Insilico Medicine Announces Positive Phase IIa Results for AI-Designed IPF Drug ISM001-055

Insilico Medicine, a clinical-stage biotechnology company utilizing generative AI for drug discovery, recently announced promising preliminary results from a Phase IIa clinical trial of ISM001-055. This novel small molecule drug targets TNIK (Traf2- and Nck-interacting kinase) and was specifically designed for treating idiopathic pulmonary fibrosis (IPF) through the application of generative AI. The Phase IIa study successfully met its primary safety endpoint and its secondary efficacy endpoints, exhibiting a dose-dependent response in forced vital capacity (FVC) among IPF patients—a crucial lung function metric.

The development process of ISM001-055, from target identification to molecular design, was facilitated by Insilico's proprietary AI platform. Detailed in a March 2024 Nature Biotechnology paper, this process identified TNIK as a novel therapeutic target for IPF. The paper included comprehensive preclinical evaluations and positive results from Phase 0 and Phase I clinical studies, highlighting ISM001-055's potential as a disease-modifying agent for IPF.

The Phase IIa trial (NCT05938920) was a randomized, double-blind, placebo-controlled study conducted in China, involving 71 IPF patients across 21 sites. Participants were randomly assigned to receive either a placebo, 30mg once daily (QD), 30mg twice daily (BID), or 60mg QD over a 12-week period. The trial commenced in April 2023, with the last follow-up visit concluded in August 2024. Concurrently, a parallel Phase IIa trial (NCT05975983) is underway in the U.S., actively recruiting patients.

The 12-week study affirmed ISM001-055's safety and tolerability across all dosage levels. Additionally, a dose-dependent improvement in FVC was observed, with the highest improvement seen in patients receiving 60mg QD of ISM001-055. Complete topline data is anticipated to be presented at an upcoming medical conference and will be submitted for publication in a peer-reviewed journal.

Dr. Toby M. Maher, a leading expert in interstitial lung disease and an investigator in the trial, expressed optimism over the results. He highlighted the significance of observing improvements in lung function within a short treatment period, suggesting ISM001-055 could offer a new therapeutic option for IPF patients. Michael Levitt, a Nobel Laureate in Chemistry, emphasized the extraordinary nature of achieving both safety and efficacy in a Phase IIa study, marking a pivotal moment in AI-powered drug discovery.

Renowned geneticist Charles Cantor and Professor Alan Aspuru-Guzik also commended the study's outcomes, emphasizing the drug's efficacy and the potential for future positive results in extended trials. Alex Zhavoronkov, co-CEO of Insilico Medicine, and Feng Ren, co-CEO and CSO, highlighted the milestone's significance, attributing the success to the capabilities of their generative AI platform and the dedicated efforts of their multidisciplinary R&D team.

Following these positive results, Insilico Medicine plans to engage with regulatory authorities to design a Phase IIb study. This next phase will explore extended treatment durations and larger patient cohorts to further investigate ISM001-055's therapeutic potential in IPF.

ISM001-055 is positioned as a first-in-class small molecule targeting TNIK, leveraging generative AI. In IPF, TNIK activation drives pathological lung fibrosis, leading to a decline in lung function. By inhibiting TNIK, ISM001-055 aims to halt or reverse these fibrotic processes, potentially offering a disease-modifying treatment for IPF patients. In February 2023, ISM001-055 received Orphan Drug Designation from the FDA for treating IPF.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease marked by progressive and irreversible lung function decline. Affecting around 5 million people globally, IPF has a poor prognosis, with a median survival of 3 to 4 years. Current treatments slow disease progression but do not stop or reverse it, highlighting the urgent need for more effective therapies. Typically diagnosed in older adults, IPF is an age-related disease, rarely seen in individuals under 50.

Insilico Medicine integrates biology, chemistry, and clinical trial analysis through advanced AI systems to develop innovative drugs for various diseases, including cancer, fibrosis, and aging-related conditions.