Insilico Medicine (3696.HK), a clinical-stage drug discovery and development company powered by generative artificial intelligence (AI), today announced that ISM8969, an orally available NLRP3 inhibitor for inflammatory and neurodegenerative diseases, recently received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) for the treatment of Parkinson’s disease.
The Phase I clinical trial will evaluate the safety, tolerability, and pharmacokinetics of ISM8969 in healthy volunteers and identify optimal dose levels recommended for further studies.
NLRP3 has emerged as a major contributor to chronic neuroinflammation and disease progression in neurodegenerative diseases. ISM8969, a novel NLRP3 inhibitor with desirable brain-penetrating properties, enabled by our AI-powered design process, offers the potential to advance Parkinson’s disease treatment into the next generation. We are excited to receive the green light from the FDA to advance this new treatment into human clinical trials and hope to spark a true paradigm shift with AI’s breakthrough advances in new drug discovery. ”
Carol Sattler, MD, Senior Vice President, Clinical Development, Non-Oncology, In Silico Medicine
Excessive activation of NLRP3 leads to overproduction of proinflammatory cytokines and chemokines, leading to persistent inflammation and tissue damage. ISM8969 aims to modulate this pathological inflammation by inhibiting NLRP3 and support neuronal survival and function in patients with neurodegenerative diseases. In December 2024, ISM8969 was nominated as an orally administered, best-in-class preclinical candidate targeting NLRP3.
It is worth noting that ISM8969 was discovered and optimized using Insilico’s Chemistry42, a comprehensive generative chemistry engine comprised of multiple applications spanning the drug discovery and discovery stages. More importantly, ISM8969 has the ability to cross the blood-brain barrier and reach the central nervous system (CNS) directly, establishing unique benefits against CNS diseases, including Parkinson’s disease, apart from a balanced druggability profile and efficacy against inflammation in both inflammatory and chronic disease mouse models.
To accelerate the global development of ISM8969, Insilico Medicine has entered into a co-development collaboration agreement with Hygtia Therapeutics. Under the agreement, Insilico grants Hygtia Therapeutics worldwide rights to research, develop, register, manufacture and commercialize ISM8969, with each party retaining 50% of the worldwide rights and interest in the program. In return, Insilico is eligible to receive up to $66 million in upfront and milestone payments.
Based on a comprehensive portfolio powered by Pharma.AI, Insilico has dozens of collaborations with the world’s leading pharmaceutical companies, including Sanofi, Lilly, Exelixis, and Menarini, with three major license-out agreements totaling up to $2.1 billion in total contract value.
Insilico leverages cutting-edge AI and automation technology to significantly improve the efficiency of preclinical drug development and establish a benchmark for AI-driven drug R&D. While traditional early-stage drug discovery typically takes an average of 4.5 years, Insilico has nominated 20 preclinical candidates from 2021 to 2024, with an average timeline from project initiation to preclinical candidate (PCC) candidate of just 12 to 18 months per program, with only 60 to 200 molecules synthesized and tested in each program.
