Insilico Completes First-in-Human Dosing in Phase I Clinical Study of AI-Driven NLRP3 Inhibitor ISM8969, Achieving First Clinical Milestone in Collaboration with Hygtia ...

Insilico Medicine, a clinical-stage biotechnology company specializing in AI-driven drug discovery, has completed first-in-human dosing in its Phase I trial of ISM8969, a small-molecule inhibitor targeting the NLRP3 inflammasome. The study, conducted in collaboration with Hygtia Therapeutics, aims to treat chronic neuroinflammation and central nervous system disorders, including Parkinson’s disease. The randomized, double-blind, placebo-controlled trial includes single and multiple ascending dose cohorts, enrolling 80 healthy participants and 20 obese adults at risk of cardiovascular disease. Cerebrospinal fluid samples will assess the drug’s ability to penetrate the blood-brain barrier and inform dose selection for future trials. The Phase I trial marks the first clinical milestone in Insilico’s co-development agreement with Hygtia Therapeutics, under which both companies share equal rights to the program. ISM8969 was developed using Insilico’s AI platform, Chemistry42, which optimized the molecule for efficacy and permeability. Preclinical studies demonstrated strong anti-inflammatory effects in mouse models, including chronic disease conditions, while also showing favorable safety and pharmacokinetic profiles. NLRP3 inflammasome inhibition is a promising approach for addressing neuroinflammation, a key driver of neurodegenerative diseases. Excessive activation of NLRP3 leads to chronic inflammation and neuronal damage, contributing to conditions like Parkinson’s. ISM8969’s ability to cross the blood-brain barrier sets it apart from other NLRP3 inhibitors currently in development, which are typically restricted to peripheral tissues. The trial’s results will provide critical insights into ISM8969’s safety, tolerability, and pharmacodynamics in humans. Insilico and Hygtia plan to use these findings to advance the drug into later-stage trials, with potential global implications for treating neuroinflammatory disorders. The collaboration also includes up to $66 million in upfront and milestone payments for Insilico as the program progresses. Hygtia Therapeutics, backed by Shenzhen Pengfu Fund and Fosun Health Capital, is co-leading the development of ISM8969. The partnership combines Insilico’s AI-driven drug discovery capabilities with Hygtia’s expertise in neuroscience, aiming to accelerate the development of innovative therapies for patients worldwide.