Clywedog’s balomenib showed sustained HbA1c and glucose improvements after short treatment in a Phase 1b type 2 diabetes study.
Written By: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
Clywedog Therapeutics reported Phase 1b results showing that three weeks of balomenib treatment produced sustained improvements in glycemic control, with placebo-adjusted HbA1c reductions persisting through Week 16, three months after the last dose.
Sustained Glycemic Effect After Treatment
The randomized, double-blind, placebo-controlled Phase 1b study (ZE63-0302-0002) evaluated balomenib, an investigational oral small-molecule menin inhibitor, in 60 adults with type 2 diabetes across three countries.
Participants received balomenib or placebo for four weeks, including a one-week dose-titration period, followed by a 12-week off-treatment observation period. At Week 12, balomenib produced a placebo-adjusted mean HbA1c reduction of 0.77 percentage points (p<0.01). The reduction remained 0.70 percentage points at Week 16 (p<0.05), approximately three months after the final dose.
Fasting plasma glucose also improved, with a placebo-adjusted reduction of 1.29 mmol/L (23 mg/dL) at Week 12 (p<0.05).
Improvements in Glucose Tolerance
An oral glucose tolerance test at Day 85, eight weeks after treatment ended, showed statistically significant improvements across several measures.
Compared with placebo, balomenib reduced total glucose exposure, measured by glucose area under the curve, by 203 mmol·min/L (p=0.019). Peak glucose fell by 2.03 mmol/L (p=0.013), while two-hour glucose decreased by 2.46 mmol/L (p=0.010). These corresponded to differences versus placebo of 11%, 11%, and 15%, respectively.
The two treatment groups had comparable glucose tolerance measurements at baseline, supporting interpretation of the post-treatment differences.
Additional exploratory measures showed improvements in body weight, lipids, triglycerides, and indirect measures of insulin sensitivity and insulin secretion, including HOMA-IR and HOMA-B.
Safety and Clinical Development
Balomenib met the Phase 1b study’s primary safety and tolerability objective. The company reported no drug-related serious or severe adverse events and no treatment-related discontinuations.
The findings also align with preclinical results in Zucker diabetic fatty rats. Thirty-five days after balomenib treatment ended, HbA1c was 5.9% in treated animals compared with 10.9% in vehicle controls (p<0.001). By comparison, animals treated with the SGLT2 inhibitor canagliflozin had HbA1c of 9.7% after the same off-treatment period.
Histologic analyses showed larger and more numerous pancreatic islets and greater insulin-positive pancreatic area in balomenib-treated animals at the end of the observation period.
Menin Inhibition and β-Cell Function
Balomenib targets menin, a regulatory protein that acts as a brake on pancreatic β-cell turnover and function. Clywedog’s approach uses time-limited inhibition of menin protein interactions to promote the preservation, proliferation, and reactivation of functional insulin-producing β cells.
The proposed mechanism could explain why glycemic effects persisted after dosing stopped. However, the Phase 1b clinical findings are exploratory, and the study was primarily intended to assess safety and tolerability rather than establish efficacy or disease modification.
Phase 2a Study Planned for Q4 2026
Clywedog plans to begin a Phase 2a study in type 2 diabetes in the fourth quarter of 2026. The randomized, double-blind, placebo-controlled study will extend balomenib treatment to 12 weeks while retaining an off-treatment follow-up period.
The study will provide an opportunity to determine whether longer exposure increases the magnitude or durability of the glycemic response observed after the shorter Phase 1b treatment course.
Reference
Clywedog Therapeutics Announces Final Results from a Phase 1b Study of Balomenib in Type 2 Diabetes Patients, Showing Glycemic Improvement Sustained for Three Months After a 3-Week Course of Treatment, Clywedog Therapeutics, 24 September 2026
Study to Assess Safety, Tolerability, PK, and PD of Multiple Doses of ZE63-0302 Administrated Orally in T2DM Patients, ClinicalTrials.gov ID NCT07234864
About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.