Biomea Fusion (BMEA) Study Result summary

Study design and patient population

• COVALENT-111 is a randomized, double-blind, placebo-controlled phase II trial evaluating icovamenib in adults with type 2 diabetes diagnosed within the last seven years, poorly controlled on up to three antidiabetic agents (excluding insulin/secretagogues).

• Participants were overweight or obese (BMI 25–40), with baseline HbA1c between 7% and 10.5%.

• 225 patients were enrolled; efficacy analysis focused on 168 per protocol patients who completed dosing prior to a clinical hold, with balanced demographics between active and placebo groups.

• Three dosing arms were tested: 100mg QD for 8 weeks, 100mg QD for 12 weeks, and 100mg QD for 8 weeks followed by 100mg BID for 4 weeks.

• Patient subtypes were defined using clinical biomarkers: SIDD, MARD, SIRD, and MOD.

Efficacy results

• Icovamenib met the primary endpoint, showing a statistically significant placebo-corrected reduction in HbA1c in the per protocol population, with the greatest reductions in insulin-deficient patients dosed for 12 weeks (SIDD Arm B: 1.47% reduction, p=0.022).

• All patients dosed for 12 weeks (Arms B/C) had a mean HbA1c reduction of 0.42% (p=0.015); SIDD/MARD subgroup had 0.84% (p=0.008).

• Insulin-resistant patients (MOD) uncontrolled on GLP-1 agonists also showed clinically meaningful HbA1c reductions (up to -0.97%).

• Twelve-week dosing outperformed 8-week dosing, and insulin-deficient subtypes showed the greatest benefit.

• Placebo corrections were made within each subtype to ensure accurate efficacy comparisons.

Safety and tolerability

• Icovamenib was well tolerated, with similar rates of adverse events in active (30%) and placebo (32%) groups; no serious adverse events, hypoglycemia, or discontinuations due to adverse events were reported.

• Most common TEAEs included diarrhea (4%), nausea (4%), hyperglycemia (4%), and headache (2-4%), mostly grade 1 or 2.

• Mild elevations in liver enzymes were observed, primarily at higher doses in the escalation phase, but not in the main study arms.

• No drug-to-drug interactions were observed during the study.

• The FDA clinical hold was lifted after protocol adjustments and enhanced monitoring.