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Phase 2TerminatedNCT06152042

COVALENT-112: icovamenib (oral menin inhibitor) in type 1 diabetes

Phase 2 trial of icovamenib (BMF-219), an oral covalent menin inhibitor, in adults with stage-3 T1D who still had some insulin production of their own. Participants took the drug for 12 weeks and were followed for 40 more. It produced a C-peptide gain at the 200 mg dose — in five people, open-label, with no placebo control. The trial is registered as terminated.

Primary endpoints

  • Mean change from baseline in stimulated C-peptide area under the curve (AUC) at 26 weeks

Results so far

52-week data reported 27 April 2026, in company press releases only. In participants diagnosed within 3 years, the 200 mg dose raised mean stimulated C-peptide AUC by about 52% at Week 12 (n=5); at Week 52 — 40 weeks after the last dose — mean C-peptide AUC was about 7% below baseline, against a roughly 47% annual decline reported in historical placebo cohorts. The 100 mg arm (n=6) showed less effect, and a cohort diagnosed 3-15 years earlier (n=9) broadly preserved C-peptide. Data presented at the ADA 86th Scientific Sessions (5-8 June 2026) showed no evidence of systemic immune activation on cytokine profiling, with inflammatory markers stable or reduced through Week 52. (The HbA1c benefit Biomea reported at ADA — a 1.2% reduction versus a 0.6% placebo increase — came from COVALENT-111 in type 2 diabetes on background GLP-1 RA therapy, not from COVALENT-112; no HbA1c result was reported for the T1D trial.) Caveats — the reported data are open-label proof-of-concept; the randomized, placebo-controlled Part 2 was never completed; the registry records the study as terminated because the sponsor made a business decision based on portfolio prioritization, not for safety; the programme was interrupted by a full FDA clinical hold placed on 6 June 2024 over possible drug-induced hepatotoxicity observed during COVALENT-111 dose escalation, and lifted on 26 September 2024. No results are posted to ClinicalTrials.gov and there is no peer-reviewed publication.

The full picture

What was tested and why it matters

Menin is a protein inside beta cells that acts as a brake on their growth. Icovamenib (BMF-219) is a once-daily pill that binds menin covalently and releases that brake for a while. COVALENT-112 was the test of that idea in type 1 diabetes: could a short course of a pill get the body to rebuild some of its own insulin-producing capacity?1

That question matters because almost everything else in the "cure" column involves importing cells — from a donor or a stem-cell line — with the surgery and immunosuppression that come with them. A pill that regrows what is already there would be a fundamentally easier proposition. COVALENT-112 is the furthest that idea has got in people.

Who was in it

Adults aged 18 to 70 with stage-3 T1D, at least one T1D autoantibody, an HbA1c of 6.5-10.0%, and — crucially — some insulin production left: entry required a C-peptide of at least 0.2 nmol/L for people diagnosed within three years, or at least 0.08 nmol/L for those diagnosed three to fifteen years ago.1 The drug acts on beta cells that still exist, so people with none left were not eligible.

Thirty-seven people enrolled across 11 sites (nine in the United States, two in Canada). Dosing was 100 mg or 200 mg once daily for 12 weeks, followed by 40 drug-free weeks of observation. The primary endpoint was the mean change from baseline in stimulated C-peptide AUC at 26 weeks.1

This trial is closed. The registry lists it as terminated — the stated reason is a sponsor business decision about portfolio prioritization, not a safety problem.1

What it found

In the cohort diagnosed within the previous three years and dosed at 200 mg, mean stimulated C-peptide AUC was about 52% above baseline at Week 12.2 Then the drug stopped. Forty weeks later, at Week 52, mean C-peptide AUC was still only about 7% below baseline, against the roughly 47% annual decline reported in historical placebo cohorts.3 The 100 mg arm showed less effect, and a longer-diagnosed cohort (three to fifteen years) broadly held its C-peptide.2

At the ADA's 86th Scientific Sessions (5-8 June 2026), Biomea added translational data: cytokine profiling showed no evidence of systemic immune activation, with inflammatory markers stable or reduced through Week 52.3

One thing that gets misreported: an HbA1c benefit was announced at those same sessions — a 1.2% reduction versus a 0.6% placebo increase — but that came from COVALENT-111 in type 2 diabetes, in people on background GLP-1 therapy.3 No HbA1c result was reported for this T1D trial. Type 2 evidence is not type 1 evidence.

How much weight to put on it

Less than the headline suggests, and here is exactly why.

The 200 mg cohort was five people. The 100 mg cohort was six; the longer-diagnosed cohort, nine. The reported data are open-label — everyone knew what they were taking. The randomized, placebo-controlled Part 2 was never completed, which is a discrepancy worth naming: the registry title still describes a "Randomized, Double-blind... Compared to Placebo" study, but the data Biomea has reported are from an open-label proof-of-concept portion.12 The 47% comparator is a historical figure from other studies, not a control arm in this one.

Every number above comes from company press releases and a conference presentation. No results are posted to ClinicalTrials.gov, and there is no peer-reviewed publication.1 That is the weakest evidence grade this site records for a human efficacy claim.

There is also a safety history. On 6 June 2024 the FDA placed a full clinical hold on the whole BMF-219 diabetes programme, prompted by possible drug-induced hepatotoxicity — liver toxicity — observed during dose escalation in COVALENT-111, the type 2 diabetes study.4 The hold was lifted on 26 September 2024.5 That is a resolved problem, not a disqualifying one, but a drug that tells cells to divide is one whose liver and proliferation signals need watching.

What would settle it

A randomized, placebo-controlled trial, properly sized, with the results published rather than announced. Biomea has said it plans a larger Phase 2 in recently diagnosed T1D with longer dosing and a combination arm pairing icovamenib with an immunosuppressive agent — an acknowledgement that regrowing beta cells does nothing if the immune attack that destroyed the first set is still running. As of 14 July 2026 that study is not registered on ClinicalTrials.gov, so we are not putting a date on it.

References

  1. ClinicalTrials.gov. Phase 2 Randomized, Double-blind Trial of BMF-219 Compared to Placebo in Participants With Type 1 Diabetes Mellitus (COVALENT-112, NCT06152042). Biomea Fusion Inc. Status terminated; 37 enrolled; 11 sites; no results posted as of 14 July 2026. https://clinicaltrials.gov/study/NCT06152042 ↩ ↩2 ↩3 ↩4 ↩5 ↩6

  2. Biomea Fusion. Positive 52-Week Results from Phase 2 COVALENT-112 Trial in Type 1 Diabetes (2026-04-27) — company press release. https://www.globenewswire.com/news-release/2026/04/27/3282109/0/en/Biomea-Fusion-Announces-Positive-52-Week-Results-from-Phase-2-COVALENT-112-Trial-in-Type-1-Diabetes-Showing-C-Peptide-Improvement-and-Durability-Following-12-Weeks-of-Icovamenib-Tr.html ↩ ↩2 ↩3

  3. Biomea Fusion. New Clinical and Translational Data for Icovamenib at the ADA 86th Scientific Sessions (2026-06-05). Source of the ~47% historical-decline comparator, the cytokine data, and the type 2 diabetes HbA1c result. https://www.globenewswire.com/news-release/2026/06/05/3307662/0/en/Biomea-Fusion-Presents-New-Clinical-and-Translational-Data-for-Icovamenib-at-the-American-Diabetes-Association-ADA-86th-Scientific-Sessions-and-Announces-Expansion-of-Ongoing-Phase.html ↩ ↩2 ↩3

  4. Biomea Fusion Announces BMF-219 in Diabetes Placed on Clinical Hold (2024-06-06) — company press release. Full FDA clinical hold over possible drug-induced hepatotoxicity observed in COVALENT-111 dose escalation. https://investors.biomeafusion.com/news-releases/news-release-details/biomea-fusion-announces-bmf-219-diabetes-placed-clinical-hold ↩

  5. Biomea Fusion. FDA Lifts Clinical Hold on BMF-219 in Type 2 and Type 1 Diabetes Trials (2024-09-26) — company press release. https://www.globenewswire.com/news-release/2024/09/26/2954087/0/en/FDA-Lifts-Clinical-Hold-on-BMF-219-in-Type-2-and-Type-1-Diabetes-Trials.html ↩