Insilico Medicine (“Insilico”), a clinical-stage generative artificial intelligence (AI)-driven drug discovery and development company, today shared positive outcomes from two Phase I studies conducted in Australia and China for ISM5411, a novel gut-restricted and PHD-specific inhibitor designed for the treatment of inflammatory bowel disease (IBD).

The studies demonstrated that ISM5411 was generally safe and well-tolerated across all dose groups, with a favorable pharmacokinetic (PK) profile that validated its gut-restrictive properties. Supported by Insilico’s generative AI platform, Chemistry42, ISM5411’s preclinical candidate (PCC) nomination was achieved in just 12 months, during which approximately 115 molecules were synthesized and screened.

The early drug discovery and preclinical data for ISM5411 were recently published in Nature Biotechnology, establishing a new PCC nomination benchmark for Insilico and underscoring its rapid drug development capabilities.

Study Findings

Two Phase I trials, conducted in parallel in Australia and China, evaluated the safety, tolerability, PK, and food effects (FE) of ISM5411. The studies included single ascending dose (SAD), multiple ascending dose (MAD), and FE parts, involving a total of 124 healthy subjects.

Key findings include:

• ISM5411 was safe and well-tolerated across all dose groups, with no serious adverse events or treatment-related discontinuations.
• Treatment-emergent adverse events (TEAEs) were mild (Grade 1) and resolved by study completion.
• PK analysis confirmed low systemic exposure and a high fecal/plasma ratio, indicative of gut-restrictive properties.
• No significant drug accumulation was observed after 14 days of multiple dosing.

Future Plans

Based on these promising results, Insilico plans to initiate a Phase II proof-of-concept study for ISM5411 in patients with active ulcerative colitis in the second half of 2025.

Expert Perspectives

“It is encouraging to see ISM5411's favorable safety and PK profiles, particularly its low systemic exposure, which highlights its potential as a gut-restricted therapy,” said Dr. Philip Ryan, Principal Investigator of the Australian Phase I study.

“These results validate the promise of AI in drug discovery, and we look forward to advancing ISM5411 into patient trials to explore its clinical benefits,” added Dr. Carol Satler, Vice President for Clinical Development, Non-Oncology at Insilico Medicine.

Innovative Drug Discovery

ISM5411 represents Insilico’s commitment to leveraging AI for rapid and efficient drug development. Since its inception, Insilico has nominated 22 preclinical candidates, with 10 programs reaching clinical stages and one completing Phase IIa trials. The fastest PCC nomination achieved by the company was nine months for the QPCTL program.

The development of ISM5411 builds on Insilico’s expertise in targeting prolyl hydroxylase domain (PHD) enzymes, which have been implicated in aging and age-related diseases.

“Our generative AI platform, Chemistry42, continues to redefine the boundaries of drug discovery,” said Alex Zhavoronkov, PhD, Founder and CEO of Insilico Medicine. “ISM5411 exemplifies our mission to deliver innovative therapies that improve patient outcomes and promote healthy longevity.”