image: ISM8969 dose dependently improved behavioral performance in open field, rotarod and grip strength tests in MPTP induced Parkinson disease (PD) model
Credit: Insilico Medicine
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Insilico Medicine has completed IND-enabling studies for ISM8969 the oral NLRP3 inhibitor, and plans to submit the Investigational New Drug (IND) application in the fourth quarter of 2025 to begin clinical validation.
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Based on the potential of ISM8969 against neurodegenerative disorders, as demonstrated in pre-clinical studies, the drug candidate will be evaluated as a novel option for Parkinson’s disease (PD) treatment.
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Empowered by Insilico Medicine’s Pharma.AI platform, ISM8969 demonstrated favorable PD/PK profiles, as well as dose-dependent efficacy in motor functions in animal models.
Cambridge, MA – Aug 14, 2025 – Insilico Medicine(“Insilico”), a clinical-stage biotechnology company driven by generative artificial intelligence (AI), today announced that ISM8969, an orally available NLRP3 inhibitor targeting inflammation and neurodegenerative disorders, has completed IND-enabling studies with favorable results. Insilico plans to submit IND application in Q4 this year, aiming to progress the candidate compound into clinical trials as a potential transformative therapy for Parkinson' s disease (PD).
PD is the second most common neurodegenerative disease in the world, resulting in high rates of disability by causing motor and non-motor symptoms including tremor, slow movement, pain, and dementia. According to a recent British Medical Journal research, about 25.2 million of the global population will be living with PD in 2050. As current PD treatments are mainly symptomatic, the strategy of targeting NLRP3 to modulate the inflammatory response, so as to control PD as a chronic inflammation-related disease, could represent a paradigm shift.
“These positive data further strengthen our belief in the potential of ISM8969, as well as the reliability of AI-driven drug discovery method, in the new field of CNS diseases,” says Feng Ren, PhD, Co-CEO and Chief Scientific Officer of Insilico Medicine. “Current treatments often cause adverse effects that limit long-term use and do not address the underlying progression of the disease, and we hope that AI could be the game-changer in the strive for novel and effective solutions.”
In IND-enabling studies, ISM8969 was assessed in PD models, through three behavioral tests reflecting motor abilities: the open field, rotarod, and grip strength. The data demonstrated a highly dose-dependent improvement of motor abilities in mice treated with ISM8969. In the dose of 20 mpk, significant improvements against the disease model was reported, with corresponding attributes approaching the performance of healthy control.
“We are thrilled to reach the milestone of IND-enabling completion, as it marks the beginning of clinical validation for ISM8969. The anti-inflammation strategy against Parkinson’s disease has never before passed the whole process of clinical validation, so the progress of ISM8969 is indeed encouraging,” says Alex Zhavoronkov, PhD, founder and CEO and CBO of Insilico Medicine. “Targeting age-related diseases including PD is a powerful approach to extending healthy longevity, and we hope Insilico can lead the way in breaking new ground and driving meaningful progress.”
ISM8969, an oral, BBB (blood-brain barrier) penetrable NLRP3 inhibitor, was nominated as a preclinical development candidate in December 2024, with the support of Insilico Medicine’s proprietary Pharma.AI platform. In comprehensive preclinical testing, ISM8969 has demonstrated a superior safety profile, balanced druggability profile, potent in vitro activity, and robust in vivo PK/PD characteristics.
In 2016, Insilico first described the concept of using generative AI for the design of novel molecules in a peer-reviewed journal, which laid the foundation for the commercially available Pharma.AI platform. Since then, Insilico keeps 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 22 developmental/preclinical candidates (DC/PCC) in its comprehensive portfolio of over 30 assets since 2021, received IND clearance for 10 molecules, and completed multiple human clinical trials for two of the most advanced pipelines, with positive results announced.
By integrating the technologies of AI and automation, Insilico has demonstrated significant efficiency boost compared to traditional drug discovery methods (often requiring 2.5-4 years), as announced in the recent key timeline benchmarks for internal DC programs from 2021 to 2024: the average time to DC is 12-18 months, with 60-200 molecules synthesized and tested per program.
About Insilico Medicine
Insilico Medicine, a global clinical stage biotechnology company powered by generative AI, is connecting biology, chemistry, medicine and science research 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, central nervous system diseases, infectious diseases, autoimmune diseases, and aging-related diseases. www.insilico.com