from 1 hour to three months. A “stable linkage” is a linkage having a half-life under physiological conditions (aqueous buffer at pH 7.4, 37°C) in the absence of enzymes of more than three months.

[0047] As used herein, the term “spacer” refers to a moiety that connects at least two other moieties with each other.

[0048] As used herein, the term “affinity” refers to the strength of the sum of non-covalent interactions between a single binding site of a molecule, such as a receptor, and its binding partner, such as a ligand. Unless indicated otherwise, as used herein, the term “affinity” refers to the intrinsic binding affinity which reflects a 1 : 1 interaction between members of a binding pair, such as between a receptor and a ligand. The affinity of a molecule X for its partner Y can generally be represented by the equilibrium dissociation constant (Kd), which is the ratio of dissociation and association rate constants (kd and ka, respectively) measured at steady state. Thus, equivalent affinities may comprise different rate constants, as long as the ratio of the rate constants remainsAscendis Pharma A / S CPX75237PC 12 January 2026 the same. Affinity may be measured by well-established methods known in the art, including those described herein.

[0049] As used herein, the term “treating” refers to curing, reducing or inhibiting further deterioration of at least one sign or symptom of a disease or stabilizing at least one sign or symptom of disease.

[0050] As used herein, the term “reagent” means a chemical compound, which comprises at least one functional group for reaction with the functional group of another chemical compound or drug. It is understood that a drug comprising a functional group such as a primary or secondary amine or hydroxyl functional group is also a reagent.

[0051] As used herein, the term “moiety” means a part of a molecule, which lacks one or more atom(s) compared to the corresponding reagent. If, for example, a reagent of the formula “H-X-H” reacts with another reagent and becomes part of the reaction product, the corresponding moiety of the reaction product has the structure “H-X-” or “-X-”, whereas each

[0052]

[0053] indicates attachment to another moiety. Accordingly, a drug moiety is released from a reversible linkage as a drug.

[0054] As used herein, the term “carbamate or carbamate-derived moiety” refers to a moiety with the structure -X1-C(=X2)-NR1-, wherein -X1-, =X2and -R1are used as defined elsewhere herein. Suitable examples of carbamate or carbamate-derived moieties are carbamate, carbamothioate, thiocarbamate, dithiocarbamate, urea, thiourea, guanidine, carbamimidate and carbamimidothioate moieties.

[0055] It is understood that if the sequence or chemical structure of a group of atoms is provided which group of atoms is attached to two moieties or is interrupting a moiety, said sequence or chemical structure can be attached to the two moieties in either orientation, unless explicitly stated otherwise. For example, a moiety “-C(O)N(R1)-” can be attached to two moieties or interrupting a moiety either as “-C(O)N(R1)-” or as “-NJ ^C O)-”. Similarly, a moietyAscendis Pharma A / S CPX75237PC 12 January 2026

[0056]

[0057] can be attached to two moieties or can interrupt a moiety either as

[0058]

[0059] or as

[0060] The term “substituted” as used herein means that one or more -H atom(s) of a molecule or moiety are replaced by a different atom or a group of atoms, which are referred to as “substituent”.

[0061] As used herein, the term “substituent” refers in certain embodiments to a moiety selected from the group consisting of halogen, -CN, -COORxl, -ORxl, -C(O)Rxl, -C(O)N(RxlRxla), -S(O)2N(RxlRxla), -S(O)N(RxlRxla), -S(O)2Rxl, -S(O)Rxl, -N(Rxl)S(O)2N(RxlaRxlb), -SRxl, -N(RxlRxla), -NO2, -OC(O)RX1, -N(Rxl)C(O)Rxla, -N(Rxl)S(O)2Rxla, -N(Rxl)S(O)Rxla, -N(Rxl)C(O)ORxla, -N(Rxl)C(O)N(RxlaRxlb), -OC(O)N(RxlRxla), -T°, C1-50 alkyl, C2.5o alkenyl and C2-5o alkynyl; wherein -T°, C1-50 alkyl, C2-so alkenyl and C2-so alkynyl are optionally substituted with one or more -Rx2, which are the same or different, and wherein C1-50 alkyl, C2-5o alkenyl and C2-so alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T°-, -C(O)O-, -O-, -C(O)-, -C(O)N(Rx3)-, -S(O)2N(Rx3)-, -S(O)N(Rx3)-, -S(O)2-, -S(O)-, -N(Rx3)S(O)2N(Rx3a)-, -S-, -N(Rx3)-, -OC(ORx3)(Rx3a)-, -N(Rx3)C(O)N(Rx3a)- and -OC(O)N(Rx3)-;

[0062] -Rxl, -Rxlaand -Rxlbare independently of each other selected from the group consisting of-H, -T°, Ci -50 alkyl, C2-5o alkenyl and C2-so alkynyl; wherein -T°, C1-50 alkyl, C2-so alkenyl and C2-5o alkynyl are optionally substituted with one or more -Rx2, which are the same or different, and wherein C1-50 alkyl, C2-so alkenyl and C2-so alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T°-, -C(O)O-, -O-, -C(O)-, -C(O)N(Rx3)-, -S(O)2N(RX3)-, -S(O)N(RX3)-; -S(O)2-, -S(O)-, -N(Rx3)S(O)2N(Rx3a)-, -S-, -N(Rx3)-, -OC(ORx3)(Rx3a)-, -N(Rx3)C(O)N(Rx3a)- and -OC(O)N(Rx3)-;Ascendis Pharma A / S CPX75237PC 12 January 2026

[0063] each T° is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl and 8- to 11-membered heterobicyclyl; wherein each T° is independently optionally substituted with one or more -Rx2, which are the same or different;

[0064] each -Rx2is independently selected from the group consisting of halogen, -CN, oxo (=0), -COORx4, -ORx4, -C(O)Rx4, -C(O)N(Rx4Rx4a), -S(O)2N(Rx4Rx4a), -S(O)N(Rx4Rx4a), -S(O)2RX4, -S(O)RX4, -N(Rx4)S(O)2N(Rx4aRx4b), -SRx4, -N(Rx4Rx4a), -NO2, -OC(O)Rx4, -N(Rx4)C(O)Rx4a, -N(Rx4)S(O)2Rx4a, -N(Rx4)S(O)Rx4a, -N(Rx4)C(O)ORx4a, -N(Rx4)C(O)N(Rx4aRx4b), -OC(O)N(Rx4Rx4a) and Ci-6alkyl; wherein Ci-6alkyl is optionally substituted with one or more halogen, which are the same or different;

[0065] each -Rx3, -Rx3a, -Rx4, -Rx4aand -Rx4bis independently selected from the group consisting of -H and Ci-6 alkyl; wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0066] In certain embodiments a maximum of 6 -H atoms of an optionally substituted molecule are independently replaced by a substituent, e.g. 5 -H atoms are independently replaced by a substituent, 4 -H atoms are independently replaced by a substituent, 3 -H atoms are independently replaced by a substituent, 2 -H atoms are independently replaced by a substituent or 1 -H atom is replaced by a substituent.

[0067] As used herein, the term “peptide” as used herein refers to a chain of at least 2 and up to and including 50 amino acid monomer moieties, which may also be referred to as “amino acid residues”, linked by peptide (amide) linkages. The amino acid monomers may be selected from the group consisting of proteinogenic amino acids and non-proteinogenic amino acids and may be D- or L-amino acids. The term “peptide” also includes peptidomimetics, such as peptoids, beta-peptides, cyclic peptides and depsipeptides and covers such peptidomimetic chains with up to and including 50 monomer moieties. The cyclic peptides may be mono-, bi-, tri- or tetracyclic peptides. The term “peptide” also includes lasso peptides.

[0068] As used herein, the term “protein” or “polypeptide” refers to at least one chain of more than 50 amino acid monomer moieties, which may also be referred to as “amino acid residues”, linkedAscendis Pharma A / S CPX75237PC 12 January 2026 by peptide linkages, in which no more than 12000 amino acid monomer moieties are linked by peptide linkages. It is understood that a protein may comprise more than one chain of amino acid residues.

[0069] It is understood that in the context of amino acid sequences single letters refer to the one-letter code of amino acids and not chemical atoms.

[0070] It is understood that the deletion or insertion of one or more amino acid residues in a sequence may change the number, i.e. position, of a particular amino acid residue within such sequence and that in such case the corresponding, i.e. homologous, amino acid positions are included. This may be indicated by the phrase “or at the corresponding positions of homologs or variants thereof’, but such corresponding positions are included even in the absence of this phrase.

[0071] As used herein the term “about” or “approx.” in combination with a numerical value is used to indicate a range ranging from and including the numerical value plus and minus no more than 10% of said numerical value. For example, the phrase “about 200” is used to mean a range ranging from and including 200 + / -10%, i.e., ranging from and including 180 to 220. It is understood that a percentage given as “about 50%” does not mean “50% + / - 10%”, i.e., ranging from and including 40 to 60%, but “about 50%” means ranging from and including 45% to 55%, i.e., plus and minus 10% of the numerical value which is 50.

[0072] As used herein, the term “polymer” means a molecule comprising repeating structural units, i.e., the monomers, connected by chemical bonds in a linear, circular, branched, crosslinked or dendrimeric way or a combination thereof, which may be of synthetic or biological origin or a combination of both. It is understood that a polymer may also comprise one or more other chemical group(s) and / or moiety / moieties, such as, for example, one or more functional group(s). Likewise, it is understood that also a peptide or protein is a polymer, even though the side chains of individual amino acid residues may be different. In certain embodiments a soluble polymer has a molecular weight of at least 0.5 kDa. If the polymer is soluble, it in certain embodiments has a molecular weight of at most 1000 kDa. It is understood that for insoluble polymers, such as hydrogels, no meaningful molecular weight ranges can be provided.

[0073] As used herein, the term “polymeric” means a reagent or a moiety comprising one or more polymer(s) or polymer moiety / moieties. A polymeric reagent or moiety may optionally alsoAscendis Pharma A / S CPX75237PC 12 January 2026 comprise one or more other moiety / moieties, which are in certain embodiments selected from the group consisting of:

[0074] • Ci-50 alkyl, C2-50 alkenyl, C2-50 alkynyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11 -membered heterobicyclyl, phenyl, naphthyl, indenyl, indanyl and tetralinyl; and

[0075] • linkages selected from the group comprising

[0076]

[0077] wherein

[0078] dashed lines indicate attachment to the remainder of the moiety or reagent, and -R and -Raare independently of each other selected from the group consisting of -H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2- methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3 -methylpentyl, 2,2- dimethylbutyl, 2, 3 -dimethylbutyl and 3, 3 -dimethylpropyl.

[0079] The person skilled in the art understands that the polymerization products obtained from a polymerization reaction do not all have the same molecular weight, but rather exhibit a molecular weight distribution. Consequently, the molecular weight ranges, molecular weights, ranges of numbers of monomers in a polymer and numbers of monomers in a polymer as used herein, refer to the number average molecular weight and number average of monomers, i.e., to the arithmetic mean of the molecular weight of the polymer or polymeric moiety and the arithmetic mean of the number of monomers of the polymer or polymeric moiety.

[0080] Accordingly, in a polymeric moiety comprising “x” monomer units any integer given for “x” therefore corresponds to the arithmetic mean number of monomers. Any range of integers given for “x” provides the range of integers in which the arithmetic mean numbers of monomers lie.Ascendis Pharma A / S CPX75237PC 12 January 2026 An integer for “x” given as “about x” means that the arithmetic mean numbers of monomers lie in a range of integers of x + / - 10%.

[0081] As used herein, the term “number average molecular weight” means the ordinary arithmetic mean of the molecular weights of the individual polymers.

[0082] As used herein, the term “PEG-based” in relation to a moiety or reagent means that said moiety or reagent comprises PEG, such as at least 10% (w / w) PEG. The remaining weight percentage of the PEG-based moiety or reagent are other moieties that in certain embodiments are selected from the following moieties and linkages:

[0083] • Ci-50 alkyl, C2-50 alkenyl, C2-50 alkynyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11 -membered heterobicyclyl, phenyl, naphthyl, indenyl, indanyl and tetralinyl; and

[0084] • linkages selected from the group comprising

[0085]

[0086] wherein

[0087] dashed lines indicate attachment to the remainder of the moiety or reagent, and -R and -Raare independently of each other selected from the group consisting of -H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2- methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3 -methylpentyl, 2,2- dimethylbutyl, 2,3 -dimethylbutyl and 3, 3 -dimethylpropyl.

[0088] The term “hyaluronic acid-based” is used accordingly.

[0089] As used herein, the term “bioorthogonal moiety” refers to a moiety resulting from a selective chemical reaction between functional groups that are not normally present in biologicalAscendis Pharma A / S CPX75237PC 12 January 2026 systems, such as, for example, a 1,2,3-triazol-derivative moiety resulting from the reaction between an azide and an activated alkyne.

[0090] As used herein, the term “PEG-based comprising at least X% PEG” in relation to a moiety or reagent means that said moiety or reagent comprises at least X% (w / w) ethylene glycol units (-CH2CH2O-), wherein the ethylene glycol units may be arranged blockwise, alternating or may be randomly distributed within the moiety or reagent; the remaining weight percentage of the PEG-based moiety or reagent are other moieties that in certain embodiments are selected from the following moieties and linkages:

[0091] • Ci-50 alkyl, C2-50 alkenyl, C2-50 alkynyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11 -membered heterobicyclyl, phenyl, naphthyl, indenyl, indanyl and tetralinyl; and

[0092] linkages selected from the group comprising

[0093]

[0094] wherein

[0095] dashed lines indicate attachment to the remainder of the moiety or reagent, and -R and -Raare independently of each other selected from the group consisting of -H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2- methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3 -methylpentyl, 2,2- dimethylbutyl, 2,3 -dimethylbutyl and 3, 3 -dimethylpropyl.

[0096] The term “hyaluronic acid-based comprising at least X% hyaluronic acid” is used accordingly.

[0097] As used herein, the term "random coil" refers to any conformation of a polymeric molecule, including proteins, in which the individual monomeric elements that form said polymeric structure are essentially randomly oriented towards the adjacent monomeric elements while stillAscendis Pharma A / S CPX75237PC 12 January 2026 being chemically bound to said adjacent monomeric elements. In particular, a polypeptide or protein having random coil conformation substantially lacks a defined secondary and tertiary structure. The nature of polypeptide random coils and their methods of experimental identification are known to the person skilled in the art. In particular, the lack of secondary and tertiary structure of a protein may be determined by circular dichroism (CD) measurements. CD spectroscopy represents a light absorption spectroscopy method in which the difference in absorbance of right- and left-circularly polarized light by a substance is measured. The secondary structure of a protein can be determined by CD spectroscopy using far-ultraviolet spectra with a wavelength between approximately 190 and 250 nm. At these wavelengths the different secondary structures commonly found in conformations each give rise to a characteristic shape and magnitude of the CD spectrum. Accordingly, by using CD spectrometry the skilled artisan is readily capable of determining whether an amino acid polymer adopts random coil conformation at physiological conditions.

[0098] The term “interrupted” means that a moiety is inserted between two carbon atoms or - if the insertion is at one of the moiety’s ends - between a carbon or heteroatom and a hydrogen atom.

[0099] As used herein, the term “Ci-4 alkyl” alone or in combination means a straight-chain or branched alkyl moiety having 1 to 4 carbon atoms. If present at the end of a molecule, examples of straight-chain or branched Ci-4 alkyl are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl. When two moieties of a molecule are linked by the Ci-4 alkyl, then examples for such Ci-4 alkyl groups are -CH2-, -CH2-CH2-, -CH(CH3)-, -CH2-CH2-CH2-, -CHfC^Hs)- and -C(CH3)2-. Each hydrogen of a C1-4 alkyl carbon may optionally be replaced by a substituent as defined above. Optionally, a C1-4 alkyl may be interrupted by one or more moieties as defined elsewhere herein.

[0100] As used herein, the term “C1-6 alkyl” alone or in combination means a straight-chain or branched alkyl moiety having 1 to 6 carbon atoms. If present at the end of a molecule, examples of straight-chain or branched C1-6 alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3 -methylpentyl, 2,2-dimethylbutyl, 2, 3 -dimethylbutyl and 3, 3 -dimethylpropyl. When two moieties of a molecule are linked by the C1-6 alkyl group, then examples for such C1-6 alkyl groups are -CH2-, -CH2-CH2-, -CH(CH3)-, -CH2-CH2-CH2-, -CH(C2HS)- and -C(CH3)2-. Each hydrogen atom of a C1-6 carbon may optionally be replacedAscendis Pharma A / S CPX75237PC 12 January 2026 by a substituent as defined above. Optionally, a Ci-6 alkyl may be interrupted by one or more moieties as defined elsewhere herein.

[0101] Accordingly, “Cnio alkyl”, “C1-20 alkyl”, “C1-30 alkyl” or “C1-50 alkyl” means an alkyl chain having 1 to 10, 1 to 20, 1 to 30 or 1 to 50 carbon atoms, respectively, wherein each hydrogen atom of the C1-10, C1-20, C1-30 or C1-50 carbon may optionally be replaced by a substituent as defined above. Optionally, a C1-10 alkyl, C1-20 alkyl, C1-30 alkyl or C1-50 alkyl may be interrupted by one or more moieties as defined elsewhere herein.

[0102] As used herein, the term “C2-6 alkenyl” alone or in combination means a straight-chain or branched hydrocarbon moiety comprising at least one carbon-carbon double bond having 2 to 6 carbon atoms. If present at the end of a molecule, examples are -CH=CH2, -CH=CH-CH3, -CH2-CH=CH2, -CH=CHCH2-CH3and -CH=CH-CH=CH2. When two moieties of a molecule are linked by the C2-6 alkenyl group, then an example for such C2-6 alkenyl is -CH=CH-. Each hydrogen atom of a C2-6 alkenyl moiety may optionally be replaced by a substituent as defined above. Optionally, a C2-6 alkenyl may be interrupted by one or more moieties as defined elsewhere herein.

[0103] Accordingly, the term “C2-10 alkenyl”, “C2-20 alkenyl” or “C2-50 alkenyl” alone or in combination means a straight-chain or branched hydrocarbon moiety comprising at least one carbon-carbon double bond having 2 to 10, 2 to 20 or 2 to 50 carbon atoms. Each hydrogen atom of a C2-10 alkenyl, C2-20 alkenyl or C2-50 alkenyl group may optionally be replaced by a substituent as defined above. Optionally, a C2-10 alkenyl, C2-20 alkenyl or C2-50 alkenyl may be interrupted by one or more moieties as defined elsewhere herein.

[0104] As used herein, the term “C2-6 alkynyl” alone or in combination means a straight-chain or branched hydrocarbon moiety comprising at least one carbon-carbon triple bond having 2 to 6 carbon atoms. If present at the end of a molecule, examples are -C=CH, -CH2-C=CH, -CH2-CH2-OCH and CH2-C=C-CH3. When two moieties of a molecule are linked by the alkynyl group, then an example is -C=C-. Each hydrogen atom of a C2-6 alkynyl group may optionally be replaced by a substituent as defined above. Optionally, one or more double bond(s) may occur. Optionally, a C2-6 alkynyl may be interrupted by one or more moieties as defined elsewhere herein.Ascendis Pharma A / S CPX75237PC 12 January 2026 Accordingly, as used herein, the term “C2-10 alkynyl”, “C2-20 alkynyl” and “C2-50 alkynyl” alone or in combination means a straight-chain or branched hydrocarbon moiety comprising at least one carbon-carbon triple bond having 2 to 10, 2 to 20 or 2 to 50 carbon atoms, respectively. Each hydrogen atom of a C2-10 alkynyl, C2-20 alkynyl or C2-50 alkynyl group may optionally be replaced by a substituent as defined above. Optionally, one or more double bond(s) may occur. Optionally, a C2-10 alkynyl, C2-20 alkynyl or C2-50 alkynyl may be interrupted by one or more moieties as defined elsewhere herein.

[0105] As mentioned above, a C1-4 alkyl, C1-6 alkyl, C1-10 alkyl, C1-20 alkyl, C1-30 alkyl, C1-50 alkyl, C2-6 alkenyl, C2-10 alkenyl, C2-20 alkenyl, C2-50 alkenyl, C2-6 alkynyl, C2-10 alkynyl, C2-20 alkenyl or C2-50 alkynyl may optionally be interrupted by one or more moieties which are preferably selected from the group consisting of

[0106]

[0107] wherein

[0108] dashed lines indicate attachment to the remainder of the moiety or reagent; and -R and -Raare independently of each other selected from the group consisting of -H, and methyl, ethyl, propyl, butyl, pentyl and hexyl.

[0109] As used herein, the term "C3-10 cycloalkyl" means a cyclic alkyl chain having 3 to 10 carbon atoms, which may be saturated or unsaturated, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, cyclononyl or cyclodecyl. Each hydrogen atom of a C3-10 cycloalkyl carbon may be replaced by a substituent as defined elsewhere herein. The term "C3-10 cycloalkyl" also includes bridged bicycles like norbomane or norbornene.

[0110] The terms “8- to 30-membered carbopolycyclyl” or “8- to 30-membered carbopolycycle” refer to a cyclic moiety of two or more rings with 8 to 30 ring atoms, where two neighboring ringsAscendis Pharma A / S CPX75237PC 12 January 2026 share at least one ring atom and that may contain up to the maximum number of double bonds (aromatic or non-aromatic ring which is fully, partially or un- saturated). Preferably an 8- to 30-membered carbopoly cyclyl means a cyclic moiety of two, three, four or five rings.

[0111] As used herein, the term "3- to 10-membered heterocyclyl" or "3- to 10-membered heterocycle" means a ring with 3, 4, 5, 6, 7, 8, 9 or 10 ring atoms that may contain up to the maximum number of double bonds (aromatic or non-aromatic ring which is fully, partially or un-saturated) wherein at least one ring atom up to 4 ring atoms are replaced by a heteroatom selected from the group consisting of sulfur (including -S(O)-, -S(O)2-), oxygen and nitrogen (including =N(O)-) and wherein the ring is linked to the rest of the molecule via a carbon or nitrogen atom. Examples for 3- to 10-membered heterocycles include aziridine, oxirane, thiirane, azirine, oxirene, thiirene, azetidine, oxetane, thietane, furan, thiophene, pyrrole, pyrroline, imidazole, imidazoline, pyrazole, pyrazoline, oxazole, oxazoline, isoxazole, isoxazoline, thiazole, thiazoline, isothiazole, isothiazoline, thiadiazole, thiadiazoline, tetrahydrofuran, tetrahydrothiophene, pyrrolidine, imidazolidine, pyrazolidine, oxazolidine, isoxazolidine, thiazolidine, isothiazolidine, thiadiazolidine, sulfolane, pyran, dihydropyran, tetrahydropyran, imidazolidine, pyridine, pyridazine, pyrazine, pyrimidine, piperazine, piperidine, morpholine, tetrazole, triazole, triazolidine, tetrazolidine, diazepane, azepine and homopiperazine. Each hydrogen atom of a 3- to 10-membered heterocyclyl or 3- to 10-membered heterocyclic group may be replaced by a substituent as defined elsewhere herein.

[0112] As used herein, the terms "8- to 11-membered heterobicyclyl" or "8- to 11-membered heterobicycle" refer to a heterocyclic moiety of two rings with 8 to 11 ring atoms, where at least one ring atom is shared by both rings and that may contain up to the maximum number of double bonds (aromatic or non-aromatic ring which is fully, partially or un-saturated), wherein at least one ring atom up to 6 ring atoms are replaced by a heteroatom selected from the group consisting of sulfur (including -S(O)-, -S(O)2-), oxygen and nitrogen (including =N(O)-) and wherein the ring is linked to the rest of the molecule via a carbon or nitrogen atom. Examples for an 8- to 11 -membered heterobicycle are indole, indoline, benzofuran, benzothiophene, benzoxazole, benzisoxazole, benzothiazole, benzisothiazole, benzimidazole, benzimidazoline, quinoline, quinazoline, dihydroquinazoline, quinoline, dihydroquinoline, tetrahydroquinoline, decahydroquinoline, isoquinoline, decahydroisoquinoline, tetrahydroisoquinoline, dihydroisoquinoline, benzazepine, purine and pteridine. The term 8- to 11-membered heterobicycle also includes spiro structures of two rings like l,4-dioxa-8-azaspiro[4.5]decaneAscendis Pharma A / S CPX75237PC 12 January 2026 or bridged heterocycles like 8-aza-bicyclo[3.2.1]octane. Each hydrogen atom of an 8- to 11-membered heterobicyclyl or 8- to 11-membered heterobicycle carbon may be replaced by a substituent as defined elsewhere herein.

[0113] Similary, the term “8- to 30-membered heteropoly cyclyl” or “8- to 30-membered heteropoly cycle” means a heterocyclic moiety of more than two rings with 8 to 30 ring atoms, of three, four or five rings, where two neighboring rings share at least one ring atom and that may contain up to the maximum number of double bonds (aromatic or non-aromatic ring which is fully, partially or unsaturated), wherein at least one ring atom up to 10 ring atoms are replaced by a heteroatom selected from the group of sulfur (including -S(O)-, -S(O)2-), oxygen and nitrogen (including =N(O)-) and wherein the ring is linked to the rest of a molecule via a carbon or nitrogen atom.

[0114] As used herein, the term “5- to 14-membered monocyclic, bicyclic or tricyclic aryl or heteroaryl” refers to aromatic ring structures with 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 ring atoms which may form a single cycle, two cycles or three cycles, wherein two neighbouring rings share at least two ring atoms and all rings within the resulting structure are aromatic. In case the 5- to 14-membered monocyclic, bicyclic or tricyclic aromatic moiety contains only carbon atoms as constituent ring atoms it is referred to as “aryl”. In case the 5- to 14-membered monocyclic, bicyclic or tricyclic aromatic moiety includes one or more heteroatoms such as N, O or S it is referred to as “heteroaryl”. A 5- to 14-membered monocyclic, bicyclic or tricyclic heteroaryl may contain any number of heteroatoms provided that the resulting structure is aromatic and isolatable. Examples for 5- to 14-membered monocyclic, bicyclic or tricyclic aryls or heteroaryls include but are not limited to phenyl, naphthyl, phenantren, pyrrole, pyrazole, imidazole, triazole, tetrazole, pyridine, pyrazine, pyridazine, pyrimidine, triazines, indole, isoindole, azaindoles, indazole, azaindazoles, purines, quinoline, isoquinoline, quinazolines, cinnolines, pteridine, benzoquinolines, isobenzoquinoline, benzopteridine, carbazole, acridine, phenazine, phenantrolines, furan, benzofurane, isobenzofuran, dibenzofuran, naphthofurane, isonaphthofuran, thiophene, benzothiophenes, naphthothiophenes, oxazoles, isoxazole, benzooxazoles, benzoisooxazoles, naphthooxazoles, naphthoisooxazoles, thiazole, isothiazole, benzothiazole, benzoisothiazoles, naphthothiazoles, naphthoisothiazoles, oxadiazole, benzooxadiazoles, naphthooxadiazoles, benzothiadiazoles, naphthothiadiazoles, phenoxazine, phenothiazine and phenoxathiine.Ascendis Pharma A / S CPX75237PC 12 January 2026 As used herein, the term "triazole" refers to heterocyclic compounds with the formula C2H3N3, having a five-membered ring of two carbons and three nitrogens, the positions of which can change resulting in multiple isomers, such as 1,2,3-triazoles and 1,2,4-triazoles.

[0115] It is understood that the phrase “the pair -Rx / -Ryis joined together with the atom to which they are attached to form a C3-10 cycloalkyl or a 3- to 10-membered heterocyclyl” in relation with a moiety of the structure

[0116]

[0117] means that -Rxand -Ryform the following structure:

[0118]

[0119] wherein R is C3-10 cycloalkyl or 3- to 10-membered heterocyclyl.

[0120] It is also understood that the phrase “the pair -Rx / -Ryis joined together with the atoms to which they are attached to form a ring A” in relation with a moiety of the structure

[0121]

[0122] means that -Rxand -Ryform the following structure:

[0123]

[0124] As used herein, "halogen" means fluoro, chloro, bromo or iodo. Suitably, halogen is fluoro or chloro.

[0125] As used herein, the term “functional group” means a group of atoms which can react with other groups of atoms. Exemplary functional groups are carboxylic acid (-(C=O)OH), primary or secondary amine (-NH2, -NH-), maleimide, thiol (-SH), sulfonic acid (-(O=S=O)OH), carbonate, carbamate (-O(C=O)N<), hydroxyl (-OH), aldehyde (-(C=O)H), ketone (-(C=O)-),Ascendis Pharma A / S CPX75237PC 12 January 2026 hydrazine (>N-N<), isocyanate, isothiocyanate, phosphoric acid (-0(P=0)0H0H), phosphonic acid (-0(P=0)0HH), haloacetyl, alkyl halide, acryloyl, aryl fluoride, hydroxylamine, disulfide, sulfonamides, sulfuric acid, vinyl sulfone, vinyl ketone, diazoalkane, oxirane and aziridine.

[0126] In case the conjugates of the present invention comprise one or more acidic or basic groups, the invention also comprises their corresponding pharmaceutically or toxicologically acceptable salts, in particular their pharmaceutically utilizable salts. Thus, the conjugates of the present invention comprising acidic groups can be used according to the invention, for example, as alkali metal salts, alkaline earth metal salts or as ammonium salts. More precise examples of such salts include sodium salts, potassium salts, calcium salts, magnesium salts or salts with ammonia or organic amines such as, for example, ethylamine, ethanolamine, triethanolamine or amino acids. Conjugates of the present invention comprising one or more basic groups, i.e. groups which can be protonated, can be present and can be used according to the invention in the form of their addition salts with inorganic or organic acids. Examples for suitable acids include hydrogen chloride, hydrogen bromide, phosphoric acid, sulfuric acid, nitric acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenedisulfonic acids, oxalic acid, acetic acid, tartaric acid, lactic acid, salicylic acid, benzoic acid, formic acid, propionic acid, pivalic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, fumaric acid, maleic acid, malic acid, sulfaminic acid, phenylpropionic acid, gluconic acid, ascorbic acid, isonicotinic acid, citric acid, adipic acid and other acids known to the person skilled in the art. For the person skilled in the art further methods are known for converting the basic group into a cation like the alkylation of an amine group resulting in a positively-charge ammonium group and an appropriate counterion of the salt. If the conjugates of the present invention simultaneously comprise acidic and basic groups, the invention also includes, in addition to the salt forms mentioned, inner salts or betaines (zwitterions). The respective salts can be obtained by customary methods, which are known to the person skilled in the art like, for example by contacting these conjugates with an organic or inorganic acid or base in a solvent or dispersant or by anion exchange or cation exchange with other salts. The present invention also includes all salts of the conjugates of the present invention which, owing to low physiological compatibility, are not directly suitable for use in pharmaceuticals but which can be used, for example, as intermediates for chemical reactions or for the preparation of pharmaceutically acceptable salts.Ascendis Pharma A / S CPX75237PC 12 January 2026 The term "pharmaceutically acceptable" means a substance that does not cause harm when administered to a patient and suitably means approved by a regulatory agency, such as the EMA (Europe) and / or the FDA (US) and / or any other national regulatory agency for use in animals, such as for use in humans.

[0127] As used herein, the term "excipient" refers to a diluent, adjuvant or vehicle with which the therapeutic, such as a drug or prodrug, is administered.

[0128] As used herein the term “liquid pharmaceutical formulation” refers to a mixture comprising a water-soluble compound, such as the conjugate of the present invention, and one or more solvents, such as water.

[0129] As used herein, the term “dry pharmaceutical formulation” means that a pharmaceutical composition is provided in a dry form. Suitable methods for drying are spray-drying and lyophilization, i.e., freeze-drying. Such dry composition has a residual water content of a maximum of 10% determined according to Karl Fischer.

[0130] In general, the term “comprise” or “comprising” also encompasses “consist of’ or “consisting of’.

[0131] In certain embodiments the conjugate or a pharmaceutically acceptable salt thereof is of formula (la) or (lb)

[0132]

[0133] wherein

[0134] -D is a drug moiety comprising at least one receptor-binding moiety -RB and at least one target-binding moiety -TB binding to FGF23;

[0135] -L1- is a linker moiety covalently and reversibly conjugated to -D;

[0136] -L2- is a spacer moiety or is absent;

[0137] -Z is a polymeric moiety;

[0138] x is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16; andAscendis Pharma A / S CPX75237PC 12 January 2026 y is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16.

[0139] In certain embodiments the conjugate is of formula (la). In certain embodiments x of formula (la) is 1, 2, 3 or 4. In certain embodiments x of formula (la) is 1. In certain embodiments x of formula (la) is 2. In certain embodiments the conjugate is of formula (la) and x is 1.

[0140] In certain embodiments the conjugate is of formula (lb). In certain embodiments y of formula (lb) is 2, 3 or 4. In certain embodiments y of formula (lb) is 2. In certain embodiments the conjugate is of formula (lb) and y is 2.

[0141] In certain embodiments the moiety -L1- is a traceless linker and the conjugates of formula (la) and formula (lb) release a moiety D-H, i.e. the free form of the drug, which comprises no traces of -L1-. In certain embodiments a part of the moiety -L1- remains attached to the drug moiety released from a conjugate of formula (la) or (lb), in which case the drug is released in a modified form.

[0142] -D is a drug moiety comprising at least one receptor-binding moiety -RB and at least one targetbinding moiety -TB, wherein the target is FGF23. Such moiety -D finds use for targeted degradation of FGF23 via at least one cell surface receptor associated with a degradation pathway.

[0143] In certain embodiments a receptor-binding moiety -RB is connected to a target-binding moiety -TB via a spacer moiety -L3-.

[0144] In certain embodiments -D comprises one moiety -RB. In certain embodiments -D comprises two moieties -RB. In certain embodiments -D comprises three moieties -RB. In certain embodiments -D comprises four moieties -RB. In certain embodiments -D comprises five moieties -RB. If -D comprises two or more moieties -RB, all moieties -RB of -D may have the same or a different structure.

[0145] In certain embodiments -D comprises one moiety -TB. In certain embodiments -D comprises two moieties -TB. In certain embodiments -D comprises three moieties -TB. In certain embodiments -D comprises four moieties -TB. In certain embodiments -D comprises fiveAscendis Pharma A / S CPX75237PC 12 January 2026 moieties -TB. If -D comprises two or more moieties -TB, all moieties -TB of -D may have the same or a different structure.

[0146] In certain embodiments the molar ratio of -RB to -TB in -D ranges from 20: 1 to 1 :20. In certain embodiments the molar ratio of -RB to -TB in -D is 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10. In certain embodiments the molar ratio of -RB to -TB in -D is 4:1, 3:1, 2:1, 1:1, 1:2, 1:3 or 1:4. In certain embodiments the molar ratio of -RB to -TB in -D is 1:1.

[0147] In certain embodiments -D is of formula (Ic)

[0148] (RB)U-(L3)V-(TB)W(IC),

[0149] wherein

[0150] -RB is a receptor-binding moiety;

[0151] -L3- is a spacer moiety;

[0152] -TB is a target-binding moiety binding to FGF23;

[0153] u is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;

[0154] v is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; and

[0155] w is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0156] It is understood that -D of formula (Ic) is substituted with -L1-. It is furthermore understood that when v is 0, -RB is directly connected to -TB.

[0157] In certain embodiments u of formula (Ic) is 1. In certain embodiments u of formula (Ic) is 2. In certain embodiments u of formula (Ic) is 3. In certain embodiments u of formula (Ic) is 4. In certain embodiments u of formula (Ic) is 5. In certain embodiments u of formula (Ic) is 6. In certain embodiments u of formula (Ic) is 7. In certain embodiments u of formula (Ic) is 8. In certain embodiments u of formula (Ic) is 9. In certain embodiments u of formula (Ic) is 10.

[0158] In certain embodiments v of formula (Ic) is 0. In certain embodiments v of formula (Ic) is 1. In certain embodiments v of formula (Ic) is 2. In certain embodiments v of formula (Ic) is 3. In certain embodiments v of formula (Ic) is 4. In certain embodiments v of formula (Ic) is 5. In certain embodiments v of formula (Ic) is 6. In certain embodiments v of formula (Ic) is 7. In certain embodiments v of formula (Ic) is 8. In certain embodiments v of formula (Ic) is 9. In certain embodiments v of formula (Ic) is 10.Ascendis Pharma A / S CPX75237PC 12 January 2026

[0159] In certain embodiments w of formula (Ic) is 1. In certain embodiments w of formula (Ic) is 2. In certain embodiments w of formula (Ic) is 3. In certain embodiments w of formula (Ic) is 4. In certain embodiments w of formula (Ic) is 5. In certain embodiments w of formula (Ic) is 6. In certain embodiments w of formula (Ic) is 7. In certain embodiments w of formula (Ic) is 8. In certain embodiments w of formula (Ic) is 9. In certain embodiments w of formula (Ic) is 10.

[0160] In certain embodiments u, v and w of formula (Ic) are independently of each other 1, 23 or 4. In certain embodiments u, v and w of formula (Ic) are 1. In certain embodiments u and w of formula (Ic) are 1 and v of formula (Ic) is 0. In certain embodiments w of formula (Ic) is 1, and u and v of formula (Ic) are independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, such as 1, 2, 4, 5 or 6. In certain embodiments w of formula (Ic) is 1, and u and v of formula (Ic) are the same integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12.

[0161] It is understood that -L3- is a branched spacer moiety if either one or both of u and w is more than 1.

[0162] -RB binds to at least one cell surface receptor associated with a degradation pathway. In certain embodiments -RB binds to one cell surface receptor associated with a degradation pathway. In certain embodiments -RB binds to two cell surface receptors associated with a degradation pathway. In certain embodiments -RB binds to three cell surface receptors associated with a degradation pathway. In certain embodiments -RB binds to four cell surface receptors associated with a degradation pathway. In certain embodiments -RB binds to five cell surface receptors associated with a degradation pathway. In certain embodiments, when -RB binds to more than one cell surface receptor associated with a degradation pathway, the cell surface receptors associated with a degradation pathway may be the same or different.

[0163] In certain embodiments the degradation pathway of the at least one cell surface receptor to which -RB binds is receptor-mediated endocytosis or endosomal degradation. In certain embodiments the degradation pathway of the at least one cell surface receptor is lysosomal degradation. In certain embodiments the degradation pathway of the at least one cell surface receptor is endosomal degradation.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -RB binds to the at least one cell surface receptor associated with a degradation pathway with a Ka of 1 mM or less, of 100 pM or less, of 10 pM or less, of 1 pM or less, of 100 nM or less, of 10 nM or less, or of 1 nM or less. The Ka is measured in the unconjugated bifunctional drug, i.e., prior to conjugation to -L1-, if -L1- releases the bifunctional drug in an unmodified form, and if -L1- releases the bifunctional drug in a modified form, the Ka is measured in the released, modified bifunctional drug.

[0164] In certain embodiments the at least one cell surface receptor associated with a degradation pathway is selected from the group consisting of the asialoglycoprotein receptor (ASGPR); mannose-6-phosphate receptor (M6PR); insulin receptor (IR); insulin-like growth factor 2 receptor (IGFR2); mannose receptor systems; Kupffer cell receptor; macrophage galactose lectin (MGL); scavenger receptor; epidermal growth factor (EGF) receptor; the Fc receptor, such as the Fc gamma receptor I and the neonatal fragment crystallizable receptor (FcRN); lysosomal integral membrane protein receptor (LIMP-2); the low density lipoprotein receptor (LDLR); the low density lipoprotein receptor-related protein 1 (LRP1); the low density lipoprotein receptor-related protein 2 (LRP2); the transferrin receptor; sortilin; and decoy receptors, such as C-X-C chemokine receptor type 7 (CXCR7), Duffy antigen / chemokine receptor (DARC), chemokine receptor D6, the atypical chemokine receptor CCX CKR, and -if -D comprises more than one moiety -RB - any combination thereof.

[0165] In certain embodiments -RB binds to at least one ASGPR, M6PR or IGF2R. In certain embodiments -RB binds to at least one ASGPR. In certain embodiments -RB binds to at least one M6PR. In certain embodiments -RB binds to at least one IGFR2.

[0166] In certain embodiments -RB comprises a small molecule moiety, a carbohydrate moiety, an antibody moiety or fragment thereof, a peptide moiety or a combination thereof.

[0167] In certain embodiments -RB comprises one or more carbohydrate moiety. In certain embodiments such carbohydrate moiety is selected from the group consisting of a monosaccharide, disaccharide, trisaccharide, tetrasaccharide, pentasaccharide, hexasaccharide and oligosaccharide, which may optionally be modified, such as phosphorylated.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -RB comprises at least one monosaccharide moiety selected from the group consisting of aldoses, aldotetroses, aldopentoses, aldohexoses, ketotrioses, ketotetroses, ketopentose, ketohexoses, amino sugars and sulfosugars.

[0168] In certain embodiments -RB comprises at least one monosaccharide moiety selected from the group consisting of aldotriose, D-glyceraldehyde, D-erythrose, D-threose, D-ribose, D-arabinose, D-xylose, D-lyxose, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose (Gal), D-talose, dihydroxyacetone, D-erythrulose, D-ribulose, D-xylulose, D-psicone, D-fructose, D-sorbose, D-tagatose, galactosamine, sialic acid, N-acetylgalactosamine (GalNAc), N-acetylglucosamine, N-acetylmannosamine, mannose-6-phosphate, mannose-6-phosphonate and sulfoquinovose.

[0169] In certain embodiments -RB comprises at least one disaccharide moiety selected from the group consisting of sucrose, lactose, maltose, trehalose, cellobiose, kojibiose, nigerose, isomaltose, sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose, gentiobiluose, mannobiose, melibiose, melibiulose, rutinose, rutinulose and xylobiose.

[0170] In certain embodiments -RB comprises at least one hexasaccharide moiety comprising one or more of glucose, galactose (Gal), mannose, N-acetylglucosamine, N-acetylgalactosamine (GalNAc), N-acetylmannosamine, mannose-6-phosphate and / or mannose-6- phosphonate moieties.

[0171] In certain embodiments -RB comprises one or more GalNAc moieties, e.g., comprises 1, 2, 3, 4, 5, 6 or more GalNAc moieties.

[0172] In certain embodiments -RB comprises one or more Gal moieties or one or more GalNAc moieties. In certain embodiment the one or more Gal moieties or one or more GalNAc moieties comprise a bridged ketal moiety.

[0173] In certain embodiments -RB comprises an antibody moiety or fragment thereof, such as a Fab moiety, a Fab' moiety, a F(ab')2 moiety, a F(ab)2 moiety, variable fragment (Fv) moiety, a domain antibody (dAb) moiety, a single domain antibody moiety or a single chain variable fragment (scFv) moiety. In certain embodiments the antibody moiety is a full-length antibody moiety. In certain embodiments the antibody moiety is an antibody fragment. In certainAscendis Pharma A / S CPX75237PC 12 January 2026 embodiments the antibody fragment is a Fab, a Fab', a F(ab')2, a F(ab)2, variable fragment (Fv), a domain antibody (dAb), a single domain antibody, or a single chain variable fragment (scFv). In certain embodiments the antibody moiety is a monospecific antibody moiety or a fragment thereof. In certain embodiments the antibody moiety is a multispecific antibody moiety or a fragment thereof. In certain embodiments the antibody moiety is a bispecific antibody moiety or fragment thereof.

[0174] In certain embodiments -RB is a full-length antibody moiety. In certain embodiments -RB is a Fab moiety.

[0175] In certain embodiments -RB comprises a peptide moiety. In certain embodiments -RB comprises a cyclic peptide moiety. In certain embodiments -RB comprises a bicyclic peptide moiety. In certain embodiments -RB comprises a tricyclic peptide moiety.

[0176] In certain embodiments -RB comprises a small molecule moiety.

[0177] In certain embodiments -RB binds to one ASGPR. In certain embodiments -RB binds to two ASGPR. In certain embodiments -RB binds to three ASGPR. In certain embodiments -RB binds to four ASGPR. In certain embodiments -RB binds to five ASGPR.

[0178] In certain embodiments -RB binds to at least one ASGPR1 and / or at least one ASGPR2. In certain embodiments -RB comprises a ligand for ASGPR. In certain embodiments -RB comprises a ligand for ASGPR1. In certain embodiments -RB comprises a ligand for ASGPR2. In certain embodiments -RB comprises a ligand binding both ASGPR1 and ASGPR2. In certain embodiments -RB is a ligand for ASGPR. In certain embodiments -RB is a ligand for ASGPR1. In certain embodiments -RB is a ligand for ASGPR2. In certain embodiments -RB is a ligand binding both ASGPR1 and ASGPR2.

[0179] In certain embodiments -RB binds to at least one ASGPR and comprises a carbohydrate moiety. In certain embodiments the carbohydrate moiety binds to at least one ASGPR1 and / or at least one ASGPR2. In certain embodiments the carbohydrate moiety is a ligand for ASGPR. In certain embodiments the carbohydrate moiety is a ligand for ASGPR1. In certain embodiments the carbohydrate moiety is a ligand for ASGPR2. In certain embodiments the carbohydrate moiety is a ligand binding to both ASGPR1 and ASGPR2.Ascendis Pharma A / S CPX75237PC 12 January 2026

[0180] In certain embodiments -RB binds to at least one ASGPR and comprises at most two carbohydrate moieties.

[0181] In certain embodiments -RB comprises one or two monosaccharide moieties and additional moieties optionally present in -RB are free of monosaccharides. In certain embodiments -RB comprises one monosaccharide moiety and additional moieties optionally present in -RB are free of monosaccharides. In certain embodiments -RB comprises two monosaccharide moieties and additional moieties optionally present in -RB are free of monosaccharides.

[0182] In certain embodiments -RB comprises at most two GalNAc moieties. In certain embodiments -RB comprises one GalNAc moietiy and additional moieties optionally present in -RB are free of GalNAcs. In certain embodiments -RB comprises two GalNAc moietiy GalNAc and additional moieties optionally present in -RB are free of GalNAcs.

[0183] In certain embodiments -RB comprises at most two Gal moieties. In certain embodiments -RB comprises one Gal moiety and additional moieties optionally present in -RB are free of Gals. In certain embodiments -RB comprises two Gal moieties and additional moieties optionally present in -RB are free of Gals.

[0184] In certain embodiment the at most two Gal moieties or at most two GalNAc moieties comprise a bridged ketal moiety.

[0185] In certain embodiments the at most two carbohydrate moieties are each in a terminal position. In certain embodiments the one carbohydrate moiety is in a terminal position. In certain embodiments the two carbohydrate moieties are on separate arms of a branched spacer moeity, wherein each carbohydrate is in a terminal position of one arm.

[0186] In certain embodiments -RB binds to at least one ASGPR and comprises one or more galactose (Gal) moieties and / or one or more N-acetylgalactosamine (GalNAc) moieties. In certain embodiments the one or more Gal moieties or one or more GalNAc moieties comprise a bridged ketal moiety.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -RB binds to at least one ASGPR and comprises one or more GalNAc moieties, such as at least 1, 2, 3, 4, 5, or 6 GalNAc moieties. In certain embodiments -RB comprises 3 GalNAc moieties. In certain embodiments -RB comprises 2 GalNAc moieties. In certain embodiments -RB comprises 1 GalNAc moiety.

[0187] In certain embodiments -RB is of formula (Id)

[0188] (CARB - i? -HL5-t

[0189] ;(Id),

[0190] wherein

[0191] -CARB is a carbohydrate moiety;

[0192] -L4- is a spacer moiety;

[0193] -L5- is a branched spacer moiety;

[0194] a is 1, 2, 3, 4, 5 or 6;

[0195] b is 0 if a is 1 or b is 1 if a is 2, 3, 4, 5 or 6; and

[0196] the dashed line indicates attachment to -L3- or -TB.

[0197] In certain embodiments -RB of formula (Id) binds to at least one ASGPR.

[0198] In certain embodiments a of formula (Id) is 1 and b of formula (Id) is 0.

[0199] In certain embodiments a of formula (Id) is 2 or more and b of formula (Id) is 1. In certain embodiments a of formula (Id) is 2 and b of formula (Id) is 1. In certain embodiments a of formula (Id) is 3 and b of formula (Id) is 1. In certain embodiments a of formula (Id) is 4 and b of formula (Id) is 1. In certain embodiments a of formula (Id) is 5 and b of formula (Id) is 1. In certain embodiments a of formula (Id) is 6 and b of formula (Id) is 1.

[0200] In certain embodiments -CARB of formula (Id) is a Gal moiety or a GalNAc moiety. In certain embodiments the Gal moiety or GalNAc moiety comprises a bridged ketal moiety. In certain embodiments -CARB of formula (Id) is a Gal moiety. In certain embodiments -CARB of formula (Id) is a GalNAc moiety.

[0201] In certain embodiments -CARB of formula (Id) is of formula (Ia#)Ascendis Pharma A / S CPX75237PC 12 January 2026

[0202]

[0203] -R1is -OH, -OC(O)R, a triazole or -Z1-*, wherein

[0204] -R is Ci-6 alkyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, phenyl, naphthyl, indenyl, indanyl or tetralinyl;

[0205] triazole or -Z1-*;

[0206]

[0207] provided that one of -R1, -R2or -R3is -Z1-*, wherein the asterisk indicates attachment to -L4-;

[0208] -R4and -R5are independently selected from the group consisting of -H, -C(O)CH3, -C(O)CH(CH3)2, -C(O)C(CH3)3and -CH2OC(O)C(CH3)3; or

[0209] -R4and -R5are cyclically linked and form a carbonate or phosphate;

[0210] -R11is -H or -CH2O-, which is connected to the carbon atom at the 1 -position;

[0211] -Z1- is -Z11-, -Zn-(C3.io cycloalkyl)-, -Zn-(3- to 10-membered heterocyclyl)- or C1-10 alkyl, which is optionally interrupted by one or more groups independently selected from the group consisting of -O-, -T- and -C(O)N(Ry1)-; which C1-10 alkyl is optionally substituted with one or more groups independently selected from the group consisting of -OH, -T and -C(O)N(Ry6Ry6a); wherein

[0212] -Ryl, -Ry6and -Ry6aare independently selected from the group consisting of -H and C1-6 alkyl;

[0213] -T- is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-io cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8- to 30-membered carbopoly cyclyl and 8- to 30-membered heteropoly cyclyl; wherein -T- is optionally substituted with C1-6 alkyl, which C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;

[0214] -Z11- is -O-, -S-, -NR21-, -C(O)NR21-, -S(O)2NR21-, -C(R22)2- orAscendis Pharma A / S CPX75237PC 12 January 2026

[0215]

[0216] wherein

[0217] =X' is =0 or =S;

[0218] t is 0 or 1;

[0219] each -R21and each -R23are independently selected from the group consisting of-H and Ci-6 alkyl;

[0220] each -R22is -H, halogen or Ci-6 alkyl; and

[0221] wherein -CARB is optionally further substituted.

[0222] In certain embodiments -R1of formula (Ia#) is -OH, -OC(O)CH3 or -OCH2C6H5. In certain embodiments -R1of formula (Ia#) is -OH.

[0223] In certain embodiments -R2of formula (Ia#) is -NHC(0)CH3.

[0224] In certain embodiments -R3of formula (Ia#) is -Z1-*, wherein

[0225]

[0226] the asterisk indicates attachment to -L4-.

[0227] In certain embodiments -R4of formula (Ia#) is -H. In certain embodiments -R5of formula (Ia#) is -H. In certain embodiments both -R4and -R5of formula (Ia#) are -H. In certain embodiments -R5of formula (Ia#) is -C(O)CH(CH3)2.

[0228] In certain embodiments -R11of formula (Ia#) is -H.

[0229] When -Z1- of formula (Ia#) is -T- or Ci -10 alkyl, -T- or C1-10 alkyl are in certain embodiments not optionally substituted. In certain embodiments -Z1- of formula (Ia#) is not further substituted. In certain embodiments -CARB of formula (Ia#) is not further substituted.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -CARB of formula (Id) is of formula (Ia#), wherein -R1is -OH; -R2is -NHC(0)CH3; and -R3is -Z1-*, wherein -Z1- is -O- and the asterisk indicates attachment of -Z1- to -L4-; and -R4, -R5and -R11are each -H.

[0230] In certain embodiments -CARB of formula (Id) is of formula (Ib#)

[0231]

[0232] wherein

[0233] the dashed line indicates attachment to -L4-;

[0234] -R1is -OH, -OC(O)R or a triazole, wherein

[0235] -R is Ci-6 alkyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, phenyl, naphthyl, indenyl, indanyl or tetralinyl;

[0236] -R2is -NHC(O)CH3, -NHC(O)CF3, -NHC(O)CH2CF3, -OH or a triazole;

[0237] -R4and -R5are independently selected from the group consisting of -H, -C(0)CH3, -C(O)CH(CH3)2, -C(O)C(CH3)3and -CH2OC(O)C(CH3)3; or

[0238] -R4and -R5are cyclically linked and form a carbonate or phosphate;

[0239] -Z1- is a moiety selected from the group consisting of -Z11-, -Zn-(C3-io cycloalkyl)-, -Z11- (3- to 10-membered heterocyclyl)- and C1-10 alkyl, which is optionally interrupted by one or more groups independently selected from the group consisting of -O-, -T- and - C(O)N(Ry1)-; which Ci -10 alkyl is optionally substituted with one or more groups independently selected from the group consisting of -OH, -T and -C(O)N(Ry6Ry6a); wherein

[0240] -Ryl, -Ry6, -Ry6aare independently selected from the group consisting of -H and C1-6 alkyl;

[0241] -T- is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8- to 30-membered carbopoly cyclyl and 8- to 30-membered heteropoly cyclyl; wherein -T- is optionally substituted with C1-6 alkyl, which C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;Ascendis Pharma A / S CPX75237PC 12 January 2026 -Z11- is selected from the group consisting of -O-, -S-, -NR21-, -C(O)NR21-, -S(O)2NR21-, -C(R22)2- and

[0242]

[0243] wherein

[0244] =X' is =0 or =S;

[0245] t is 0 or 1;

[0246] -R21and each -R23are independently -H or Ci-6 alkyl;

[0247] each -R22is independently selected from the group consisting of -H, halogen and Ci-6 alkyl; and

[0248] wherein -CARB is optionally further substituted.

[0249] In certain embodiments -CARB of formula (Ib#) is not further substituted.

[0250] In certain embodiments -Z1- of formula (Ib#) is in an alpha configuration

[0251]

[0252] In certain embodiments -Z1- of formula (Ib#) is in a beta configuration

[0253]

[0254] In certain embodiments -R1of formula (Ib#) is -OH, -OC(O)CH3 or -OCH2CeH5. In certain embodiments -R1of formula (lb#) is -OH.Ascendis Pharma A / S CPX75237PC 12 January 2026

[0255] In certain embodiments -R2of formula (Ib#) is -NHC(O)CH3.

[0256] In certain embodiments -R4of formula (Ib#) is -H. In certain embodiments -R5of formula (Ib#) is -H. In certain embodiments both -R4and -R5of formula (Ib#) are -H. In certain embodiments -R5of formula (Ib#) is -C(O)CH(CH3)2.

[0257] In certain embodiments -Z1- of formula (Ib#) is -Zn-(C3-io cycloalkyl)- or -Zn-(3- to 10-membered heterocyclyl)-. In certain embodiments the 3- to 10-membered heterocyclyl is a 5- or 6-membered heterocyclyl. In certain embodiments the 3- to 10-membered heterocyclyl is a 5-membered heterocyclyl. In certain embodiments the 5-membered heterocyclyl is a triazole. In certain embodiments the triazole is a 1,2,3-triazole moiety. In certain embodiments -Z11- of formula (Ib#) is -C(R22)2-. In certain embodiments at least one -R22of formula (Ib#) is -H. In certain embodiments both -R22of formula (Ib#) are -H. In certain embodiments -Z11- of formula (Ib#) is -O-. In certain embodiments -Z11- of formula (Ib#) is -S-. In certain embodiments -Z11- of formula (Ib#) is -NR21, wherein -R21of formula (Ib#) is -H or C1-6 alkyl. In certain embodiments -Z1- of formula (Ib#) is -C(R22)2-triazole-. In certain embodiments at least one -R22of formula (Ib#) is -H. In certain embodiments both -R22of formula (Ib#) are -H.

[0258] In certain embodiments -Z1- of formula (Ib#) is

[0259]

[0260] wherein the unmarked dashed line indicates attachment to the C-atom at position 1 and the dashed line marked with the asterisk indicates attachment to -L4-.

[0261] In certain embodiments -Z1- of formula (Ib#) is -Z11-. In certain embodiments -Z11- is -C(R22)2-. In certain embodiments at least one -R22is -H. In certain embodiments both -R22are -H, and -Z11- is -CH2-. In certain embodiments -Z11- is -O-. In certain embodiments -Z11- is -S-. In certain embodiments -Z11- is -NR21, wherein -R21is -H or C1-6 alkyl.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -Z1- of formula (Ib#) is a 5- or 6-membered cycloalkyl or 5- or 6-membered heterocyclyl. In certain embodiments -Z1- of formula (Ib#) is

[0262]

[0263] wherein the unmarked dashed line indicates attachment to the C-atom at position 1 and the dashed line marked with the asterisk indicates attachment to -L4-.

[0264] In certain embodiments -Z1- of formula (Ib#) is -O-, -S-, -C(R22)2-, -NR21-, -C(O)NR21- or

[0265]

[0266] wherein =X' is =0 or =S; t is 0 or 1; -R21and each -R23are independently selected from the group consisting of -H and Ci-6 alkyl; and each -R22is independently selected from the group consisting of -H, halogen and Ci-6 alkyl.

[0267] In certain embodiments -Z1- of formula (Ib#) is Ci-6 alkyl. In certain embodiments -Z1- of formula (Ib#) is methyl. In certain embodiments -Z1- of formula (Ib#) is ethyl. In certain embodiments -Z1- of formula (Ib#) is n-propyl. In certain embodiments -Z1- of formula (Ib#) is isopropyl. In certain embodiments -Z1- of formula (Ib#) is n-butyl. In certain embodiments -Z1- of formula (Ib#) is isobutyl. In certain embodiments -Z1- of formula (Ib#) is sec-butyl. In certain embodiments -Z1- of formula (Ib#) is tert-butyl. In certain embodiments -Z1- of formula (Ib#) is n-pentyl. In certain embodiments -Z1- of formula (Ib#) is 2-methylbutyl. In certain embodiments -Z1- of formula (Ib#) is 2,2-dimethylpropyl. In certain embodiments -Z1- of formula (Ib#) is n-hexyl. In certain embodiments -Z1- of formula (Ib#) is 2-methylpentyl. In certain embodiments -Z1- of formula (Ib#) is 3 -methylpentyl. In certain embodiments -Z1- of formula (Ib#) is 2,2-dimethylbutyl. In certain embodiments -Z1- of formula (Ib#) is 2,3-dimethylbutyl. In certain embodiments -Z1- of formula (Ib#) is 3, 3 -dimethylpropyl.

[0268] In certain embodiments -Z1- of formula (Ib#) is -O-, -S-, -CH2-, -NH- or

[0269]

[0270] Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -Z1- of formula (Ib#) is -O-.

[0271] In certain embodiments -CARB of formula (Id) is

[0272]

[0273] wherein

[0274] -R5is -C(O)CH3or -C(O)CH(CH3)2, and

[0275] the dashed line indicates attachment to -L4-.

[0276] In certain embodiments -CARB of formula (Id) is of formula (Ib#-a). In certain embodiments -CARB of formula (Id) is of formula (Ib#-b). In certain embodiments -CARB of formula (Id) is of formula (Ib#-c). In certain embodiments -CARB of formula (Id) is of formulaAscendis Pharma A / S CPX75237PC 12 January 2026 (Ib#-d). In certain embodiments -CARB of formula (Id) is of formula (Ib#-e). In certain embodiments -CARB of formula (Id) is of formula (Ib#-f).

[0277] In certain embodiments -CARB of formula (Id) is

[0278]

[0279] wherein

[0280] nl is 1, 2, 3, 4, 5 or 6; and

[0281] the dashed line indicates attachment to -L4-.

[0282] In certain embodiments -CARB of formula (Id) is

[0283]

[0284] wherein n2 is 1, 2, 3, 4, 5 or 6; and

[0285] the dashed line indicates attachment to -L4-.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -CARB is of formula (Ib#), -R5and -R4are cyclically linked and form a carbonate or phosphate. In certain embodiments -CARB of formula (Id) is

[0286]

[0287] wherein

[0288] the dashed line indicates attachment to -L4-;

[0289] n2 is 1, 2, 3, 4, 5 or 6; and

[0290] Y4+is a suitable counterion, such as potassium, sodium, lithium or ammonium.

[0291] In certain embodiments -CARB of formula (Id) is of formula (Ic#)

[0292]

[0293] the dashed line indicates attachment to -L4-;

[0294] -R2, -R4, -R5and -Z1- are used as defined for formula (Ib#);

[0295] -R11is used as defined for formula (Ia#);

[0296] -R3is -H, -OH, -CH3, -OCH3 or -OCH2CH=CH; and

[0297] -CARB is optionally substituted.

[0298] In certain embodiments the C-atom to which -Z1- of formula (Ic#) is attached to is substituted with an oxo (=0) group.

[0299] In certain embodiments -CARB of formula (Ic#) is not substituted.

[0300] In certain embodiments -CARB of formula (Ic#) isAscendis Pharma A / S CPX75237PC

[0301] 12 January 2026

[0302]

[0303] wherein the dashed line indicates attachment to -L4-.

[0304] In certain embodiments -CARB of formula (Ic#) is of formula (Ic#-c)

[0305]

[0306] wherein the dashed line indicates attachment to -L4-.

[0307] In certain embodiments -CARB of formula (Id) is of formula (Id#)

[0308]

[0309] "

[0310] wherein

[0311] the dashed line indicates attachment to -L4-;

[0312] -R1, -R4, -R5and -Z1- are used as defined for formula (Ib#); -R3is used as defined for formula (Ic#); and

[0313] -CARB is optionally substituted.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -Z1- of formula (Id#) is

[0314]

[0315] wherein

[0316] the unmarked dashed line indicates attachment to the remainder of formula (Id#) and the dashed line marked with the asterisk indicates attachment to -L4-.

[0317] In certain embodiments -Z1- of formula (Id#) is

[0318]

[0319] wherein

[0320] the unmarked dashed line indicates attachment to the remainder of formula (Id#) and the dashed line marked with the asterisk indicates attachment to -L4-.

[0321] In certain embodiments -CARB of formula (Id#) is not further substituted.

[0322] In certain embodiments -CARB of formula (Id#) isAscendis Pharma A / S CPX75237PC 12 January 2026

[0323]

[0324] wherein

[0325] -R6is independently -H or Ci-6 alkyl; and

[0326] the dashed line indicates attachment to -L4-.

[0327] In certain embodiments of -R3of formula (Id#) is -H.

[0328] In certain embodiments -CARB of formula (Id#) is

[0329]

[0330] wherein

[0331] the dashed line indicates attachment to -L4-;

[0332] -R1, -R4and -R5are used as defined for formula (Ib#);

[0333] -R11is used as defined for formula (Ia#);

[0334] -Z2- is absent or is -O-, -S-, NR25-, -N(C(0)CH3)- or -C(R22)2-;

[0335] ring A is absent or a 5- or 6-membered cycloalkyl or 5- or 6-membered heterocyclyl; -Z3- is -Z12-, -Z12-alkyl, -Z12-(C3-IO cycloalkyl)-, -Z12-(3- to 10-membered heterocyclyl)- or Ci-io alkyl, which is optionally interrupted by one or more groups independently selected from the group consisting of -O-, -T- and -C(O)N(Ry1)-; andAscendis Pharma A / S CPX75237PC 12 January 2026 which Ci-io alkyl is optionally substituted with one or more groups independently selected from the group consisting of -OH, -T and -C(O)N(Ry6Ry6a);

[0336] -Ryl, -Ry6and -Ry6aare independently selected from the group consisting of -H and Ci-6 alkyl;

[0337] -T- is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8- to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropolycyclyl, wherein -T- is optionally substituted with C1-6 alkyl, which is optionally substituted with one or more halogen, which are the same or different; and -Z12- is selected from the group consisting of -O-, -S-, -NR26-, -C(O)NR26-, -NR26C(O)-, -S(O)2NR26- and -C(R22)2-;

[0338] -R25and -R26are independently selected from the group consisting of -H, C1-6 alkyl, and Ci -6 acyl;

[0339] each -R22is independently selected from the group consisting of -H, halogen and Ci -6 alkyl; and

[0340] wherein -CARB is optionally substituted.

[0341] In certain embodiments -Z2- of formulae (Ie#’), (Ie#”) or (Ie#) is absent. In certain embodiments -Z2- of formulae (Ie#’), (Ie#”) or (Ie#) is -C(R22)2-, wherein -R22is -H or C1-6 alkyl. In certain embodiments -Z2- of formulae (Ie#’), (Ie#”) or (Ie#) is -CH2-. In certain embodiments -Z2- of formulae (Ie#’), (Ie#”) or (Ie#) is -NR25, wherein -R25is selected from the group consisting of -H, C1-6 alkyl and C1-6 acyl. In certain embodiments -Z2- of formulae (Ie#’), (Ie#”) or (Ie#) is -N(C(0)CH3)-. In certain embodiments -Z2- of formulae (Ie#’), (Ie#”) or (Ie#) is -NH-. In certain embodiments -Z2- of formulae (Ie#’), (Ie#”) or (Ie#) is -S-. In certain embodiments -Z2- of formulae (Ie#’), (Ie#”) or (Ie#) is -O-.

[0342] In certain embodiments -CARB of formula (Ie#) is

[0343]

[0344] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0345]

[0346] wherein

[0347] ring A, -R1, -R4, -R5, -R11, -R25and -Z3and are as defined for formula (Ie#) and the dashed line indicates attachment to -L4-.

[0348] In certain embodiments ring A of formula (le**), (le**’), (le**”), (If**), (Ig#), (Ih#) or (Ii#) is a 5- or 6-membered cycloalkyl or 5- or 6-membered heterocyclyl. In certain embodiments ring A of formula (Ie#), (Ie#’), (le**”), (if*), (Ig**), (Ih**) or (li**) is a 5-membered heterocyclyl selected from the group consisting of triazole, thiadiazole, thiophene, oxazole, isoxazole, isothiazole, thiazole, oxadiazole and furan. In certain embodiments ring A of formula (le**), (le**’), (Ie#”), (If**), (Ig**), (Ih**) or (li**) is a 6-membered heterocyclyl selected from the group consisting of pyridine, pyrimidine, pyridazine, pyrazine and triazine. In certain embodiments ring A of formula (le**), (le**’), (le**’ ’), (If**), (Ig**), (Ih**) or (li**) is triazole. In certain embodiments ring A of formula (le**), (le**’), (le**”), (If**), (Ig**), (Ih**) or (li**) is pyridine. In certain embodiments ring A of formula (le**), (le**’), (le**”), (If**), (Ig**), (Ih**) or (li**) is pyrimidine. In certain embodiments ring A of of formula (le**), (le**’), (le**”), (If**), (Ig**), (Ih**) or (li**) is thiadiazole.

[0349] In certain embodiments of formula (le**), (le**’), (le**”), (If**), (Ig**), (Ih**) or (li**) ring A is absent. In certain embodiments of formula (le**), (le**’), (le**”), (If**), (Ig**), (Ih**) or (li**) ring A is phenyl.

[0350] In certain embodiments the ring A of formula (Ig**) is absent and -R25is -H or Ci-6 acyl. In certain embodiments -R25is -C(0)CH3. In certain embodiments -R25is -H.

[0351] In certain embodiments -CARB of formula (Id) isAscendis Pharma A / S CPX75237PC 12 January 2026

[0352]

[0353] wherein

[0354] the dashed line indicates attachment to -L4-;

[0355] -R1, -R4, -R5, -R25and -Z3- are used as defined for formula (Ie#);

[0356] Y1, Y2and Y3are independently N or CR27;

[0357] -R24and -R27are independently selected from the group consisting of -H, Ci-6 alkyl and Ci-6 alkyl substituted with one or more halogen, which are the same or different; and halogen; and

[0358] wherein -CARB is optionally substituted.

[0359] In certain embodiments -Z3- of formula (le**), (le**’), (le**”), (If**), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**) or (Im**) is selected from the group consisting of -O-, -CH2O-, -OCH2-, -OCH2-(3- to 10-membered heterocyclyl)-, -OCH2-(C3-IO cycloalkyl)-, -CIBO-Q- to 10-membered heterocyclyl)- and -CH20-(C3-IO cycloalkyl)-.

[0360] In certain embodiments -Z3- of formula (Ie#), (Ie#’), (le**”), (If**), (Ig#), (Ih#), (Ii#), (Ij#), (Ik#), (Il#) or (Im**) is

[0361]

[0362] wherein the unmarked dashed line indicates attachment to the remainder of formula (le**), (le**’), (le**”), (if*), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**) or (Im**), respectively, and the dashed line marked with the asterisk indicates attachment to -L4-.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -Z3- of formula (le**), (le**’), (le**”), (If**), (Ig#), (Ih**), (Ii#), (Ij#), (Ik#), (Il#) or (Im**) is -O-, -S-, -NR26-, -C(O)NR26-, -NR26C(O)-, -S(O)2NR26- or -C(R22)2-; wherein -R26is -H, Ci-6 alkyl or Ci-6 acyl; and each -R22is independently selected from the group consisting of -H, halogen and Ci-6 alkyl.

[0363] In certain embodiments -Z3- of formula (le**), (le**’), (le**”), (if*), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**) or (Im**) is -CH2-. In certain embodiments -Z3- of formula (le**), (le**’), (le**”), (If**), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**) or (Im**) is -CH2CH2-. In certain embodiments -Z3- of formula (le**), (le**’), (le**”), (If*), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**) or (Im**) is -CH2CH2CH2-. In certain embodiments -Z3- of formula (le**), (le**’), (le**”), (If**), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**) or (Im**) is -NHSO2-(CI-6 alkyl)-. In certain embodiments -Z3- of formula (le**), (le**’), (le**”), (If**), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**) or (Im**) is -N(C(O)CH3)-(CI-6alkyl)-.

[0364] In certain embodiments -Z3- of formula (le**), (le**’), (le**”), (If**), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**) or (Im**) is -S- or -NR26-, wherein -R26is -H or Ci-6 alkyl.

[0365] In certain embodiments at least one of Y1, Y2and Y3of formula (Ik**) is N. In certain embodiments at least two of Y1, Y2and Y3of formula (Ik**) are N. In certain embodiments Y1and Y3of formula (Ik**) are N and Y2of formula (Ik**) is CR25. In certain embodiments Y1and Y2of formula (Ik**) are N and Y3of formula (Ik**) is CR25. In certain embodiments Y1and Y2of formula (Ik**) are CR25and Y3of formula (Ik**) is N. In certain embodiments -R25is -H. In certain embodiments -R25is Ci-6 alkyl or Ci-6 alkyl substituted with one or more halogen, which are the same or different. In certain embodiments -R25is -CF3.

[0366] In certain embodiments -CARB of formula (le**) isAscendis Pharma A / S CPX75237PC 12 January 2026

[0367]

[0368] In certain embodiments -CARB of formula (Id) is

[0369]

[0370] whereinAscendis Pharma A / S CPX75237PC 12 January 2026 the dashed line indicates attachment to -L4-,

[0371] -R1, -R4, -R5, and -Z1- are defined as for formula (Ib#);

[0372] -Y1- and -Y2- are independently selected from the group consisting of -O-, -S-, -NR28- and -C(R22)2-;

[0373] -R28is -H, Ci-6 alkyl or -C(O)R22;

[0374] each -R22is independently selected from the group consisting of -H, halogen and Ci -6 alkyl;

[0375] ring B is a 5- or 6-membered cycloalkyl or 5- or 6-membered heterocyclyl; and wherein -CARB is optionally further substituted.

[0376] In certain embodiments -Y1- of formula (In1) is connected to the sugar ring via an alpha configuration. In certain embodiments -Y1- of formula (In1) is connected to the sugar ring via a beta configuration.

[0377] In certain embodiments -Y1- of formula (In#) or (In#l) is -O-. In certain embodiments -Y1- of formula (In#) or (In#l) is -S-. In certain embodiments -Y1- of formula (In#) or (In#l) is -NR28-. In certain embodiments -Y1- of formula (In#) or (In#l) is -C(R22)2- and each -R22is -H.

[0378] In certain embodiments -Y2- of formula (In#) or (In#l) is -NR28-, wherein -R28is -H. In certain embodiments -Y2- of formula (In#) or (In#l) is -NR28-, wherein -R28is -C(O)R22. In certain embodiments -R22is methyl.

[0379] In certain embodiments the ring B of formula (In#) or (In#l) is a 5- or 6-membered heterocyclyl. In certain embodiments the ring B is a 5-membered heterocyclyl. In certain embodiments the ring B is a 6-membered heterocyclyl.

[0380] In certain embodiments -CARB of formula (Id) is

[0381] <

[0382]

[0383] wherein the dashed line indicates attachment to -L4-.Ascendis Pharma A / S CPX75237PC 12 January 2026

[0384] In certain embodiments -R1of formula (Ia#), (Ia#-1), (Ib#), (Id#), (Ie#), (Ie#’), (le**”), (if*), (Ig#), (Ih#), (Ii#), (Ij#), (Ik#), (Il#), (Im#), (In#) or (In#) is -OH. In certain embodiments -R1of formula (la**), (Ia**-1), (lb**), (Id**), (le**), (le**’), (le**”), (if*), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**), (Im**), (In**) or (In** ) is -OC(O)R, wherein -R is a Ci-6 alkyl. In certain embodiments -R1of formula (la**), (Ia**-1), (lb**), (Id**), (le**), (le**’), (le**”), (If**), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**), (Im**), (In**) or (In** ) is triazole. In certain embodiments the triazole is

[0385]

[0386] , wherein the dashed line indicates attachment to the remainder of formula (la**), (Ia**-1), (lb**), (Id**), (le**), (le**’), (le**”), (if*), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**), (Im**), (In**) or (In** ).

[0387] In certain embodiments -R1of formula (la**), (Ia**-1), (lb**), (Id**), (le**), (le**’), (le**”), (If**), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**), (Im**), (In**) or (In** ) is a substituted triazole. In certain embodiments the triazole is a 1,2,3-triazole and the substituent is at the 4- or 5-position. In certain embodiments the substituent on the triazole moiety includes but is not limited to Ci-6 alkyl, C2- 6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, phenyl, naphthyl, indenyl, indanyl and tetralinyl.

[0388] In certain embodiments -R2of formula (la**), (Ia**-1), (lb**) or (Ic**) is -NHC(0)CH3. In certain embodiments -R2of formula (la**), (Ia**-1), (lb**) or (Ic**) is -NHC(0)CF3. In certain embodiments -R2of formula (la**), (Ia**-1), (lb**) or (Ic**) is -NHC(O)CH2CF3. In certain embodiments -R2of formula (la**), (la**- 1), (lb**) or (Ic**) is -OH. In certain embodiments -R2of formula (la**), (Ia**-1), (lb**) or (Ic**) is a triazole. In certain embodiments the triazole is

[0389]

[0390] , wherein the dashed line indicates attachment to the remainder of formula (la**), (la**- 1), (lb**) or (Ic**).

[0391] In certain embodiments -R2of formula (la**), (Ia**-1), (lb**) or (Ic**) is a substituted triazole. In certain embodiments the triazole is a 1,2,3-triazole and the substituent is at the 4- or 5-position. In certain embodiments the substituent on the triazole moiety includes but is not limited to Ci-6Ascendis Pharma A / S CPX75237PC 12 January 2026 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, phenyl, naphthyl, indenyl, indanyl and tetralinyl.

[0392] In certain embodiments at least one of -R4and -R5of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id**),(Ie**), (le**’), (le**”), (if*), (Ig**), (Ih**), (Ii#), (Ij#), (Ik#), (Il#), (Im#), (In#), or (In** ) is -C(O)CH3, -C(O)CH(CH3)2 or -C(O)C(CH3)3. In certain embodiments at least one of -R4and -R5of formula (la**), (Ia**-1), (lb**), (Ic**), (Id**), (le**), (le**’), (le**”), (if*), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**), (Im**), (In**) or (In**‘) is -CH2OC(O)C(CH3)3. In certain embodiments -R4of formula (la**), (Ia**-1), (lb**), (Ic**), (Id**), (le**), (le**’), (le**”), (If**), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**), (Im**), (In**), or (In**‘ ) is -CH2OC(O)C(CH3)3 and -R5is -H. In certain embodiments both -R4and -R5are -CH2OC(O)C(CH3)3. In certain embodiments -R4and -R5are cyclically linked and form a carbonate or phosphate. In certain embodiments -R4and -R5are cyclically linked and form a carbonate or phosphate as shown in formulae (Io**) and (Ip**)

[0393]

[0394] wherein

[0395] -R1, -R2, -R3are defined as for formula (la**); and

[0396] Y4+is a suitable counterion, such as potassium, sodium, lithium or ammonium.

[0397] In certain embodiments both -R4and -R5of formula (la**), (Ia**-1), (lb**), (Ic**), (Id**), (le**), (le**’), (le**”), (If*), (Ig**), (Ih**), (li**), (Ij**), (Ik**), (II**), (Im**), (In**) or (In**‘) are -H.

[0398] In certain embodiments -Z1- of formula (la**), (Ia**-1), (lb**), (Ic**), (Id**), (In**) or (In**‘) is -Z11-(C3-10 cycloalkyl)- or -Zn-(3- to 10-membered heterocyclyl)-. In certain embodiments the 3- to 10-membered heterocyclyl is a 5- or 6-membered heterocyclyl. In certain embodiments the 3-to 10-membered heterocyclyl is a 5-membered heterocyclyl. In certain embodiments the 5-membered heterocyclyl is a triazole. In certain embodiments the triazole is a 1,2,3-triazole moiety. In certain embodiments -Z11- of formula (la**), (Ia**-1), (lb**), (Ic**), (Id**), (In**) or (In**‘) is -C(R22)2-. In certain embodiments at least one -R22of formula (la**), (la**- 1), (lb**), (Ic**), (Id**), (In**) or (In**‘) is -H. In certain embodiments both -R22of formula ((la**), (la**- 1), (lb**), (Ic**), (Id**), (In**) or (In**‘) are -H. In certain embodiments -Z11- of formula (la**), (Ia**-1), (lb**), (Ic**), (Id**),Ascendis Pharma A / S CPX75237PC 12 January 2026 (In#) or (In#‘) is -O-. In certain embodiments -Z11- of any one of (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is -S-. In certain embodiments -Z11- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is -NR21, wherein -R21of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is -H or Ci-6 alkyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is -C(R22)2-triazole-. In certain embodiments at least one -R22of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is -H. In certain embodiments both -R22of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) are -H.

[0399] In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is -Z11-. In certain embodiments -Z11- is -C(R22)2-. In certain embodiments at least one -R22is -H. In certain embodiments both -R22are -H, and -Z11- is -CH2-. In certain embodiments -Z11- is -O-. In certain embodiments -Z11- is -S-. In certain embodiments -Z11- is -NR21, wherein -R21is -H or C1-6 alkyl.

[0400] In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is -C(O)NH- or -NHC(O)-. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is -S(O)2NH-. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is -NHC(O)NH-or -NHC(S)NH-.

[0401] In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is a 5- or 6-membered cycloalkyl or 5- or 6-membered heterocyclyl.

[0402] In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is selected from the group consisting of -O-, -S-, -C(R22)2-, -NR21-, -C(O)NR21- and

[0403] 1

[0404]

[0405] , wherein =X is =0 or =S; t is 0 or 1; -R and each -R are independently selected from the group consisting of -H or C1-6 alkyl; and each -R22is independently selected from the group consisting of -H, halogen and C1-6 alkyl.

[0406] In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is C1-6 alkyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is methyl. In certain embodiments -Z1- of formula ((Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘)Ascendis Pharma A / S CPX75237PC 12 January 2026 is ethyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is n-propyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is isopropyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is n-butyl. In certain embodiments -Z1- of formula ((Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is isobutyl. In certain embodiments -Z1- of formula ((Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is sec-butyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is tert-butyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is n-pentyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is 2-methylbutyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is 2,2-dimethylpropyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is n-hexyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is 2-methylpentyl. In certain embodiments -Z1- of formula ((Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is 3 -methylpentyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is 2,2-dimethylbutyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is 2, 3 -dimethylbutyl. In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is 3, 3 -dimethylpropyl.

[0407] In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is -O-,

[0408]

[0409] In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is -O-.

[0410] In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is of formula (Id#-i). In certain embodiments -Z1- of formula ((Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is of formula (Id#-ii). In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is of formula (Id#-iii). In certain embodiments -Z1- of formula (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is of formula (Id#-iv). In certain embodiments -Z1- of any one of formulae (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is of formula (Id#-v).

[0411] In certain embodiments -Z1- of any one of formulae (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is of formula (Id#-vi). In certain embodiments -Z1- of any one of formulae (Ia#), (Ia#-1), (Ib#),Ascendis Pharma A / S CPX75237PC 12 January 2026 (Ic#), (Id#), (In#) or (In#‘) is of formula (Id#-vii). In certain embodiments -Z1- of any one of formulae (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is of formula (Id#-viii). In certain embodiments -Z1- of any one of formulae (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is of formula (Id#-ix). In certain embodiments -Z1- of any one of formulae (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is of formula (Id#-x). In certain embodiments -Z1- of any one of formulae (Ia#), (Ia#-1), (Ib#), (Ic#), (Id#), (In#) or (In#‘) is of formula (Id#-xi).

[0412] In certain embodiments a of formula (Id) is 2 or 3, b of formula (Id) is 1 and -CARB of formula (Id) is of formula (Ib#-a), (Ib#-c), (Ib#-d), (Ib#-e), (Ib#-f), (Ic#-a), (Id#-a), (Id#-b) or (Id#-c) as defined herein.

[0413] In certain embodiments a of formula (Id) is 1, 2 or 3, b is 0 or 1 and -CARB of formula (Id) is of formula (Ib#-g), (Ib#-h), (Ib#-i), (Ib#-1) or (Ib#-m) as defined herein.

[0414] In certain embodiments a of formula (Id) is 1, 2 or 3; b is 0 or 1 and -CARB of formula (Id) is of formula (Ie#-a), (Ie#-b), (Ie#-c), (Ie#-d), (Ie#-e), (Ie#-f), (Ie#-g), (Ie#-h), (Ie#-i), (Ie#-j) or (Ie#-k) as defined herein.

[0415] In certain embodiments a of formula (Id) is 1, 2 or 3; b is 0 or 1 and -CARB of formula (Id) is of formula (In#-a) or (In#-b) as defined herein.

[0416] In certain embodiments a of formula (Id) is 2, b of formula (Id) is 1 and -CARB of formula (Id) is of formula (Ib#-a), (Ib#-c), (Ib#-d), (Ib#-e), (Ib#-f), (Ic#-a), (Id#-a), (Id#-b) or (Id#-c) as defined herein.

[0417] In certain embodiments a of formula (Id) is 1, b of formula (Id) is 0 and -CARB of formula (Id) is of formula (Ib#-g), (Ib#-h), (Ib#-i), (Ib#-1) or (Ib#-m) as defined herein.

[0418] In certain embodiments a of formula (Id) is 2, b is 1 and -CARB of formula (Id) is of formula (Ib#-g), (Ib#-h), (Ib#-i), (Ib#-1) or (Ib#-m) as defined herein.

[0419] In certain embodiments a of formula (Id) is 1, b is 0 and -CARB of formula (Id) is of formula (Ie#-a), (Ie#-b), (Ie#-c), (Ie#-d), (Ie#-e), (Ie#-f), (Ie#-g), (Ie#-h), (Ie#-i), (Ie#-j) or (Ie#-k) as defined herein.Ascendis Pharma A / S CPX75237PC 12 January 2026

[0420] In certain embodiments a of formula (Id) is 2; b is 1 and -CARB of formula (Id) is of formula (Ie#-a), (Ie#-b), (Ie#-c), (Ie#-d), (Ie#-e), (Ie#-f), (Ie#-g), (Ie#-h), (Ie#-i), (Ie#-j) or (Ie#-k) as defined herein.

[0421] In certain embodiments a of formula (Id) is 1, b is 0 and -CARB of formula (Id) is of formula (Ic#-c) as defined herein. In certain embodiments a of formula (Id) is 2, b is 1 and -CARB of formula (Id) is of formula (Ic#-c) as defined herein.

[0422] In certain embodiments a of formula (Id) is 1 b is 0 and -CARB of formula (Id) is of formula (In#-a) or (In#-b) as defined herein.

[0423] In certain embodiments a of formula (Id) is 2; b is 1 and -CARB of formula (Id) is of formula (In#-a) or (In#-b) as defined herein.

[0424] In certain embodiments -CARB of formula (Id) is of formula (Ib#-a).

[0425] In certain embodiments -RB is of formula (Id), wherein -CARB is of formula (Ib#-a), -L4- is a spacer moiety, -L5- is a branched spacer moiety, a is 3 and b is 1.

[0426] In certain embodiments CARB of formula (Id) is of formula (Iq#)

[0427]

[0428] wherein

[0429] -R2is selected from the group consisting of -OR6-(C3-io cycloalkyl)-, -OR6-(3- to 10-membered heterocyclyl)-, -OR6-(8- to 11 -membered heterobicyclyl)-, -NR6-(C3-io cycloalkyl)-, -NR6-(3- to 10-membered heterocyclyl)- and -NR6-(8-to 11-membered heterobicyclyl)-, wherein R2is optionally substituted with 1, 2, 3, or 4 substituentsAscendis Pharma A / S CPX75237PC 12 January 2026 independently selected from the group consisting of alkyl, alkenyl, haloalkyl, -OR6, F, Cl, Br, I, S, -NR6R7, cyano, nitro, and -C(O)R10;

[0430] -R6and -R7are independently selected at each occurrence from the group consisting of -H, alkyl, arylalkyl, alkenyl, C3-10 cycloalkyl, haloalkyl, 3- to 10-membered heterocyclyl, and -C(O)R10;

[0431] -R10is independently selected from the group consisting of -H, alkyl, haloalkyl, arylalkyl, alkenyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, -OR8, and - NR8R9;

[0432] -R8and -R9are independently selected at each occurrence from the group consisting of -H, alkyl, arylalkyl, alkenyl, C3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; -R3is -H, -OH, -CH3, -OCH3, or -OCH2CH=CH;

[0433] -R11is -H or -CH2O-, which is connected to the carbon atom at the 1 -position;

[0434] -Z1- is a moiety selected from the group consisting of -Z11-, -Zn-(C3-io cycloalkyl)-, -Zn-(3- to 10-membered heterocyclyl)- and C1-10 alkyl, which is optionally interrupted by one or more groups independently selected from the group consisting of -O-, -T- and -C(O)N(Ry1)-; which Ci -10 alkyl is optionally substituted with one or more groups independently selected from the group consisting of -OH, -T and -C(O)N(Ry6Ry6a); wherein

[0435] -Ryl, -Ry6and -Ry6aare independently selected from the group consisting of -H and Ci -6 alkyl;

[0436] -T- is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8- to 30-membered carbopoly cyclyl and 8- to 30-membered heteropoly cyclyl; wherein -T- is optionally substituted with C1-6 alkyl, which C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;

[0437] -Z11- is selected from the group consisting of -O-, -S-, -NR21-, -C(O)NR21-, -S(O)2NR21-, -C(R22)2- and

[0438]

[0439] whereinAscendis Pharma A / S CPX75237PC 12 January 2026 =X' is =0 or =S;

[0440] t is 0 or 1;

[0441] each -R21and each -R23are independently -H or Ci-6 alkyl;

[0442] each -R22is independently selected from the group consisting of -H, halogen and Ci-6 alkyl; and

[0443] wherein -CARB is optionally further substituted.

[0444] In certain embodiments -R2of formula (Iq#) is selected from the group consisting of

[0445]

[0446] In certain embodiments CARB of formula (Iq#) is selected from the group consisting of

[0447]

[0448] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0449]

[0450] wherein

[0451] the dashed line indicates attachment to -L4-.

[0452] In certain embodiments a of formula (Id) is 1, b is 0 and -CARB of formula (Id) is of formula (Iq#-a) as defined herein. In certain embodiments a of formula (Id) is 2, b is 1 and -CARB of formula (Id) is of formula (Iq#-a) as defined herein.

[0453] In certain embodiments -L4- is a spacer moiety selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50 alkyl, C2.5o alkenyl and C2.5o alkynyl; wherein -T-, Ci-50 alkyl, C2-so alkenyl and C2-so alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50 alkyl, C2-so alkenyl and C2-so alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-and -OC(O)N(Ry3)-;Ascendis Pharma A / S CPX75237PC 12 January 2026 -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, Ci-50 alkyl, C2-50 alkenyl and C2-50 alkynyl; wherein -T, C1-50 alkyl, C2-50 alkenyl and C2-50 alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-50 alkyl, C2-50 alkenyl and C2-50 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)- and -OC(O)N(Ry4)-;

[0454] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopolycyclyl and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0455] each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and Ci-6alkyl; wherein Ci-6alkyl is optionally substituted with one or more halogen, which are the same or different; and

[0456] each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H and Ci-6 alkyl, wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0457] In certain embodiments -L4- is a spacer moiety selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(0)2N(Ryla)-, -S-, -N(Ry1)-, -0C(0Ryl)(Ryla)-, -N(Ryl)C(0)N(Ryla)-, -0C(0)N(Ryl)-, Ci-50 alkyl, C2-50 alkenyl and C2-50 alkynyl; wherein -T-, C1-50 alkyl, C2-50 alkenyl and C2-50 alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50 alkyl, C2-50 alkenyl and C2-50 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)- and -0C(0)N(Ry3)-;

[0458] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, Ci-10 alkyl, C2-10 alkenyl and C2-10 alkynyl; wherein -T, C1-10 alkyl, C2-10 alkenyl and C2-10 alkynyl are optionally substituted with one or more -Ry2, which are the same or different, andAscendis Pharma A / S CPX75237PC 12 January 2026 wherein Ci-io alkyl, C2-10 alkenyl and C2-10 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)- and -OC(O)N(Ry4)-;

[0459] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopolycyclyl and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0460] -Ry2is selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5) C(0)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; and

[0461] each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0462] In certain embodiments -L4- is a spacer moiety selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(0)2N(Ryla)-, -S-, -N(Ry1)-, -0C(0Ryl)(Ryla)-, -N(Ryl)C(0)N(Ryla)-, -0C(0)N(Ryl)-, Ci-50 alkyl, C2-50 alkenyl and C2-50 alkynyl; wherein -T-, C1-50 alkyl, C2-50 alkenyl and C2-50 alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50 alkyl, C2-50 alkenyl and C2-50 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)- and -0C(0)N(Ry3)-;

[0463] -Ryland -Rylaare independently selected from the group consisting of -H, -T, C1-10 alkyl, C2-10 alkenyl and C2-10 alkynyl;

[0464] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopolycyclyl and 8- to 30-membered heteropolycyclyl; each -Ry2is independently selected from the group consisting of halogen and C1-6 alkyl; andAscendis Pharma A / S CPX75237PC 12 January 2026 each -Ry3, and -Ry3aand -Ry5bis independently of each other selected from the group consisting of -H and Ci-6 alkyl; wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0465] In certain embodiments -L4- is a C1-20 alkyl chain, which is optionally interrupted by one or more groups independently selected from -C(O)-, -N(Ry1)-, -O-, -S-, -T- and -C(O)N(Ry1)-; and which C1-20 alkyl chain is optionally substituted with one or more groups independently selected from halogen, -OH, -T and -N(RylRyla); wherein -Ryland -Rylaare independently selected from the group consisting of H and C1-4 alkyl and wherein T is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11 -membered heterobicyclyl, 8-to 30-membered carbopolycyclyl and 8- to 30-membered heteropolycyclyl, which is optionally substituted with one or more oxo (=0) or halogen.

[0466] In certain embodiments -L4- has a molecular weight ranging from 14 g / mol to 750 g / mol.

[0467] In certain embodiments -L4- comprises a moiety selected from the group consisting of

[0468]

[0469] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0470]

[0471] wherein

[0472] -R and -Raare independently of each other selected from the group consisting of -H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3 -methylpentyl, 2,2-dimethylbutyl, 2,3- dimethylbutyl and 3, 3 -dimethylpropyl.

[0473] In certain embodiments -L4- comprises repeating ethylene glycol moieties (-CH2CH2O-). In certain embodiments -L4- comprises 1 to 25 ethylene glycol moieties, such as 2 to 15 or 3 to 10 ethylene glycol moieties. In certain embodiments -L4- comprises 2 or more ethylene glycol moieties, such as 3, 4, 5, 6, 7, 8, 9 or 10 ethylene glycol moieties. In certain embodiments -Incomprises 2 ethylene glycol moieties. In certain embodiments -L4- comprises 3 ethylene glycol moieties. In certain embodiments -L4- comprises 4 ethylene glycol moieties. In certain embodiments -L4- comprises 5 ethylene glycol moieties.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments of -L4- comprises one or more triazole moieties. In certain embodiments -L4- comprises one or more 1,2, 3 -triazole moieties. In certain embodiments the one or more 1,2, 3 -triazole moiety is

[0474]

[0475] wherein the dashed lines indicate attachment to the remainder of -L4-; and

[0476] wl, ul and ql are independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25.

[0477] In certain embodiments wl, ul and ql are independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12. In certain embodiments wl, ul and ql are independently 1, 2, 3, 4, 5 or 6.

[0478] In certain embodiments of -L4- comprises a moiety

[0479]

[0480] In certain embodiments -L4- is of formula (le)

[0481]

[0482] wherein

[0483] the unmarked dashed line indicates attachment to -Z1- of -CARB;

[0484] the dashed line marked with the asterisk indicates attachment to -L5-, -L3- or -TB; andAscendis Pharma A / S CPX75237PC 12 January 2026 nl, n2 and n3 are independently an integer ranging from 0 to 25.

[0485] In certain embodiments the dashed line marked with the asterisk in formula (le) indicates attachment to -L5-. In certain embodiments the dashed line marked with the asterisk in formula (le) indicates attachment to -L3-. In certain embodiments the dashed line marked with the asterisk in formula (le) indicates attachment to -TB.

[0486] In certain embodiments nl of formula (le) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments nl of formula (le) is 0. In certain embodiments nl of formula (le) is 1. In certain embodiments nl of formula (le) is 2. In certain embodiments nl of formula (le) is 3. In certain embodiments nl of formula (le) is 4. In certain embodiments nl of formula (le) is 5. In certain embodiments nl of formula (le) is 6. In certain embodiments nl of formula (le) is 7. In certain embodiments nl of formula (le) is 8. In certain embodiments nl of formula (le) is 9. In certain embodiments nl of formula (le) is 10.

[0487] In certain embodiments n2 of formula (le) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments n2 of formula (le) is 0. In certain embodiments n2 of formula (le) is 1. In certain embodiments n2 of formula (le) is 2. In certain embodiments n2 of formula (le) is 3. In certain embodiments n2 of formula (le) is 4. In certain embodiments n2 of formula (le) is 5. In certain embodiments n2 of formula (le) is 6. In certain embodiments n2 of formula (le) is 7. In certain embodiments n2 of formula (le) is 8. In certain embodiments n2 of formula (le) is 9. In certain embodiments n2 of formula (le) is 10.

[0488] In certain embodiments n3 of formula (le) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments n3 of formula (le) is 0. In certain embodiments n3 of formula (le) is 1. In certain embodiments n3 of formula (le) is 2. In certain embodiments n3 of formula (le) is 3. In certain embodiments n3 of formula (le) is 4. In certain embodiments n3 of formula (le) is 5. In certain embodiments n3 of formula (le) is 6. In certain embodiments n3 of formula (le) is 7. In certain embodiments n3 of formula (le) is 8. In certain embodiments n3 of formula (le) is 9. In certain embodiments n3 of formula (le) is 10.

[0489] In certain embodiments nl of formula (le) is 4, n2 of formula (le) is 2 and n3 of formula (le) is 2.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -L4- is of formula (le-a)

[0490]

[0491] wherein

[0492] the unmarked dashed line indicates attachment to -Z1- of -CARB; and

[0493] the dashed line marked with the asterisk indicates attachment to -L5-, -L3- or -TB.

[0494] In certain embodiments the dashed line marked with the asterisk in formula (le) indicates attachment to -L5-. In certain embodiments the dashed line marked with the asterisk in formula (le) indicates attachment to -L3-. In certain embodiments the dashed line marked with the asterisk in formula (le) indicates attachment to -TB.

[0495] In certain embodiments -L4- is of formula (If)

[0496]

[0497] wherein

[0498] the unmarked dashed line indicates attachment to -Z1- of -CARB;

[0499] the dashed line marked with the asterisk indicates attachment to -L5-, -L3- or -TB; and n is an integer ranging from 0 to 25.

[0500] In certain embodiments the dashed line marked with the asterisk in formula (If) indicates attachment to -L5-. In certain embodiments the dashed line marked with the asterisk in formula (If) indicates attachment to -L3-. In certain embodiments the dashed line marked with the asterisk in formula (If) indicates attachment to -TB.

[0501] In certain embodiments n of formula (If) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments n of formula (If) is 0. In certain embodiments n of formula (If) is 1. In certain embodiments n of formula (If) is 2. In certain embodiments n of formula (If) is 3. In certain embodiments n of formula (If) is 4. In certain embodiments n of formula (If) is 5. In certain embodiments n of formula (If) is 6. In certain embodiments n of formula (If) is 7. In certainAscendis Pharma A / S CPX75237PC 12 January 2026 embodiments n of formula (If) is 8. In certain embodiments n of formula (If) is 9. In certain embodiments n of formula (If) is 10.

[0502] In certain embodiments the dashed line marked with the asterisk in formula (If-a) indicates attachment to -L5-. In certain embodiments the dashed line marked with the asterisk in formula (If-a) indicates attachment to -L3-. In certain embodiments the dashed line marked with the asterisk in formula (If-a) indicates attachment to -TB.

[0503] In certain embodiments -L4- is of formula (Ig)

[0504]

[0505] wherein

[0506] the unmarked dashed line indicates attachment to -Z1- of -CARB;

[0507] the dashed line marked with the asterisk indicates attachment to -L5-, -L3- or -TB; and nl, n2 and n3 are independently an integer ranging from 0 to 25.

[0508] In certain embodiments the dashed line marked with the asterisk in formula (Ig) indicates attachment to -L5-. In certain embodiments the dashed line marked with the asterisk in formula (Ig) indicates attachment to -L3-. In certain embodiments the dashed line marked with the asterisk in formula (Ig) indicates attachment to -TB.

[0509] In certain embodiments nl of formula (Ig) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments nl of formula (Ig) is 0. In certain embodiments nl of formula (Ig) is 1. In certain embodiments nl of formula (Ig) is 2. In certain embodiments nl of formula (Ig) is 3. In certain embodiments nl of formula (Ig) is 4. In certain embodiments nl of formula (Ig) is 5. In certain embodiments nl of formula (Ig) is 6. In certain embodiments nl of formula (Ig) is 7. In certain embodiments nl of formula (Ig) is 8. In certain embodiments nl of formula (Ig) is 9. In certain embodiments nl of formula (Ig) is 10.

[0510] In certain embodiments n2 of formula (Ig) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments n2 of formula (Ig) is 0. In certain embodiments n2 of formula (Ig) is 1. In certain embodiments n2 of formula (Ig) is 2. In certain embodiments n2 of formula (Ig) is 3. In certainAscendis Pharma A / S CPX75237PC 12 January 2026 embodiments n2 of formula (Ig) is 4. In certain embodiments n2 of formula (Ig) is 5. In certain embodiments n2 of formula (Ig) is 6. In certain embodiments n2 of formula (Ig) is 7. In certain embodiments n2 of formula (Ig) is 8. In certain embodiments n2 of formula (Ig) is 9. In certain embodiments n2 of formula (Ig) is 10.

[0511] In certain embodiments n3 of formula (Ig) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments n3 of formula (Ig) is 0. In certain embodiments n3 of formula (Ig) is 1. In certain embodiments n3 of formula (Ig) is 2. In certain embodiments n3 of formula (Ig) is 3. In certain embodiments n3 of formula (Ig) is 4. In certain embodiments n3 of formula (Ig) is 5. In certain embodiments n3 of formula (Ig) is 6. In certain embodiments n3 of formula (Ig) is 7. In certain embodiments n3 of formula (Ig) is 8. In certain embodiments n3 of formula (Ig) is 9. In certain embodiments n3 of formula (Ig) is 10.

[0512] In certain embodiments nl, n2 and n3 of formula (Ig) are each 1.

[0513] In certain embodiments nl of formula (Ig) is 2, n2 of formula (Ig) is land n3 of formula (Ig) is 1.

[0514] In certain embodiments -L4- is of formula (Ir)

[0515]

[0516] wherein

[0517] the unmarked dashed line indicates attachment to -Z1- of -CARB;

[0518] the dashed line marked with the asterisk indicates attachment to -L5-, -L3- or -TB; and n is an integer ranging from 0 to 25.

[0519] In certain embodiments the dashed line marked with the asterisk in formula (Ir) indicates attachment to -L5-. In certain embodiments the dashed line marked with the asterisk in formula (Ir) indicates attachment to -L3-. In certain embodiments the dashed line marked with the asterisk in formula (Ir) indicates attachment to -TB.

[0520] In certain embodiments n of formula (Ir) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments n of formula (Ir) is 0. In certain embodiments n of formula (Ir) is 1. In certainAscendis Pharma A / S CPX75237PC 12 January 2026 embodiments n of formula (Ir) is 2. In certain embodiments n of formula (Ir) is 3. In certain embodiments n of formula (Ir) is 4. In certain embodiments n of formula (Ir) is 5. In certain embodiments n of formula (Ir) is 6. In certain embodiments n of formula (Ir) is 7. In certain embodiments n of formula (Ir) is 8. In certain embodiments n of formula (Ir) is 9. In certain embodiments n of formula (Ir) is 10.

[0521] In certain embodiments -L4- is of formula (Ir-a)

[0522]

[0523] wherein

[0524] the unmarked dashed line indicates attachment to -Z1- of -CARB; and

[0525] the dashed line marked with the asterisk indicates attachment to -L5-, -L3- or -TB.

[0526] In certain embodiments the dashed line marked with the asterisk in formula (Ir-a) indicates attachment to -L5-. In certain embodiments the dashed line marked with the asterisk in formula (Ir-a) indicates attachment to -L3-. In certain embodiments the dashed line marked with the asterisk in formula (Ir-a) indicates attachment to -TB.

[0527] In certain embodiments -L4- is of formula (Is)

[0528]

[0529] wherein

[0530] the unmarked dashed line indicates attachment to -Z1- of -CARB;

[0531] the dashed line marked with the asterisk indicates attachment to -L5-, -L3- or -TB; and nl, n2 and n3 are independently an integer ranging from 0 to 25.

[0532] In certain embodiments the dashed line marked with the asterisk in formula (Is) indicates attachment to -L5-. In certain embodiments the dashed line marked with the asterisk in formula (Is) indicates attachment to -L3-. In certain embodiments the dashed line marked with the asterisk in formula (Is) indicates attachment to -TB.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments nl of formula (Is) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments nl of formula (Is) is 0. In certain embodiments nl of formula (Is) is 1. In certain embodiments nl of formula (Is) is 2. In certain embodiments nl of formula (Is) is 3. In certain embodiments nl of formula (Is) is 4. In certain embodiments nl of formula (Is) is 5. In certain embodiments nl of formula (Is) is 6. In certain embodiments nl of formula (Is) is 7. In certain embodiments nl of formula (Is) is 8. In certain embodiments nl of formula (Is) is 9. In certain embodiments nl of formula (Is) is 10.

[0533] In certain embodiments n2 of formula (Is) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments n2 of formula (Is) is 0. In certain embodiments n2 of formula (Is) is 1. In certain embodiments n2 of formula (Is) is 2. In certain embodiments n2 of formula (Is) is 3. In certain embodiments n2 of formula (Is) is 4. In certain embodiments n2 of formula (Is) is 5. In certain embodiments n2 of formula (Is) is 6. In certain embodiments n2 of formula (Is) is 7. In certain embodiments n2 of formula (Is) is 8. In certain embodiments n2 of formula (Is) is 9. In certain embodiments n2 of formula (Is) is 10.

[0534] In certain embodiments n3 of formula (Is) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments n3 of formula (Is) is 0. In certain embodiments n3 of formula (Is) is 1. In certain embodiments n3 of formula (Is) is 2. In certain embodiments n3 of formula (Is) is 3. In certain embodiments n3 of formula (Is) is 4. In certain embodiments n3 of formula (Is) is 5. In certain embodiments n3 of formula (Is) is 6. In certain embodiments n3 of formula (Is) is 7. In certain embodiments n3 of formula (Is) is 8. In certain embodiments n3 of formula (Is) is 9. In certain embodiments n3 of formula (Is) is 10.

[0535] In certain embodiments n3 of formula (Is) is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In certain embodiments n3 of formula (Is) is 0. In certain embodiments n3 of formula (Is) is 1. In certain embodiments n3 of formula (Is) is 2. In certain embodiments n3 of formula (Is) is 3. In certain embodiments n3 of formula (Is) is 4. In certain embodiments n3 of formula (Is) is 5. In certain embodiments n3 of formula (Is) is 6. In certain embodiments n3 of formula (Is) is 7. In certain embodiments n3 of formula (Is) is 8. In certain embodiments n3 of formula (Is) is 9. In certain embodiments n3 of formula (Is) is 10.

[0536] In certain embodiments nl of formula (Is) is 4, n2 of formula (Is) is 2, n3 of formula (Is) is 2, and n4 of formula (Is) is 2.Ascendis Pharma A / S CPX75237PC 12 January 2026

[0537] In certain embodiments -L4- is of formula (Is-a)

[0538]

[0539] wherein

[0540] the unmarked dashed line indicates attachment to -Z1- of -CARB; and

[0541] the dashed line marked with the asterisk indicates attachment to -L5-, -L3- or -TB.

[0542] In certain embodiments the dashed line marked with the asterisk in formula (Is-a) indicates attachment to -L5-. In certain embodiments the dashed line marked with the asterisk in formula (Is-a) indicates attachment to -L3-. In certain embodiments the dashed line marked with the asterisk in formula (Is-a) indicates attachment to -TB.

[0543] In certain embodiments the moiety CARB-L4- of formula (Id) is of formula (le-al)

[0544]

[0545] wherein the dashed line marked with the asterisk indicates attachment to -L5-, -L3- or -TB.

[0546] In certain embodiments the moiety CARB-L4- of formula (Id) is of formula (If-al)

[0547] """

[0548]

[0549] al),

[0550] wherein the dashed line marked with the asterisk indicates attachment to -L5-, -L3- or -TB.

[0551] In certain embodiments the moiety CARB-L4- of formula (Id) is of formula (Ig-al)Ascendis Pharma A / S CPX75237PC 12 January 2026

[0552]

[0553] wherein the dashed line marked with the asterisk indicates attachment to -L5-, -L3- or -TB.

[0554] In certain embodiments -RB is of formula (Id), wherein -CARB is of formula (Ib#-a), -L4- is of formula (le) with nl being 4, n2 being 2 and n3 being 3.

[0555] In certain embodiments -RB is of formula (Id), wherein -CARB is of formula (Ib#-a), -L4- is of formula (Is-a), a is 1 and b is 0.

[0556] In certain embodiments -RB is of formula (Id), wherein -CARB is of formula (Ib#-a), -L4- is of formula (Is-a), a is 1 and b is 0.

[0557] In certain embodiments -RB is of formula (Id), wherein -CARB is of formula (Ic#-c), -L4- is of formula (Ir-a), a is 1 and b is 0.

[0558] In certain embodiments -RB is of formula (Id), wherein -CARB is of formula (Iq#-a), -L4- is of formula (Ir-a), a is 1 and b is 0.

[0559] In certain embodiments of -L4- comprises a moiety selected from the group consisting of

[0560]

[0561] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0562]

[0563] wherein

[0564] each x is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0565] y is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0566] each unmarked dashed line independently indicates attachment to the rest of -L4-; and the dashed line marked with the asterisk indicates attachment to -L3- or -TB.

[0567] -L5- is a branched spacer moiety, i.e., a spacer moiety comprising at least one branching point.

[0568] In certain embodiments -L5- comprises at least one branching point. L5- comprises one branching point. L5- comprises two branching points. L5- comprises three branching points. In certain embodiments -L5- comprises at least one branching point which is connected to three moieties. In certain embodiments the -L5- comprises at least one branching point which is connected to four moieties. In certain embodiments a branching point which is connected to three moieties is a nitrogen. In certain embodiments a branching point which is connected to four moieties is a carbon atom. Each of the moieties to which a branching point is connectedAscendis Pharma A / S CPX75237PC 12 January 2026 may also be referred to as “arm” and such arm may be linear, branched, cyclic or dendritic. In certain embodiments such arm is a linear moiety.

[0569] In certain embodiments each branching point is independently selected from the group consisting of -N<, -CR< and >C<, wherein -R is -H or C1-6 alkyl.

[0570] In certain embodiments each arm of -L5- comprises independently a C1-20 alkyl chain, which is optionally interrupted by one or more groups independently selected from -C(O)-, -N(Ry1)-, -O-, -S-, -T- and -C(O)N(Ry1)-; which Ci -20 alkyl chain is optionally substituted with one or more groups independently selected from halogen, -OH, -T and -N(RylRyla); wherein -Ryland -Rylaare independently selected from the group consisting of H and C1-4 alkyl and wherein T is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30- membered carbopoly cyclyl and 8- to 30-membered heteropoly cyclyl, which is optionally substituted with one or more oxo (=0) or halogen.

[0571] In certain embodiments -L5- is

[0572]

[0573] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0574]

[0575] wherein

[0576] each x is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0577] y is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0578] each unmarked dashed line independently indicates attachment to a moiety -L4-; andAscendis Pharma A / S CPX75237PC 12 January 2026 the dashed line marked with the asterisk indicates attachment to -L3- or -TB.

[0579] In certain embodiments -L5- is of formula (Ih-a). In certain embodiments -L5- is of formula (Ih-b). In certain embodiments -L5- is of formula (Ih-c). In certain embodiments -L5- is of formula (Ih-d). In certain embodiments -L5- is of formula (Ih-e). In certain embodiments -L5- is of formula (Ih-f). In certain embodiments -L5- is of formula (Ih-g). In certain embodiments -L5- is of formula (Ih-h). In certain embodiments -L5- is of formula (Ih-i). In certain embodiments -L5- is of formula (Ih-j). In certain embodiments -L5- is of formula (Ih-k). In certain embodiments -L5- is of formula (Ih-1). In certain embodiments -L5- is of formula (Hirn). In certain embodiments -L5- is of formula (Ih-n). In certain embodiments -L5- is of formula (Ih-o). In certain embodiments -L5- is of formula (Ih-p). In certain embodiments -L5- is of formula (Ih-q).

[0580] In certain embodiments -RB is of formula (Id), wherein -CARB is of formula (Ib#-a), -L4- is of formula (le) with nl being 4, n2 being 2 and n3 being 2, -L5- is of formula (Ih-a), a of formula (Id) is 3 and b of formula (Id) is 1.

[0581] In certain embodiments -RB is of formula (Id), -CARB is of formula (Ib#-a), -L4- is of formula (le) with nl being 4, n2 being 2 and n3 being 2, -L5- is of formula (Ih-b), a of formula (Id) is 3 and b of formula (Id) is 1.

[0582] In certain embodiments -L5- is selected from the group consisting of

[0583]

[0584] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0585]

[0586] wherein

[0587] each x is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0588] y is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0589] each unmarked dashed line independently indicates attachment to a moiety -L4-; and the dashed line marked with the asterisk indicates attachment to -L3- or -TB.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -L5- is of formula (Illh-a). In certain embodiments -L5- is of formula (Illh-b). In certain embodiments -L5- is of formula (Illh-c). In certain embodiments -L5- is of formula (Illh-d). In certain embodiments -L5- is of formula (Illh-e). In certain embodiments -L5- is of formula (Illh-f). In certain embodiments -L5- is of formula (Illh-g). In certain embodiments -L5- is of formula (Illh-h). In certain embodiments -L5- is of formula (Illh-i). In certain embodiments -L5- is of formula (Illh-j). In certain embodiments -L5- is of formula (Illh-k). In certain embodiments -L5- is of formula (IIIh-1). In certain embodiments -L5- is of formula (Illh-m). In certain embodiments -L5- is of formula (Illh-n). In certain embodiments -L5- is of formula (Illh-o).

[0590] In certain embodiments -RB is of formula (Id), -CARB is of formula (Ib#-a), -L4- is of formula (le-a), -L5- is of formula (Illh-g), a is 2 and b is 1.

[0591] In certain embodiments -RB is of formula (Id), -CARB is of formula (Ib#-a), -L4- is of formula (le-a), -L5- is of formula (Illh-h), a is 2 and b is 1.

[0592] In certain embodiments -RB of formula (Ic) is

[0593]

[0594] Ascendis Pharma A / S CPX75237PC

[0595] 12 January 2026

[0596]

[0597] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0598]

[0599] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0600]

[0601] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0602]

[0603] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0604]

[0605] wherein the dashed line indicates attachment to -L3- or -TB.

[0606] In certain embodiments -RB of formula (Ic) is of formula (H-l). In certain embodiments -RB of formula (Ic) is of formula (H-2). In certain embodiments -RB of formula (Ic) is of formula (H-3). In certain embodiments -RB of formula (Ic) is of formula (H-4). In certainAscendis Pharma A / S CPX75237PC 12 January 2026 embodiments -RB of formula (Ic) is of formula (H-5). In certain embodiments -RB of formula (Ic) is of formula (H-6). In certain embodiments -RB of formula (Ic) is of formula (H-7). In certain embodiments -RB of formula (Ic) is of formula (H-8). In certain embodiments -RB of formula (Ic) is of formula (H-9). In certain embodiments -RB of formula (Ic) is of formula (H-10). In certain embodiments -RB of formula (Ic) is of formula (H-ll). In certain embodiments -RB of formula (Ic) is of formula (H-12). In certain embodiments -RB of formula (Ic) is of formula (H-13). In certain embodiments -RB of formula (Ic) is of formula (H-14).

[0607] In certain embodiments -RB of formula (Ic) is of formula (H-l), which can also be drawn as

[0608]

[0609] wherein

[0610] the dashed line indicates attachment to -L3- or -TB.

[0611] In certain embodiments -RB of formula (Id) is of formula (H-l). In certain embodiments -RB of formula (Id) is of formula (H-2). In certain embodiments -RB of formula (Id) is of formula (H-3). In certain embodiments -RB of formula (Id) is of formula (H-4). In certain embodiments -RB of formula (Id) is of formula (H-5). In certain embodiments -RB of formula (Id) is of formula (H-6). In certain embodiments -RB of formula (Id) is of formula (H-7). In certain embodiments -RB of formula (Id) is of formula (H-8). In certain embodiments -RB of formula (Id) is of formula (H-9). In certain embodiments -RB of formula (Id) is of formula (H-10). In certain embodiments -RB of formula (Id) is of formula (H-ll). In certain embodiments -RB of formula (Id) is of formula (H-12). In certain embodiments -RB of formula (Id) is of formula (H-13). In certain embodiments -RB of formula (Id) is of formula (H-14).

[0612] In certain embodiments -RB of formula (Ic) is selected from the group consisting ofAscendis Pharma A / S CPX75237PC

[0613] 12 January 2026

[0614]

[0615] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0616]

[0617] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0618]

[0619] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0620]

[0621] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0622]

[0623] wherein the dashed line indicates attachment to -L3- or -TB.

[0624] In certain embodiments -RB of formula (Ic) is of formula (J-l). In certain embodiments -RB of formula (Ic) is of formula (J-2). In certain embodiments -RB of formula (Ic) is of formula (J-3). In certain embodiments -RB of formula (Ic) is of formula (J-4). In certain embodiments -RB of formula (Ic) is of formula (J-5). In certain embodiments -RB of formula (Ic) is of formula (J-6). In certain embodiments -RB of formula (Ic) is of formula (J-7). In certain embodiments -RB of formula (Ic) is of formula (J-8). In certain embodiments -RB of formula (Ic) is of formula (J-9). In certain embodiments -RB of formula (Ic) is of formula (J- 10). In certain embodiments -RB of formula (Ic) is of formula (J-l 1). In certain embodiments -RB of formula (Ic) is of formula (J- 12). In certain embodiments -RB of formula (Ic) is of formula (J-13). In certain embodiments -RB of formula (Ic) is of formula (J-14). In certain embodiments -RB of formula (Ic) is of formula (J- 15). In certain embodiments -RB of formula (Ic) is of formula (J- 16).Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -RB of formula (Id) is of formula (J-l). In certain embodiments -RB of formula (Id) is of formula (J-2). In certain embodiments -RB of formula (Id) is of formula (J-3). In certain embodiments -RB of formula (Id) is of formula (J-4). In certain embodiments -RB of formula (Id) is of formula (J-5). In certain embodiments -RB of formula (Id) is of formula (J-6). In certain embodiments -RB of formula (Id) is of formula (J-7). In certain embodiments -RB of formula (Id) is of formula (J-8). In certain embodiments -RB of formula (Id) is of formula (J-9). In certain embodiments -RB of formula (Id) is of formula (J- 10). In certain embodiments -RB of formula (Id) is of formula (J-l 1). In certain embodiments -RB of formula (Id) is of formula (J- 12). In certain embodiments -RB of formula (Id) is of formula (J-13). In certain embodiments -RB of formula (Id) is of formula (J-14). In certain embodiments -RB of formula (Id) is of formula (J- 15). In certain embodiments -RB of formula (Id) is of formula (J- 16).

[0625] In certain embodiments -RB of formula (Ic) is of formula (J-l), which can also be drawn as

[0626]

[0627] wherein

[0628] the dashed line indicates attachment to -L3- or -TB.

[0629] In certain embodiments -RB comprises an antibody moiety or fragment thereof, such as a Fab moiety, a Fab' moiety, a F(ab')2 moiety, a F(ab)2 moiety, variable fragment (Fv) moiety, a domain antibody (dAb) moiety, a single domain antibody moiety or a single chain variable fragment (scFv) moiety. In certain embodiments such antibody moiety is a full-length antibody moiety. In certain embodiments such antibody moiety is an antibody moiety fragment, such as a Fab or scFv. In certain embodiments such antibody is a monospecific antibody moiety or a fragment thereof. In certain embodiments such antibody is a multispecific antibody moiety or fragment thereof. In certain embodiments such antibody is a bispecific antibody moiety or fragment thereof.

[0630] In certain embodiments -RB binds to at least one ASGPR and comprises an antibody moiety or fragment thereof, such as a Fab moiety, a Fab' moiety, a F(ab')2 moiety, a F(ab)2 moiety, variableAscendis Pharma A / S CPX75237PC 12 January 2026 fragment (Fv) moiety, a domain antibody (dAb) moiety, a single domain antibody moiety or a single chain variable fragment (scFv) moiety. In certain embodiments such antibody moiety binding to ASGPR is a full-length antibody moiety. In certain embodiments such antibody moiety binding to ASGPR is an antibody moiety fragment, such as a Fab or scFv. In certain embodiments such antibody binding to ASGPR is a monospecific antibody moiety or a fragment thereof. In certain embodiments such antibody binding to ASGPR is a multispecific antibody moiety or fragment thereof. In certain embodiments such antibody binding to ASGPR is a bispecific antibody moiety or fragment thereof.

[0631] In certain embodiments the antibody moiety or fragment thereof binding to ASGPR comprises the heavy chain variable region sequence of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO:30 or SEQ ID NO:32.

[0632] In certain embodiments the antibody moiety or fragment thereof binding to ASGPR comprises a light chain variable region sequence selected from the group consisting of SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29 and SEQ ID NO:31.

[0633] In certain embodiments the antibody moiety or fragment thereof binding to ASGPR comprises a) a heavy chain variable region sequence of SEQ ID NO: 13 and a light chain variable region sequence of SEQ ID NO: 19;

[0634] b) a heavy chain variable region sequence of SEQ ID NO: 13 and a light chain variable region sequence of SEQ ID NO:20;

[0635] c) a heavy chain variable region sequence of SEQ ID NO: 13 and a light chain variable region sequence of SEQ ID NO:21;

[0636] d) a heavy chain variable region sequence of SEQ ID NO: 13 and a light chain variable region sequence of SEQ ID NO:22;

[0637] e) a heavy chain variable region sequence of SEQ ID NO: 13 and a light chain variable region sequence of SEQ ID NO:23;

[0638] f) a heavy chain variable region sequence of SEQ ID NO: 13 and a light chain variable region sequence of SEQ ID NO:24;

[0639] g) a heavy chain variable region sequence of SEQ ID NO: 14 and a light chain variable region sequence of SEQ ID NO:25;Ascendis Pharma A / S CPX75237PC 12 January 2026 h) a heavy chain variable region sequence of SEQ ID NO: 15 and a light chain variable region sequence of SEQ ID NO:26;

[0640] i) a heavy chain variable region sequence of SEQ ID NO: 16 and a light chain variable region sequence of SEQ ID NO:27;

[0641] j) a heavy chain variable region sequence of SEQ ID NO: 17 and a light chain variable region sequence of SEQ ID NO:28;

[0642] k) a heavy chain variable region sequence of SEQ ID NO:30 and a light chain variable region sequence of SEQ ID NO:29;

[0643] l) a heavy chain variable region sequence of SEQ ID NO: 13 and a light chain variable region sequence of SEQ ID NO:25;

[0644] m) a heavy chain variable region sequence of SEQ ID NO: 13 and a light chain variable region sequence of SEQ ID NO:26;

[0645] n) a heavy chain variable region sequence of SEQ ID NO: 13 and a light chain variable region sequence of SEQ ID NO:27;

[0646] o) a heavy chain variable region sequence of SEQ ID NO: 13 and a light chain variable region sequence of SEQ ID NO:28;

[0647] p) a heavy chain variable region sequence of SEQ ID NO: 13 and a light chain variable region sequence of SEQ ID NO:29; or

[0648] q) a heavy chain variable region sequence of SEQ ID NO:32 and a light chain variable region sequence of SEQ ID NO: 31.

[0649] In certain embodiments the antibody moiety fragment binding to ASGPR is a Fab comprising a light chain sequence of SEQ ID NO:4 and a heavy chain sequence of SEQ ID NO:5.

[0650] In certain embodiments the antibody moiety binding to ASGPR comprises a human Fc region.

[0651] In certain embodiments the antibody moiety binding to ASGPR comprises a modification within the interface between the two heavy chains in the CH3 domain, wherein i) in the CH3 domain of one heavy chain an amino acid residue is replaced with an amino acid residue having a larger side chain volume, thereby generating a protuberance ("knob") within the interface in the CH3 domain of one heavy chain which is positionable in a cavity ("hole") within the interface in the CH3 domain of the other heavy chain and ii) in the CH3 domain of the other heavy chain, an amino acid residue is replaced with an amino acid residue having a smaller side chain volume, thereby generating a cavity ("hole") within the interface in the second CH3Ascendis Pharma A / S CPX75237PC 12 January 2026 domain within which a protuberance ("knob") within the interface in the first CH3 domain is positionable.

[0652] In certain embodiments the antibody moiety binding to ASGPR comprises the amino acid substitution T366W and optionally the amino acid substitution S354C in one of the antibody heavy chains, and the amino acid substitutions T366S, L368A, Y407V and optionally Y349C in the other of the antibody heavy chains.

[0653] In certain embodiments the antibody binding to ASGPR comprises in the Fc region a modification reducing binding affinity of the antibody to an Fc receptor, or an Fc gamma receptor; wherein said Fc receptor is an activating Fc receptor and wherein the activating Fc receptor is Fc gamma receptor Illa (CD16a), Fc gamma receptor I (CD64), Fc gamma receptor Ila (CD32) or Fc fragment of IgA receptor (CD89). In certain embodiments the antibody binding to ASGPR comprises an amino acid substitution in the Fc region at a position selected from the group consisting of P329, L234 and L235 (Kabat numbering).

[0654] In certain embodiments the antibody binding to ASGPR comprises the amino acid substitutions P329G, L234A and L235A in the Fc region (Kabat numbering).

[0655] In certain embodiments -RB binds to at least one M6PR. In certain embodiments a moiety -RB binding to M6PR comprises a hexasaccharide moiety comprising one or more of glucose, galactose (Gal), mannose, N-acetylglucosamine, N-acetylgalactosamine (GalNAc), N-acetylmannosamine, mannose-6-phosphate and / or mannose-6- phosphonate moieties.

[0656] In certain embodiments -RB binds to at least one IGF2R. In certain embodiments a moiety -RB binding to IGF2R comprises a hexasaccharide moiety comprising one or more of glucose, galactose (Gal), mannose, N-acetylglucosamine, N-acetylgalactosamine (GalNAc), N-acetylmannosamine, mannose-6-phosphate and / or mannose-6- phosphonate moieties.

[0657] In certain embodiments a moiety -RB binding to at least one M6PR and / or at least one IGF2R isAscendis Pharma A / S CPX75237PC

[0658] 12 January 2026

[0659]

[0660] Ascendis Pharma A / S CPX75237PC

[0661] 12 January 2026

[0662]

[0663] Ascendis Pharma A / S CPX75237PC

[0664] 12 January 2026

[0665]

[0666] Ascendis Pharma A / S CPX75237PC

[0667] 12 January 2026

[0668]

[0669] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0670]

[0671] wherein the dashed line indicates attachment to -L3- or -TB.

[0672] In certain embodiments -RB is of formula (G-l). In certain embodiments -RB is of formula (G-2). In certain embodiments -RB is of formula (G-3). In certain embodiments -RB is of formula (G-3). In certain embodiments -RB is of formula (G-4). In certain embodiments -RB is of formula (G-5). In certain embodiments -RB is of formula (G-6). In certain embodiments -RB is of formula (G-7). In certain embodiments -RB is of formula (G-8). In certain embodiments -RB is of formula (G-9). In certain embodiments -RB is of formula (G-10). In certain embodiments -RB is of formula (G-l 1). In certain embodiments -RB is of formula (G-12).

[0673] In certain embodiments -RB binds to at least one LRP1. Such moiety -RB may comprise an amino acid sequence selected from the group consisting of

[0674] Ac-VKFNKPFVFLNleIEQNTK-NH2 (SEQ ID NO:33), VKFNKPFVFLMIEQNTK (SEQ ID NO:34),

[0675] TWPKHFDKHTFYSILKLGKH-OH (SEQ ID NO: 35), TFFYGGSRGKRNNFKTEEY-OH (SEQ ID NO: 36), LRI<LRI<RLLRDADDLLRI<LRI<RLLRDADDL (SEQ ID NO: 37), TEELRVRLASHLRKLRKRLL (SEQ ID NO: 38), EAKIEKHNHYQKQLEIAHEKLR (SEQ ID NO: 39) and TFFYGGSRGKRNNFKTEEY (SEQ ID NO:40);

[0676] wherein

[0677] Ac indicates an acetylated N-terminus, and

[0678] Nle is norleucine.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -RB binds to at least one LDLR. Such moiety -RB may comprise an amino acid sequence selected from the group consisting of

[0679] CM-Thz-RLRG-Pen (cyclized c-Pen) (SEQ ID NO:41),

[0680] CMPRLRGC (cyclized C-C) (SEQ ID NO:42),

[0681] HLDCMPRGCFRN (cyclized C-C) (SEQ ID NO:43),

[0682] CQVKSMPRC (cyclized C-C) (SEQ ID NO:44),

[0683] CTTPMPRLC (cyclized C-C) (SEQ ID NO:45),

[0684] CKAPQMPRC (cyclized C-C) (SEQ ID NO:46),

[0685] CLNPSMPRC (cyclized C-C) (SEQ ID NO:47),

[0686] CLVSSMPRC (cyclized C-C) (SEQ ID NO:48),

[0687] CLQPMPRLC (cyclized C-C) (SEQ ID NO:49),

[0688] CPVSSMPRC (cyclized C-C) (SEQ ID NO:50),

[0689] CQSPMPRLC (cyclized C-C) (SEQ ID NO: 51),

[0690] CLTPMPRLC(cyclized C-C) (SEQ ID NO: 52),

[0691] DSGLCMPRLRGCDPR (SEQ ID NO:53),

[0692] TPSAHAMALQSLSVG (SEQ ID NO:54),

[0693] Ac-DSGLCMPRLRGCDPR-NH2 (SEQ ID NO:55),

[0694] Pr-CMPRLRGC-NH2(SEQ ID NO: 56),

[0695] Pr-CMPRLRGC-NH2(cyclized C-C) (SEQ ID NO:57),

[0696] Pr-CMThzRLRG-Pen-NH2(cyclized C-Pen) (SEQ ID NO: 58),

[0697] AC-CMPRLGC-NH2(cyclized C-C) (SEQ ID NO: 59),

[0698] AC-CMPRLRGC-NH2(cyclized C-C) (SEQ ID NO: 60),

[0699] Ac-D-Pen-M-Thz-RLRGC-NH2(cyclized Pen-C) (SEQ ID NO:61),

[0700] Pr-CM-Thz-RLRG-Pen-NH2(cyclized c-Pen) (SEQ ID NO: 62),

[0701] Pr-CM-Thz-RLR-Sar-Pen-NH2(cyclized C-Pen) (SEQ ID NO:63),

[0702] Pr-CM-Pip-RLR-Sar-C-NH2(cyclized C-C) (SEQ ID NO:64),

[0703] Pr-CM-Pip-RLRG-Pen-NH2(cyclized c-Pen) (SEQ ID NO: 65) and

[0704] Pr-CM-Pip-RLR-Sar-Pen-NH2(cyclized c-Pen) (SEQ ID NO:66);

[0705] wherein Pr indicates a propionylated N-terminus;

[0706] Ac indicates an acetylated N-terminus;

[0707] Thz is thiazolidine-4-carboxylic acid;

[0708] Pen is penicillamine;

[0709] Pip is pipecolic acid; and

[0710] Sar is sarcosineAscendis Pharma A / S CPX75237PC 12 January 2026

[0711] In certain embodiments a moiety -RB binding to at least one LDLR comprises two cysteine residues or a cysteine and penicillamine residue (Pen), which form a disulfide bond.

[0712] In certain embodiments -RB binds to at least one Fc gamma receptor I. Such moiety -RB may comprise an amino acid sequence selected from the group consisting of TDTCLMLPLLLGCDEE (SEQ ID NO: 67),

[0713] DPICWYFPRLLGCTTL (SEQ ID NO: 68),

[0714] WYPCYIYPRLLGCDGD (SEQ ID NO: 69),

[0715] GNICMLIPGLLGCSYE (SEQ ID NO:70),

[0716] VNSCLLLPNLLGCGDD (SEQ ID NO:71),

[0717] TPVCILLPSLLGCDTQ (SEQ ID NO:72),

[0718] TVLCSLWPELLGCPPE (SEQ ID NO:73),

[0719] TFSCLMWPWLLGCESL (SEQ ID NO:74),

[0720] FGTCYTWPWLLGCEGF (SEQ ID NO: 75),

[0721] SLFCRLLLTPVGCVSQ (SEQ ID NO: 76),

[0722] HLLVLPRGLLGCTTLA (SEQ ID NO: 77),

[0723] TSLCSMFPDLLGCFNL (SEQ ID NO:78),

[0724] SHPCGRLPMLLGCAES (SEQ ID NO: 79),

[0725] TSTCSMVPGPLGAVSTW (SEQ ID NO:80),

[0726] KDPCTRWAMLLGCDGE (SEQ ID NO: 81),

[0727] IMTCSVYPFLLGCVDK (SEQ ID NO:82) and

[0728] IHSCAHVMRLLGCWSR (SEQ ID NO:83),

[0729] wherein any of the Fc gamma receptor I binding moieties containing two cysteine residues optionally form a disulfide bond.

[0730] In certain embodiments -RB binds to at least one FcRN. Such moiety -RB may comprise an amino acid sequence selected from the group consisting of

[0731] Ac-NH-QRFCTGHFGGLYPCNGP-CONH2 (SEQ ID NO: 84),

[0732] Ac-NH-RF-Pen-TGHFG-Sar-NMeLeu-YPC-CONH2 (SEQ ID NO:85), and succinic anhydride N-N dimerized SYN1327,

[0733] wherein any of the FcRN binding moieties containing two cysteine residues optionally form a disulfide bond;

[0734] Ac indicates an acetylated N-terminus;Ascendis Pharma A / S CPX75237PC 12 January 2026 Pen is Penicillamine;

[0735] Sar is sarcosine; and

[0736] NMel,eu is N-methylleucine.

[0737] In certain embodiments -RB binds to at least one transferrin receptor. Such moiety -RB may comprise an amino acid sequence selected from the group consisting of CGGGPFWWWP (SEQ ID NO: 86),

[0738] CGGGHKYLRW (SEQ ID NO: 87),

[0739] CGGGKRIFMV (SEQ ID NO:88),

[0740] CGGGKWHYLR (SEQ ID NO: 89),

[0741] THRPPMWSPVWP (SEQ ID NO: 90),

[0742] HAIYPRH (SEQ ID NO:91),

[0743] HRPPMWSPVWP (SEQ ID NO:92) and

[0744] THRPPMWSPVWP (SEQ ID NO:93).

[0745] In certain embodiments -RB binds to at least one macrophage scavenger receptor. Such moiety -RB may comprise an amino acid sequence selected from the group consisting of LSLERFLRCWSDAPA (SEQ ID NO:94),

[0746] LERFLRCWSDAPA (SEQ ID NO: 95),

[0747] RFLRCWSDAPA (SEQ ID NO: 96),

[0748] LRCWSDAPA (SEQ ID NO: 97),

[0749] CWSDAPA (SEQ ID NO:98) and

[0750] DWFKAFYDKVAEKFKEAF (SEQ ID NO: 99).

[0751] In certain embodiments -L3- is a linear or branched spacer moiety. In certain embodiments -L3- is a linear spacer moiety. In certain embodiments -L3- is a branched spacer moiety.

[0752] In certain embodiments -L3- is a spacer moiety selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50 alkyl, C2.5o alkenyl and C2.5o alkynyl; wherein -T-, Ci-50 alkyl, C2-so alkenyl and C2-so alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50 alkyl, C2-so alkenyl and C2-so alkynyl areAscendis Pharma A / S CPX75237PC 12 January 2026 optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-and -OC(O)N(Ry3)-;

[0753] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, Ci-50 alkyl, C2-so alkenyl and C2-so alkynyl; wherein -T, C1-50 alkyl, C2-so alkenyl and C2-so alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-50 alkyl, C2-so alkenyl and C2-so alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)- and -OC(O)N(Ry4)-;

[0754] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopolycyclyl and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0755] each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and Ci-6alkyl; wherein Ci-6alkyl is optionally substituted with one or more halogen, -CN, oxo (=0), -C00Ry5, -0Ry5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -N02, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b) or -OC(O)N(Ry5Ry5a), which are the same or different;

[0756] each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H and Ci-6 alkyl, wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different; and

[0757] optionally -L3- is substituted with one or more moieties -L1-, one or more further moieties -RB, one or more further moieties -TB or any combination thereof.

[0758] In certain embodiments -L3- is a spacer moiety selected from the group consisting of -T-, -C(0)0-, -0-, -C(0)-, -C(0)N(Ry1)-, -S(0)2N(Ry1)-, -S(0)N(Ry1)-, -S(0)2-,Ascendis Pharma A / S CPX75237PC 12 January 2026 -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, Ci-50 alkyl, C2-50 alkenyl and C2-50 alkynyl; wherein -T-, C1-50 alkyl, C2-50 alkenyl and C2-50 alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50 alkyl, C2-50 alkenyl and C2-50 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)- and -OC(O)N(Ry3)-;

[0759] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, Ci-10 alkyl, C2-10 alkenyl and C2-10 alkynyl; wherein -T, C1-10 alkyl, C2-10 alkenyl and C2-10 alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-10 alkyl, C2-10 alkenyl and C2-10 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)- and -OC(O)N(Ry4)-;

[0760] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopolycyclyl and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0761] -Ry2is selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5) C(0)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, -CN, oxo (=0), -C00Ry5, -0Ry5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b) or -OC(O)N(Ry5Ry5a), which are the same or different;

[0762] each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; and

[0763] optionally -L3- is substituted with one or more moieties -L1-, one or more further moieties -RB, one or more further moieties -TB or any combination thereof.Ascendis Pharma A / S CPX75237PC 12 January 2026

[0764] In certain embodiments -L3- is a spacer moiety selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, Ci-50 alkyl, C2-so alkenyl and C2-so alkynyl; wherein -T-, C1-50 alkyl, C2-so alkenyl and C2-so alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50 alkyl, C2-so alkenyl and C2-so alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)- and -OC(O)N(Ry3)-;

[0765] -Ryland -Rylaare independently selected from the group consisting of -H, -T, C1-10 alkyl, C2-10 alkenyl and C2-10 alkynyl;

[0766] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl and 8- to 30-membered heteropolycyclyl; each -Ry2is independently selected from the group consisting of halogen and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more -NH2, -OH, oxo (=0), -COOH or -SH, and each -Ry3, and -Ry3ais independently of each other selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; and

[0767] optionally -L3- is substituted with one or more moieties -L1-, one or more further moieties -RB, one or more further moieties -TB or any combination thereof.

[0768] In certain embodiments -L3- is a C1-30 alkyl chain, which is optionally interrupted by one or more groups independently selected from -C(O)-, -N(Ry1)-, -O-, -S-, -T- and -C(O)N(Ry1)-; and which Ci-30 alkyl chain is optionally substituted with one or more groups independently selected from halogen, -OH, -T, -N(RylRyla) and -Ry2; wherein -Ryland -Rylaare independently selected from the group consisting of H and C1-4 alkyl, -Ry2is independently selected from the group consisting of halogen and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more -NH2, -OH, oxo (=0), -COOH or -SH, and T is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11 -membered heterobicyclyl, 8-to 30-membered carbopolycyclyl and 8- to 30-membered heteropolycyclyl, which is optionally substituted with one or more oxo (=0) or halogen; andAscendis Pharma A / S CPX75237PC 12 January 2026 optionally -L3- is substituted with one or more moieties -L1-, one or more further moieties -RB, one or more further moieties -TB or any combination thereof.

[0769] In certain embodiments at least one -H of -L3- is substituted with -L1-. In certain embodiments at least one -H of -L3- is substituted with a further moiety -RB. In certain embodiments at least one -H of -L3- is substituted with a further moiety -TB. In certain embodiments at least one -H of -L3- is substituted with a further moiety -RB and at least one -H of -L3- is substituted with -L1-. In certain embodiments at least one -H of -L3- is substituted with a further moiety -TB and at least one -H of -L3- is substituted with -L1-. In certain embodiments at least one -H of -L3- is substituted with a further moiety -RB, at least one -H of -L3- is substituted with a further moiety -TB and at least one -H of -L3- is substituted with -L1-.

[0770] In certain embodiments -L3- comprises one or more moieties selected from the group consisting of

[0771]

[0772] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0773]

[0774] wherein

[0775] -R and -Raare independently of each other selected from the group consisting of -H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3 -methylpentyl, 2,2-dimethylbutyl, 2,3- dimethylbutyl and 3, 3 -dimethylpropyl.

[0776] In certain embodiments -L3- comprises one or more moieties selected from the group consisting of

[0777]

[0778] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0779]

[0780] In certain embodiments -L3- comprises a moiety selected from the group consisting of

[0781]

[0782] In certain embodiments -L3- comprises a bioorthogonal moiety selected from the group consisting of formula:Ascendis Pharma A / S CPX75237PC 12 January 2026

[0783]

[0784] Ascendis Pharma A / S CPX75237PC 12 January 2026

[0785]

[0786] wherein -R is selected from the group consisting of -H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3 -methylpentyl, 2,2-dimethylbutyl, 2, 3 -dimethylbutyl and 3, 3 -dimethylpropyl-.

[0787] In certain embodiments the bioorthogonal moiety is of formula (k-q) or (k-r). In a large number of conjugates, such as in a pharmaceutical formulation or in a batch, the bioorthogonal moiety may also be a mixture of formula (k-q) and (k-r).

[0788] In certain embodiments -L3- comprises at least one amino acid moiety. In certain embodiments -L3- comprises at least one proteinogenic amino acid moiety. In certain embodiments -L3- comprises at least one non-proteinogenic amino acid moiety.

[0789] In certain embodiments the at least one proteinogenic amino acid moiety is selected from the group consisting of alanine (A or Ala), cysteine (C or Cys), aspartic acid (D or Asp), glutamic acid (E or Glu), phenylalanine (F or Phe), glycine (G or Gly), histidine (H or His), isoleucine (I or lie), lysine (K or Lys), leucine (L or Leu), methionine (M or Met), asparagine (N or Asn), proline (P or Pro), glutamine (Q or Gin), arginine (R or Arg), serine (S or Ser), threonine (T or Thr), valine (V or Vai), tryptophan (W or Trp) and tyrosine (Y or Tyr).Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments the at least one non-proteinogenic amino acid moiety comprises a functional group in its side chain selected from the group consisting of carbonyl, azide, oxime, and hydroxylamine.

[0790] In certain embodiments the at least one non-proteinogenic amino acid moiety is selected from the group consisting of D-stereoisomers of each of the proteinogenic amino acids, pyrrolysine (Pyl, O), selenocysteine (Sec, U), 2-aminoadipic acid (2- AAA), 3 -aminoadipic acid (bAad), beta-alanine (bAla), 2-aminobutyric acid (Abu), 4-aminobutyric acid (4Abu), 6-aminocaproic acid (Acp), 2-aminoheptanoic acid (Ahe), 2-aminoisobutyric acid (Aib), 3-aminoisobutyric acid (bAib), 2-aminopimelic acid (Apm), 2,4-diaminobutyric acid (Dbu), desmosine (Des), 2,2'-diaminopimelic acid (Dpm), 2,3-diaminoproprionic acid (Dpr), N-ethyl glycine (EtGly), N-ethylasparagine (EtAsn), hydroxylysine (Hyl), allo-hydroxylysine (aHyl), 3 -hydroxyproline (3Hyp), 4-hydroxyproline (4Hyp), isodesmosine (Ide), allo-isoleucine (alle), N-methylglycine (MeGly), N-methylisoleucine (Melle), 6-N-methyllysine (MeLys), N-methylvaline (MeVal), norvaline (Nva), norleucine (Nle) and ornithine (Orn).

[0791] In certain embodiments the at least one non-proteinogenic amino acid moiety is selected from the group consisting of N6-((2-azidoethoxy)-carbonyl)-L-lysine, N6-azidoethoxy-L-lysine, N6-propargylethoxy-L-lysine, BCN-L-lysine, norbornene lysine, trans-cyclooctene (TCO)-lysine, methyltetrazine lysine, allyloxy carbonyllysine, 2-amino-8-oxononanoic acid, 2-amino-8-oxooctanoic acid, p-acetyl-L-phenylalanine, p-azidomethyl-L-phenylalanine, p-iodo-L-phenylalanine, m-acetylphenylalanine, 2-amino-8-oxononanoic acid, p-propargyloxyphenylalanine, p-propargyl-phenylalanine, 3-methyl-phenylalanine, L-Dopa, fluorinated phenylalanine, isopropyl-L-phenylalanine, p-azido-L-phenylalanine, p-acyl-L-phenylalanine, p-benzoyl-L-phenylalanine, p-bromophenylalanine, p-amino-L-phenylalanine, isopropyl-L-phenylalanine, O-allyltyrosine, O-methyl-L-tyrosine, O-4-allyl-L-tyrosine, 4-propyl-L-tyrosine, phosphonotyrosine, tri-O-acetyl-GlcNAcp-serine, L-phosphoserine, phosphonoserine, L-3 -(2-naphthyl)alanine, 2-amino-3 -((2-((3 -(benzyloxy)-3 -oxopropyl)amino)ethyl)selanyl)propanoic acid, 2-amino-3-(phenylselanyl)propanoic and selenocysteine.

[0792] In certain embodiments -L3- comprises a peptide moiety. In certain embodiments the peptide moiety comprises naturally occurring amino acids. In certain embodiments the peptide moiety comprises at least one non-proteinogenic amino acid, e.g., at least 2, at least 3, at least 4, at leastAscendis Pharma A / S CPX75237PC 12 January 2026 5, at least 8, at least 10, at least 15, at least 20 or more non-proteinogenic amino acids. In certain embodiments the peptide moiety has a linear structure. In certain embodiments the peptide moiety has a branched structure. In certain embodiments the peptide moiety has a branched structure with at least 2, such as at least 3, at least 4, at least 5, at least 6, at least 7 or at least 8 branching points. In certain embodiments the peptide moiety has a cyclic structure.

[0793] In certain embodiments -L3- comprises a peptide moiety, wherein the peptide moiety comprises at least 2 amino acid residues. In certain embodiments the peptide moiety comprises at least 3, such as at least 4, at least 5, at least 6, at least 7, at least 8, at least 9 or at least 10 amino acid residues. In certain embodiments the peptide moiety comprises from about 2 to about 100 amino acid residues, such as form about 3 to about 50 amino acids or from about 4 to 20 amino.

[0794] In certain embodiments -L3- comprises a peptide moiety comprising one or more glycine residue and one or more serine residue. In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of GGGGS (SEQ ID NO: 100). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence (GGGGS)n, wherein n is an integer ranging from 1 to 20. In certain embodiments n is an integer from 1 to 4. In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of GGGGS (SEQ ID NO: 100). In certain embodiments -L3- a peptide moiety with the amino acid sequence of (GGGGS)? (SEQ ID NO: 101). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of (GGGGS)s (SEQ ID NO: 102). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of (GGGGS)4 (SEQ ID NO: 103). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of GGGGG (SEQ ID NO: 131). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of (GGGGG)n, wherein n is an integer ranging from 1 to 20. In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of GSGSGS (SEQ ID NO: 132). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of (GSGSGS)n, wherein n is an integer ranging from 1 to 20. In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of GSGGGTGGGSG (SEQ ID NO: 133).

[0795] In certain embodiments -L3- comprises a peptide moiety comprising one or more alanine residue, one or more serine residue and one or more proline residue. In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence ofAscendis Pharma A / S CPX75237PC 12 January 2026 ASPAAPAPASPAAPAPSAPAA (SEQ ID NO: 134). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of ASAAAPAAASAAASAPSAAAA (SEQ ID NO: 135). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of AASPAAPSAPPAAASPAAPSAPPAA (SEQ ID NO: 136). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of ASPASA (SEQ ID NO: 137). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of ASP ASP AS A (SEQ ID NO: 138). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of PAGSP (SEQ ID NO: 139). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of GSAPG (SEQ ID NO: 140). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of GASTP (SEQ ID NO: 141). In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of GPSAT (SEQ ID NO: 142).

[0796] In certain embodiments -L3- comprises a peptide moiety with the amino acid sequence of GK. In certain embodiments -L3- comprises a peptide moiety of GK(K)-NH2, wherein (K) is a L-lysyl attached to the side chain of the L-lysyl residue K.

[0797] In certain embodiments -L3- comprises one or more polyethylene glycol (PEG) subunit -CH2CH2O-. In certain embodiments -L3- comprises between 1 and 500 PEG subunits, such as 1 to 250 PEG subunits, 1 to 100 PEG subunits or 1 to 50 PEG subunits. In certain embodiments -L3- comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 PEG subunits. In certain embodiments -L3- comprises 12 PEG subunits.

[0798] In certain embodiments -L3- comprises a moiety of formula (1-1)

[0799]

[0800] In certain embodiments -L3- comprises a moiety of formula (1-2)

[0801]

[0802] whereinAscendis Pharma A / S CPX75237PC 12 January 2026 nl is an integer ranging from 0 to 10; and

[0803] n2 is an integer ranging from 0 to 250.

[0804] In certain embodiments nl of formula (1-2) is an integer ranging from 1 to 6, i.e., nl is 1, 2, 3, 4, 5 or 6.

[0805] In certain embodiments n2 of formula (1-2) is an integer ranging from 1 to 20, i.e., n2 is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0806] In certain embodiments -L3- is a moiety of formula (1-2), wherein nl is 1 and n2 is 12. In certain embodiments -L3- is a moiety of formula (1-2), wherein nl is 2 and n2 is 12.

[0807] In certain embodiments -L3- comprises a moiety selected from the group consisting of -(CH2)nC(=O)NHNHC(=O)(CH2)nON=CH2X1C(=O)-; -(CH2)nX3C(=O)-;

[0808] -(CH2)nC(=O)-;

[0809] -(CH2)nC(=O)NHNHC(=O)(CH2)nON=CH2X1C(=O)NH(CH2)nCH(C=(O)NH2)-; -(CH2)nX3C(=O)NH(CH2)nCH(C=(O)NH2)-;

[0810] -(CH2)nC(=O)NH(CH2)nCH(C=(O)NH2)-; -((CH2)nO)t(CH2)mC(=O)-;

[0811] -((CH2)nO)t(CH2)m-; -(CH2)nC(=O)NH((CH2)nO)t(CH2)m-; -(CH2)n-;

[0812] -(CH2)nNHC(=O)(CH2)m-; -(CH2)nNHC(=O)(CH2)nC(=O)NH(CH2)m-;

[0813] -((CH2)nO)t(CH2)nNHC(=O)(CH2)m-; -((CH2)nO)tCH2)mC(=O)NH(CH2)m-;

[0814]

[0815] -((CH2)nO)t(CH2)nC(=O)NH(CH2)m-; -(CH2)mNHC(=O)((CH2)nO)t(CH2)m-;

[0816] -(CH2)nC(=O)NH(CH2)m-; -(CH2)nNHC(=O)((CH2)nO)t(CH2)m-;

[0817] -(CH2)nNHC(=O)(CH2)nO(CH2)m-; -(CH2)nNH(CH2)m-;

[0818] -((CH2)nO)tCH2)nC(=O)NH(CH2)m-; -(CH2)nNHC(=O(CH2)nX3(CH2)m-; -C(=O)-; -C(=O)(CH2)nC(=O)-; -C(=O)((CH2)nO)t(CH2)mC(=O)-; -C(=O)((CH2)nO)t(CH2)m-; -((CH2)nO)t(CH2)mX3(CH2)nO(CH2)nNHC(=O)((CH2)nO)t(CH2)mC(=O)-, -C(=O)(CH2)nC(=O)NH((CH2)nO)t(CH2)m-;

[0819] -C(=O)NHNHC(=O)(CH2)nON=CH2X1C(=O)NH(CH2)nCH(C=(O)NH2)-;

[0820] -X3C(=O)NH(CH2)nCH(C=(O)NH2)-;

[0821] -C(=O)(CH2)nC(=O)NHNHC(=O)(CH2)nON=CH2X1C(=O)-; -C(=O)(CH2)nX3C(=O)-;Ascendis Pharma A / S CPX75237PC 12 January 2026 -C(=O)(CH2)nNHC(=O)(CH2)nC(=O)NH(CH2)m-;

[0822] -C(=O)((CH2)nO)t(CH2)nNHC(=O)(CH2)m-;

[0823] -C(=O)((CH2)nO)tCH2)mC(=O)NH(CH2)m-; -C(=O)(CH2)nO(CH2)m-; -C(=O)(CH2)n-; -C(=O)NH((CH2)nO)t(CH2)m-; -C(=O)(CH2)nNH(CH2)n-;

[0824] -C(=O)(CH2)nNH(CH2)mC(=O)-; -C(=O)(CH2)nX3(CH2)m-;

[0825] -C(=O)((CH2)nO)t(CH2)nX3(CH2)m-; -C(=O)(CH2)nNHC(=O)(CH2)m-;

[0826] -C(=O)(CH2)nNHC(=O)((CH2)nO)t(CH2)m-; -C(=O)(CH2)nNHC(=O)(CH2)nO(CH2)m-; -C(=O)(CH2)nNH(CH2)m-; -C(=O)((CH2)nO)tCH2)nC(=O)NH(CH2)m-;

[0827] -C(=O)(CH2)nNHC(=O(CH2)nX3(CH2)m-; -C(=O)NH(CH2)nX3(CH2)m-;

[0828] -C(=O)NH(CH2)nNHC(=O)(CH2)m-; -C(=O)NH(CH2)nNHC(=O)(CH2)nO(CH2)m-; -C(=O)NH(CH2)nNHC(=O)(CH2)nX3(CH2)m-; -C(=O)NH(CH2)nNHC(=O)-;

[0829] -C(=O)NH((CH2)nO)t(CH2)nX3(CH2)m-; -C(=O)(CH2)nNHC(=O)(CH2)nX3(CH2)m-; -C(=O)((CH2)nO)t(CH2)nNHC(=O)(CH2)nX3(CH2)m-;

[0830] -C(=O)((CH2)nO)t(CH2)nC(=O)NH(CH2)m-;

[0831] -C(=O)(CH2)mNHC(=O)((CH2)nO)t(CH2)m- and -C(=O)(CH2)nC(=O)NH(CH2)m-; wherein

[0832] t is an integer ranging from 1 to 40;

[0833] m is an integer ranging from 1 to 10;

[0834] n is an integer ranging from 1 to 18;

[0835] -X1- is

[0836]

[0837] In certain embodiments -L3- comprises a moietyAscendis Pharma A / S CPX75237PC 12 January 2026

[0838]

[0839] In certain embodiments -L3- is a branched spacer moiety, such as a trivalent or a tetravalent spacer moiety. For example, -L3- can be of one of the following general formula:Ascendis Pharma A / S CPX75237PC 12 January 2026

[0840]

[0841] wherein each unmarked dashed line independently indicates attachment to -RB, -L4-, -L5- or -L1- and the dashed line marked with the asterisk indicates attachment to -TB.

[0842] In certain embodiments at least two or more moieties -L3- connect, for example, multiple moieties -RB or -L1- with one moiety -TB. In such cases, multiple moieties -RB or -L1- are connected via at least two or more branching points. By way of illustration, three moieties -L3-can be described by one of the following general formulae:

[0843]

[0844] wherein each unmarked dashed line independently indicates attachment to -RB, -L4-, -L5- or -L1-; and

[0845] the dashed line marked with the asterisk indicates attachment to -TB.

[0846] In certain embodiments -D comprises two or more moieties -L3-, each being trivalent moieties, which when linked together can provide for multiple branching points for covalent attachment of -RB or -L1- and be described by the following general formula:

[0847]

[0848] Ascendis Pharma A / S CPX75237PC 12 January 2026 where t is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and

[0849] wherein each unmarked dashed line independently indicates attachment to -RB, -L4-, -L5- or -L1-; and

[0850] the dashed line marked with the asterisk indicates attachment to -TB.

[0851] In certain embodiments -L3- has the general formula

[0852]

[0853] wherein the unmarked dashed line indicates attachment to -L5-;

[0854] the dashed line marked with the asterisk indicates attachment to -TB; and

[0855] the dashed line marked with # indicates attachment to -L1-.

[0856] In certain embodiments -L3- comprises a polypeptide scaffold where one or more of the sidechain groups of the amino acid residues have been modified to attach a moiety -RB or -L1-. It is understood that -RB or -L1- can be conjugated to amino acid residues, such as Asp, Lys, Orn, Glu, and Ser, of a spacer comprising a polypeptide via a suitable conjugation chemistry. In certain embodiments -L3- comprises a polylysine polypeptide. In certain embodiments -L3- comprises a polyornithine polypeptide. In certain embodiments -L3- comprises a polyserine polypeptide. In certain embodiments -L3- comprises a polyaspartate polypeptide.

[0857] In certain embodiments the polypeptide can be a randomly polymerized polymer, either having an average length or having a defined length. In certain embodiments the polypeptide spacer segment has a length of 2 to 100 amino acid residues, such as 5 to 90 or 10 to 50 amino acid residues.

[0858] In certain embodiments -L3- comprises a moietyAscendis Pharma A / S CPX75237PC 12 January 2026

[0859]

[0860] In certain embodiments -L3- is of formula (I-13a)

[0861]

[0862] wherein the unmarked dashed line indicates attachment to -L4-, -L5- or -RB;

[0863] the dashed line marked with # indicates attachment to -L1-; and

[0864] the dashed line marked with the asterisk indicates attachment to -TB.

[0865] In certain embodiments the unmarked dashed line in formula (I- 13 a) indicates attachment to -L4-. In certain embodiments the unmarked dashed line in formula (I-13a) indicates attachment to -L5-. In certain embodiments the unmarked dashed line in formula (I-13a) indicates attachment to -RB.

[0866] In certain embodiments -L3- comprises a moiety

[0867]

[0868] wherein

[0869] nl is an integer ranging from 0 to 10; andAscendis Pharma A / S CPX75237PC 12 January 2026 n2 is an integer ranging from 0 to 250.

[0870] In certain embodiments nl of formula (1-14) is 0, 1, 2, 3, 4, 5 or 6.

[0871] In certain embodiments n2 of formula (1-14) is an integer ranging from 1 to 20.

[0872] In certain embodiments -L3- is of formula (I- 14a)

[0873]

[0874] wherein the unmarked dashed line indicates attachment to -L4-, -L5- or -RB;

[0875] the dashed line marked with # indicates attachment to -L1-; and

[0876] the dashed line marked with the asterisk indicates attachment to -TB.

[0877] In certain embodiments the unmarked dashed line in formula (I- 14a) indicates attachment to -L4-. In certain embodiments the unmarked dashed line in formula (I-14a) indicates attachment to -L5-. In certain embodiments the unmarked dashed line in formula (I-14a) indicates attachment to -RB.

[0878] In certain embodiments -L3- is a moiety of formula (I- 14b)

[0879]

[0880] wherein

[0881] nl is an integer ranging from 0 to 10;

[0882] n2 is an integer ranging from 0 to 250;Ascendis Pharma A / S CPX75237PC 12 January 2026 n3 is an interger ranging from 0 to 10; and

[0883] wherein the unmarked dashed line indicates attachment to -L4-, -L5- or -RB;

[0884] the dashed line marked with # indicates attachment to -L1-; and

[0885] the dashed line marked with the asterisk indicates attachment to -TB.

[0886] In certain embodiments nl of formula (I-14b) is 1. In certain embodiments nl of formula (I-14b) is 2. In certain embodiments nl of formula (I-14b) is 3. In certain embodiments nl of formula (I- 14b) is 4. In certain embodiments nl of formula (I- 14b) is 5. In certain embodiments nl of formula (I-14b) is 6. In certain embodiments nl of formula (I-14b) is 7. In certain embodiments nl of formula (I- 14b) is 8. In certain embodiments nl of formula (I- 14b) is 9. In certain embodiments nl of formula (I- 14b) is 10.

[0887] In certain embodiments n2 of formula (I-14b) is 6. In certain embodiments n2 of formula (I-14b) is 12. In certain embodiments n2 of formula (I-14b) is 18. In certain embodiments n2 of formula (I-14b) is 24. In certain embodiments n2 of formula (I-14a) is 30. In certain embodiments n2 of formula (I- 14b) is 36. In certain embodiments n2 of formula (I- 14b) is 48. In certain embodiments n2 of formula (I- 14b) is 60. In certain embodiments n2 of formula (I-14b) is 72. In certain embodiments n2 of formula (I- 14b) is 80.

[0888] In certain embodiments n3 of formula (I-14b) is 1. In certain embodiments n3 of formula (I-14b) is 2. In certain embodiments n3 of formula (I-14b) is 3. In certain embodiments n3 of formula (I- 14b) is 4. In certain embodiments n3 of formula (I- 14b) is 5. In certain embodiments n3 of formula (I-14b) is 6. In certain embodiments n3 of formula (I-14b) is 7. In certain embodiments n3 of formula (I- 14b) is 8. In certain embodiments n3 of formula (I- 14b) is 9. In certain embodiments n3 of formula (I- 14b) is 10.

[0889] In certain embodiments the unmarked dashed line in formula (I- 14b) indicates attachment to -L4-. In certain embodiments the unmarked dashed line in formula (I- 14b) indicates attachment to -L5-. In certain embodiments the unmarked dashed line in formula (I- 14b) indicates attachment to -RB.

[0890] In certain embodiments -L3- is a moiety of formula (L3-i)Ascendis Pharma A / S CPX75237PC 12 January 2026

[0891]

[0892] wherein

[0893] the unmarked dashed line indicates attachment to -L4-, -L5-, or -RB;

[0894] the dashed line marked with an asterisk indicates attachment to -TB;

[0895] the dashed line marked with an # indicates attachment to -L1- as described elsewhere herein, such as to -L1- which is a moiety -Lla-Llb-, wherein -Lla- is of formula (Xll-a) and -Llb- is of formula (Xll-b);

[0896] -G- is a branched spacer moiety;

[0897] -Y- is a bioorthogonal group as described elsewhere herein;

[0898] -W- is a moiety selected from the group consisting of

[0899]

[0900] wherein

[0901] -X6- is selected from the group consisting of -O-, -C(O)-, -S-, -SO2-, -N(R6)- and -C(O)N(R6)-;

[0902] -R6is selected from the group consisting of -H, -T and C1-10 alkyl;

[0903] n and o are each independently an integer ranging from 1 to 20;

[0904] p is an integer ranging from 0 to 50; and

[0905] m is an integer ranging from 1 to 20; and

[0906] -V- is a moiety selected from the group consisting of

[0907]

[0908] wherein

[0909] -X4- is selected from the group consisting of -O-, -S- and -N(R10)-;

[0910] =X5is selected from the group consisting of =0, =S and =NR10;

[0911] -X7is selected from the group consisting of -OR10, -SR10and -N(R10a)(R10b); each -R10, -R10aand -R10bis independently selected from the group consisting of -H, -CN, -T, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consistingAscendis Pharma A / S CPX75237PC 12 January 2026 of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)- and -0C(0)N(R12)-;

[0912] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopolycyclyl and 8- to 30- membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0913] each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and Ci-6alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b) or -OC(O)N(Ry5Ry5a), which are the same or different;

[0914] each -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;

[0915] each -R11is independently selected from the group consisting of -C(0)0H, halogen, -N02, -CN, -OH, -OCH3, -N(R12)(R12a) and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; each -R12and -R12ais independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; and

[0916] r is 0 or 1.

[0917] In certain embodiments -G- of formula (L3-i) is of formula (g-i)Ascendis Pharma A / S CPX75237PC 12 January 2026

[0918]

[0919] wherein

[0920] the unmarked dashed line indicates attachment to -L4-, -L5-, or -RB;

[0921] the dashed line marked with an asterisk indicates attachment to -TB;

[0922] the dashed line marked with an # indicates attachment to -Y- of formula (L3-i);

[0923] -BP< is selected from the group consisting of -N< and -C(R8)<;

[0924] -R8is selected from the group consisting of -H, Ci-6 alkyl, C2-6 alkenyl and C2-6 alkynyl; -C1-, -C2- and -C3- are independently of each other selected from the group consisting of Ci-50 alkyl, C2-50 alkenyl and C2-50 alkynyl; wherein C1-50 alkyl, C2-50 alkenyl and C2-50 alkynyl are optionally substituted with one or more -R9, which are the same or different and wherein C1-50 alkyl, C2-50 alkenyl and C2-50 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-,-C(O)-, -C(O)N(R10)-, -S(O)2N(R10)-, -S(O)N(R10)-, -S(O)2-, -S(O)-, -N(R10)S(O)2N(R10a)-, -S-, -N(R10)-, -OC(OR10)(R10a)-, -N(R10)C(O)N(R10a)- and -OC(O)N(R10)-;

[0925] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -R9, which are the same or different;

[0926] each -R9is independently selected from the group consisting of halogen, -CN, oxo, (=0), -C00R11, -OR11, -C(0)Rn, -C(0)N(RnRlla), -S(0)2N(RnRlla), -S(0)N(RnRlla), -S(O)2Rn, -S(O)Rn, -N(R11)S(0)2N(RllaRllb), -SR11, -N(RnRlla), -NO2, -0C(0)Rn, -N(Rn)C(0)Rlla, -N(Rn)S(0)2Rlla, -N(Rn)S(0)Rlla, -N(Rn)C(0)0Rlla, -N(Rn)C(0)N(RllaRllb), -0C(0)N(RnRlla) and Ci-6alkyl; wherein Ci-6alkyl is optionally substituted with one or more halogen, which are the same or different; and

[0927] each -R10, -R10a, -R11, -Rllaand -Rllbis independently selected from the group consisting of -H, and Ci-6 alkyl, wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0928] In certain embodiments -G- of formula (L3-i) is of formula (g-ii):Ascendis Pharma A / S CPX75237PC 12 January 2026

[0929]

[0930] wherein the unmarked dashed line indicates attachment to -L4-, -L5-, or -RB as described elsewhere herein;

[0931] the dashed line marked with the asterisk indicates attachment to -TB as described elsewhere herein;

[0932] the dashed line marked with # indicates attachment to -Y- of formula (L3-i);

[0933] -Y- is a biorthogonal moiety as described elsewhere herein;

[0934] ql is an integer ranging from 1 to 20;

[0935] each q2 is independently 0 or 1;

[0936] each q3 is independently an integer ranging from 0 to 20; and

[0937] each q4 is independently an integer ranging from 0 to 20.

[0938] In certain embodiments -G- is of formula (g-iii):

[0939]

[0940] wherein the unmarked dashed line indicates attachment to -L4-, -L5-, or -RB as described elsewhere herein;

[0941] the dashed line marked with the asterisk indicates attachment to -TB as described elsewhere herein;

[0942] the dashed line marked with # indicates attachment to -Y- of formula (L3-i);

[0943] -Y- is a biorthogonal moiety as described elsewhere herein;

[0944] ql is 1, 2, 3, or 4;

[0945] q2 is 0 or 1; and

[0946] each q3 is independently 0, 1, 2, 3 or 4.

[0947] In certain embodiments -L3- comprises a moiety of formula (a)Ascendis Pharma A / S CPX75237PC 12 January 2026

[0948]

[0949] the unmarked dashed line indicates attachment to the rest of -L3-, such as a bioorthogonal group -Y- as described elsewhere herein;

[0950] the dashed line marked with an # indicates attachment to -L1- as described elsewhere herein, such as to -L1- which is a moiety -Lla-Llb-, wherein -Lla- is of formula (Xll-a) and -Llb- is of formula (Xll-b);

[0951] m is an integer ranging from 0 to 20;

[0952] -X4- is selected from the group consisting of -O-, -S- and -N(R10)-;

[0953] =X5is selected from the group consisting of =0, =S and =NR10;

[0954] -R10is selected from the group consisting of -H, -CN, -T, Ci-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)- and -0C(0)N(R12)-;

[0955] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0956] each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and Ci-6alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b) or -OC(O)N(Ry5Ry5a), which are the same or different;Ascendis Pharma A / S CPX75237PC 12 January 2026 each -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H and Ci-6 alkyl, wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different;

[0957] each -R11is independently selected from the group consisting of -C(O)OH, halogen, -NO2, -CN, -OH, -OCH3, -N(R12)(R12a) and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; each -R12and -R12ais independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0958] In certain embodiments -L3- comprises a moiety of formula (b)

[0959]

[0960] the unmarked dashed line indicates attachment to the rest of -L3-, such as a bioorthogonal group -Y- as described elsewhere herein;

[0961] the dashed line marked with an # indicates attachment to -L1- as described elsewhere herein, such as to -L1- which is a moiety -Lla-Llb-, wherein -Lla- is of formula (Xll-a) and -Llb- is of formula (Xll-b);

[0962] m is an integer ranging from 1 to 20;

[0963] -X4- is selected from the group consisting of -O-, -S- and -N(R10)-;

[0964] =X5is selected from the group consisting of =0, =S and =NR10;

[0965] -X7- is selected from the group consisting of -OR10, -SR10and -N(R10a)(R10b);

[0966] each -R10, -R10aand -R10bis independently selected from the group consisting of -H, -CN, -T, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)- and -0C(0)N(R12)-;

[0967] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl and 8- to 30-memberedAscendis Pharma A / S CPX75237PC 12 January 2026 heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0968] each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -COORy5, -ORy5, -C(O)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -OC(O)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and Ci-6alkyl; wherein Ci-6 alkyl is optionally substituted with one or more halogen, -CN, oxo (=0), -C00Ry5, -0Ry5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -N02, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b) or -OC(O)N(Ry5Ry5a), which are the same or different;

[0969] each -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H and Ci-6 alkyl, wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different;

[0970] each -R11is independently selected from the group consisting of -C(0)0H, halogen, -N02, -CN, -OH, -OCH3, -N(R12)(R12a) and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; each -R12and -R12ais independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0971] In certain embodiments -L3- comprises a moiety of formula (c)

[0972]

[0973] the unmarked dashed line indicates attachment to the rest of -L3-, such as a bioorthogonal group -Y- as described elsewhere herein;

[0974] the dashed line marked with an # indicates attachment to -L1- as described elsewhere herein, such as to -L1- which is a moiety -Lla-Llb-, wherein -Lla- is of formula (Xll-a) and -Llb- is of formula (Xll-b);

[0975] m is an integer ranging from 1 to 20;

[0976] -X4- is selected from the group consisting of -O-, -S- and -N(R10)-;Ascendis Pharma A / S CPX75237PC 12 January 2026 =X5is selected from the group consisting of =0, =S and =NR10;

[0977] -R10is selected from the group consisting of -H, -CN, -T, Ci-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)- and -0C(0)N(R12)-;

[0978] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0979] each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -0Ry5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and Ci-6alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, -CN, oxo (=0), -C00Ry5, -0Ry5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b) or -OC(O)N(Ry5Ry5a), which are the same or different;

[0980] each -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;

[0981] each -R11is independently selected from the group consisting of -C(0)0H, halogen, -NO2, -CN, -OH, -OCH3, -N(R12)(R12a) and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; each -R12and -R12ais independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments m of formula (L3-i), (g), (a), (b) or (c) is 1. In certain embodiments m of formula (L3-i), (g), (a), (b) or (c) is 2. In certain embodiments m of formula (L3-i), (g), (a), (b) or (c) is 3. In certain embodiments m of formula (L3-i), (g), (a), (b) or (c) is 4. In certain embodiments m of formula (L3-i), (g), (a), (b) or (c) is 5. In certain embodiments m of formula (L3-i), (g), (a), (b) or (c) is 6. In certain embodiments m of formula (L3-i), (g), (a), (b) or (c) is 7. In certain embodiments m of formula (L3-i), (g), (a), (b) or (c) is 8.

[0982] In certain embodiments formulas (a), (b) and (c) correspond to variables -W-V- of formula (L3-

[0983] In certain embodiments -Y- of formula (L3-i), (g) (a), (b) or (c) is of formula (k-a). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-b). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-c). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-d). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-e). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-f). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-g). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-h). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-i). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-j). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-k). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-1). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-m). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-n). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-o). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-p). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-q). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-r). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-s). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-t). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-u). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-v). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-w). In certain embodiments -Y- of formula (L3-i), (g), (a), (b) or (c) is of formula (k-x).Ascendis Pharma A / S CPX75237PC 12 January 2026

[0984] In certain embodiments -L3- comprises a moiety of formula (a-i) or (a-ii)

[0985]

[0986] wherein

[0987] the unmarked dashed line indicates attachment to the rest of -L3-;

[0988] the dashed line marked with an # indicates attachment to -L1- as described elsewhere herein, such as to -L1- which is a moiety -Lla-Llb-, wherein -Lla- is of formula (Xll-a) and -Llb- is of formula (Xll-b);

[0989] m is an integer ranging from 0 to 20;

[0990] -X4- is selected from the group consisting of -O-, -S- and -N(R10)-;

[0991] =X5is selected from the group consisting of =0, =S and =NR10;

[0992] -R10is selected from the group consisting of -H, -CN, -T, Ci-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)- and -0C(0)N(R12)-;

[0993] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0994] each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a),Ascendis Pharma A / S CPX75237PC 12 January 2026 -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -OC(O)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and Ci-6alkyl; wherein Ci-6 alkyl is optionally substituted with one or more halogen, -CN, oxo (=0), -COORy5, -ORy5, -C(O)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -OC(O)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b) or -OC(O)N(Ry5Ry5a), which are the same or different;

[0995] each -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H and Ci-6 alkyl, wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different;

[0996] each -R11is independently selected from the group consisting of -C(0)0H, halogen, -NO2, -CN, -OH, -OCH3, -N(R12)(R12a) and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; each -R12and -R12ais independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0997] In certain embodiments -L3- comprises a moiety of formula (b-i) or (b-ii)

[0998]

[0999] wherein

[1000] the unmarked dashed line indicates attachment to the rest of -L3-;Ascendis Pharma A / S CPX75237PC 12 January 2026 the dashed line marked with an # indicates attachment to -L1- as described elsewhere herein, such as to -L1- which is a moiety -Lla-Llb-, wherein -Lla- is of formula (Xll-a) and -Llb- is of formula (Xll-b);

[1001] m is an integer ranging from 0 to 20;

[1002] -X4- is selected from the group consisting of -O-, -S- and -N(R10)-;

[1003] =X5is selected from the group consisting of =0, =S and =NR10;

[1004] -X7is selected from the group consisting of -OR10, -SR10and -N(R10a)(R10b);

[1005] each -R10, -R10aand -R10bis independently selected from the group consisting of -H, -CN, -T, Ci-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)- and -0C(0)N(R12)-;

[1006] each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[1007] each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and Ci-6alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b) or -OC(O)N(Ry5Ry5a), which are the same or different;

[1008] each -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;Ascendis Pharma A / S CPX75237PC 12 January 2026 each -R11is independently selected from the group consisting of -C(O)OH, halogen, -NO2, -CN, -OH, -OCH3, -N(R12)(R12a) and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; each -R12and -R12ais independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[1009] In certain embodiments a -L3- comprises a moiety of formula (c-i) or (c-ii)

[1010]

[1011] wherein

[1012] the unmarked dashed line indicates attachment to the rest of -L3-;

[1013] the dashed line marked with an # indicates attachment to -L1- as described elsewhere herein, such as to -L1- which is a moiety -Lla-Llb-, wherein -Lla- is of formula (Xll-a) and -Llb- is of formula (Xll-b);

[1014] m is an integer ranging from 0 to 20;

[1015] -X4- is selected from the group consisting of -O-, -S- and -N(R10)-;

[1016] =X5is selected from the group consisting of =0, =S and =NR10;

[1017] -R10is selected from the group consisting of -H, -CN, -T, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)- and -0C(0)N(R12)-;Ascendis Pharma A / S CPX75237PC 12 January 2026 each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[1018] each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and Ci-6alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b) or -OC(O)N(Ry5Ry5a), which are the same or different;

[1019] each -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;

[1020] each -R11is independently selected from the group consisting of -C(0)0H, halogen, -N02, -CN, -OH, -OCH3, -N(R12)(R12a) and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; each -R12and -R12ais independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[1021] If more than one moiety -L3- is present in a conjugate and / or in a multitude of conjugates, such as in a pharmaceutical composition, -L3- may be present in the form of a mixture of the moieties of formula (a-i) and (a-ii), (b-i) and (b-ii) or (c-i) and (c-ii).

[1022] In certain embodiments -L3- comprises a moiety of formula (a-iii) or (a-iv)Ascendis Pharma A / S CPX75237PC 12 January 2026

[1023]

[1024] the unmarked dashed line indicates attachment to the rest of -L3-;

[1025] the dashed line marked with an # indicates attachment to -L1- as described elsewhere herein, such as to -L1- which is a moiety -Lla-Llb-, wherein -Lla- is of formula (Xll-a) and -Llb- is of formula (Xll-b); and

[1026] m is an integer ranging from 0 to 20.

[1027] In certain embodiments a -L3- comprises a moiety of formula (b-iii) or (b-iv)

[1028]

[1029] the unmarked dashed line indicates attachment to the rest of -L3-;

[1030] the dashed line marked with an # indicates attachment to -L1- as described elsewhere herein, such as to -L1- which is a moiety -Lla-Llb-, wherein -Lla- is of formula (Xll-a) and -Llb- is of formula (Xll-b); and

[1031] m is an integer ranging from 0 to 20.Ascendis Pharma A / S CPX75237PC 12 January 2026

[1032] In certain embodiments -L3- comprises a moiety of formula (c-iii) or (c-iv)

[1033]

[1034] wherein

[1035] the unmarked dashed line indicates attachment to the rest of -L3-;

[1036] the dashed line marked with an # indicates attachment to -L1- as described elsewhere herein, such as to -L1- which is a moiety -Lla-Llb-, wherein -Lla- is of formula (Xll-a) and -Llb- is of formula (Xll-b); and

[1037] m is an integer ranging from 0 to 20.

[1038] In certain embodiments -L3- is of formula (a-iii). In certain embodiments -L3- is of formula (a-iv). In certain embodiments -L3- is of formula (b-iii). In certain embodiments -L3- is of formula (b-iv). In certain embodiments -L3- is of formula (c-iii). In certain embodiments -L3- is of formula (c-iv).

[1039] In certain embodiments m of formula (a-iii), (a-iv), (b-iii), (b-iv), (c-iii) or (c-iv) is 0. In certain embodiments m of formula (a-iii), (a-iv), (b-iii), (b-iv), (c-iii) or (c-vi) is 1. In certain embodiments m of formula (a-iii), (a-iv), (b-iii), (b-iv), (c-iii) or (c-vi) is 2. In certain embodiments m of formula (a-iii), (a-iv), (b-iii), (b-iv), (c-iii) or (c-vi) is 3. In certain embodiments m of formula (a-iii), (a-iv), (b-iii), (b-iv), (c-iii) or (c-vi) is 4. In certain embodiments m of formula (a-iii), (a-iv), (b-iii), (b-iv), (c-iii) or (c-vi) is 5. In certain embodiments m of formula (a-iii), (a-iv), (b-iii), (b-iv), (c-iii) or (c-vi) is 6. In certain embodiments m of formula (a-iii), (a-iv), (b-iii), (b-iv), (c-iii) or (c-vi) is 7. In certain embodiments m of formula (a-iii), (a-iv), (b-iii), (b-iv), (c-iii) or (c-vi) is 8.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -L3- is attached to Ar1of -Lla- to positions that are not in ortho position relative to the carbon atom marked with the asterisk in formula (la). If Ar1of -Lla- is phenyl, -L3- is in certain embodiments attached to Ar1in meta or para position of the carbon atom marked with the asterisk.

[1040] In certain embodiments -L3- comprises a moiety selected of the group consisting of

[1041]

[1042] In certain embodiments -L3- is selected from the group consisting of

[1043]

[1044] Ascendis Pharma A / S CPX75237PC 12 January 2026

[1045] >

[1046]

[1047] wherein the unmarked dashed line indicates attachment to -L4-, -L5- or -RB;

[1048] the dashed line marked with # indicates attachment to -L1-; and

[1049] each dashed line marked with the asterisk indicates attachment to -TB.

[1050] In certain embodiments the unmarked dashed line in any one of formulae (I- 15a), (I- 16a), (I-17a), (I- 18a), and (I- 19a) indicates attachment to -L4-. In certain embodiments the unmarked dashed line in any one of formulae (I- 15a), (I- 16a), (I- 17a), (I- 18a), and (I- 19a) indicates attachment to -L5-. In certain embodiments the unmarked dashed line in any one of formulae (I- 15a), (I- 16a), (I- 17a), (I- 18a), and (I- 19a) indicates attachment to -RB.

[1051] In certain embodiments -L3- is

[1052]

[1053] Ascendis Pharma A / S CPX75237PC

[1054] 12 January 2026

[1055]

[1056] Ascendis Pharma A / S CPX75237PC 12 January 2026

[1057]

[1058] Ascendis Pharma A / S CPX75237PC 12 January 2026

[1059]

[1060] wherein

[1061] the unmarked dashed line indicates attachment to -L4-, -L5- or -RB;

[1062] the dashed line marked with # indicates attachment to -L1-;

[1063] the dashed line marked with *Jand the dashed line marked with *2each indicate attachment to a sulfur of -TB; and

[1064] a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[1065] In certain embodiments the dashed line marked with *Jand the dashed line marked with *2in any one of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (I-21a), (I-21a-i), (I-21-b) and (I-21b-i) interchangeably indicate attachment to a sulfur of the heavy chain moiety and the sulfur of a light chain moiety of a Fab fragment.

[1066] In certain embodiments the unmarked dashed line in any one of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (I-21a), (I-21a-i), (I-21-b) and (I-21b-i) indicates attachment to -L4-. In certain embodiments the unmarked dashed line in any one of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (I-21a), (I-21a-i), (I-21-b) and (I-21b-i) indicates attachment to -L5-. In certain embodiments the unmarked dashed line in any one of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (1-2 la), (I-21a-i), (1-21-b) and (I-21b-i) indicates attachment to -RB.

[1067] In certain embodiments a of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (1-2 la), (1-21 a-i), (I-21-b) and (1-2 Ib-i) is 3. In certain embodiments a of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (1-2 la), (1-21 a-i), (1-21-b) and (1-2 Ib-i) is 1. In certain embodiments a of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (1-2 la), (1-21 a-i), (1-21-b) and (1-2 Ib-i) is 2. In certain embodiments a of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (I-21a), (I-21a-i), (I-21-b) and (I-21b-i) is 4.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments a of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (1-2 la), (1-21 a-i), (I-21-b) and (1-2 Ib-i) is 5. In certain embodiments a of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (1-2 la), (1-21 a-i), (1-21-b) and (1-2 Ib-i) is 6. In certain embodiments a of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (1-2 la), (1-21 a-i), (1-21-b) and (1-2 Ib-i) is 7. In certain embodiments a of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (I-21a), (I-21a-i), (I-21-b) and (I-21b-i) is 8. In certain embodiments a of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (1-2 la), (1-21 a-i), (I-21-b) and (1-2 Ib-i) is 9. In certain embodiments a of formula (I-20a), (I-20a-i), (I-20b), (I-20b-i), (I-21a), (I-21a-i), (I-21-b) and (I-21b-i) is 10.

[1068] In certain embodiments -L3- is of formula (I-20a). In certain embodiments -L3- is of formula (I-20a-i). In certain embodiments -L3- is of formula (I-20b). In certain embodiments -L3- is of formula (I-20b-i). In certain embodiments -L3- is of formula (1-2 la). In certain embodiments -L3- is of formula (1-21 a-i). In certain embodiments -L3- is of formula (1-2 lb). In certain embodiments -L3- is of formula (1-2 Ib-i).

[1069] In a plurality of conjugates -L3- is in certain embodiments a mixture of the respective stereoisomers, i.e., is a mixture of (I-20a) and (I-20b), (I-20a-i) and (I-20b-i), (1-21 a) and(I-21b) or (1-21 a-i) and (1-2 Ib-i).

[1070] In certain embodiments -L3- is

[1071]

[1072] Ascendis Pharma A / S CPX75237PC 12 January 2026

[1073]

[1074] wherein

[1075] the unmarked dashed line indicates attachment to -L4-, -L5- or -RB;

[1076] the dashed line marked with and the dashed line marked with *2each indicate attachment to a sulfur of -TB;

[1077] nl is an integer ranging from 0 to 10;

[1078] n2 is an integer ranging from 0 to 250;

[1079]

[1080] wherein

[1081] the dashed line marked with # indicates attachment to -L1-; and

[1082] the unmarked dashed line indicates attachment the remainder of -L3-, i.e., to the carbonyl to the right of -R1.

[1083] In certain embodiments -L3- is

[1084]

[1085] Ascendis Pharma A / S CPX75237PC 12 January 2026

[1086]

[1087] wherein

[1088] the unmarked dashed line indicates attachment to -L4-, -L5- or -RB;

[1089] the dashed line marked with *Jand the dashed line marked with *2each indicate attachment to a sulfur of -TB;

[1090] nl is an integer ranging from 0 to 10;

[1091] n2 is an integer ranging from 0 to 250;

[1092]

[1093] wherein

[1094] the dashed line marked with # indicates attachment to -L1-;

[1095] the unmarked dashed line indicates attachment the remainder of -L3-, i.e., to the carbonyl to the right of -R1; and

[1096] and a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[1097] In a plurality of conjugates or intermediates thereof comprising -L3- of formula (1-22) or (I-23) -R1is present as a mixture of formula (I-a) and (I-b). In a plurality of conjugates or intermediates thereof comprising -L3- of formula (I-22-i) or (I-23-i) -R1is present as a mixture of formula (I-a-i) and (I-b-i). In an individual conjugate or intermediate thereof comprising -L3- of formula (1-22) or (1-23) -R1is either of formula (I-a) or (I-b). In an individualAscendis Pharma A / S CPX75237PC 12 January 2026 conjugate or intermediate thereof comprising -L3- of formula (1-22) or (1-23) -R1- is either of formula (I-a-i) or (I-b-i).

[1098] In certain embodiments nl in formula (1-22), (I-22-i), (1-23) and (I-23-i) is 0, 1, 2, 3, 4, 5 or 6.

[1099] In certain embodiments n2 of formula (1-22), (I-22-i), (1-23) and (I-23-i) is an integer ranging from 1 to 20.

[1100] In certain embodiments nl of formula (1-22), (I-22-i), (1-23) and (I-23-i) is 1 and n2 of formula (1-22), (I-22-i), (1-23) and (I-23-i) is 12.

[1101] In certain embodiments a of formula (1-22), (I-22-i), (1-23) and (I-23-i) is 3. In certain embodiments a of formula (1-22), (I-22-i), (1-23) and (I-23-i) is 1. In certain embodiments a of formula (1-22), (I-22-i), (1-23) and (I-23-i) is 2. In certain embodiments a of formula (1-22), (I-22-i), (1-23) and (I-23-i) is 4. In certain embodiments a of formula (1-22), (I-22-i), (1-23) and (I-23-i) is 5. In certain embodiments a of formula (1-22), (I-22-i), (1-23) and (I-23-i) is 6. In certain embodiments a of (1-22), (I-22-i), (1-23) and (I-23-i) is 7. In certain embodiments a of formula (1-22), (I-22-i), (1-23) and (I-23-i) is 8. In certain embodiments a of formula (1-22), (I-22-i), (1-23) and (I-23-i) is 9. In certain embodiments a of formula (1-22), (I-22-i), (1-23) and (I-23-i) is 10.

[1102] In certain embodiments the unmarked dashed line in formula (1-22), (I-22-i), (1-23) and (1-23-i) indicates attachment to -L4-. In certain embodiments the unmarked dashed line in formula (I- 22), (I-22-i), (1-23) and (I-23-i) indicates attachment to -L5-. In certain embodiments the unmarked dashed line in formula (1-22), (I-22-i), (1-23) and (I-23-i) indicates attachment to -RB.

[1103] In certain embodiments -L3- is of formula (1-22). In certain embodiments -L3- is of formula (I- 23). In certain embodiments -L3- is of formula (I-22-i). In certain embodiments -L3- is of formula (I-23-i).

[1104] In certain embodiments -L3- is of formula (1-24)Ascendis Pharma A / S CPX75237PC 12 January 2026

[1105]

[1106] wherein

[1107] the unmarked dashed line indicates attachment to -TB,

[1108] the dashed line marked with the asterisk indicates attachment to -L4-, -L5- or -RB; and

[1109]

[1110] the dashed line marked with # indicates attachment to -L1-;

[1111] the unmarked dashed line indicates attachment the remainder of -L3-, i.e., to the carbonyl to the right of -R1; and

[1112] and a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[1113] In certain embodiments a of formula (I-24a) and (I-24b) is 3. In certain embodiments a of formula (I-24a) and (I-24b) is 1. In certain embodiments a of formula (I-24a) and (I-24b) is 2. In certain embodiments a of formula (I-24a) and (I-24b) is 4. In certain embodiments a of formula (I-24a) and (I-24b) is 5. In certain embodiments a of formula (I-24a) and (I-24b) is 6. In certain embodiments a of formula (I-24a) and (I-24b) is 7. In certain embodiments a of formula (I-24a) and (I-24b) is 8. In certain embodiments a of formula (I-24a) and (I-24b) is 9. In certain embodiments a of formula (I-24a) and (I-24b) is 10.

[1114] In certain embodiments the unmarked dashed line in formula (1-24) indicates attachment to a sulfur, such as to the sulfur of a thiol side chain of an amino acid residue, such as a cysteine residue.Ascendis Pharma A / S CPX75237PC 12 January 2026

[1115] In certain embodiments the thiosuccinimide in -L3- of formula (1-24) is opened to avoid a retro- Michael reaction. Such ring opening can for example be obtained through incubation at elevated pH, such as at a pH of about 9. The resulting structure may be of formula (I-24i) or (I-24ii)

[1116]

[1117] wherein

[1118] the unmarked dashed line indicates attachment to -TB,

[1119] the dashed line marked with the asterisk indicates attachment to -L4-, -L5- or -RB; and

[1120]

[1121] the dashed line marked with # indicates attachment to -L1-;

[1122] the unmarked dashed line indicates attachment the remainder of -L3-, i.e., to the carbonyl to the right of -R1; and

[1123] and a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.Ascendis Pharma A / S CPX75237PC 12 January 2026

[1124] In certain embodiments the unmarked dashed line in formula (I-24i) and (I-24ii) indicates attachment to a sulfur, such as to the sulfur of a thiol side chain of an amino acid residue, such as a cysteine residue.

[1125] In a plurality of conjugates or intermediates thereof comprising a moiety -L3- of formula (1-24), (I-24i) and / or (I-24ii) -R1is present as a mixture of the moieties of formula (I-24a) and (I-24b). In a single conjugate or intermediate thereof -R1is present as either (I-24a) or (I-24b). Furthermore, in a plurality of conjugates or intermediates comprising a moiety -L3- of formula (1-24), -L3- may after the opening of the thiosuccinimide ring be present as a mixture of moieties -L3- of formula (I-24i) and (I-24ii), which mixture may optionally also comprises moieties of formula (1-24), if for example, the ring opening was not complete. Such a plurality of conjugates or intermediates may, for example, be in the form of a batch or a pharmaceutical composition.

[1126] In certain embodiments -L3- is of formula (I-24-i)

[1127]

[1128] wherein

[1129] the unmarked dashed line indicates attachment to -TB,

[1130] the dashed line marked with the asterisk indicates attachment to -L4-, -L5- or -RB; and

[1131]

[1132] wherein

[1133] the dashed line marked with # indicates attachment to -L1-; andAscendis Pharma A / S CPX75237PC 12 January 2026 the unmarked dashed line indicates attachment the remainder of -L3-, i.e., to the carbonyl to the right of -R1.

[1134] As described above for formula (1-24), also the thiosuccinimide moiety of formula (I-24-i) may in certain embodiments be opened and the resulting structures are analogous to those described for (I-24i) and (I-24ii). In a plurality of conjugates or intermediates thereof comprising a moiety -L3- of formula (I-24-i) -R1is present as a mixture of the moieties of formula (I-24a-i) and (I-24b-i). In a single conjugate or intermediate thereof -R1is present as either (I-24a-i) or (I-24b-i).

[1135] The target-binding moiety -TB binds to FGF23 as a target that will be degraded via a degradation pathway, such as receptor-mediated endocytosis or lysosomal degradation.

[1136] In certain embodiments -TB binds to the extracellular target with a Ka of less than 1 pM, such as 300 nM or less, 100 nM or less, 30 nM or less, 10 nM or less, 3 nM or less or 1 nM or less, e.g., as measured in an in vitro binding assay. The Ka is measured in the unconjugated bifunctional drug, i.e., prior to conjugation to -L1-, if -L1- releases the bifunctional drug in an unmodified form, and if -L1- releases the bifunctional drug in a modified form, the Ka is measured in the released, modified bifunctional drug.

[1137] In certain embodiments -TB comprises a biomolecule. In certain embodiments -TB is a biomolecule. In certain embodiments the biomolecule is selected from the group consisting of peptides, polypeptides, proteins, polynucleotides, polysaccharides, glycans, glycoproteins, lipids, enzymes, antibodies and antibody fragments and combinations thereof.

[1138] In certain embodiments -TB comprises a polypeptide moiety. In certain embodiments -TB is a polypeptide moiety.

[1139] In certain embodiments -TB comprises a polypeptide moiety that binds to a soluble target protein. In certain embodiments -TB comprises a receptor moiety binding to FGF23 or a receptor fragment moiety. In certain embodiments -TB is a receptor moiety binding to the soluble target protein or a receptor fragment moiety binding to the soluble target protein. In certain embodiments -TB is a full-length receptor moiety, a receptor fragment moiety or a functional variant thereof. In certain embodiments -TB is a cell surface receptor moiety or aAscendis Pharma A / S CPX75237PC 12 January 2026 fragment thereof. In certain embodiments the receptor fragment moiety is a receptor ectodomain moiety. In certain embodiments the receptor ectodomain moiety is an engineered ectodomain. In some embodiments -TB is a designed ankyrin repeat protein (DARPin) moiety.

[1140] In certain embodiments -TB comprises a cyclic peptide moiety. In certain embodiments -TB comprises a bicyclic peptide moiety. In certain embodiments -TB comprises a tricyclic peptide moiety.

[1141] In certain embodiments -TB is a cyclic peptide moiety. In certain embodiments -TB is a bicyclic peptide moiety. In certain embodiments -TB is a tricyclic peptide moiety.

[1142] In certain embodiments the polypeptide moiety or cyclic peptide moiety comprises a non-proteinogenic amino acid moiety.

[1143] In certain embodiments the non-proteinogenic amino acid moiety is as described elsewhere herein.

[1144] In certain embodiments -TB comprises an antibody moiety or fragment thereof that binds to an extracellular target, such as an extracellular target protein, extracellular target sugar or extracellular target lipid.

[1145] In certain embodiments -TB comprises an antibody moiety. In certain embodiments -TB is an antibody moiety. In certain embodiments the antibody moiety is a monoclonal antibody moiety. In certain embodiments the antibody moiety is a human antibody moiety. In certain embodiments the antibody moiety is a humanized antibody moiety. In certain embodiments the antibody moiety is a chimeric antibody moiety. In certain embodiments the antibody moiety is a full-length antibody moiety. In certain embodiments the antibody moiety is an IgG antibody moiety, such as an IgGl, IgG2, IgG3 or IgG4 antibody moiety.

[1146] In certain embodiments -TB comprises an antibody fragment moiety. In certain embodiments -TB is an antibody fragment moiety. In certain embodiments the antibody fragment moiety comprises a Fab, a Fab', a F(ab')2, a F(ab)2, a variable fragment (Fv), a domain antibody (dAb), a single domain antibody or a single chain variable fragment (scFv). In certain embodiments the antibody fragment moiety is a Fab, a Fab', a F(ab')2, a F(ab)2, aAscendis Pharma A / S CPX75237PC 12 January 2026 variable fragment (Fv), a domain antibody (dAb), a single domain antibody or a single chain variable fragment (scFv).

[1147] In certain embodiments -TB is a monospecific antibody moiety or a fragment thereof. In certain embodiments -TB is a multispecific antibody moiety or a fragment thereof. In certain embodiments -TB is a bispecific antibody moiety or fragment thereof.

[1148] In certain embodiments the antibody moiety or fragment thereof binds to the extracellular target with a Ka of less than 500nM, less than lOOnM, less than 10 nM, less than 1 nM or less than O.lnM as measured by surface plasmon resonance (SPR). The Ka is measured in the unconjugated bifunctional drug, i.e., prior to conjugation to -L1-, if -L1- releases the bifunctional drug in an unmodified form, and if -L1- releases the bifunctional drug in a modified form, the Ka is measured in the released, modified bifunctional drug.

[1149] In certain embodiments -TB comprises an antibody moiety or fragment thereof which binds to a soluble extracellular target protein. In certain embodiments the antibody moiety or fragment thereof binds to a cell surface receptor ligand.

[1150] In certain embodiments -TB is an antibody moiety or fragment thereof and -RB is site-specifically covalently linked to the antibody moiety or fragment thereof either directly or via the spacer moiety -L3-. In certain embodiments -RB or -L3- can be covalently linked to the antibody or antibody fragment via a site-specific cysteine modification on the antibody moiety or fragment thereof and a thiol-reactive group. -RB can be covalently linked to the antibody moiety or fragment thereof via one or more lysine residues of the antibody moiety or fragment thereof and an amine-reactive group.

[1151] In certain embodiments cysteine residues that do not participate in disulfide bridges are engineered into an antibody or fragment thereof, such as a Fab, by mutation of one or more codons. Reducing these unpaired cysteines yields a sulfhydryl group suitable for conjugation. Preferred positions for incorporating engineered cysteines include positions S112C, S113C, A114C, S115C, A176C, S180C, S239C, S252C, V286C, V292C, S357C, A359C, S398C and S428C (Kabat numbering) on the human IgGl heavy chain and positions VI 10C, S114C, S121C, S127C, S168C and V205C (Kabat numbering) on the human Ig kappa light chain.Ascendis Pharma A / S CPX75237PC 12 January 2026 Mutation of a cysteine residue known to participate in an existing disulfide bridge may also be engineered such that the resulting unpaired cysteine partner is available for site-specifically covalently linking -RB or -L3- to the antibody moiety or fragment thereof. Examples of engineered cysteine mutations include light chain constant C214 mutations, for example C214A.

[1152] In certain embodiments -TB is burosumab, a human monoclonal antibody marketed as CRYSVITA®. The heavy chain of burosumab has the sequence of SEQ ID NO: 143 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG QPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[1153] The light chain of burosumab has the sequence of SEQ ID NO: 144 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1154] In certain embodiments -TB is an antibody comprising heavy and a light chains, which have at least 95% homology, such as 95%, 96%, 97%, 98% or 99% homology, to the heavy chains of burosumab and at least 95% homology, such as 95%, 96%, 97%, 98% or 99% homology, to light chains of burosumab.

[1155] In certain embodiments -TB is a Fab fragment, such as a Fab fragment of burosumab. In certain embodiments each chain of such Fab fragment has at least 95% homology to the corresponding sequence of burosumab. In certain embodiments each chain of such Fab fragment comprises a total of at most 5 amino acid deletions, amino acid insertions and / or amino acid exchanges compared to the corresponding chain of burosumab. In certain embodiments each chain of such Fab fragment comprises a total of at most 4 amino acid deletions, amino acid insertions and / orAscendis Pharma A / S CPX75237PC 12 January 2026 amino acid exchanges compared to the corresponding chain of burosumab. In certain embodiments each chain of such Fab fragment comprises a total of at most 3 amino acid deletions, amino acid insertions and / or amino acid exchanges compared to the corresponding chain of burosumab. In certain embodiments each chain of such Fab fragment comprises a total of at most 2 amino acid deletions, amino acid insertions and / or amino acid exchanges compared to the corresponding chain of burosumab. In certain embodiments each chain of such Fab fragment comprises a total of 1 amino acid deletion, amino acid insertion and amino acid exchange compared to the corresponding chain of burosumab.

[1156] In certain embodiments -TB is a Fab fragment that has a light chain with the sequence of SEQ ID NO: 144, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165. SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 174, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, SEQ ID NO: 184 or SEQ ID NO: 185. These sequences are as follows:

[1157] SEQ ID NO: 155 CAIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFP PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1158] SEQ ID NO: 156 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACCVTHQGLSSPVTKSFNRGEC

[1159] SEQ ID NO: 157 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSCSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECAscendis Pharma A / S CPX75237PC 12 January 2026

[1160] SEQ IDNO:158 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQCPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1161] SEQ ID ON:159 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDICRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1162] SEQ IDNO:160 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLCSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1163] SEQ IDNO:161 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWCVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1164] SEQ IDNO:162 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGCSSPVTKSFNRGEC

[1165] SEQ IDNO:163 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPPAscendis Pharma A / S CPX75237PC 12 January 2026 SDECLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1166] SEQ IDNO:164 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALCSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1167] SEQ IDNO:165 AIQLTQSPSSLSACVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1168] SEQ IDNO:166 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFCGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1169] SEQ IDNO:167 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLCISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1170] SEQ IDNO:168 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGCASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1171] SEQ IDNO:169Ascendis Pharma A / S CPX75237PC 12 January 2026 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVCKSFNRGEC

[1172] SEQ IDNO:170 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPCTKSFNRGEC

[1173] SEQ IDNO:171 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLICDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1174] SEQ IDNO:174 CPPAIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTY SLS STLTLSKADYEKHKVYACEVTHQGLS SP VTKSFNRGEC

[1175] SEQ IDNO:178 AIQLTQSPSSLSASVGDRVTITCRASQGISSCLVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1176] SEQ IDNO:179 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDCFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECAscendis Pharma A / S CPX75237PC 12 January 2026

[1177] SEQ ID NO: 180 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDACSLESGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1178] SEQ ID NO: 181 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGSCTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1179] SEQ ID NO: 184 AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVP SRFSGSGCGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1180] SEQ ID NO: 185 ACQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGV PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFP PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[1181] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 144 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 144, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 144. In certain embodiments the light chain has the sequence of SEQ ID NO: 144.

[1182] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 155 or is a Fab fragment that has a light chain with a sequence that has at most a totalAscendis Pharma A / S CPX75237PC 12 January 2026 of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 155, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 155. In certain embodiments the light chain has the sequence of SEQ ID NO: 155.

[1183] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 156 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 156, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 156. In certain embodiments the light chain has the sequence of SEQ ID NO: 156.

[1184] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 157 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 157, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 157. In certain embodiments the light chain has the sequence of SEQ ID NO: 157.

[1185] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 158 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 158, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 158. In certain embodiments the light chain has the sequence of SEQ ID NO: 158.

[1186] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 159 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 159, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 159. In certain embodiments the light chain has the sequence of SEQ ID NO: 159.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 160 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 160, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 160. In certain embodiments the light chain has the sequence of SEQ ID NO: 160.

[1187] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 161 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 161, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 161. In certain embodiments the light chain has the sequence of SEQ ID NO: 161.

[1188] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 162 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 162, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 162. In certain embodiments the light chain has the sequence of SEQ ID NO: 162

[1189] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 163 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 163, such as a light chain having 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 163. In certain embodiments the light chain has the sequence of SEQ ID NO: 163.

[1190] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 164 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 164, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 164. In certain embodiments the light chain has the sequence of SEQ ID NO: 164.Ascendis Pharma A / S CPX75237PC 12 January 2026

[1191] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 165 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 165, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 165. In certain embodiments the light chain has the sequence of SEQ ID NO: 165.

[1192] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 166 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 166, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 166. In certain embodiments the light chain has the sequence of SEQ ID NO: 166.

[1193] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 167 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 167, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 167. In certain embodiments the light chain has the sequence of SEQ ID NO: 167.

[1194] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 168 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 168, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 168. In certain embodiments the light chain has the sequence of SEQ ID NO: 168.

[1195] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 169 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 169, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / orAscendis Pharma A / S CPX75237PC 12 January 2026 amino acid exchanges compared to SEQ ID NO: 169. In certain embodiments the light chain has the sequence of SEQ ID NO: 169.

[1196] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 170 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 170, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 170. In certain embodiments the light chain has the sequence of SEQ ID NO: 170.

[1197] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 171 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 171, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 171. In certain embodiments the light chain has the sequence of SEQ ID NO: 171.

[1198] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 174 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 174, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 174. In certain embodiments the light chain has the sequence of SEQ ID NO: 174.

[1199] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 178 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 178, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 178. In certain embodiments the light chain has the sequence of SEQ ID NO: 178.

[1200] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 179 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared toAscendis Pharma A / S CPX75237PC 12 January 2026 SEQ ID NO: 179, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 179. In certain embodiments the light chain has the sequence of SEQ ID NO: 179.

[1201] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 180 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 180, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 180. In certain embodiments the light chain has the sequence of SEQ ID NO: 180.

[1202] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 181 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 181, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 181. In certain embodiments the light chain has the sequence of SEQ ID NO: 181.

[1203] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 184 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 184, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 184. In certain embodiments the light chain has the sequence of SEQ ID NO: 184.

[1204] In certain embodiments -TB is a Fab fragment with a light chain having the sequence of SEQ ID NO: 185 or is a Fab fragment that has a light chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 185, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 185. In certain embodiments the light chain has the sequence of SEQ ID NO: 185.

[1205] In certain embodiments -TB is a Fab fragment that has a heavy chain with the sequence of SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ IDAscendis Pharma A / S CPX75237PC 12 January 2026 NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO: 173, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 182, SEQ ID NO: 183, or SEQ ID NO: 186. These sequences are as follows:

[1206] SEQ ID NO: 145 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1207] SEQ ID NO: 146 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHLC AA

[1208] SEQ ID NO: 147 CQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPIS GSTSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGT MVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFP AVLQS SGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1209] SEQ ID NO: 148 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQCPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1210] SEQ ID NO: 149 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSCSTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHLAscendis Pharma A / S CPX75237PC 12 January 2026 SEQ ID NO:150 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASCKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1211] SEQ ID NO:151 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNCKVDKKVEPKSCDKTHL

[1212] SEQ ID NO:152 QCQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1213] SEQ ID NO:153 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSC

[1214] SEQ ID NO:154 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCD

[1215] SEQ ID NO:173 CVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTMAscendis Pharma A / S CPX75237PC 12 January 2026 VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1216] SEQ IDNO:175 QVQLVQSGAEVKKPGASVKVSCKASGCTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1217] SEQ IDNO:176 QVQLVQSGAEVKKPGASVKVSCKASGYCFTNHYMHWVRQAPGQGLEWMGIINPIS GSTSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGT MVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFP AVLQS SGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1218] SEQ IDNO:177 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG CTSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1219] SEQ IDNO:182 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG SCSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1220] SEQ IDNO:183 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STCNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1221] SEQ IDNO:186Ascendis Pharma A / S CPX75237PC 12 January 2026 QCQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISG STSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF P AVLQ SSGL YSLS S VVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

[1222] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 145 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 145, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 145. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 145.

[1223] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 146 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 146, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 146. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 146.

[1224] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 147 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 147, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 147. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 147.

[1225] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 148 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 148, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 148. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 148.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 149 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 149, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 149. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 149.

[1226] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 150 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 150, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 150. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 150.

[1227] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 151 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO:151, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 151. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 151.

[1228] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 152 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 152, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 152. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 152.

[1229] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 153 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 153, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 153. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 153.Ascendis Pharma A / S CPX75237PC 12 January 2026

[1230] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 154 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 154, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 154. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 154.

[1231] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 173 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 173, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 173. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 173.

[1232] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 175 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 175, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 175. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 175.

[1233] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 176 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 176, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 176. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 176.

[1234] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 177 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 177, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / orAscendis Pharma A / S CPX75237PC 12 January 2026 amino acid exchanges compared to SEQ ID NO: 177. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 177.

[1235] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 182 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 182, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 182. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 182.

[1236] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 183 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 183, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 183. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 183.

[1237] In certain embodiments -TB is a Fab fragment with a heavy chain having the sequence of SEQ ID NO: 186 or is a Fab fragment that has a heavy chain with a sequence that has at most a total of 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 186, such as 1, 2, 3, 4 or 5 amino acids additions, amino acid deletions and / or amino acid exchanges compared to SEQ ID NO: 186. In certain embodiments the heavy chain has the sequence of SEQ ID NO: 186.

[1238] In certain embodiments the N-terminal glutamin (Q) of SEQ ID NO: 145, SEQ ID NO: 146, SEQ IDNO:148, SEQ IDNO:149, SEQ IDNO:150, SEQ IDNO:151, SEQ IDNO:152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 182, SEQ ID NO: 183, or SEQ ID NO: 186 undergoes pyroglutamate formation during expression.

[1239] In certain embodiments -TB is a Fab fragment that has a light chain of SEQ ID NO: 170 and a heavy chain of SEQ ID NO: 145.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -RB or -L3- is site-specifically covalently linked to the antibody or antibody fragment via a functional group selected from the group consisting of N-[ -maleimidopropyloxy] succinimide ester) (BMPS), N-[s-maleimidocaproyloxy] succinimide ester (EMCS), N-[y-maleimidobutyryloxy]succinimide ester (GMBS), 1,6-hexane-bis-vinylsulfone (HBVS), succinimidyl-4-(N-maleimidomethyl)cyclohexane-l-carboxy-(6-amidocaproate) (LC-SMCC), maleimidobenzoyl n-hydroxysuccinimide ester (MBS), 4-(4-N-Maleimidophenyl)-butyric acid hydrazide (MPBH), succinimidyl 3-(bromoacetamido)propionate (SBAP), succinimidyl iodoacetate (SIA), N-succinimidyl(4-iodoacetyl)aminobenzoate (SIAB), succinimidyl 4-(N-maleimido- methyl)cyclohexane-l-carboxylate (SMCC), succinimidyl 4-(p-maleimido-phenyl)butyrate (SMPB), succinimidyl-6-(P-maleimidopropionamido)hexanoate (SMPH), sulfo-EMCS, sulfo-GMBS, N-(K-Maleimidoundecanoyloxy)sulfosuccinimide ester (sulfo-KMUS), sulfo-MBS, sulfo-SIAB, sulfo-SMCC, sulfo-SMPB and succinimidyl-(4-vinylsulfone)benzoate (SVSB). The present disclosure further contemplates that the conjugates described herein may be prepared using any suitable methods as disclosed in the art (see for example Bioconjugate Techniques (Hermanson ed., 2d ed. 2008)).

[1240] In certain embodiments -D is synthesized by protein expression, e.g. where -RB is an antibody fragment, such as a Fab or scFv, -L3- is a protein or peptide moiety and -TB is an antibody fragment, such as a Fab or scFv.

[1241] In certain embodiments -TB is a peptide or protein moiety and -L3- is bonded through an amide bond to a lysine residue of the peptide or protein moiety. In certain embodiments -TB is a peptide or protein moiety and -L3- is conjugated through an amide bond to the N-terminus of the peptide or protein moiety. In certain embodiments -TB is a peptide or protein moiety and -L3- is conjugated through a thioether bond to a cysteine residue of the peptide or protein moiety. In certain embodiments -TB is a polypeptide moiety and -L3- is conjugated through an amide bond to the C-terminus of the polypeptide moiety. In certain embodiments -TB is a peptide or protein moiety and is connected to -L3- through a sulfur atom of a thiol of an amino acid residue, such as a cysteine, of -TB and the linkage between -TB and -L3- is a thiosuccinimide.

[1242] In certain embodiments -TB is a peptide or protein moiety and -L3- is conjugated through an amide bond to a lysine residue of the peptide moiety. In certain embodiments -TB is a peptideAscendis Pharma A / S CPX75237PC 12 January 2026 or protein moiety and -L3- is conjugated through an amide bond to the N-terminus of the peptide moiety. In certain embodiments -TB is a peptide or protein moiety and -L3- is conjugated through a thioether bond to a cysteine residue of the peptide moiety. In certain embodiments -TB is a peptide or protein moiety and -L3- is conjugated through an amide bond to the C-terminus of the peptide or protein moiety.

[1243] In certain embodiments -TB is an antibody moiety or fragment thereof and -L3- is conjugated through an amide bond to a lysine residue of the antibody moiety or fragment thereof. In certain embodiments -TB is an antibody moiety or fragment thereof and -L3- is conjugated through an amide bond to the N-terminus of the polypeptide moiety. In certain embodiments -TB is an antibody moiety or fragment and -L3- is conjugated through an amide bond to the C-terminus of the antibody moiety or fragment. In certain embodiments -TB is an antibody moiety or fragment thereof and -L3- is conjugated through a thioether bond to a cysteine residue of the antibody moiety or fragment thereof. In certain embodiments -TB is an antibody moiety or fragment thereof and -L3- is conjugated through two thioether bonds to two cysteine residues of the antibody moiety or fragment thereof, wherein the two cysteine residues are from an opened cysteine-cysteine disulfide bond in the antibody moiety or fragment thereof. In certain embodiments the opened cysteine-cysteine disulfide bond is an interchain disulfide bond. In certain embodiments the opened inter chains disulfide bonds are conjugated to -L3- via a rebridging reagent. In certain embodiments the rebridging reagent is selected from the group consisting of dibromomaleimides, pyridazinediones, bissulfones, dibromopyri-dazinediones, 2-(diphenylphosphino) -benzenesulfonic acid (diPPBS), 3,4-disubstituted maleimides, bromomaleimides, arsenous acid, dibromopyridazinediones, alkynes, allyl sulfones, divinyl triazine, arylenedipropiolo-nitriles, oxSTEF, arylene-dipropiolonitrile and divinylpyrimidine (DVP).

[1244] In certain embodiments -TB is a polypeptide moiety or an antibody moiety or fragment thereof and -L3- is attached via a site-specific conjugation. Site-specific conjugation may, for example, result in homogeneous loading and minimization of conjugate subpopulations with potentially altered antigen-binding or pharmacokinetics. In certain embodiments conjugation may comprise engineering of cysteine substitutions at positions on the polypeptide moiety or antibody moiety or fragment thereof, such as on the heavy and / or light chains of an antibody moiety or fragment thereof that provide reactive thiol groups and do not disrupt polypeptide or antibody or fragment thereof folding and assembly or alter polypeptide or antigen binding.Ascendis Pharma A / S CPX75237PC 12 January 2026

[1245] In certain embodiments selenocysteine is cotranslationally inserted into a polypeptide or antibody sequence by recoding the stop codon UGA from termination to selenocysteine insertion, allowing site specific covalent conjugation at the nucleophilic selenol group of selenocysteine in the presence of the other natural amino acids. In certain embodiments sitespecific conjugation to polypeptides or antibodies include engineering of non-natural amino acids, including, e.g., p-acetylphenylalanine (p-acetyl-Phe), p-azidomethyl-N-phenylalanine (p-azidomethyl-Phe), and azidolysine (azido-Lys) at specific linkage sites, and can further include engineering unique functional tags, including, such as LPXTG, LLQGA, sialic acid and GlcNac, for enzyme mediated conjugation. All such methodologies are contemplated for use in connection with making the conjugates described herein.

[1246] In certain embodiments -TB comprises a polynucleotide moiety that binds to FGF23. In certain embodiments -TB is a nucleic acid aptamer that binds to FGF23. In certain embodiments -TB comprises a small molecule drug moiety that binds to FGF23. In certain embodiments -TB comprises a small molecule drug moiety that is an inhibitor of FGF23 or a ligand moiety of FGF23. -L3- may be covalently attached to the small molecule moiety via substitution at any suitable site of the small molecule moiety such that binding to the target protein is substantially retained.

[1247] In certain embodiments -D is a bifunctional drug comprising at least one ASGPR-binding moiety -RB, wherein the at least one -RB comprises at most two carbohydrate moieties and additional moieties optionally present in -RB are free of carbohydrates, and -TB, wherein -TB is an antibody or fragment thereof, such as a Fab. In certain embodiments -D is a bifunctional drug comprising at least one ASGPR-binding moiety -RB, wherein the at least one -RB comprises one carbohydrate moiety and additional moieties optionally present in -RB are free of carbohydrates, and -TB, wherein -TB is an antibody or fragment thereof, such as a Fab. In certain embodiments -D is a bifunctional drug comprising at least one ASGPR-binding moiety -RB , wherein the at least one -RB comprises two carbohydrate moieties and additional moieties optionally present in -RB are free of carbohydrates, and -TB, wherein -TB is an antibody or fragment thereof, such as a Fab.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -L1-i s attached to -RB. In certain embodiments -L1- is attached to -L3-. In certain embodiments -L1- is attached to -TB.

[1248] In certain embodiments -L1- is attached to -D through a functional group of the corresponding drug selected from the group consisting of a carboxylic acid, primary amine, secondary amine, maleimide, thiol, sulfonic acid, carbonate, carbamate, hydroxyl, aldehyde, ketone, hydrazine, isocyanate, isothiocyanate, phosphoric acid, phosphonic acid, haloacetyl, alkyl halide, acryloyl, aryl fluoride, hydroxylamine, sulfate, disulfide, vinyl sulfone, vinyl ketone, diazoalkane, oxirane, guanidine and aziridine. In certain embodiments -L1- is attached to -D through an amine functional group of the corresponding drug. In certain embodiments -L1- is attached to -D through an amine functional group of the corresponding drug, such as through a primary or secondary amine functional group. In certain embodiments -L1- is attached to -D through a hydroxyl functional group of the corresponding drug.

[1249] It is understood that all embodiments describing attachment of -L1- to an amino acid residue or to an N-terminal amine functional group of -D require the presence of at least one suitable amino acid residue or of a peptide or protein moiety, respectively.

[1250] In certain embodiments -L1- may be attached to a proteinogenic or non-proteinogenic amino acid residue of -D, such as a proteinogenic or non-proteinogenic amino acid residue of -RB, -L3- or -TB. In certain embodiments -L1- is attached to a proteinogenic amino acid residue of -D, such as to a proteinogenic amino acid residue selected from the group consisting of cysteine, methionine, histidine, lysine, tryptophan, serine, threonine, tyrosine, aspartic acid, glutamic acid, glutamine and arginine. In certain embodiments such proteinogenic amino acid residue is selected from the group consisting of cysteine, histidine, lysine, tryptophan, serine, threonine, tyrosine, aspartic acid, glutamic acid and arginine. In certain embodiments attachment of -L1- is to a non-proteinogenic amino acid residue of -D. Examples for such non-proteinogenic amino acid residues are as described elsewhere herein.

[1251] In certain embodiments -L1- is attached to a cysteine residue of -D. In certain embodiments -L1- is attached to a histidine residue of -D. In certain embodiments -L1- is attached to a lysine residue of -D. In certain embodiments -L1- is attached to a tryptophan residue of -D. In certain embodiments -E S attached to a serine residue of -D. In certain embodiments -L1- is attached to a threonine residue of -D. In certain embodiments -L1- isAscendis Pharma A / S CPX75237PC 12 January 2026 attached to a tyrosine residue of -D. In certain embodiments -L1- is attached to an aspartic acid residue of -D. In certain embodiments -L1- is attached to a glutamic acid residue of -D. In certain embodiments -L1- is attached to an arginine residue of -D.

[1252] In certain embodiments -L1- is a traceless linker, i.e., the reversible bond is between -D and -L1-. In certain embodiments -L1- releases -D in a modified form, i.e., the reversible bond is within -L1- and accordingly -D is released as a conjugate comprising a part of -L1-. The reversible linkage may be selected from the group consisting of amide, ester, carbamate, acetal, aminal, imine, oxime, hydrazone, disulfide and acylguanidine. In certain embodiments -L1- is connected to -D through a linkage selected from the group consisting of amide, ester, carbamate and acylguanidine. It is understood that these linkages may not be reversible per se, but that reversibility may be an effect of certain groups of atoms or moieties present in -L1-. In certain embodiments the reversible linkage is a carbamate linkage. In certain embodiments the reversible linkage is an amide linkage.

[1253] In certain embodiments -L1- is connected to -D via a nitrogen of an amine functional group of -D.

[1254] In certain embodiments -L1- is connected to -D via the nitrogen of the e-amino group of a lysine residue of -D or via the nitrogen of the N-terminal amine of -D. In certain embodiments -L1- is connected to -D via the nitrogen of the e-amino group of a lysine residue or via the nitrogen of the N-terminal amine and the linkage formed between -D and -L1- is a carbamate. In certain embodiments -L1- is connected to -D via the nitrogen of the e-amino group of a lysine residue or via the nitrogen of the N-terminal amine and the linkage formed between -D and -L1- is an amide.

[1255] In certain embodiments -L1- is connected to -D via the nitrogen of the e-amino group of a lysine residue of -D. In certain embodiments -L1- is connected to -D via the nitrogen of the e-amino group of a lysine residue of -D and the linkage formed between -D and -L1- is a carbamate. In certain embodiments -L1- is connected to -D via the nitrogen of the e-amino group of a lysine residue of -D and the linkage formed between -D and -L1- is an amide.

[1256] In certain embodiments -L1- is connected to -D via the nitrogen of the N-terminal amine of -D. In certain embodiments -L1- is connected to -D via the nitrogen of the N-terminal amine of -DAscendis Pharma A / S CPX75237PC 12 January 2026 and the linkage formed between -D and -L1- is a carbamate. In certain embodiments -L1- is connected to -D via the nitrogen of the N-terminal amine of -D and the linkage formed between -D and -L1- is an amide.

[1257] In certain embodiments -L1- has a structure as disclosed in WO 2009 / 095479 A2. Accordingly, in certain embodiments the moiety -L1- is of formula (II):

[1258]

[1259] wherein the dashed line indicates attachment to a nitrogen of -D by forming an amide bond;

[1260] -X- is -C(R4R4a)-, -N(R4)-, -O-, -C(R4R4a)-C(R5R5a)-, -C(R5R5a)-C(R4R4a)-, -C(R4R4a)-N(R6)-, -N(R6)-C(R4R4a)-, -C(R4R4a)-O-, -O-C(R4R4a)-, or -C(R7R7a)-;

[1261] X1is C or S(O);

[1262] -X2- is -C(R8R8a)- or -C(R8R8a)-C(R9R9a)-;

[1263] =X3is =0, =S or =N-CN;

[1264] -R1, -Rla, -R2, -R2a, -R4, -R4a, -R5, -R5a, -R6, -R8, -R8a, -R9and -R9aare independently selected from the group consisting of -H and Ci-6 alkyl;

[1265] -R3and -R3aare independently selected from the group consisting of -H and Ci-6 alkyl, provided that in case one of -R3and -R3aor both are other than -H they are connected to N to which they are attached through an sp3-hybridized carbon atom;

[1266] -R7is -N(R10R10a), or -NR10-(C=O)-Rn;

[1267] -R7a, -R10, -R10aand -R11are independently of each other -H or Ci-6 alkyl; optionally, one or more of the pairs -Rla / -R4a, -Rla / -R5a, -Rla / -R7a, -R4a / -R5aand -R8a / -R9aform a chemical bond;

[1268] optionally, one or more of the pairs -RJ / -Rla, -R2 / -R2a, -R4 / -R4a, -R5 / -R5a, -R8 / -R8aand -R9 / -R9aare joined together with the atom to which they are attached to form a C3-10 cycloalkyl or 3- to 10-membered heterocyclyl;

[1269] optionally, one or more of the pairs -RV-R4, -RV-R5, -RV-R6, -RJ / -R7a, -R4 / -R5, -R4 / -R6, -R8 / -R9and -R2 / -R3are joined together with the atoms to which they are attached to form a ring A;Ascendis Pharma A / S CPX75237PC 12 January 2026 optionally, R3 / R3aare joined together with the nitrogen atom to which they are attached to form a 3- to 10-membered heterocycle;

[1270] A is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl and 8- to 11 -membered heterobicyclyl; and

[1271] wherein -L1- is substituted with at least one -L2-Z and wherein -L1- is optionally further substituted, provided that the hydrogen marked with the asterisk in formula (II) is not replaced by -L2-Z or a substituent.

[1272] In certain embodiments -L1- is of formula (II), but wherein the dashed line indicates attachment to -L2-Z and wherein -L1- is substituted with at least one moiety -D, in certain embodiments with one moiety -D. In such embodiments -L1- is not a traceless linker moiety and -D is released in a modified form with parts of -L1- conjugated to -D. All other variables are as defined elsewhere herein for formula (II).

[1273] In certain embodiments -L1- of formula (II) is substituted with one moiety -L2-Z.

[1274] In certain embodiments -L1- of formula (II) is not further substituted.

[1275] It is understood that if -R3 / -R3aof formula (II) are joined together with the nitrogen atom to which they are attached to form a 3 - to 10-membered heterocycle, only such 3- to 10-membered heterocycles may be formed in which the atoms directly attached to the nitrogen are sp3-hybridized carbon atoms. In other words, such 3- to 10-membered heterocycle formed by -R3 / -R3atogether with the nitrogen atom to which they are attached has the following structure:

[1276]

[1277] wherein

[1278] the dashed line indicates attachment to the rest of -L1-;

[1279] the ring comprises 3 to 10 atoms comprising at least one nitrogen; and

[1280] R#and R##represent an sp3-hydridized carbon atom.

[1281] It is also understood that the 3- to 10-membered heterocycle may be further substituted.Ascendis Pharma A / S CPX75237PC 12 January 2026

[1282] Exemplary embodiments of suitable 3- to 10-membered heterocycles formed by -R3 / -R3aof formula (II) together with the nitrogen atom to which they are attached are the following:

[1283]

[1284] wherein

[1285] dashed lines indicate attachment to the rest of the molecule; and

[1286] -R is selected from the group consisting of -H and Ci-6 alkyl.

[1287] -L1- of formula (II) may optionally be further substituted. In general, any substituent may be used as far as the cleavage principle is not affected, i.e. the hydrogen marked with the asterisk in formula (II) is not replaced and the nitrogen of the moiety

[1288] R■

[1289] N-l-R3a'1

[1290] of formula (II) remains part of a primary, secondary or tertiary amine, i.e. -R3and -R3aare independently of each other -H or are connected to -N< through an sp3-hybridized carbon atom.

[1291] In certain embodiments -L1- has a structure as disclosed in W02016 / 020373A1. Accordingly, in certain embodiments the moiety -L1- is of formula (III):

[1292]

[1293] wherein

[1294] the dashed line indicates attachment to a primary or secondary amine or hydroxyl of -D by forming an amide or ester linkage, respectively;

[1295] -R1, -Rla, -R2, -R2a, -R3and -R3aare independently of each other selected from the group consisting of -H, -C(R8R8aR8b), -C(=O)R8, -ON, -C(=NR8)R8a, -CR8(=CR8aR8b), -OCR8and -T;Ascendis Pharma A / S CPX75237PC 12 January 2026 -R4, -R5and -R5aare independently of each other selected from the group consisting of -H, -C(R9R9aR9b) and -T;

[1296] al and a2 are independently of each other 0 or 1;

[1297] each -R6, -R6a, -R7, -R7a, -R8, -R8a, -R8b, -R9, -R9aand -R9bare independently of each other selected from the group consisting of -H, halogen, -CN, -COOR10, -OR10, -C(O)R10, -C(O)N(R10R10a), -S(O)2N(R10R10a), -S(O)N(R10R10a), -S(O)2R10, -S(O)R10, -N(R10)S(O)2N(R10aR10b), -SR10, -N(R10R10a), -NO2, -OC(O)R10, -N(R10)C(O)R10a, -N(R10)S(O)2R10a, -N(R10)S(O)R10a, -N(R10)C(O)OR10a, -N(R10)C(O)N(R10aR10b), -OC(O)N(R10R10a), -T, C1-20 alkyl, C2.20alkenyl and C2.20alkynyl; wherein -T, C1-20 alkyl, C2.2o alkenyl and C2.2o alkynyl are optionally substituted with one or more -R11, which are the same or different and wherein C1-20 alkyl, C2.2o alkenyl and C2.2o alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)- and -OC(O)N(R12)-;

[1298] each -R10, -R10aand -R10bis independently selected from the group consisting of -H, -T, C1-20 alkyl, C2.2o alkenyl and C2.2o alkynyl; wherein -T, C1-20 alkyl, C2.2o alkenyl and C2.

[1299] 2o alkynyl are optionally substituted with one or more -R11, which are the same or different and wherein C1-20 alkyl, C2.2o alkenyl and C2.2o alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)-and -OC(O)N(R12)-;

[1300] each T is independently of each other selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl and 8- to 11 -membered heterobicyclyl; wherein each T is independently optionally substituted with one or more -R11, which are the same or different;

[1301] each -R11is independently of each other selected from halogen, -CN, oxo (=0), -COOR13, -OR13, -C(O)R13, -C(O)N(R13R13a), -S(O)2N(R13R13a), -S(O)N(R13R13a), -S(O)2R13, -S(O)R13, -N(R13)S(O)2N(R13aR13b), -SR13, -N(R13R13a), -NO2, -OC(O)R13, -N(R13)C(O)R13a, -N(R13)S(O)2R13a, -N(R13)S(O)R13a, -N(R13)C(O)OR13a, -N(R13)C(O)N(R13aR13b), -OC(O)N(R13R13a) and Ci-6alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;Ascendis Pharma A / S CPX75237PC 12 January 2026 each -R12, -R12a, -R13, -R13aand -R13bis independently selected from the group consisting of -H and Ci-6 alkyl; wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different;

[1302] optionally, one or more of the pairs -RJ / -Rla, -R2 / -R2a, -R3 / -R3a, -R6 / -R6aand -R7 / -R7aare joined together with the atom to which they are attached to form a C3-10 cycloalkyl or a 3- to 10-membered heterocyclyl;

[1303] optionally, one or more of the pairs -RV-R2, -RV-R3, -RV-R4, -RV-R5, -RV-R6, -RV-R7, -R2 / -R3, -R2 / -R4, -R2 / -R5, -R2 / -R6, -R2 / -R7, -R3 / -R4, -R3 / -R5, -R3 / -R6, -R3 / -R7, -R4 / -R5, -R4 / -R6, -R4 / -R7, -R7-R6, -R7-R7and -R6 / -R7are joined together with the atoms to which they are attached to form a ring A;

[1304] A is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl and 8- to 11 -membered heterobicyclyl;

[1305] wherein -L1- is substituted with at least one -L2-Z and wherein -L1- is optionally further substituted.

[1306] In certain embodiments -L1- is of formula (III), but wherein the dashed line indicates attachment to -L2-Z and wherein -L1- is substituted with at least one moiety -D, in certain embodiments with one moiety -D. In such embodiments -L1- is not a traceless linker moiety and -D is released in a modified form with parts of -L1- conjugated to -D. All other variables are as defined elsewhere herein for formula (III).

[1307] In certain embodiments -L1- of formula (III) is substituted with one moiety -L2-Z.

[1308] The optional further substituents of -L1- of formula (III) are preferably as described elsewhere herein.

[1309] In certain embodiments -L1- of formula (III) is not further substituted.

[1310] In certain embodiments -L1- has a structure as disclosed in EP1536334B1, W02009 / 009712A1, W02008 / 034122A1, WO2009 / 143412A2, WO2011 / 082368A2, and US8618124B2, which are herewith incorporated by reference.Ascendis Pharma A / S CPX75237PC 12 January 2026 In certain embodiments -L1- has a structure as disclosed in US8946405B2 and US8754190B2. Accordingly, in certain embodiments -L1- is of formula (IV):

[1311]

[1312] (IV),

[1313] wherein

[1314] the dashed line indicates attachment to -D through a functional group selected from the group consisting of -OH, -SH and -NH2;

[1315] m is 0 or 1;

[1316] at least one or both of -R1and -R2is / are independently of each other selected from the group consisting of -CN, -NO2, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkenyl, optionally substituted alkynyl, -C(O)R3, -S(O)R3, -S(O)2R3, and -SR4;

[1317] one and only one of -R1and -R2is selected from the group consisting of -H, optionally substituted alkyl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl;

[1318] -R3is selected from the group consisting of -H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -OR9and -N(R9)2;

[1319] -R4is selected from the group consisting of optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;

[1320] each -R5is independently selected from the group consisting of -H, optionally substituted alkyl, optionally substituted alkenylalkyl, optionally substituted alkynylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;

[1321] -R9is selected from the group consisting of -H and optionally substituted alkyl;

[1322] -Y- is absent and -X- is -O- or -S-; or

[1323] -Y- is -N(Q)CH2- and -X- is -O-;

[1324] Qis selected from the group consisting of optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;

[1325] optionally, -R1and -R2may be joined to form a 3 to 8-membered ring; andAscendis Pharma A / S CPX75237PC 12 January 2026 optionally, both -R9together with the nitrogen to which they are attached form a heterocyclic ring;

[1326] wherein -L1- is substituted with -L2-Z and wherein -L1- is optionally further substituted.

[1327] In certain embodiments -L1- is of formula (IV), but wherein the dashed line indicates attachment to -L2-Z and wherein -L1- is substituted with at least one moiety -D, in certain embodiments with one moiety -D. In such embodiments -L1- is not a traceless linker moiety and -D is released with a modified form with parts of -L1- conjugated to -D. All other variables are as defined elsewhere herein for formula (IV).

[1328] In certain embodiments -L1- of formula (IV) is substituted with one moiety -L2-Z.

[1329] In certain embodiments -L1- of formula (IV) is not further substituted.

[1330] Only in the context of formula (IV) the terms used have the following meaning:

[1331] The term “alkyl” as used herein includes linear, branched or cyclic saturated hydrocarbon groups of 1 to 8 carbons, or in some embodiments 1 to 6 or 1 to 4 carbon atoms.

[1332] The term “alkoxy” includes alkyl groups bonded to oxygen, including methoxy, ethoxy, isopropoxy, cyclopropoxy, cyclobutoxy and similar.

[1333] The term “alkenyl” includes non-aromatic unsaturated hydrocarbons with carbon-carbon double bonds.

[1334] The term “alkynyl” includes non-aromatic un...

Claims

Ascendis Pharma A / S CPX75237PC 12 January 2026 Claims1. A conjugate or a pharmaceutically acceptable salt thereof comprising at least one moiety -D, which is conjugated via at least one moiety -LJ(-L2)a- to at least one moiety -Z, wherein -L1- is conjugated to -D, and wherein-D is a drug moiety comprising at least one receptor-binding moiety -RB and at least one target-binding moiety -TB binding to FGF23;-L1- is a reversible linker moiety;-L2- is a spacer moiety;a is 1 or 0; and-Z is a polymeric moiety.

2. A conjugate or a pharmaceutically acceptable salt thereof is of formula (la) or (lb)wherein-D is a drug moiety comprising at least one receptor-binding moiety -RB and at least one target-binding moiety -TB binding to FGF23;-L1- is a linker moiety covalently and reversibly conjugated to -D;-L2- is a spacer moiety or is absent;-Z is a polymeric moiety;x is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16; and y is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16.

3. The conjugate or the pharmaceutically acceptable salt thereof of claim 1 or 2, wherein -D is of formula (Ic)(RB)U-(L3)V-(TB)W(IC),wherein-RB is a receptor-binding moiety;-L3- is a spacer moiety;-TB is a target-binding moiety;u is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;Ascendis Pharma A / S CPX75237PC 12 January 2026 v is O, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; and w is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

4. The conjugate or the pharmaceutically acceptable salt thereof of claim 3, wherein u, v and w of formula (Ic) are 1.

5. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 4, wherein -RB binds to at least one ASGPR, M6PR or IGF2R.

6. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 5, wherein -RB binds to at least one ASGPR.

7. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 6, wherein -RB is of formula (Id)wherein-CARB is a carbohydrate moiety;-L4- is a spacer moiety;-L5- is a branched spacer moiety;a is 1, 2, 3, 4, 5 or 6;b is 0 if a is 1 or b is 1 if a is 2, 3, 4, 5 or 6; andthe dashed line indicates attachment to -L3- or -TB.

8. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 7, wherein -RB comprises one or more GalNAc moieties, such as at least 1, 2, 3, 4, 5, or 6 GalNAc moieties.

9. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 8, wherein -RB comprises 3 GalNAc moieties.

10. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 8, wherein -RB comprises at most two GalNAc moieties.Ascendis Pharma A / S CPX75237PC 12 January 202611. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 9, wherein -RB is of formula (H-l)whereinthe dashed line indicates attachment to -L3-.

12. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 8 or 10, wherein -RB is selected from the group consisting of formula (J- 1 ), (J-2), (J-3), (J- 4), (J-5), (J-6), (J-7), (J-8), (J-9), (J-10), (J-l 1), (J-12), (J-13), (J-14), (J-15) and (J-16).

13. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 8, 10 or 12, wherein -RB is of formula (J-l)whereinthe dashed line indicates attachment to -L3- or -TB.

14. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 3 to 13, wherein -L3- is a moiety of formula (L3-i)<whereinthe unmarked dashed line indicates attachment to -L4-, -L5-, or -RB;the dashed line marked with an asterisk indicates attachment to -TB;Ascendis Pharma A / S CPX75237PC 12 January 2026 the dashed line marked with an # indicates attachment to -L1- as described elsewhere herein, such as to -L1- which is a moiety -Lla-Llb-, wherein -Lla- is of formula (XII- a) and -Llb- is of formula (Xll-b);-G- is a branched spacer moiety;-Y- is a bioorthogonal group;-W- is a moiety selected from the group consisting of"wherein-X6- is selected from the group consisting of -O-, -C(O)-, -S-, -SO2-, -N(R6)- and -C(O)N(R6)-;-R6is selected from the group consisting of -H, -T and C1-10 alkyl;n and o are each independently an integer ranging from 1 to 20;p is an integer ranging from 0 to 50; andm is an integer ranging from 1 to 20; and-V- is a moiety selected from the group consisting ofwherein-X4- is selected from the group consisting of -O-, -S- and -N(R10)-;=X5is selected from the group consisting of =0, =S and =NR10;-X7is selected from the group consisting of -OR10, -SR10and -N(R10a)(R10b); each -R10, -R10aand -R10bis independently selected from the group consisting of -H, -CN, -T, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, and wherein Ci -6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)- and -OC(O)N(R12)-;each -R11is independently selected from the group consisting of -C(O)OH, halogen, -NO2, -CN, -OH, -OCH3, -N(R12)(R12a) and C1-6 alkyl; whereinAscendis Pharma A / S CPX75237PC 12 January 2026 Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different;each -R12and -R12ais independently selected from the group consisting of -H and Ci-6 alkyl; wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different; andr is 0 or 1.

15. The conjugate or the pharmaceutically acceptable salt thereof of claim 14, wherein -G- of formula (L3-i) is of formula (g-ii):wherein the unmarked dashed line indicates attachment to -L4-, -L5-, or -RB;the dashed line marked with the asterisk indicates attachment to -TB;the dashed line marked with # indicates attachment to -Y- of formula (L3-i);ql is an integer ranging from 1 to 20;each q2 is independently 0 or 1;each q3 is independently an integer ranging from 0 to 20; andeach q4 is independently an integer ranging from 0 to 20.

16. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 3 to 15, wherein -L3- is of formula (1-24)whereinthe unmarked dashed line indicates attachment to -TB,Ascendis Pharma A / S CPX75237PC 12 January 2026 the dashed line marked with the asterisk indicates attachment to -L4-, -L5- or -RB; andthe dashed line marked with # indicates attachment to -L1-;the unmarked dashed line indicates attachment the remainder of -L3-, i.e., to the carbonyl to the right of -R1; andand a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

17. The conjugate or the pharmaceutically acceptable salt thereof of claim 16, wherein a is 3.

18. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 17, wherein -L1- is of formula -Lla-Llb-, wherein -Lla- is of formula (Xll-a)whereinthe dashed line indicates attachment to -Llb-;-X1- is selected from the group consisting of -O-, -S- and -N(R3)-;Ar1is a 5- to 14-membered monocyclic, bicyclic or tricyclic aryl or heteroaryl, whereinoptionally each carbon atom of Ar1in ortho position to the carbon atom marked with the asterisk is independently substituted with a moiety selected from the group consisting of halogen, -CN, -NO2, -T, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R4, which are the same or different; and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R5)-, -S(O)2N(R5)-,Ascendis Pharma A / S CPX75237PC 12 January 2026 -S(O)N(R5)-, -S(O)2-, -S(O)-, -N(R5)S(O)2N(R5)-, -S-, -N(R5)-, -OC(OR5)(R5)-, -N(R5)C(O)N(R5)- and -OC(O)N(R5)-;optionally each carbon atom of Ar1not in ortho position to the carbon atom marked with the asterisk is independently substituted with a moiety selected from the group consisting of -C(O)OH, -C(O)NH2, halogen, -CN, -NO2, -T, -OH, Ci-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, wherein Ci-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R4, which are the same or different; and wherein Ci-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R5)-, -S(O)2N(R5)-, -S(O)N(R5)-, -S(O)2-, -S(O)-, -N(R5)S(O)2N(R5)-, -S-, -N(R5)-, -OC(OR5)(R5)-, -N(R5)C(O)N(R5)- and -OC(O)N(R5)-; and wherein two or more substituents of Ar1- are optionally joined together with the atom(s) to which they are attached to form a C3-10 cycloalkyl or a 3- to 10-membered heterocyclyl;-Llb- is of formula (Xll-b)whereinthe unmarked dashed line indicates attachment to -Lla-;=X2is selected from the group consisting of =0, =S and =NR3;-X3- is selected from the group consisting of -C(O)-, -S(O)2- and -C(R2)(R2a)-; -R1is selected from the group consisting of -CN, -T, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R4, which are the same or different, and wherein Ci -6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(R5)-, -S(O)2N(R5)-, -S(O)N(R5)-, -S(O)2-, -S(O)-, -N(R5)S(O)2N(R5)-, -S-, -N(R5)-, -OC(OR5)(R5)-, -N(R5)C(O)N(R5)- and -0C(0)N(R5)-;each -R2and -R2ais independently selected from the group consisting of -H, -C(0)0H, -C(0)NH2, halogen, -CN, -T, -OH, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionallyAscendis Pharma A / S CPX75237PC 12 January 2026 substituted with one or more -R4, which are the same or different; and wherein Ci -6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R5)-, -S(O)2N(R5)-, -S(O)N(R5)-, -S(O)2-, -S(O)-, -N(R5)S(O)2N(R5)-, -S-, -N(R5)-, -OC(OR5)(R5)-, -N(R5)C(O)N(R5)- and -OC(O)N(R5)-;each -R3, -R3aand -R3bis independently selected from the group consisting of -H, -CN, -T, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl, and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more -R4, which are the same or different; and wherein C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R5)-, -S(O)2N(R5)-, -S(O)N(R5)-, -S(O)2-, -S(O)-, -N(R5)S(O)2N(R5)-, -S-, -N(R5)-, -OC(OR5)(R5)-, -N(R5)C(O)N(R5)- and -OC(O)N(R5)-;each -R4is independently selected from the group consisting of -C(O)OH, halogen, -NO2, -CN, -OH, -OCH3, -N(R5)(R5) and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; each -R5is independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;one or more of the pairs -RV-R2, -RJ / -R2a, -R2 / -R2, -R2a / -R2a, -R2 / -R2a, -R2 / -R3a, -R2a / -R3a, -R2 / -R3b, -R2a / -R3band -R3a / -R3bare optionally joined together with the atom(s) to which they are attached to form a C3-10 cycloalkyl, a 3- to 10-membered heterocyclyl or an 8- to 11-membered heterobicyclyl, with the provision that the pair -R2 / -R2ais formed by a moiety -R2and a moiety -R2athat are attached to the same or adjacent carbon atom;each -T and -T- is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl and 8- to 11-membered heterobicyclyl, wherein -T and -T- are each independently optionally substituted with one or more -R4, which are the same or different; andn is 1, 2 or 3; andAscendis Pharma A / S CPX75237PC 12 January 2026 wherein one of -Lla- and -Llb- is substituted with -D and the other one is substituted with -L2-Z, with the provision that when -X3- is -C(O)- or -S(O)2-, -R3ais -H and is not substituted with -L2-Z or -D.

19. The conjugate or the pharmaceutically acceptable salt thereof of claim 18, wherein -Lla- is of formula (Xll-a), whereinAr1is a 5- to 6-membered monocyclic aryl or heteroaryl, and whereinoptionally each carbon atom of Ar1in ortho position to the carbon atom marked with the asterisk is independently substituted with a moiety selected from the group consisting of halogen, -CN and Ci-6 alkyl wherein Ci-6 alkyl is optionally substituted with one or more -R4, which are the same or different; and wherein Ci-6 alkyl is are optionally interrupted by one or more groups selected from the group consisting of -O- and -S-;optionally each carbon atom not in ortho position to the carbon atom marked with the asterisk is independently substituted with a moiety selected from the group consisting of halogen, -CN and Ci-6 alkyl, wherein Ci-6 alkyl is optionally substituted with one or more -R4, which are the same or different; and wherein is optionally interrupted by one or more groups selected from the group consisting of -O-, -C(O)N(R5)-, -N(R5)-, -N(R5)C(O)N(R5)- and -OC(O)N(R5)-; andwherein two or more Ar1-substituents are optionally joined together with the atom(s) to which they are attached to form a C3-10 cycloalkyl or a 3- to 10-membered heterocyclyl;-X1- is -O-; and-Llb- is of formula (Xll-b), wherein=X2is selected from the group consisting of =0 and =S;-X3- is selected from the group consisting of -C(O)- and -C(R2)(R2a)-;each -R1is selected from the group consisting of -T, C1-6 alkyl and C2-6 alkenyl, wherein C1-6 alkyl and C2-6 alkenyl are optionally substituted with one or more -R4, which are the same or different, and wherein C1-6 alkyl and C2-6 alkenyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(0)N(R5)-, -N(R5)- and -0C(0)N(R5)-;each -R2and -R2ais independently selected from the group consisting of -H, -T and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more -R4, which are the same or different; and wherein C1-6 alkyl is optionally interrupted by one or moreAscendis Pharma A / S CPX75237PC 12 January 2026 groups selected from the group consisting of -T-, -O-, -C(O)N(R5)-, -S-, -N(R5)-, -N(R5)C(O)N(R5)- and -OC(O)N(R5)-; each -R3, -R3aand -R3bis independently selected from the group consisting of -H, -T and Ci-6 alkyl, wherein Ci-6 alkyl is optionally substituted with one or more -R4, which are the same or different; and wherein Ci-6 alkyl is optionally interrupted by one or more groups selected from the group consisting of -T-, -O-, -C(O)N(R5)-, -S(O)2N(R5)-, -N(R5)S(O)2N(R5)-, -S-, -N(R5)-, -N(R5)C(O)N(R5)- and -OC(O)N(R5)-;with the provision that when -X3- is -C(O)-, -R3ais -H and is not substituted with -L2-Z or -Deach -R4is independently selected from the group consisting of halogen, -CN, -OH, -C(O)OH and Ci-6 alkyl; wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different;each -R5is independently selected from the group consisting of -H and Ci-6 alkyl; one or more of the pairs -R2 / -R2, -R2a / -R2a, -R2 / -R2aare optionally joined together with the atom(s) to which they are attached to form a C3-10 cycloalkyl, with the provision that the pair -R2 / -R2ais formed by a moiety -R2and a moiety -R2athat are attached to the same or adjacent carbon atom;each -T and -T- is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, C3-10 cycloalkyl and 3- to 10-membered heterocyclyl; and n is 1 or 2.

20. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 19, wherein -L1- is of formula (Xll-c-i)(Xll-c-i),whereinthe unmarked dashed line indicates attachment to -L2-; andthe dashed line marked with the asterisk indicates attachment to -L3-.

21. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 20, wherein -L2- is selected from the group consisting of -T-, -C(O)O-, -O-,Ascendis Pharma A / S CPX75237PC 12 January 2026 -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, Ci-50 alkyl, C2-so alkenyl and C2-so alkynyl; wherein -T-, C1-50 alkyl, C2-5o alkenyl and C2-so alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein Ci-50 alkyl, C2-so alkenyl and C2-so alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)- and -OC(O)N(Ry3)-;-Ryland -Rylaare independently of each other selected from the group consisting of-H, -T, Ci -50 alkyl, C2-5o alkenyl and C2-so alkynyl; wherein -T, C1-50 alkyl, C2-so alkenyl and C2-5o alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-50 alkyl, C2-so alkenyl and C2-so alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)- and -OC(O)N(Ry4)-;each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -COORy5, -ORy5, -C(O)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -OC(O)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a) and Ci-6alkyl; wherein Ci-6alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H and Ci-6 alkyl, wherein Ci-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

22. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 21, wherein -L2- is a C1-20 alkyl chain, which is optionally interrupted by one or moreAscendis Pharma A / S CPX75237PC 12 January 2026 groups independently selected from -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)- and -OC(O)N(Ry1)-; and which C1-20 alkyl chain is optionally substituted with one or more groups independently selected from -OH, -T and -C(O)N(Ry6Ry6a); wherein -Ryl, -Ryla, -Ry6and -Ry6aare independently selected from the group consisting of -H and C1-4 alkyl and wherein T is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopolycyclyl and 8- to 30-membered heteropoly cyclyl.

23. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 22, wherein -L2- is of formula (IX-f)whereinthe dashed line marked with the asterisk indicates attachment to -L1-;the unmarked dashed line indicates attachment to -Z; ands2 is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20.

24. The conjugate or the pharmaceutically acceptable salt thereof of claim 23, wherein s2 is 5.

25. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 20, wherein -L2- is absent.

26. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 25, wherein -Z has a molecular weight ranging from 1 kDa to 1000 kDa, such as from 2 kDa to 500 kDa, from 3 kDa to 200 kDa, from 5 kDa to 120 kDa, from 10 kDa to 100 kDa or from 15 kDa to 80kDa.

27. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 26, wherein -Z is a PEG-based polymer.Ascendis Pharma A / S CPX75237PC 12 January 202628. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 27, wherein -Z is of formula (D-i)whereinpl, p2, p3, p4 are independently of each other an integer ranging from 70 to 900; b is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; andthe dashed line indicates attachment to -L2- or -L1-.

29. The conjugate or the pharmaceutically acceptable salt thereof of claim 28, wherein b is 3 or 5.

30. The conjugate or the pharmaceutically acceptable salt thereof of claim 28 or 29, wherein pl, p2, p3 and p4 are an integer ranging from 200 to 250.

31. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 30, wherein -TB is an antibody binding to FGF23.

32. The conjugate or the pharmaceutically acceptable salt thereof of claim 31 , wherein -TB is burosumab or an antibody having at least 95% sequence homology to burosumab.

33. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 30, wherein -TB is a Fab fragment.

34. The conjugate or the pharmaceutically acceptable salt thereof of claim 33, wherein the Fab fragment has a heavy chain having the sequence of SEQ ID NO: 145, SEQ IDAscendis Pharma A / S CPX75237PC 12 January 2026 NO: 146, SEQ ID NO: 147, SEQ IDNO:148, SEQ IDNO:149, SEQ IDNO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:173, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 182, SEQ ID NO: 183, or SEQ ID NO: 186.

35. The conjugate or the pharmaceutically acceptable salt thereof of claim 33 or 34, wherein the Fab fragment has a light chain having the sequence of SEQ ID NO: 144, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO:159, SEQ IDNO:160, SEQ IDNO:161, SEQ IDNO:162, SEQ IDNO:163, SEQ ID NO: 164, SEQ ID NO:

165. SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 174, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, SEQ ID NO: 184 or SEQ ID NO: 185.

36. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 33 to 35, wherein the Fab fragment has a light chain of SEQ ID NO: 170 and a heavy chain of SEQ ID NO: 145.

37. A pharmaceutical composition comprising at least one of the conjugates or the pharmaceutically acceptable salt thereof of any one of claims 1 to 36 and at least one excipient.

38. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 36 or the pharmaceutical composition of claim 37 for use as a medicament.

39. The conjugate or the pharmaceutically acceptable salt thereof or the pharmaceutical composition for use of claim 38, wherein the medicament is for the treatment of autosomal dominant hypophosphatemic rickets; X-linked hypophosphatemia; autosomal recessive hypophosphatemic rickets type 1, 2, and 3; tumor-induced osteomalacia or hypophosphatemic rickets with hypercalciuria.

40. The conjugate or the pharmaceutically acceptable salt thereof or the pharmaceutical composition for use of claim 38 or 39, wherein the medicament is for the treatment of XLH.Ascendis Pharma A / S CPX75237PC 12 January 202641. The conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 36 or the pharmaceutical composition of claim 37 for use in the treatment of a disease.

42. The conjugate or the pharmaceutically acceptable salt thereof or the pharmaceutical composition for use of claim 41, wherein the disease is autosomal dominant hypophosphatemic rickets; X-linked hypophosphatemia; autosomal recessive hypophosphatemic rickets type 1, 2, and 3; tumor-induced osteomalacia or hypophosphatemic rickets with hypercalciuria.

43. The conjugate or the pharmaceutically acceptable salt thereof or the pharmaceutical composition for use of claim 41 or 42, wherein the disease is XLH.

44. Use of at least one conjugate or the pharmaceutically acceptable salt thereof of any one of claims 1 to 36 or the pharmaceutical composition of claim 37 for the manufacture of a medicament.

45. The use of claim 44, wherein the medicament is for the treatment of autosomal dominant hypophosphatemic rickets; X-linked hypophosphatemia; autosomal recessive hypophosphatemic rickets type 1, 2, and 3; tumor-induced osteomalacia or hypophosphatemic rickets with hypercalciuria.

46. The use of claim 44 or 45, wherein the medicament is for the treatment of XLH.

47. A method of treating a patient suffering from a disease, wherein the method comprises the step of administering to said patient a pharmaceutically effective dose of at least one of the conjugates or the pharmaceutically acceptable salt thereof of any one of claims 1 to 36 or the pharmaceutical composition of claim 37.

48. The method of claim 47, wherein the disease is autosomal dominant hypophosphatemic rickets; X-linked hypophosphatemia; autosomal recessive hypophosphatemic rickets type 1, 2, and 3; tumor-induced osteomalacia or hypophosphatemic rickets with hypercalciuria.Ascendis Pharma A / S CPX75237PC12 January 202649. The method of claim 47 or 48, wherein the disease is XLH.

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