What type of peptide is Apitegromab?

Apitegromab (SRK-015) is a fully human IgG4-lambda monoclonal antibody that selectively binds to the pro- and latent forms of myostatin, preventing its activation in skeletal muscle. Developed by Scholar Rock, it is the first muscle-targeted therapy to demonstrate clinical benefit in spinal muscular atrophy (SMA), achieving its primary endpoint in the Phase 3 SAPPHIRE trial with a statistically significant 1.8-point HFMSE improvement over placebo. It is also being explored for lean mass preservation during obesity treatment, with the Phase 2 EMBRAZE trial showing 54.9% lean mass preservation when combined with tirzepatide.

What is the half-life of Apitegromab?

The reported half-life of Apitegromab is Mean apparent terminal half-life of 24-31 days across dose groups (1-30 mg/kg) in the Phase 1 study. Consistent with typical IgG4 pharmacokinetics and FcRn-mediated recycling.. Half-life can vary depending on the route of administration, formulation, and individual factors. This information is based on available preclinical or pharmacokinetic data.

What is the amino acid sequence of Apitegromab?

The amino acid sequence of Apitegromab is Full amino acid sequence not publicly disclosed. Apitegromab is a fully human IgG4-lambda monoclonal antibody consisting of two heavy chains (gamma-4 isotype with S228P stabilization) and two light chains (lambda type) connected by disulfide bonds.. Apitegromab is a fully human IgG4-lambda monoclonal antibody (~150 kDa) that selectively binds promyostatin and latent myostatin with high affinity. It targets the prodomain of myostatin, which has low sequence homology with other TGF-beta superfamily members, providing high selectivity. No cross-reactivity with GDF-11, activin A, BMP-9/10, or TGF-beta1.. This sequence determines its biological activity and binding properties.

How stable is Apitegromab in storage?

Apitegromab is typically supplied as a lyophilized powder for maximum stability. Apitegromab is a fully human IgG4-lambda monoclonal antibody (~150 kDa) that selectively binds promyostatin and latent myostatin with high affinity. It targets the prodomain of myostatin, which has low sequence homology with other TGF-beta superfamily members, providing high selectivity. No cross-reactivity with GDF-11, activin A, BMP-9/10, or TGF-beta1.. When reconstituted, it should be stored refrigerated at 2-8 degrees C and protected from light. Lyophilized powder should be stored at -20 degrees C.

Apitegromab: Molecular Structure

Chemical properties, amino acid sequence, and structural analysis

✓Reviewed byDr. Research Team(MD (composite credential representing medical review team), PhD in Pharmacology)

📅Updated February 12, 2026

Verified

📌TL;DR

•Molecular formula: Complex immunoglobulin
•Molecular weight: 150000 Da
•Half-life: Mean apparent terminal half-life of 24-31 days across dose groups (1-30 mg/kg) in the Phase 1 study. Consistent with typical IgG4 pharmacokinetics and FcRn-mediated recycling.

Amino Acid Sequence

Full amino acid sequence not publicly disclosed. Apitegromab is a fully human IgG4-lambda monoclonal antibody consisting of two heavy chains (gamma-4 isotype with S228P stabilization) and two light chains (lambda type) connected by disulfide bonds.

248 amino acids

Formula

Complex immunoglobulin

Molecular Weight

150000 Da

Half-Life

Mean apparent terminal half-life of 24-31 days across dose groups (1-30 mg/kg) in the Phase 1 study. Consistent with typical IgG4 pharmacokinetics and FcRn-mediated recycling.

Amino acid sequence diagram for Apitegromab — Color-coded amino acid sequence of Apitegromab

Molecular Structure#

Apitegromab is a fully human monoclonal antibody of the IgG4-lambda subclass, with an approximate molecular weight of 150 kDa. Its structure consists of:

2 heavy chains: Gamma-4 isotype (~50 kDa each), likely with S228P mutation to prevent Fab-arm exchange
2 light chains: Lambda type (~25 kDa each)
Disulfide bonds: Inter-chain and intra-chain disulfide bridges
Glycosylation: N-linked glycosylation at Asn297 in the Fc region

IgG4-Lambda Subclass#

Apitegromab uses the IgG4 isotype with lambda light chains:

Property	Characteristic	Functional Relevance
Heavy chain	Gamma-4 (IgG4)	Minimal effector function
Light chain	Lambda	Antigen-binding specificity
ADCC activity	Very low	Avoids immune-mediated cell killing
Complement activation	Minimal	Reduces inflammatory risk
Half-life	24-31 days	Supports Q4W dosing
Fab-arm exchange	Stabilized (S228P)	Maintains bispecific integrity

Unique Targeting Mechanism#

Promyostatin vs Active Myostatin#

Unlike trevogrumab (which binds all myostatin forms including the active dimer) or bimagrumab (which blocks the receptor), apitegromab selectively targets the inactive precursor forms:

Myostatin Form	Apitegromab	Trevogrumab	Bimagrumab
Promyostatin (precursor)	High affinity binding	Binds	Not applicable
Latent myostatin (propeptide-bound)	High affinity binding	Binds	Not applicable
Active myostatin (mature dimer)	Does not bind	Binds	Blocked at receptor
GDF-11	No cross-reactivity	No cross-reactivity	Blocked at receptor
Activin A	No cross-reactivity	No cross-reactivity	Blocked at receptor

Prodomain Selectivity#

The basis for apitegromab's selectivity is the low sequence homology between the myostatin prodomain and the prodomains of other TGF-beta superfamily members. This means apitegromab cannot bind to:

GDF-11 proforms
Activin A proforms
BMP-9/10 proforms
TGF-beta1 proforms

Pharmacokinetics#

From the Phase 1 study (PMID 33963971):

Parameter	Value	Notes
Molecular weight	~150 kDa	Full IgG4-lambda antibody
Half-life	24-31 days	Mean across 1-30 mg/kg doses
PK profile	Linear, dose-proportional	Across evaluated dose range
Target engagement	Dose-dependent latent myostatin increase	Robust target saturation
Immunogenicity	No ADAs detected	In Phase 1 and TOPAZ studies
Bioavailability	IV administration	100% (IV route)
Metabolism	Lysosomal degradation	FcRn-mediated recycling

Target-Mediated Drug Disposition#

Apitegromab demonstrates dose-dependent and sustained increases in serum latent myostatin concentrations, indicating robust target engagement. This pharmacodynamic biomarker confirms that apitegromab captures and stabilizes latent myostatin in circulation, preventing its activation in muscle tissue.

Comparison with Other Anti-Myostatin Approaches#

Molecule	Type	Target Specificity	Myostatin Form Targeted
Apitegromab (SRK-015)	Human IgG4-lambda	Pro/latent myostatin only	Upstream (activation blockade)
Trevogrumab (REGN1033)	Human IgG4-kappa	Myostatin (all forms)	All forms (direct neutralization)
Bimagrumab (BYM338)	Human IgG1-lambda	ActRIIA/ActRIIB	Receptor level (broad blockade)
Domagrozumab (PF-06252616)	Humanized IgG1	Active myostatin	Downstream (mature form)
Follistatin	Natural glycoprotein	Myostatin + activin A	Ligand trap (multiple targets)

Production#

Apitegromab is produced in mammalian cell culture using recombinant DNA technology under GMP conditions. Fill-finish manufacturing is performed at contracted facilities (the FDA CRL was related to manufacturing observations at the Catalent fill-finish facility, not the drug substance itself).

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