Biomea Fusion Shares Early Type 1 Diabetes Data as COVALENT-112 Shows C-Peptide Gains with Icovamenib

Key Points

• Icovamenib produced a notable efficacy signal in COVALENT‑112: the 200 mg group in patients diagnosed within three years showed a mean 52% increase in stimulated C‑peptide AUC at week 12 and C‑peptide was largely preserved at week 52 (only a 7.1% decline), versus the typical rapid early decline in type 1 diabetes.
• The results are exploratory and based on about half the planned enrollment after a May 2024 clinical hold, so findings are limited and require larger, controlled trials; the company reported a generally favorable safety profile through 52 weeks and participants remained on exogenous insulin throughout the study.
• Biomea plans an investigator‑led Phase II (~40 patients) with longer dosing, placebo control, comprehensive immune/metabolic assessments and the option to test combination strategies (including a JAK inhibitor) to evaluate durability and potential immune modulation.

Biomea Fusion NASDAQ: BMEA executives highlighted early, exploratory clinical data for icovamenib in type 1 diabetes, presenting top-line results from the company’s COVALENT-112 proof-of-concept study focused on safety, tolerability, and signals of beta cell function. Management said the results mark a milestone in expanding its menin inhibitor platform into metabolic disease, while emphasizing the limited sample size and the need for more rigorous follow-up studies.

Rationale: targeting beta cell biology through menin inhibition

CEO Michael J.M. Hitchcock said the company is pursuing “a fundamentally different approach” in type 1 diabetes by targeting beta cell biology rather than focusing solely on insulin delivery or glucose monitoring. Juan Pablo Frías, Biomea’s CMO and chair of its scientific advisory board, framed the unmet need: beyond insulin replacement, he said there are currently no approved therapies in stage 3 type 1 diabetes that address the progressive loss of endogenous insulin production or restore beta cell function.

Frías pointed to physiologic states such as pregnancy and lactation in which menin levels are naturally reduced, enabling beta cell expansion and increased insulin production. Icovamenib is designed to replicate that biology pharmacologically by reducing menin levels, with the goal of supporting—and potentially restoring—beta cell function.

He also reviewed preclinical and translational findings cited by the company, including glucose-lowering in a streptozotocin rat model during oral glucose tolerance testing and ex vivo human islet data showing reduced menin protein levels and beta cell proliferation under hyperglycemic (but not normoglycemic) conditions.

COVALENT-112 design and enrollment interruption

Frías said COVALENT-112 enrolled patients across a wide range of disease duration—those diagnosed within the last three years and those diagnosed up to 15 years ago—to evaluate icovamenib’s effect across different stages. Patients received icovamenib plus standard-of-care insulin for 12 weeks and were followed through 52 weeks to evaluate on-treatment effects and durability. Two once-daily dose levels, 100 mg and 200 mg, were studied to assess dose response.

Enrollment was interrupted in May 2024 due to a clinical hold, and Frías said the data presented reflect “approximately half” the number of patients originally planned.

Top-line efficacy signal: stimulated C-peptide increase at 12 weeks

In cohort 1 (diagnosed within three years), Frías reported that patients in the 200 mg group showed a mean 52% increase from baseline in stimulated C-peptide mean area under the curve (AUC) at week 12, during the dosing period. He said this contrasted with the expected natural history decline.

On durability, Frías said that at week 52, C-peptide mean AUC in the same 200 mg group was “largely preserved,” with a 7.1% decline from baseline. He compared that to literature suggesting C-peptide declines by almost 50% per year in the early years following diagnosis.

Hitchcock said the magnitude of the on-treatment C-peptide response and its persistence after treatment cessation “stands in clear contrast to the natural history of type 1 diabetes,” while stressing the study’s small, exploratory nature and open questions around dosing, duration, durability, and the autoimmune process.

Safety and standard-of-care insulin

Frías summarized a “generally favorable safety and tolerability profile” with “no new safety signals observed through 52 weeks.” During Q&A, the company reiterated that patients remained on exogenous insulin throughout COVALENT-112. Frías said participants were “all on exogenous insulin throughout the trial period,” and co-founder, President and COO Ramses Erdtmann emphasized that background insulin is standard of care in such studies.

Frías and Erdtmann also described the mixed meal tolerance test used to evaluate beta cell function, explaining that C-peptide is measured at intervals over four hours after a mixed meal stimulus to assess insulin secretion.

Next steps: investigator-led phase II with longer dosing and potential immune modulation

Biomea outlined plans for an investigator-led phase II study in collaboration with U.S. type 1 diabetes centers. Frías said the study is currently designed to enroll adults within three years of diagnosis who retain measurable C-peptide, using a threshold greater than 0.2 nanomoles per liter. Erdtmann said the planned study size is 40 patients and suggested the design is intended to deliver answers quickly.

According to Frías, the proposed design includes extended icovamenib treatment duration, placebo control, and comprehensive immune and metabolic assessments, with the potential to incorporate a JAK inhibitor to explore combination strategies. He told analysts the phase II design was not final, but described a framework in which participants would receive icovamenib initially for six months, after which some would continue icovamenib, some would discontinue, and others would receive immune modulation either alongside continued icovamenib or after stopping icovamenib.

Asked about JAK inhibitor use in type 1 diabetes, Frías said it would be “extremely small” and limited to investigational use. He characterized combining a beta cell–focused approach with immune modulation as “complementary rather than synergistic.”

On dosing, Frías said the titration schedule has not been fully determined, but the company has “generally” considered a ramp such as four weeks at 100 mg before escalating. A company representative referred to as “Steve” said the company does not anticipate drug-drug interactions between icovamenib and immunosuppressant agents and cited the type 2 diabetes study COVALENT-111, where a 100 mg to 200 mg ramp did not show clinically significant ALT elevations in one cohort.

Biomea said additional details are expected at an upcoming scientific conference. Frías confirmed that cohort 2 data (patients with longer disease duration) would be presented later, while Erdtmann cautioned that the effect in the three- to 15-year cohort was “not as impressive” as cohort 1, even if it showed some durability.

About Biomea Fusion NASDAQ: BMEA

Biomea Fusion, Inc NASDAQ: BMEA is a clinical‐stage biopharmaceutical company headquartered in Carlsbad, California. The company is dedicated to the discovery and development of small molecule therapies that target epigenetic regulators implicated in cancer. By leveraging a proprietary chemistry and drug discovery platform, Biomea Fusion aims to design precision medicines that modulate gene expression pathways involved in the initiation and progression of hematological malignancies and solid tumors.

The company's lead clinical asset, BMF-219, is an orally bioavailable inhibitor of the menin–mixed‐lineage leukemia (MLL) protein–protein interaction.

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