Maritide

An antibody-peptide conjugate developed by Amgen. Presented by Jay Bradner at Session VII.

Mechanism: The Geometry Is the Drug

Three components working in concert:

1. Antibody that antagonizes GIPR — guided by human genetics (loss-of-function GIPR polymorphisms protect from obesity and T2D)
2. Two GLP-1 agonist peptides at a specific position at the junction of CDRs and Fc domains — for spatial presentation, not half-life extension
3. At one specific position, induces physical heterodimerization between GIPR and GLP-1R

Downstream Effects

• Amplified cyclic AMP signaling and beta-arrestin recruitment
• Signaling to central nucleus of amygdala, nucleus of solitary tract, parabrachial nucleus
• Deep central appetite suppression as primary mode of action

Clinical Data

• Phase 2 (chronic weight management): profound, sustained weight loss without plateau through 52 weeks at monthly dosing
• Phase 2 (obesity + T2D): significant weight loss, HbA1c reduction, hs-CRP reduction at 140–420 mg SC once monthly
• Phase 3 ongoing
• Quarterly (every 12 weeks) dosing: top-line results reported as successful

Significance

• The PCSK9 analogy: when genetics says inhibit, make a blocker — Amgen followed the same logic for GIPR
• Monthly/quarterly dosing is an adherence argument for reaching populations at scale
• Invented by Muriel Véniant-Ellison — approached obesity without ADC oncology-centric blinders

“I had a flu shot this year, but I didn’t ask my doctor if there was a weekly version of it.”