Biomea Fusion (NASDAQ:BMEA) reported top-line results from a Phase Ib multiple ascending-dose study of BMF-650, an investigational oral small-molecule GLP-1 receptor agonist being developed for weight management. The company said the 28-day study showed weight reduction across active-treatment cohorts, while reported gastrointestinal adverse events were mild or moderate.
The randomized, double-blind, placebo-controlled Phase I trial enrolled overweight or obese participants. The multiple ascending-dose portion initially included four active-treatment cohorts, each with eight BMF-650 participants and two placebo participants, for 32 active and eight pooled placebo participants. A fifth cohort was added under confinement after pharmacokinetic data from Cohort 4 raised concerns that some participants may not have consistently taken study drug.
Weight-Loss Findings
Frías said 14 of 16 weekly dosing observations across the initial four cohorts showed additional weight reduction, with reductions generally increasing at higher administered doses. At doses of 200 mg once daily or higher, mean weekly weight loss was approximately 1 kilogram.
In the confined fifth cohort, participants began at 200 mg once daily and escalated after one week to 400 mg once daily for the remaining three weeks. BMF-650 recipients in that cohort lost an average of about 1.55 kg per week, or 6.2 kg and 6.1% of body weight after four weeks.
The company cautioned that the Cohort 5 efficacy findings should be interpreted carefully. The two placebo participants also lost weight after consuming about 33% of the 2,100 calories presented daily, an outcome Biomea said complicated interpretation of placebo-adjusted weight loss in the confined setting.
Safety and Pharmacokinetics
Biomea said BMF-650 was generally well tolerated across five active dose cohorts, involving 40 participants in the multiple ascending-dose study. All treatment-emergent adverse events were mild or moderate, with no severe or serious treatment-emergent adverse events, dose modifications, or treatment discontinuations attributed to adverse events.
Selected gastrointestinal events included nausea in seven participants, constipation in four, vomiting in three and diarrhea in two. In the highest-dose cohort, the company reported a 12.5% incidence each for nausea and vomiting, no diarrhea, and 25% constipation. Biomea noted that comparisons with other oral GLP-1 programs are limited because studies have differed in size, duration, dose-escalation schedules and adverse-event reporting.
Mean fasting glucose declined by 9.2 mg/dL in the pooled active group, compared with 3.5 mg/dL for pooled placebo. Mean heart rate increased by 6.4 beats per minute in the active group versus 0.8 beats per minute in placebo, though the company reported no heart-rate-related adverse events.
In Cohort 5 on day 28, mean 24-hour exposure was approximately 79,000 hour nanograms per milliliter, and the peak-to-trough ratio was about 1.7. Frías said the preliminary pharmacokinetic results support once-daily administration and showed clinically relevant exposure.
Development Plans and Partnership Strategy
BMF-650 was designed with lower receptor potency and sustained systemic exposure in an effort to reduce acute GLP-1 activity in the gastrointestinal tract while retaining weight-loss activity, Biomea said. The company said the Phase I findings support further evaluation of the 400 mg dose and potentially simpler titration schedules.
Interim Chief Executive Officer Mick Hitchcock said Biomea may conduct another Phase I cohort, potentially evaluating direct initiation at 400 mg in a non-confined setting. Before a longer-duration clinical study, the company plans to complete 13-week toxicology studies in rats and cynomolgus monkeys. Thorsten Kirschberg, Biomea’s head of research, said those studies would support a potential 13-week clinical weight-loss study.
Biomea said it intends to advance BMF-650 toward Phase II development but does not currently expect to independently fund a large global obesity program. Instead, the company said it aims to position the program for a strategic partnership or licensing arrangement covering late-stage development and commercialization, while continuing to prioritize development of its menin inhibitor, Icovamenib, in diabetes.
About Biomea Fusion (NASDAQ:BMEA)
Biomea Fusion, Inc is a clinical-stage biopharmaceutical company focused on discovering and developing small-molecule medicines for serious diseases with significant unmet medical needs. The company’s research platform is centered on covalent chemistry, an approach designed to create potentially durable interactions between medicines and their biological targets.
Biomea’s lead investigational product is icovamenib, formerly known as BMF-219, an oral covalent menin inhibitor. The company has evaluated icovamenib in oncology indications, including certain blood cancers, and is also investigating its potential in metabolic diseases such as diabetes.
