Insilico Medicine Receives IND Approval from FDA for ISM8969, an AI-empowered Potential Best-in-class NLRP3 Inhibitor

• Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) paves the way for ISM8969 clinical study in the United States. The Phase I clinical trial aims to evaluate safety, tolerability, and pharmacokinetics profiles.
• ISM8969 is a novel oral therapeutic candidate developed through Insilico's Pharma.AI, with best-in-class potential, unique brain penetrant traits, and favorable druggability profiles demonstrated in preclinical studies.
• Insilico Medicine has entered into a co-development collaboration agreement with Hygtia Therapeutics, with both parties each holding 50% of the global rights and interests to the program. In return, Insilico is eligible to receive up to $66 million in upfront and milestone payments.

CAMBRIDGE, Mass., Jan. 23, 2026 /PRNewswire/ -- Insilico Medicine (3696.HK), a clinical-stage drug discovery and development company driven by generative artificial intelligence (AI), today announced that ISM8969, an orally available NLRP3 inhibitor targeting inflammation and neurodegenerative disorders, has recently received investigational new drug (IND) clearance from the U.S. Food and Drug Administration (FDA), intended for the treatment of Parkinson's Disease. 

The Phase I clinical trial plans to evaluate the safety, tolerability, and pharmacokinetics of ISM8969 in healthy volunteers, and to identify the optimal dose level(s) to be recommended for further investigation.

"NLRP3 has emerged as a key contributor to chronic neuroinflammation and disease progression in neurodegenerative disorders. A novel NLRP3 inhibitor, ISM8969 with the desired brain penetrant property made possible via our AI-powered design process, offers the potential to advance Parkinson's Disease treatment to the next generation," says Carol Satler, MD, PhD, Senior Vice President for Clinical Development, Non-Oncology, Insilico Medicine. "We are excited to get the greenlight from FDA to advance this novel therapeutic to human clinical trials, and we hope to induce a genuine paradigm shift with AI breakthrough in novel drug discovery." 

Excessive activation of NLRP3 triggers overproduction of pro-inflammatory cytokines and chemokines, resulting in sustained inflammation and tissue damage. By inhibiting NLRP3, ISM8969 aims to modulate this pathological inflammation, supporting neuronal survival and function among patients with neurodegenerative diseases. In December 2024, ISM8969 was nominated as an orally administered, potential best-in-class preclinical candidate targeting NLRP3.

It is worth noting that ISM8969 was discovered and optimized using Insilico's Chemistry42, the comprehensive generative chemistry engine consisting of multiple applications across the drug design and discovery stages. More importantly, with the ability to cross the blood-brain barrier and reach the central nervous system (CNS) directly, ISM8969 establishes its distinctive advantage against CNS disorders including Parkinson's Disease, apart from a balanced druggability profile and efficacy against inflammation in both inflammatory and chronic disease mice 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 both parties each holding 50% of the global rights and interests to the program. In return, Insilico is eligible to receive up to $66 million in upfront and milestone payments.

Based on its comprehensive portfolio empowered by Pharma.AI, Insilico has achieved dozens of collaborations with global leading pharma companies including Sanofi, Lilly, Exelixis and Menarini, and the three key license-out deals sum up to a maximum total contract value of up to US $2.1 billion.

Harnessing state-of-the-art AI and automation technologies, Insilico has significantly improved the efficiency of preclinical drug development, setting a benchmark for AI-driven drug R&D. While traditional early-stage drug discovery typically requires 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) nomination—of just 12 to 18 months per program, with only 60 to 200 molecules synthesized and tested in each program.

About Insilico Medicine

Insilico Medicine is a pioneering global biotechnology company dedicated to integrating artificial intelligence and automation technologies to accelerate drug discovery, drive innovation in the life sciences, and extend healthy longevity to people on the planet. The company was listed on the Main Board of the Hong Kong Stock Exchange on December 30, 2025, under the stock code 03696.HK.

By integrating AI and automation technologies and deep in-house drug discovery capabilities, Insilico is delivering innovative drug solutions for unmet needs including fibrosis, oncology, immunology, pain, and obesity and metabolic disorders. Additionally, Insilico extends the reach of Pharma.AI across diverse industries, such as advanced materials, agriculture, nutritional products and veterinary medicine. For more information, please visit www.insilico.com

SOURCE Insilico Medicine