MariTide: Molecular Structure
Chemical properties, amino acid sequence, and structural analysis
📌TL;DR
- •Molecular formula: Complex antibody-peptide conjugate
- •Molecular weight: 153514 Da
- •Half-life: Approximately 21 days (~3x longer than weekly GLP-1 agonists), enabling monthly or less frequent dosing
Amino Acid Sequence
114 amino acids
Formula
Complex antibody-peptide conjugate
Molecular Weight
153514 Da
Half-Life
Approximately 21 days (~3x longer than weekly GLP-1 agonists), enabling monthly or less frequent dosing
Molecular Structure and Properties#
MariTide (maridebart cafraglutide, AMG 133) is a first-in-class antibody-peptide conjugate with a molecular weight of 153,514 Da. It represents a fundamentally different molecular format from standard peptide-based anti-obesity therapies. Rather than being a single peptide, MariTide combines a full-length monoclonal antibody with two conjugated GLP-1 agonist peptides.
Structural Architecture#
MariTide is composed of three functional components:
- Anti-GIPR monoclonal antibody: A fully human monoclonal antibody that binds to and antagonizes the GIP receptor
- Two GLP-1 analogue peptides: GLP-1 receptor agonist peptides conjugated to the antibody
- Amino acid linkers: Connect the GLP-1 peptides to the antibody backbone
Component Details#
| Component | Function | Properties |
|---|---|---|
| Anti-GIPR antibody | GIPR antagonism | Fully human IgG, long half-life |
| GLP-1 peptides (x2) | GLP-1R agonism | Analogue peptides, conjugated |
| Linkers | Connection | Amino acid-based |
Chemical Properties#
| Property | Value |
|---|---|
| Chemical class | Antibody-peptide conjugate |
| Molecular weight | 153,514 Da (~153.5 kDa) |
| Molecular formula | Not publicly disclosed |
| CAS number | Not publicly disclosed |
| Receptor targets | GLP-1R (agonist) and GIPR (antagonist) |
| Half-life | ~21 days |
| Dosing frequency | Monthly or less frequent |
| Administration | Subcutaneous injection |
Half-Life and Dosing#
MariTide's ~21-day half-life is approximately 3 times longer than the longest-acting FDA-approved weekly medications for obesity (semaglutide and tirzepatide have half-lives of ~7 days and ~5 days, respectively). This extended half-life is derived from the antibody component, which confers the typical IgG antibody pharmacokinetic profile.
| Therapy | Half-Life | Dosing |
|---|---|---|
| MariTide | ~21 days | Monthly or less |
| Semaglutide | ~7 days | Weekly |
| Tirzepatide | ~5 days | Weekly |
| Liraglutide | ~13 hours | Daily |
Comparison with Tirzepatide#
MariTide and tirzepatide both target GLP-1R and GIPR but with opposite GIP strategies:
| Feature | MariTide | Tirzepatide |
|---|---|---|
| Format | Antibody-peptide conjugate | Acylated peptide |
| Molecular weight | ~153.5 kDa | ~4.8 kDa |
| GLP-1R | Agonism (via peptides) | Agonism |
| GIPR | Antagonism (via antibody) | Agonism (GIP-biased) |
| Half-life | ~21 days | ~5 days |
| Dosing | Monthly | Weekly |
| Developer | Amgen | Eli Lilly |
Receptor Pharmacology#
MariTide's unique mechanism:
- GLP-1 receptor: The two conjugated GLP-1 analogue peptides activate GLP-1 receptors, producing appetite suppression, insulin secretion, and gastric emptying delay
- GIP receptor: The antibody component binds to and blocks GIPR, preventing GIP-mediated signaling
A mechanistic study showed that when both GLP-1R and GIPR are expressed on the same cell, MariTide binds both receptors simultaneously, triggering receptor internalization and amplifying endosomal cAMP signaling. This dual engagement may contribute to its efficacy.
The GIP Agonism vs Antagonism Debate#
A central question in obesity pharmacology is whether GIP receptor agonism (tirzepatide) or antagonism (MariTide) is superior. Both approaches produce ~20% weight loss when combined with GLP-1 agonism. This suggests that the key effect may be modulation of GIP signaling (either direction) rather than its specific direction. Phase 3 data and potential head-to-head studies will help resolve this question.
Drug Delivery#
MariTide is expected to be delivered via a patient-friendly autoinjector device, providing a single-injection monthly administration. The subcutaneous route of administration is consistent with other antibody therapeutics.
Related Reading#
Frequently Asked Questions About MariTide
What type of peptide is MariTide?
MariTide (maridebart cafraglutide, AMG 133) is a first-in-class antibody-peptide conjugate developed by Amgen that combines GLP-1 receptor agonism with GIP receptor antagonism. Unlike tirzepatide (GLP-1/GIP dual agonist), MariTide blocks the GIP receptor while activating GLP-1. Its ~21-day half-life enables monthly or less frequent dosing. In Phase 2, MariTide achieved up to 16.2% weight loss at 52 weeks in obesity and up to 12.3% in obesity with T2D, with no plateau. Phase 3 MARITIME program initiated.
What is the half-life of MariTide?
The reported half-life of MariTide is Approximately 21 days (~3x longer than weekly GLP-1 agonists), enabling monthly or less frequent dosing. 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 MariTide?
The amino acid sequence of MariTide is Fully human anti-GIPR monoclonal antibody conjugated to two GLP-1 analogue agonist peptides via amino acid linkers. Antibody-peptide conjugate (153,514 Da) combining anti-GIPR antagonist monoclonal antibody with two GLP-1 receptor agonist peptides. This sequence determines its biological activity and binding properties.
How stable is MariTide in storage?
MariTide is typically supplied as a lyophilized powder for maximum stability. Antibody-peptide conjugate (153,514 Da) combining anti-GIPR antagonist monoclonal antibody with two GLP-1 receptor agonist peptides. 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.
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