MBX Biosciences announced positive topline results from its Phase 1 clinical trial of MBX 1416, a long-acting glucagon-like peptide 1 (GLP-1) receptor antagonist, for the treatment of post-bariatric hypoglycemia (PBH). The randomized, double-blind, placebo-controlled study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of MBX 1416 in healthy adult volunteers.
The trial, conducted in the United States, enrolled 69 subjects across single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. Key findings include that MBX 1416 was generally well-tolerated with a favorable safety profile. No dose-related serious adverse events were observed, and the majority of treatment-emergent adverse events were mild or moderate in severity. Injection site reactions, predominantly characterized by erythema, were commonly observed.
Pharmacokinetic Profile
Pharmacokinetic results demonstrated dose-proportional increases in MBX 1416 concentrations in both the SAD and MAD cohorts. In the MAD cohort, the median half-life was approximately 90 hours, supporting once-weekly administration. At steady state, the median Tmax was between 36 and 48 hours.
Pharmacodynamic Effects
In the MAD cohort, MBX 1416 appeared to increase GLP-1 within 60 minutes of a mixed meal tolerance test, suggesting a potential therapeutic benefit in PBH patients. Consistent with the known GLP-1 antagonism effect on gastric motility, a slight acceleration of gastric emptying was observed based on acetaminophen exposure. Furthermore, the drug-drug interaction portion of the trial showed that MBX 1416 had no meaningful effect on rosuvastatin exposure, a commonly prescribed statin.
Next Steps
MBX Biosciences intends to discuss these results with the U.S. Food and Drug Administration (FDA) in an End-of-Phase 1 meeting in mid-2025. Pending alignment with the FDA, a Phase 2 study of MBX 1416 in patients with PBH is anticipated to initiate in the second half of 2025.
Management Commentary
"We are encouraged by the positive topline Phase 1 results in healthy volunteers that showed MBX 1416 was generally well-tolerated with a favorable safety profile and a promising pharmacokinetic profile supportive of once-weekly dosing," said Kent Hawryluk, President and Chief Executive Officer of MBX Biosciences. "We also observed an apparent increase in GLP-1 peak during the first hour after a mixed meal tolerance test, which is an encouraging signal that we believe may translate into a therapeutic benefit in patients with PBH. Based on these results, we intend to initiate a Phase 2 study in patients with PBH in the second half of 2025 to further optimize dosing, pending alignment with the FDA on our proposed study design."
About Post-Bariatric Hypoglycemia
Post-bariatric hypoglycemia (PBH) is a rare and serious complication of bariatric surgery, characterized by repeated episodes of symptomatic hypoglycemia triggered by exaggerated secretion of GLP-1 levels following a meal. These episodes can occur multiple times per day and manifest with severe symptoms, such as dizziness, confusion, loss of consciousness, or seizure. Currently, there are no approved pharmacotherapies to treat PBH.
