Biomea Fusion (BMEA) Study result summary

Study design and rationale

• Randomized, double-blind, placebo-controlled Phase I GLP-131 study in overweight or obese adults; multiple-ascending-dose treatment lasted 28 days.

• Five active cohorts and placebo; Cohort 5 received 200 mg QD for one week, then 400 mg QD for three weeks under confinement.

• BMF-650 was designed as a selective, biased oral GLP-1 receptor agonist with ~26-fold lower potency and ~2–3-fold higher bioavailability than orforglipron in nonclinical studies; lower acute GI activation and sustained exposure were hypothesized to support weight loss with improved GI tolerability.

Weight reduction

• Day 29 mean weight change was -0.1% with pooled placebo and -1.5%, -2.1%, -3.2% and -2.1% in Cohorts 1–4, respectively.

• Fourteen of 16 weekly dosing observations showed further weight reduction; at doses ≥200 mg QD, mean weekly reduction was ~0.97 kg.

• Cohort 5 lost 6.20 kg (6.1%) by Day 29, averaging 1.55 kg/week; losses at 400 mg QD were 1.4, 1.4 and 1.7 kg across the three weeks, with no observed attenuation.

• Cohort 5 results were interpreted separately because two placebo participants consumed ~33% of offered food; Cohort 4 had an unexpected first-week weight increase and possible compliance issues, prompting consideration of an open-setting Cohort 6.

Safety and tolerability

• Among 40 active participants, 70% had TEAEs; all were mild or moderate, with no severe or serious TEAEs, TEAE-related dose modifications or discontinuations.

• Across active cohorts, nausea occurred in 17.5%, constipation in 10.0%, vomiting in 7.5% and diarrhea in 5.0%; Cohort 5 GI events were Grade 1.

• Fasting glucose fell by a mean 9.2 mg/dL in pooled active participants versus 3.5 mg/dL with placebo; mean heart rate rose 6.4 bpm versus 0.8 bpm, with no related adverse events.

• No ALT/AST elevations were reported.