Insilico Medicine announced positive preliminary results from its Phase IIa clinical trial of ISM001-055, a novel drug designed using generative AI for the treatment of idiopathic pulmonary fibrosis (IPF). The trial met its primary endpoint of safety and tolerability, as well as secondary efficacy endpoints, demonstrating a dose-dependent response in forced vital capacity (FVC), a critical measure of lung function in IPF patients. The results suggest a potential new therapeutic option for this devastating disease, which affects approximately 5 million people worldwide and has a median survival of 3 to 4 years post-diagnosis.
Targeting TNIK with AI
ISM001-055 is a first-in-class small molecule that targets Traf2- and Nck-interacting kinase (TNIK). Insilico's AI platform identified TNIK as a novel therapeutic target in IPF and designed ISM001-055 to inhibit it. TNIK plays a role in pathological fibrosis in the lungs, contributing to the progressive decline in lung function seen in IPF. By inhibiting TNIK, ISM001-055 aims to halt or reverse fibrotic processes. The development of ISM001-055 was detailed in a March 2024 Nature Biotechnology paper, showcasing its preclinical evaluation and positive Phase 0 & Phase I clinical studies.
Phase IIa Trial Design and Results
The Phase IIa study (NCT05938920) was a randomized, double-blind, placebo-controlled trial conducted across 21 sites in China. It enrolled 71 patients with IPF, who were randomized to receive either placebo, 30mg of ISM001-055 once daily (QD), 30mg twice daily (BID), or 60mg QD for 12 weeks. Patient enrollment began in April 2023, and the last subject's follow-up visit was completed in August 2024. A parallel Phase IIa trial (NCT05975983) is ongoing in the U.S.
The study met its primary endpoint of safety and tolerability across all dose levels. Positive results were also reported for the secondary efficacy endpoint, with a dose-dependent FVC improvement observed. The largest improvement in FVC was seen in patients receiving 60mg QD of ISM001-055. Complete topline data will be released at an upcoming medical conference and submitted for publication in a peer-reviewed journal.
Expert Commentary
Toby M. Maher, MD, PhD, a leading expert in interstitial lung disease and an investigator in the trial, stated, "These results are very encouraging, particularly the dose-dependent response in FVC. IPF is a devastating disease, and seeing improvements in lung function over just 12 weeks of treatment is a promising indication that ISM001-055 may provide a new therapeutic option for patients."
Alex Zhavoronkov, PhD, co-CEO of Insilico Medicine, added, "This study result represents a critical milestone in AI-powered drug discovery... While we expected the drug to be safe, we did not expect to see such a clear dose-dependent efficacy signal after such a short dosing period. IPF is a very diverse disease and it is very rare to see improvement in FVC."
Future Directions
Following these positive results, Insilico Medicine plans to engage regulatory authorities to discuss the design of a Phase IIb study. The company aims to explore extended treatment durations and larger patient cohorts to further investigate the therapeutic potential of ISM001-055 in IPF. This includes a continued focus on understanding the dual-action mechanism of INS018_055, which targets both fibrosis and inflammation, potentially addressing gaps left by traditional therapies.
