MBX Biosciences Doses First Participant in Phase 1 Trial of MBX 4291 for the Treatment of Obesity

MBX Biosciences, Inc. recently announced dosing of the first participant in its Phase 1 trial of MBX 4291, the company’s Precision Endocrine Peptide (PEP) glucagon-like peptide-1 (GLP-1)/ glucose-dependent insulinotropic polypeptide (GIP) co-agonist prodrug candidate for the treatment of obesity.

“Initiation of our first clinical trial in obesity is a significant milestone for the company and an important step in addressing this global public health issue,” said Kent Hawryluk, President and Chief Executive Officer of MBX Biosciences. “MBX 4291 has demonstrated positive preclinical results and is designed to be a best-in-class weight loss prodrug, with the potential for convenient once-monthly administration, improved weight loss, and better gastrointestinal tolerability compared to currently available treatment options. We look forward to topline results anticipated in 2027.”

The Phase 1 trial is a randomized, double-blind, placebo-controlled first-in-human study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending doses of MBX 4291 in adult participants with obesity. The Phase 1 trial will include:

Part A Single Ascending Dose (SAD): single ascending doses of MBX 4291 or matching placebo will be administered in 5 cohorts consisting of 8 participants each. Participants will be randomized on Study Day 1 to receive MBX 4291 or matching placebo in a 3:1 ratio. Participants in each cohort will be followed for 63 days after the single study intervention administration.

Part B Multiple Ascending Dose (MAD) (4 weeks): multiple ascending doses of MBX 4291 or matching placebo will be administered in 3 cohorts consisting of 8 participants each. Participants will be randomized on Study Day 1 to receive MBX 4291 or matching placebo in a 3:1 ratio. Participants in each cohort will receive a total of 4 study intervention administrations one week apart and will be followed for 71 days after the first study intervention administration.

Following completion of Parts A and B, the company plans to evaluate multiple ascending doses of MBX 4291, or matching placebo, administered over 12 weeks in up to two cohorts consisting of 30 participants each in a 2:1 randomization ratio. Participants are expected to receive up to a total of 12 study intervention administrations one week or one week and one month apart with increasing doses of MBX 4291 and will be followed for 120 days after the first dose.

More information on the trial can be found at www.clinicaltrials.gov, identifier NCT07142707.

MBX 4291 is an investigational long-acting GLP-1/GIP receptor co-agonist prodrug candidate in development as a potential treatment for obesity. It was designed using the company’s novel, proprietary PEP platform as a long-acting dual agonist designed to address the unmet need with existing obesity therapies. MBX 4291 is designed to provide improved tolerability, increased adherence to treatment at maximum efficacious doses, and to achieve greater long-term weight loss and greater improvement in weight-related comorbidities.

In preclinical studies, the active component of MBX 4291 demonstrated a similar activity profile and body weight loss as tirzepatide, an approved weekly GLP-1/GIP co-agonist. Extended duration of action of the active component of MBX 4291 was observed in additional preclinical studies compared to tirzepatide, supporting the potential for once-monthly administration.

MBX Biosciences is a biopharmaceutical company focused on the discovery and development of novel precision peptide therapies based on its proprietary PEP platform, for the treatment of endocrine and metabolic disorders. The Company is advancing a pipeline of novel candidates for endocrine and metabolic disorders with clinically validated targets, established endpoints for regulatory approval, significant unmet medical needs and large potential market opportunities. The Company’s pipeline includes canvuparatide (MBX 2109) for the treatment of chronic hypoparathyroidism (HP) in Phase 2 development; imapextide (MBX 1416) for the treatment of post-bariatric hypoglycemia (PBH) in Phase 2 development; and an obesity portfolio that includes MBX 4291 in Phase 1 development, as well as multiple discovery and pre-clinical obesity candidates. The Company is based in Carmel, Indiana. To learn more, please visit  https://mbxbio.com/.