What type of peptide is Trevogrumab?

Trevogrumab (REGN1033) is a fully human IgG4 monoclonal antibody that selectively binds and neutralizes myostatin (GDF-8), the primary negative regulator of skeletal muscle mass. Developed by Regeneron Pharmaceuticals, it is being evaluated in the Phase 2 COURAGE trial in combination with semaglutide for preserving lean mass during weight loss in patients with obesity. At 26 weeks, adding trevogrumab to semaglutide preserved approximately 50% of lean mass that would otherwise be lost, while also increasing fat mass loss compared to semaglutide alone.

What is the amino acid sequence of Trevogrumab?

The amino acid sequence of Trevogrumab is Full amino acid sequence not publicly disclosed. Trevogrumab is a fully human IgG4-kappa monoclonal antibody consisting of two heavy chains (gamma-4 isotype) and two light chains (kappa type) connected by disulfide bonds.. Trevogrumab is a fully human IgG4-kappa monoclonal antibody (~150 kDa) that selectively binds myostatin (GDF-8) with high affinity. The antibody binds all three forms of myostatin: the mature dimer, the latent complex, and the precursor proform. It shows no cross-reactivity with GDF-11, distinguishing it from broader receptor-level inhibitors.. This sequence determines its biological activity and binding properties.

How stable is Trevogrumab in storage?

Trevogrumab is typically supplied as a lyophilized powder for maximum stability. Trevogrumab is a fully human IgG4-kappa monoclonal antibody (~150 kDa) that selectively binds myostatin (GDF-8) with high affinity. The antibody binds all three forms of myostatin: the mature dimer, the latent complex, and the precursor proform. It shows no cross-reactivity with GDF-11, distinguishing it from broader receptor-level inhibitors.. 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.

Trevogrumab: Molecular Structure

Q: What is the half-life of Trevogrumab?

The reported half-life of Trevogrumab is Specific half-life not publicly reported. As an IgG4 antibody, the expected half-life is approximately 21 days, 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.

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: Specific half-life not publicly reported. As an IgG4 antibody, the expected half-life is approximately 21 days, consistent with typical IgG4 pharmacokinetics and FcRn-mediated recycling.

Amino Acid Sequence

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

221 amino acids

Formula

Complex immunoglobulin

Molecular Weight

150000 Da

Half-Life

Specific half-life not publicly reported. As an IgG4 antibody, the expected half-life is approximately 21 days, consistent with typical IgG4 pharmacokinetics and FcRn-mediated recycling.

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

Molecular Structure#

Trevogrumab is a fully human monoclonal antibody of the IgG4-kappa subclass, with an approximate molecular weight of 150 kDa. Like all IgG antibodies, it consists of:

2 heavy chains: Gamma-4 isotype (~50 kDa each)
2 light chains: Kappa type (~25 kDa each)
Disulfide bonds: Inter-chain and intra-chain disulfide bridges maintaining quaternary structure
Glycosylation: N-linked glycosylation at Asn297 in the Fc region (typical for IgG antibodies)

IgG4 Subclass Properties#

The choice of IgG4 isotype is significant for trevogrumab's function:

Property	IgG4 Characteristic	Relevance to Trevogrumab
Effector function	Minimal ADCC and CDC	Avoids immune-mediated cell killing
Complement activation	Very low	Reduces inflammatory side effects
FcRn binding	Normal	Maintains long serum half-life
Fab-arm exchange	Possible in vivo	S228P mutation typically introduced to prevent
Half-life	~21 days	Supports Q2W or Q4W dosing intervals

IgG4 is preferred over IgG1 for neutralizing antibodies like trevogrumab because its minimal effector function reduces the risk of unwanted immune activation while still providing high-affinity target engagement.

Target Binding Properties#

Myostatin Selectivity#

Trevogrumab was generated using Regeneron's VelocImmune technology, which produces fully human antibodies from genetically engineered mice. A critical feature of REGN1033 is its selectivity:

Ligand	Binding by Trevogrumab	Binding by ActRIIB-Fc (e.g., ACE-031)
Myostatin (GDF-8)	High affinity	Yes
GDF-11	No cross-reactivity	Yes
Activin A	No binding	Yes
BMP-9/10	No binding	Yes

This selectivity profile distinguishes trevogrumab from receptor-level inhibitors like bimagrumab (anti-ActRII antibody) or ACE-031 (ActRIIB-Fc fusion), which block multiple TGF-beta superfamily ligands.

Myostatin Forms Recognized#

REGN1033 binds all three physiological forms of myostatin:

Mature myostatin dimer: The active signaling form (~25 kDa homodimer)
Latent myostatin complex: Mature myostatin bound to its propeptide, preventing receptor interaction
Myostatin precursor (proform): The unprocessed full-length protein before furin cleavage

This comprehensive binding profile ensures neutralization of myostatin regardless of its processing state.

Pharmacokinetics#

Parameter	Value	Notes
Molecular weight	~150 kDa	Full IgG4 antibody
Expected half-life	~21 days	Consistent with IgG4 class
Administration	Subcutaneous injection	Self-administration possible
Absorption	Slow, from SC depot	Typical for SC antibody dosing
Metabolism	Lysosomal degradation	FcRn-mediated recycling extends half-life
Elimination	Catabolism + target-mediated	Target-mediated disposition at low doses

Comparison with Other Anti-Myostatin Approaches#

Molecule	Type	MW	Target	Selectivity
Trevogrumab (REGN1033)	Human IgG4 mAb	~150 kDa	Myostatin directly	Highly selective
Bimagrumab (BYM338)	Human IgG1 mAb	~145 kDa	ActRIIA/ActRIIB	Broad (multiple ligands)
Apitegromab (SRK-015)	Humanized IgG4 mAb	~150 kDa	Latent myostatin	Selective (latent form only)
ACE-031 (ramatercept)	ActRIIB-Fc fusion	~90 kDa	ActRIIB ligand trap	Broad (discontinued)
Domagrozumab (PF-06252616)	Humanized IgG1 mAb	~150 kDa	Myostatin	Selective

Production and Manufacturing#

As a fully human monoclonal antibody, trevogrumab is produced in mammalian cell culture (likely CHO cells) using recombinant DNA technology. The manufacturing process involves:

Cell line development and banking
Large-scale bioreactor cultivation
Protein A chromatography purification
Formulation for subcutaneous delivery
Sterile fill-finish under GMP conditions

This complex manufacturing distinguishes antibody therapeutics from synthetic peptides, which can be produced by chemical synthesis. Trevogrumab cannot be synthesized by peptide synthesis methods.

Frequently Asked Questions About Trevogrumab

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