Insilico's ISM5411 Shows Positive Phase 1 Results for Inflammatory Bowel Disease

In CAMBRIDGE, MA, on January 7, 2025, Insilico Medicine, a clinical-stage company focusing on AI-driven drug discovery, announced promising results from their Phase I trials of ISM5411 conducted in Australia and China. ISM5411 is a new gut-restricted inhibitor aimed at treating Inflammatory Bowel Disease (IBD), developed using Insilico's innovative Chemistry42 platform, which leverages generative reinforcement learning to optimize drug design.

The Phase I trials involved assessing the safety, tolerability, pharmacokinetics (PK), and food effects of ISM5411. Both studies conducted parallel investigations in Australia and China, encompassing 76 and 48 healthy participants respectively. These trials were structured to include single ascending dose (SAD), multiple ascending dose (MAD), and food effects parts. The results indicated that ISM5411 was largely safe and well-tolerated, with no serious adverse events or treatment-related adverse events causing discontinuation. The occurrence of treatment-emergent adverse events was similar between the treatment and placebo groups. Most adverse events were mild and resolved by the end of the study period. Importantly, there were no significant changes in red blood cell count or hemoglobin levels.

The pharmacokinetics of ISM5411 in human subjects aligned with Insilico's preclinical models. The drug showed no significant accumulation over 14 days of administration across various dosing groups, confirming its gut-restrictive properties. ISM5411 demonstrated low systemic exposure and a high fecal/plasma ratio, suggesting a favorable PK profile.

Dr. Philip Ryan, the Principal Investigator for the Australian study, expressed satisfaction with the results, highlighting the potential for ISM5411's gut-restrictive attributes and its prospects for further clinical development. Dr. Carol Satler, Vice President for Clinical Development at Insilico, also emphasized the significance of these findings, especially in light of the limited treatment options currently available for IBD. She expressed optimism about moving to the next phase of trials, which are expected to commence in the latter half of 2025 and will focus on evaluating ISM5411 in patients with active ulcerative colitis.

Inflammatory bowel disease, encompassing conditions like ulcerative colitis and Crohn’s disease, represents a chronic inflammation of the gastrointestinal tract. It poses significant risks, including the potential development of colitis-associated cancer. Unlike traditional therapies that primarily aim to reduce inflammation, Insilico's approach also emphasizes promoting epithelial repair.

The founder and CEO of Insilico Medicine, Dr. Alex Zhavoronkov, underscored the burden that IBD places on patients and health systems globally. He reaffirmed Insilico's commitment to leveraging AI for creating innovative therapies that not only manage disease but also enhance patient quality of life and longevity. Since 2016, Insilico has been at the forefront of integrating generative AI in drug discovery, evident in their comprehensive research programs and clinical advancements.

In 2022, Insilico identified ISM5411 as a preclinical candidate after a year of intensive research and development, during which approximately 115 molecules were synthesized and screened, facilitated by their advanced generative chemistry engine. The discovery and development processes surrounding ISM5411 have been recognized in leading scientific publications, underscoring the role of Insilico's AI tools in optimizing drug candidate design.

Insilico's forward momentum in drug development is further illustrated by their earlier work on ISM001_055, another promising therapeutic candidate that successfully progressed to Phase II clinical trials. This ongoing innovation exemplifies Insilico's strategic use of AI in revolutionizing drug discovery, showcasing the company's ability to consistently advance significant therapeutic programs to clinical stages.