Biomea Fusion, a clinical-stage biopharmaceutical company, announced the clinical hold placed on its human trial has been lifted by the FDA. The phase II T1D trial, COVALENT-112, was placed on hold on June 6^th of this year following liver toxicity concerns.

COVALENT-112 hopes to protect and proliferate beta cells in people with established T1D. The mechanism of action is a menin inhibitor, called BMF-219, taken orally, which intends “to enable the proliferation, preservation, and reactivation of a patient’s own healthy, functional, insulin-producing beta cells.” Menin is a protein discovered in 1988 that is associated with a number of endocrine-related diseases, including diabetes. Biomea’s theory is that inhibiting the action of menin, a protein thought to control and limit beta-cell growth, will stop the autoimmune attack and allow cells to reproduce. Early results have been positive.

Biomea is testing its menin inhibitor drug for several different diseases, including T1D.

T1D Study Includes Fully Established

The COVALENT-112 study includes individuals who have fully established T1D. The two groups tested in the study are:

• People who have had T1D long-term (3-15 years from diagnosis)
• Newly diagnosed (<3 years from diagnosis)

Early results were positive, demonstrating the drug increased C-Peptide levels in dosed participants, including an individual with long-term T1D who saw a reduction in daily insulin needs after four weeks.

COVALENT-112 is still in the early stages of testing, and only time will tell if this therapy is viable. If the trial is successful, it has the potential to become a Practical Cure for T1D via the Cell Regeneration and Immune System Modification pathways.

Hold Lifted: Increased Safety Protocol Moving Forward

Biomea is concurrently testing BMF-219 in separate T1D and T2D trials. Issues with the T2D trial (called COVALENT-111) caused the T1D trial to receive an FDA hold last June. The hold came as a surprise, occurring only one month after Biomea released positive initial data from COVALENT-112.

The FDA hold was implemented in response to elevated liver enzymes in the dose escalation phase of Biomea’s T2D trial, raising concerns of possible liver damage. It is important to note that although the T1D trial was placed on full clinical hold as well, the concerns of liver toxicity were limited to the T2D trial, though safety profiles from both were reviewed.

Following the investigation, results showed that elevated liver enzymes are predictable and avoidable, only occurring in those with a higher beginning dosage of 200mg. The elevated values did not translate to serious liver injury or impairment. Patients who received a lower starting dose of 100mg and later increased to 200mg after sixty days did not experience elevations.

The FDA’s recommendations for trials testing BMF-219 will be implemented. This includes a single-step escalation from 100mg to 200mg and increased safety monitoring and patient surveillance.

Initial Trial Results: Promising Improvement in C-Peptide

One month before the hold, Biomea Fusion released positive early results for COVALENT-112, highlighting two patients in the study. New study data is anticipated later this year.

Patient 1

• 58-year-old individual diagnosed with T1D three years ago.
• Taking 200mg of BMF-219 daily.
• Fasting C-peptide increased by 80% after eight weeks of dosing.
• C-peptide increased up to 200% during a mixed meal test.

Patient 2

•  24-year-old diagnosed with T1D seven years ago.
• Taking 100mg of BMF-219 once daily.
• After four weeks of dosing, the participant saw an increase in C-peptide of 16%.
• During mixed meal testing, a 30% increase in C-Peptide, approaching near-normal glucose response without meal-time insulin.
• The patient had a reduction in daily insulin usage over this four-week period.

Potential Practical Cure Project

COVALENT-112 has the characteristics of a potential Practical Cure for T1D. It is being tested on people with fully established T1D, addresses in concept both cell supply and cell protection, and does not require chronic immunosuppression. For cell supply, it relies on regenerating latent beta cell mass, similar to Faustman Lab’s BCG Practical Cure project. The menin inhibitor, taken as an oral medication, provides the cell protection.

Due to the clinical hold, COVALENT-112 was not included in JDCA’s most recent annual Practical Cure overview report, but was noted as a “close call.” Now that the hold has been lifted, it will be included.

As with every potential Practical Cure project, there are hurdles that must be overcome. The most pressing hurdles pertain to time. How long will it take before enough beta cells are regenerated that a long-term T1D patient is insulin independent? Without immunosuppression or aggressive protective measures seen in other projects, how will the regenerated beta cells be protected long-term, especially in a short-term drug? Funding concerns exacerbate the question of time. With no marketed drugs, Biomea Fusion is dependent on investors, grants, and shareholders to operate. Within hours of the clinical hold last June, the company’s stock fell almost 66%. Since then, company value has been crawling upward but remains less than half of its value earlier this year.

JDCA looks forward to seeing updated results from the trial later this year and will keep you updated on the latest news as it unfolds.

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Appendix: Additional Trial Details
COVALENT-112 is a phase II trial testing two oral dose levels of BMF-219, a potent and selective covalent menin inhibitor created using the company’s proprietary Fusion System. The study began in December 2023.

Purpose: To evaluate the safety and efficacy of BMF-219 in restoring beta cell function in adults with established T1D and demonstrated beta cell destruction.
Dosing: 100mg or 200mg of BMF-219 for twelve weeks followed by a forty-week off-period.
Enrollment Goal: 190 patients

• Cohort 1: T1D patients diagnosed within three years of study start date.
• Cohort 2: T1D patients with a diagnosis between three and fifteen years.

Locations: Thirty locations in the US and Canada

• If you are interested in participating in this study, you can do so here.

Estimate Study Completion Date: August 2025