Insilico Medicine, a clinical-stage company leveraging generative artificial intelligence (AI) for drug discovery and development, has announced promising results for its novel drug, ISM5411, aimed at treating Inflammatory Bowel Disease (IBD). This gut-restricted and PHD-specific inhibitor was designed and optimized using Insilico’s AI-driven Chemistry42 platform, which employs advanced AI and machine learning techniques to streamline the drug design process, making it more efficient and innovative.
Successful Phase I Clinical Trials
The main focus of recent developments is the successful completion of two Phase I clinical trials of ISM5411 conducted in Australia and China. These trials assessed the safety, tolerability, pharmacokinetics (PK), and food effects (FE) of the drug. A total of 124 healthy subjects participated, with 76 in Australia and 48 in China. The trials included single ascending dose (SAD), multiple ascending dose (MAD), and food effect (FE) parts, providing comprehensive data on various aspects of the drug’s performance in healthy individuals.
Philip Ryan, MD, PhD, the Principal Investigator of the Australian Phase I study, expressed satisfaction with the safety and PK profiles of ISM5411. He emphasized the low systemic exposure, which indicates the gut-restricted property of the drug. This important finding suggests that ISM5411 can be further developed clinically without significant systemic exposure-related side effects, potentially offering a safer treatment option for patients suffering from IBD, a condition where innovative therapies are urgently needed due to limited existing options.
Carol Satler, MD, PhD, Vice President for Clinical Development, Non-Oncology at Insilico Medicine, emphasized the importance of the Phase I results and the validation of the gut-restricted pharmacokinetic profile of ISM5411. She noted the challenges and limitations associated with current IBD treatments and expressed hope that new therapies like ISM5411 can offer significant benefits to patients. The Phase I results indicate that ISM5411 has the potential to address these limitations, providing a much-needed alternative for IBD patients.
Safety and Tolerability of ISM5411
The data from the Phase I studies revealed that ISM5411 was generally safe and well-tolerated across all dose groups, with no reports of serious adverse events or treatment-related adverse events leading to discontinuation. The occurrence rate of treatment-emergent adverse events (TEAEs) was comparable between the treatment groups and placebo groups in both studies. Most TEAEs were mild (Grade 1) and resolved by the end of the studies, indicating that ISM5411 has a favorable safety profile.
Additionally, no clinically significant increases in red blood cell count or hemoglobin were observed. The human pharmacokinetics (PK) of ISM5411 in healthy volunteers aligned with preclinical models, showing no significant drug accumulation after multiple doses across all groups. The drug exhibited a favorable PK profile, confirming its gut-restrictive properties with very low systemic exposure and a high fecal/plasma ratio in healthy volunteers. This further supports the potential of ISM5411 as a safe and effective treatment for IBD, with minimal risk of systemic side effects.
Future Plans and Broader Achievements
Based on these promising Phase I results, Insilico Medicine plans to initiate a Phase 2 proof-of-concept study to evaluate ISM5411 in patients with active ulcerative colitis in the second half of 2025. Alex Zhavoronkov, PhD, Founder and CEO of Insilico Medicine, explained the significant impact IBD has on patients’ quality of life and healthcare systems. Unlike current therapies that primarily focus on anti-inflammatory strategies, Insilico’s approach aims to develop therapies that address the root causes of intestinal inflammation and promote epithelial repair. This innovative approach has the potential to significantly improve patient outcomes.
Zhavoronkov stressed the company’s commitment to pioneering AI-driven drug discovery and development since 2016, with the goal of delivering innovative therapies that improve disease control, reduce adverse effects, and enhance overall health and longevity. In January 2022, ISM5411 was nominated as a preclinical candidate for IBD after the company synthesized and screened approximately 115 molecules in just 12 months using their generative chemistry engine. This rapid development underscores the efficiency and potential of Insilico’s AI-driven approach.
Insilico’s AI-Driven Drug Discovery Process
Insilico Medicine, a clinical-stage company, is using generative artificial intelligence (AI) to revolutionize drug discovery and development. Recently, the company announced encouraging results for its new drug, ISM5411, which targets Inflammatory Bowel Disease (IBD). This innovative drug is gut-restricted and acts as a PHD-specific inhibitor, specifically targeting pathways involved in IBD. The creation and optimization of ISM5411 were made possible through Insilico’s AI-driven Chemistry42 platform. This advanced platform leverages cutting-edge AI and machine learning techniques to enhance the drug design process, making it more efficient and groundbreaking. By utilizing these state-of-the-art technologies, Insilico can streamline the development of new medications, bringing innovative treatments to market faster. This could potentially transform the way complex diseases like IBD are treated in the future, offering hope and better health outcomes for millions of people suffering from these challenging conditions.
