In an exciting development for the treatment of ulcerative colitis (UC), British biopharmaceutical company, BenevolentAI, has reported positive results from a Phase Ia clinical study of its drug, BEN-8744. This innovative therapy shows promise as a potential first-in-class treatment for patients suffering from moderate to severe UC, a chronic inflammatory bowel disease that affects millions worldwide.

The study, conducted on healthy volunteers, aimed to assess the safety, tolerability, and pharmacokinetics of BEN-8744 – an orally administered drug that inhibits Phosphodiesterase 10 (PDE10). PDE10 is an enzyme involved in the regulation of intracellular signalling molecules, whose inhibition could potentially reduce inflammation and improve the integrity of the bowel’s lining. Notably, the study achieved its primary objective, with no Serious Adverse Events (SAEs) reported across any of the dose cohorts. This result is particularly significant given the challenges previously faced by PDE10 inhibitors in clinical development for central nervous system (CNS) conditions, which were limited by CNS-associated adverse effects.

BenevolentAI’s approach to developing BEN-8744 was informed by its proprietary AI-driven platform, which identified PDE10 as a novel target for UC treatment. Recognising the need to avoid the CNS side effects encountered by other PDE10 inhibitors, the company engineered BEN-8744 to be peripherally restricted, thereby minimising its penetration into the CNS. The positive safety profile emerging from this study suggests that this strategy is successfully mitigating the risk of such side effects.

Dr. Anne Phelan, Chief Scientific Officer at BenevolentAI, highlighted the encouraging safety and tolerability profile of BEN-8744 as indicating a promising future for the drug in the treatment of UC. This comes against the backdrop of significant unmet needs in UC treatment, where sustained remission rates are low, and existing treatments often come with severe side effects.

The potential of BEN-8744 extends beyond UC. Preliminary data suggest its efficacy could apply to other inflammatory bowel diseases, such as Crohn’s disease, indicating a wider applicability and the possibility of addressing a broader patient population.

Ulcerative colitis and Crohn’s disease are the two main forms of inflammatory bowel disease, impacting millions globally. UC, in particular, is a lifelong condition that results in inflammation and ulcers in the inner lining of the colon and rectum. It affects over 1.9 million patients in the major markets, with approximately 31% suffering from moderate-to-severe disease. The path to effective treatment is fraught with challenges, as a significant portion of patients does not respond to the main treatment methods, leading to a continuous search for safer and more effective therapeutic options.

As an innovator at the intersection of artificial intelligence and biopharmaceuticals, BenevolentAI is leveraging its capabilities to uncover novel disease-biology insights, predict new therapeutic targets, and expedite the drug discovery process. With London as its headquarters and facilities in Cambridge (UK) and New York, the company is reshaping the future of medicine by pushing the boundaries of drug discovery to develop treatments for complex diseases.

The journey of BEN-8744, from its inception to this successful Phase Ia trial, underscores the transformative potential of merging AI-based drug discovery with targeted pharmacological design. As BenevolentAI prepares for further studies and evaluations, the UC patient community watches closely, hopeful for a new treatment on the horizon that could significantly improve their quality of life.