0001193125-26-215676
SEC filingMBX Biosciences reported initial Phase 1 data for obesity candidate MBX 4291 showing 7% mean weight loss at 8 weeks, nominated MBX 5765 as amycretin prodrug candidate, and achieved POC for imapextide in PBH but will not advance it further.
MBX Biosciences disclosed preliminary blinded data from its ongoing Phase 1 trial of MBX 4291, a GLP-1/GIP co-agonist prodrug engineered via the PEP platform for gradual release and extended exposure to support once-monthly dosing. In SAD Part A (four cohorts completed: 15-180 mg), MBX 4291 showed dose-proportional pharmacokinetics with Tmax of 13-14 days and sustained exposure; it was generally well tolerated with mild, dose-dependent GI events, reaching MTD at 180 mg. The first MAD Part B cohort (30 mg weekly x4 + 120 mg monthly, n=8 incl. 2 placebo) demonstrated gradual accumulation, T1/2Cmax of 26 days, mean 7% weight loss at 8 weeks, and excellent tolerability with only one mild diarrhea event and no nausea/vomiting. These results validate the platform's potential for improved tolerability through flattened PK profiles versus existing incretins requiring lengthy titrations. The company expanded its obesity pipeline by nominating MBX 5765, combining GLP-1/GIP/glucagon/DACRA activities for once-monthly dosing with expected superior efficacy/tolerability; IND-enabling studies start Q2 2026. A GLP-1/GIP/GCG triple agonist nomination is on track for Q3 2026. Separately, once-weekly imapextide met POC in Phase 2a STEADI trial for post-bariatric hypoglycemia, showing dose-dependent glucose nadir improvements (17-34%) and insulin peak reductions (11-45%), but MBX will deprioritize Phase 2b due to focus on obesity/hypoparathyroidism assets like canvuparatide. Data from MBX 4291's 12-week MAD Part C remain on track for Q4 2026. This catalyst-rich update positions MBX to address obesity market needs for convenience, tolerability, and muscle-sparing weight loss amid projected $90B+ market growth.