CAMBRIDGE, Massachusetts, Jan 7, 2024 — Insilico Medicine ('Insilico'), a clinical-stage generative artificial intelligence (AI)-driven drug discovery and development company, today announces positive results from two Phase I studies in Australia and China of ISM5411, a novel gut-restricted and PHD specific Inhibitor designed and optimized with the support of Insilico's Chemistry42 commercially-available generative reinforcement learning platform, for Inflammatory Bowel Disease (IBD).
"It is pleased to see the good safety and PK profiles of ISM5411, especially the low systemic exposure across all dose groups.These results are suggestive of the gut-restrictive property of ISM5411 and good potential for further clinical development," says Philip Ryan, MD, PhD, the Principal Investigator of ISM5411 Phase I study in Australia. "As an advanced technology, AI has played important roles in drug discovery and clinical research. We are looking forward to following ISM5411 as it progresses into patient trials, where we hope to see clinical benefits stemming from this technology."
"These positive Phase I results from the IBD program are highly encouraging, particularly in validating the gut-restricted pharmacokinetic profile," says Carol Satler, MD, PhD, Vice President for Clinical Development, Non-Oncology, Insilico Medicine, who will support the further development of ISM5411 for the treatment of IBD. "Given the limited therapeutic options and the challenges with current IBD treatments, we believe that new therapies will benefit patients in the near future. We look forward to advancing the next phase of validation in patients."
Two Phase I studies investigating the safety, tolerability, pharmacokinetics (PK), and food effects (FE) of ISM5411 were conducted in Australia and China in parallel. These studies included single ascending dose (SAD), multiple ascending dose (MAD) and FE parts involving 76 healthy subjects in Australia and 48 healthy subjects in China. Safety and PK data collection has been completed for both studies.
The data indicates that ISM5411 was generally safe and well tolerated across all dose groups of two Phase I studies, with no reports of serious adverse events or treatment-related adverse events (TRAEs) leading to discontinuation. The overall occurrence rate of treatment-emergent adverse events (TEAEs) was comparable between all treatment groups and pooled placebo groups in both studies. Most reported TEAEs were Grade 1 and resolved by the end of studies. No clinically significant increases in red blood cell count or hemoglobin were reported.
The observed human PK of ISM5411 in healthy volunteers was in line with the Company's preclinical modeling, with no significant drug accumulation observed after 14 days of multiple administration across all dosing groups. ISM5411 also exhibited a favorable PK profile for validating gut-restrictive properties, with very low systemic exposure and a high fecal/plasma ratio in healthy volunteers.
