Insilico Medicine announced positive topline results from its Phase IIa trial of ISM001-055, a novel drug candidate for Idiopathic Pulmonary Fibrosis (IPF) developed using generative AI. The multi-site trial in China demonstrated significant improvements in lung function, dose-dependent efficacy, and good tolerability across all dosing regimens, positioning ISM001-055 as a potential breakthrough treatment for IPF patients.
Phase IIa Trial Results
The Phase IIa study enrolled 71 IPF patients across 21 sites in China. Participants were administered one of three dosing regimens: 30 mg once daily (QD), 30 mg twice daily (BID), or 60 mg once daily (QD), or a placebo for 12 weeks. The results indicated a 98.4 mL mean improvement in FVC (Forced Vital Capacity) at the highest dose (60mg QD), compared to a mean FVC decline of -62.3 mL in the placebo group. ISM001-055 also demonstrated similar improvements in percent predicted FVC (ppFVC) and meaningful quality-of-life benefits.
Zuojun Xu, M.D., Professor of Peking Union Medical College and the principal investigator in the Phase IIa trial, stated, "I am very impressed by the positive results observed in IPF patients treated with ISM001-055, particularly the encouraging improvement in FVC... [suggesting] its capability to stop or even reverse it."
Targeting TNIK with AI
Insilico's generative AI technology identified TNIK (Traf2- and NCK-interacting kinase) as a key therapeutic target. TNIK activation contributes to pulmonary fibrosis. ISM001-055 inhibits TNIK, potentially offering a disease-modifying therapy. The drug's discovery, design, and development were detailed in Nature Biotechnology in March 2024, with medicinal chemistry findings in the Journal of Medicinal Chemistry in October 2024.
The Need for New IPF Treatments
IPF is a chronic, progressive lung disease affecting approximately 5 million people worldwide, with a median survival of 3-4 years. Current treatments primarily slow disease progression, highlighting the urgent need for disease-modifying therapies. ISM001-055, a first-in-class small molecule, targets TNIK to potentially halt or reverse fibrosis, offering a new approach to treating IPF.
Generative AI in Drug Development
ISM001-055 is the first drug discovered and developed using generative AI to reach this clinical stage. Insilico’s AI engine, Pharma.AI, integrates biology, chemistry, and clinical trial data to accelerate drug development. Since 2016, Pharma.AI has supported the nomination of over 20 preclinical candidates, with nine IND approvals.
"We are thrilled with the positive results from this Phase IIa clinical trial, which underscore the potential of AI to facilitate the development of innovative therapies and improve patient outcomes," said Alex Zhavoronkov, Founder and CEO of Insilico Medicine.
Next Steps
Insilico Medicine plans to initiate regulatory discussions and pursue a pivotal trial of ISM001-055 for IPF. The company will also share full Phase IIa data at upcoming medical conferences and publish it in leading journals. Competitors like Boehringer Ingelheim and GRI Bio are also advancing in the IPF space, but ISM001-055's ability to improve FVC positions it as a unique contender.
