Expert: First-in-class bispecific antibody-peptide conjugate: a fully human anti-GIPR antagonist monoclonal antibody conjugated at E384C positions to two GLP-1 receptor agonist peptide analogues via (GGGGS)3 linkers. MW ~153.5 kDa. GIP receptor antagonism reduces GIP-mediated lipogenesis and adipocyte differentiation. Long antibody half-life enables Q4W or less-frequent dosing. The GIP agonism vs antagonism paradox remains unresolved — both approaches (tirzepatide agonist, maritide antagonist) yield ~20% weight loss, suggesting possible functional convergence via chronic receptor desensitization.

Everyday: A two-in-one molecule that activates one hunger-reducing hormone (GLP-1) while blocking another hormone (GIP) that may promote fat storage. Think of it as pressing the brake on appetite while also cutting off a signal that tells your body to hold onto fat. The antibody design makes it last long enough for monthly injections instead of weekly.

Targets: ["GLP-1","GIP"]

Primary EP: [{"id":"wl-72wk","name":"% change in body weight from baseline at Week 72","type":"PRIMARY","unit":"%","results":[],"timepoint":"Week 72","description":"Co-primary endpoint with responder rate. 72 wee

Primary EP: [{"id":"mace","name":"Major adverse cardiovascular events (MACE)","type":"PRIMARY","results":[],"description":"CV outcomes in patients with established ASCVD. SELECT (semaglutide): 20% MACE reduction

Primary EP: [{"id":"wl-72wk","name":"% change in body weight at Week 72","type":"PRIMARY","unit":"%","results":[],"timepoint":"Week 72","description":"Weight loss in obesity patients WITH T2D. Phase 2 Cohort B sh

Primary EP: [{"id":"mace-hf","name":"Composite of CV death and heart failure events","type":"PRIMARY","results":[],"description":"Mortality and morbidity outcomes in HFpEF/HFmrEF with obesity. SELECT (semaglutide

Primary EP: [{"id":"ahi","name":"Change in AHI (apnea-hypopnea index)","type":"PRIMARY","results":[],"description":"AHI measures severity of sleep apnea. Tirzepatide (SURMOUNT-OSA) showed ~50% AHI reduction. Popu

Primary EP: [{"id":"ahi","name":"Change in AHI","type":"PRIMARY","results":[],"description":"AHI in OSA patients NOT on PAP therapy. 52-week treatment period."}]

Primary EP: [{"id":"wl-52wk","name":"Body weight change at Week 52 (ITT)","type":"PRIMARY","unit":"%","results":[{"ci":"-15.0 to -9.7","unit":"%","value":-12.3,"arm_id":"a-140-fixed"},{"unit":"%","value":-14.6,"a

Safety: GI AEs mild, transient, first-dose. Disc. rate: 12-27% fixed dose, ~7.8% with escalation, 0% with PK-LDI. No BMD changes. Favorable fat:lean ratio.

Primary EP: [{"id":"safety","name":"Safety and tolerability","type":"PRIMARY","results":[{"value":"Most TEAEs mild and transient; no increase with dose","arm_id":"mad-420"}],"timepoint":"Day 85","description":"In

MariTide - Obesity - Ph2 Part 2 - Maintenance/Quarterly Dosing Data H1 2026

MariTide - T2D + Obesity - Ph3 - Topline (MARITIME-2) Early 2027

MariTide - Obesity - Ph3 - Topline (MARITIME-1) Early 2027

MariTide - Obesity - BLA Filing 2027-2028

MariTide - HFpEF - Ph3 - Outcomes (MARITIME-HF) 2028+

MARITIDE (AMG 133) — KEY FACTS: WHAT IT IS: First-in-class bispecific that blocks GIP receptor + activates GLP-1 receptor. Antibody backbone gives it long half-life = monthly or quarterly dosing (vs weekly for Wegovy/Zepbound). THE GIP PARADOX: Tirzepatide (Zepbound) ACTIVATES GIP and gets ~20% weight loss. Maritide BLOCKS GIP and also gets ~20% weight loss. Nobody fully understands why opposite approaches work similarly. Leading theory: chronic GIP agonism may cause receptor desensitization, functionally converging with antagonism. PHASE 2 RESULTS (NEJM, Jun 2025): Obesity (no T2D): -16.2% weight loss at 52 wks (420mg Q4W, ITT); up to -19.9% (completers) Obesity + T2D: -12.3% weight loss at 52 wks (420mg Q4W, ITT); up to -17.0% (completers) Weight loss NOT plateaued at 52 weeks — Phase 3 at 72 weeks could exceed 20% HbA1c: -1.2 to -1.6 pts reduction (T2D cohort) vs +0.1 placebo 70-96% of prediabetics normalized to <5.7% No bone mineral density loss (key safety differentiator) GI TOLERABILITY (THE RISK): Fixed-dose: 12-27% discontinuation from GI AEs (nausea, vomiting) Dose escalation arms: ~7.8% GI discontinuation (much better) Phase 3 uses optimized 8-week escalation: 21mg -> 35mg -> 70mg -> target PK-LDI study (n=121): ZERO GI discontinuations with low-dose initiation PHASE 3 PROGRAM (MARITIME): 6 studies underway as of Q4 2025 earnings. MARITIME-1 (obesity, no T2D): ~3,500 pts, FULLY ENROLLED, readout early 2027 MARITIME-2 (obesity + T2D): FULLY ENROLLED, readout early 2027 MARITIME-HF (HFpEF/HFmrEF): ~5,000 pts, enrolling MARITIME-OSA-1/2 (sleep apnea): recruiting MARITIME-ASCVD: enrolling COMPETITIVE POSITIONING: vs Zepbound: similar weight loss but MONTHLY dosing (key differentiator) vs CagriSema: CagriSema ~22.7% at 68wks may be best-in-class, but weekly vs Orforglipron: oral daily ~14-15%, launches Q2 2026 — years ahead Maritide bull case: monthly/quarterly dosing is a paradigm shift for adherence Maritide bear case: 2029-2030 launch, 3-4 years late to market PEAK SALES: $4-10B+ (UBS $10B+ bull, Goldman $3.75B risk-adjusted bear) Amgen guiding $2.6B CapEx in 2026 for manufacturing buildout. Sources: NEJM 10.1056/NEJMoa2504214, Amgen Q4:25 earnings, JPM 2026, Nature Metabolism Feb 2024