London, UK – [Insert Date] – Clywedog Therapeutics has announced compelling final results from its Phase Ib clinical trial of balomenib, an investigational oral drug targeting type 2 diabetes (T2D). The study demonstrated sustained improvements in key glycemic measures, including hemoglobin A1c (HbA1c) and fasting plasma glucose, for a significant period after treatment cessation. These promising outcomes, particularly the drug’s robust safety and tolerability profile, are propelling Clywedog Therapeutics towards the initiation of a larger Phase IIa study later this year.
The Phase Ib trial, a meticulously designed placebo-controlled, double-blind, and randomized study, enrolled 60 adults diagnosed with type 2 diabetes across three different countries. The primary objective of this early-stage investigation was to meticulously assess the tolerability and safety of balomenib at the four-week mark. While glycemic measures were considered exploratory endpoints in this initial phase, the observed reductions in HbA1c and fasting plasma glucose have exceeded expectations and are now a central focus for future development.
The trial’s design involved participants receiving either balomenib or a placebo in a precise 1:1 allocation for a duration of 28 days. This treatment period included a crucial one-week pre-dosing titration phase, designed to carefully introduce the medication and monitor for any immediate reactions. Following the active treatment, participants entered an extended 12-week off-treatment observation period, allowing researchers to evaluate the drug’s residual effects and durability. The final patient visit for this pivotal study took place on July 11, 2026, marking the culmination of data collection.
Promising Glycemic Reductions Maintained Post-Treatment
The results from the observation period are particularly noteworthy. At week 12, a substantial three months after the final dose of balomenib was administered, the placebo-adjusted mean reduction in HbA1c reached an impressive 0.77%. This significant decline highlights the enduring impact of the short-term treatment. Furthermore, this reduction was maintained, with a mean reduction of 0.70% observed at week 16.
Beyond HbA1c, the trial also reported substantial improvements in fasting plasma glucose. At week 12, the placebo-adjusted mean reduction in fasting plasma glucose was 1.29 mmol/L, equivalent to 23 mg/dL. This indicates a consistent and sustained lowering of blood sugar levels in the fasting state, a critical indicator for diabetes management.
Further insights into balomenib’s impact were provided by an oral glucose tolerance test conducted at day 85, which falls eight weeks after the final dose. This test revealed placebo-adjusted reductions of 203 mmol·min/L in total glucose area under the curve, a 2.03 mmol/L decrease in peak glucose levels, and a 2.46 mmol/L reduction in glucose levels two hours post-administration. These translate to respective differences of 11%, 11%, and 15% compared to the placebo group, underscoring the drug’s ability to improve the body’s response to glucose intake even after treatment has ceased. Clywedog Therapeutics emphasized that the treatment and placebo groups exhibited superimposable characteristics at baseline, ensuring the validity of the observed differences.
Safety and Tolerability: A Cornerstone of Balomenib’s Profile
Crucially, the Phase Ib trial’s primary endpoint—evaluating tolerability and safety at week 4—was met with overwhelmingly positive results. No unexpected drug-related adverse events or serious adverse events were reported throughout the study. This robust safety profile is a significant advantage for any new therapeutic agent, especially in the management of a chronic condition like type 2 diabetes where long-term treatment is often required.
Furthermore, there were no treatment-related discontinuations due to adverse events, indicating that participants tolerated balomenib well. The study maintained high participant adherence, with 28 to 30 participants in each arm remaining evaluable at every scheduled assessment through week 16. This high completion rate provides a strong dataset for analysis and further strengthens the confidence in balomenib’s safety and tolerability.
The participants in the trial were individuals with established type 2 diabetes, characterized by mean baseline HbA1c levels of 8.84% in the balomenib group and 8.52% in the placebo group. These individuals were also receiving a range of background antidiabetic therapies, utilizing up to three different agents, excluding insulin. This cohort represents a typical patient population encountered in clinical practice, making the observed efficacy and safety data particularly relevant.
Expert Insights: Unlocking Balomenib’s Potential Mechanism
Iain Dukes, CEO of Clywedog Therapeutics, expressed considerable enthusiasm regarding the trial’s outcomes. "The central observation is that after only a three-week course of treatment, balomenib produced sustained improvements in glycaemic control consistent with a disease-modifying mechanism of action," Dukes stated. He elaborated on the proposed mechanism, suggesting that "inhibition of menin signalling resulted in pluralistic improvements in insulin sensitivity and insulin secretion." This suggests that balomenib may not just manage symptoms but address underlying physiological dysfunctions in type 2 diabetes. Dukes further speculated that these beneficial effects "should be expected to deepen following longer courses of treatment," hinting at the potential for even greater benefits with extended therapeutic durations.
The scientific rationale behind balomenib lies in its novel mechanism of action, targeting the menin pathway. Menin is a protein that plays a critical role in the development and function of the endocrine pancreas, including insulin secretion and sensitivity. By inhibiting menin signaling, balomenib aims to restore the delicate balance of glucose regulation in individuals with type 2 diabetes. The observed improvements in both insulin sensitivity and secretion, as alluded to by the CEO, align with this proposed mechanism and are highly encouraging for the future of the drug.
The Road Ahead: Advancing to Phase IIa
Buoyed by these positive Phase Ib results, Clywedog Therapeutics is poised to advance balomenib into the next stage of clinical development. The company has announced plans to initiate a Phase IIa randomized, double-blind, placebo-controlled study in the fourth quarter of 2026. This upcoming study is designed to build upon the findings of the Phase Ib trial, with a particular focus on evaluating a more extended 12-week treatment course. Following this treatment period, participants will undergo a subsequent off-treatment follow-up period, allowing for further assessment of the drug’s durability and long-term effects.
The Phase IIa trial will be instrumental in further elucidating the optimal dosing regimen and treatment duration for balomenib, as well as confirming its efficacy and safety in a larger patient population. Success in this phase would pave the way for larger, more definitive Phase IIb and Phase III trials, bringing balomenib closer to potential regulatory approval and offering a new therapeutic option for the millions of individuals worldwide living with type 2 diabetes. The sustained glycemic control observed in the Phase Ib trial, coupled with an excellent safety profile, positions balomenib as a promising candidate in the ongoing global effort to combat this pervasive chronic disease.
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