BenevolentAI ??announced it has submitted a Clinical Trial Application (CTA) to the UK Medicines and Healthcare Products Regulatory Agency (MHRA) for BEN-8744, an oral phosphodiesterase 10 (PDE10) inhibitor in development for the treatment of ulcerative colitis (UC). Subject to obtaining MHRA approval on the CTA, BenevolentAI plans to initiate a Phase I clinical trial of BEN-8744, anticipated to commence in the first half of 2023. BEN-8744 is an orally administered, peripherally restricted small molecule PDE10 inhibitor under development as a first-in-class treatment for ulcerative colitis and with the potential for other indications within inflammatory bowel disease.

BEN-8744 is differentiated by its novel mechanism of action; there is an opportunity to further differentiate BEN-8744 based on safety and efficacy. PDE10 reduces intracellular levels of the signalling molecule cGMP. Restoration of cGMP levels by PDE10 inhibition is anticipated to have a direct anti-inflammatory and disease-modifying benefit.

BenevolentAI will look to demonstrate that BEN-8744 is effective in treating moderate-to-severe cases of UC and with fewer side effects than the anti-TNF and JAK inhibitors that are currently the dominant form of treatment for this disease. BenevolentAI has filed for second medical use and composition of matter patents in respect of BEN-8744. BEN-8744 is a wholly owned asset in the BenevolentAI drug programme pipeline.

UC is a chronic disease that causes inflammation and ulceration of the inner lining of the colon and rectum. UC affects 0.4% of the US population, and 31% of patients have moderate-to-severe disease. 20-40% of those patients with moderate-to-severe UC do not respond to anti-TNF, the main treatment approach, and currently available treatments can have severe side effects.