Insilico Medicine ("Insilico", HKEX: 3696), a clinical-stage biotechnology company powered by generative artificial intelligence (AI), today announced it has achieved the first clinical milestone in its co-development collaboration with Hygtia Therapeutics with the completion of first-in-human dosing in the Phase I study of ISM8969. ISM8969 is a potentially best-in-class, orally available, brain-penetrant small-molecule inhibitor of the NLRP3 inflammasome being developed to treat chronic neuroinflammation and central nervous system (CNS) disorders, including Parkinson's disease.
As the first study in the clinical development of ISM8969, this single-center, Phase I, randomized, double-blind, placebo-controlled trial, including both single ascending dose (SAD) and multiple ascending dose (MAD) cohorts, will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of orally administered ISM8969 in healthy participants and in obese adult participants at risk of cardiovascular disease. The Phase I study is conducted in Australia and is expected to enroll 80 healthy participants as well as 20 obese adult participants at risk of cardiovascular disease.
In addition, the study will collect cerebrospinal fluid (CSF) samples to assess ISM8969's penetration into the central nervous system and to characterize its PK/PD profile in the target compartment. The data collected from this study are expected to provide critical evidence to inform dose selection and support therapeutic relevance in future clinical development.
Advancing ISM8969 from an AI-generated concept to first-in-human dosing is a major step forward, as well as the first clinical milestone in our collaboration with Hygtia Therapeutics. Developing an effective NLRP3 inhibitor that can safely penetrate the blood-brain barrier has long been a challenge for the industry. Leveraging Chemistry42, we precisely optimized the molecule to deliver strong preclinical efficacy and favorable permeability. We look forward to evaluating its translational potential in this Phase 1 trial and to continuing our close collaboration with Hygtia to advance innovative neuroscience therapies for patients worldwide."
Feng Ren, PhD, Co-CEO and Chief Scientific Officer, Insilico Medicine
The NLRP3 inflammasome is a vital component of the body's innate immune response. However, its excessive or chronic activation triggers an overproduction of pro-inflammatory cytokines, driving sustained neuroinflammation and cell damage that leads to the progression of debilitating neurodegenerative conditions. By inhibiting NLRP3, ISM8969 aims to modulate this pathological inflammation, supporting neuronal survival and function among patients with neurodegenerative disease.
In preclinical evaluation studies, ISM8969 exhibited a balanced druggability profile, with promising in vitro activity and safety, favorable in vivo PK/PD profile, as well as efficacy against inflammation in multiple mouse disease models, including acute inflammatory disease and chronic disease models. Compared with other clinically advanced peripherally restricted NLRP3 inhibitors, ISM8969 is BBB-penetrant and can access the CNS, enabling potential treatment of neuroinflammation-related diseases. Based on these preclinical data, Insilico nominated ISM8969 as the program's preclinical candidate in December 2024.
To accelerate the global development of this candidate, Insilico has entered into an exclusive global strategic co-development collaboration with Hygtia Therapeutics, an incubatee of Shenzhen Pengfu Fund of Fosun Health Capital and Fosun Pharma. Under the agreement, both parties hold a 50% stake in the global rights and interests of the program, with Insilico leading the IND submission and Phase I clinical trial. Insilico remains eligible to receive up to $66 million in upfront and milestone payments as the program progresses.
As an AI-native biotechnology company, Insilico is redefining the efficiency of preclinical drug development through its advanced AI and automation platform, setting a new standard for the industry. While traditional early-stage drug discovery typically takes 2.5 to 4 years, Insilico has consistently reached preclinical candidate (PCC) nomination in an average of just 12 to 18 months, with only 60 to 200 molecules synthesized and tested per program. Since 2021, the company has nominated 31 PCCs, 13 of which have received IND approval or clearance.
While expanding the practical applications of its technology in drug discovery and life science research, Insilico is also continuously enhancing the performance of its AI platform. Drawing on extensive experience and datasets from its training platform, the company has distilled thousands of benchmarks and integrated them into MMAI Gym. Serving as both a "trainer and benchmark" for scientific AI, MMAI Gym enables organizations to train models for domain-specific reasoning while rigorously evaluating their performance on real-world tasks, advancing the path toward pharma superintelligence. To date, Human Longevity and Liquid AI have collaborated with Insilico, joining as partners of MMAI Gym.
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