Insilico Reaches First Clinical Milestone for AI-Developed NLRP3 Inhibitor ISM8969
Thursday, June 18, 2026
Insilico Medicine has completed first-in-human dosing in the Phase I clinical study of ISM8969, marking the first clinical milestone in its co-development partnership with Hygtia Therapeutics. ISM8969 is an orally administered, brain-penetrant small-molecule inhibitor of the NLRP3 inflammasome being developed for the treatment of chronic neuroinflammation and central nervous system disorders, including Parkinson’s disease.
The Phase I trial is a single-centre, randomised, double-blind, placebo-controlled study being conducted in Australia. It includes both single ascending dose (SAD) and multiple ascending dose (MAD) cohorts and is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ISM8969. The study is expected to enrol 80 healthy participants and 20 obese adults who are at risk of cardiovascular disease.
Researchers will also collect cerebrospinal fluid samples to assess the drug’s ability to penetrate the central nervous system and to better understand its pharmacokinetic and pharmacodynamic profile. The findings are expected to support dose selection and future clinical development plans.
ISM8969 targets the NLRP3 inflammasome, a key component of the body's innate immune system. Excessive activation of NLRP3 can trigger chronic inflammation and cell damage, contributing to the progression of neurodegenerative diseases. By inhibiting NLRP3 activity, ISM8969 is designed to reduce harmful inflammation and support neuronal function.
In preclinical studies, the candidate demonstrated favourable safety, pharmacokinetic and pharmacodynamic characteristics, along with anti-inflammatory activity across several disease models. Unlike many advanced NLRP3 inhibitors that are restricted to peripheral tissues, ISM8969 can cross the blood-brain barrier, enabling it to target neuroinflammation within the central nervous system. Based on these results, Insilico selected ISM8969 as a preclinical candidate in December 2024.
To support global development, Insilico entered into an exclusive strategic co-development agreement with Hygtia Therapeutics. Under the partnership, both companies share equal global rights to the programme. Insilico is responsible for the investigational new drug submission and Phase I clinical study and remains eligible for up to $66 million in upfront and milestone payments.
Insilico stated that the advancement of ISM8969 into clinical testing highlights the growing role of artificial intelligence in drug discovery. Since 2021, the company has nominated 31 preclinical candidates, with 13 receiving investigational new drug approval or clearance. The company continues to expand its AI platform capabilities through initiatives such as MMAI Gym, which supports the training and evaluation of scientific AI models for pharmaceutical research and development.
Source: insilico.com/
