Insilico Received Positive Topline Results from Two Phase 1 Trials of ISM5411, New Drug Designed Using Generative AI for the Treatment of Inflammatory Bowel Disease

• Two separate Phase I studies conducted in Australia and in China indicate that ISM5411 was generally safe and well tolerated in all dose groups, demonstrating a favorable PK profile in validating gut-restrictive properties.
• Supported by Insilico's commercially-available generative AI platform Chemistry42, the preclinical candidate (PCC) nomination of ISM5411 took only 12 months, during which approximately 115 molecules were synthesised and screened.
• The early drug discovery and development process and preclinical data of ISM5411 were recently published in Nature Biotechnology, which represents the new PCC nomination record published in a peer-reviewed journal, beating Insilico's previous record of 18 months also published in Nature Biotechnology in 2024.
• Since 2019, Insilico nominated 22 preclinical candidates out of its own chemistry and biology platform, 10 programs reached clinical stage, 1 successfully completed Phase IIa. The fastest PCC nomination was 9 months (QPCTL program).
• Previously, Insilico implicated PHD1/2 targets in aging and multiple age-related diseases expanding its portfolio of dual-purpose aging and disease longevity therapeutics.

CAMBRIDGE, Mass., Jan. 7, 2025 /PRNewswire/ -- 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.

Based on these results, Insilico Medicine expects to initiate a Phase 2 proof-of-concept study evaluating ISM5411 in active ulcerative colitis patients in the second half of 2025. For more information about Insilico's clinical trials please visit ClinicalTrials.gov (NCT06012578) .

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, comprising primarily ulcerative colitis and Crohn's disease, which also increases the risk of colitis-associated cancer. In a departure from current standard therapies that focus on anti-inflammatory strategies, Insilico's research is focused on developing therapies that not only reduce intestinal inflammation, but also promote epithelial repairment.

"IBD as a chronic condition impacts the quality of life for millions of patients worldwide and places a heavy burden on healthcare systems." says Alex Zhavoronkov, PhD, Founder and CEO of Insilico Medicine. "Powered by generative AI, the field we pioneered since 2016, Insilico is committed to delivering effective and innovative therapies that improve disease control, reduce disease burden, minimise adverse side effects, improve overall health and productive longevity. The PHD program further demonstrates Insilico's ability to consistently advance valuable programs to the clinical stage."

In January 2022, Insilico nominated ISM5411 as a preclinical candidate for IBD, after taking only 12 months to synthesize and screen approximately 115 molecules, supported by its integrated generative chemistry engine. The early drug discovery and development process and preclinical data of ISM5411 were recently published in Nature Biotechnology, highlighting the role of Chemistry42 and its submodules in supporting drug candidate design and optimization.

Previously, Insilico implicated PHD1/2 targets in aging and multiple age-related diseases expanding its portfolio of dual-purpose aging and disease longevity therapeutics.

Earlier in 2024, Insilico published a Nature Biotechnology paper presenting the entire R&D journey from AI algorithms to Phase II clinical trials of ISM001_055, the company's lead drug pipeline with AI-discovered target and AI-designed structure in early 2024. Following that, Insilico has recently announced positive preliminary results from a Phase IIa trial, where ISM001_055 showed favorable safety and tolerability across all dose levels, as well as dose-dependent response in forced vital capacity (FVC), after only 12 weeks of dosage.

In 2016, Insilico first described the concept of using generative AI to design novel molecules in a peer-reviewed journal, which laid the foundation for the commercially available Pharma.AI platform. Since then, Insilico has kept integrating technical breakthroughs into Pharma.AI platform, which is currently a generative AI-powered solution spanning across biology, chemistry, medicine development and science research. Powered by Pharma.AI, Insilico has nominated 21 preclinical candidates in its comprehensive portfolio of over 30 therapeutic assets since 2021 and has received IND clearance for 10 molecules.

About Insilico Medicine

Insilico Medicine, a clinical stage end-to-end artificial intelligence (AI)-driven drug discovery company, is connecting biology, chemistry, and clinical trials analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques for novel target discovery and the generation of novel molecular structures with desired properties. Insilico Medicine is developing breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system diseases, infectious diseases, autoimmune diseases, and aging-related diseases.

Website: www.insilico.com