CAMBRIDGE, Mass., June 3, 2025 — Insilico Medicine, a clinical-stage biotechnology company powered by generative AI, today announced promising Phase IIa trial results for Rentosertib (ISM001-055), its AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis (IPF). The findings were published in Nature Medicine (Impact Factor: 58.7) and presented at the 2025 American Thoracic Society (ATS) International Conference.
Groundbreaking Efficacy Data
The GENESIS-IPF trial (Generative AI Enabled Novel Experimental Study of ISM001-055 in Subjects with IPF), a randomized, double-blind, placebo-controlled Phase IIa study, enrolled 71 IPF patients across 22 sites in China. Participants received one of the following: placebo, 30 mg Rentosertib once daily (QD), 30 mg twice daily (BID), or 60 mg QD for 12 weeks.
Key findings:
- Patients on 60 mg QD Rentosertib demonstrated the greatest improvement in lung function, with a mean FVC increase of +98.4 mL.
- In contrast, the placebo group showed a mean decline of -20.3 mL in FVC.
- Safety and tolerability were consistent across groups, with most adverse events (AEs) mild to moderate and serious AEs rare—all resolved upon discontinuation.
AI-Powered Discovery Validated
Rentosertib is the first AI-designed drug to show clinical proof-of-concept in a randomized trial. Developed via Insilico’s Pharma.AI platform, it targets TNIK (Traf2- and Nck-interacting kinase)—a novel, AI-identified driver of fibrosis.
“This study marks a transformative moment for AI in drug discovery. It validates the ability of generative AI not just to identify novel targets, but to create molecules that show real-world clinical benefit,”
- Alex Zhavoronkov, PhD, Founder and CEO, Insilico Medicine.
Exploratory Biomarker Validation
Exploratory biomarker analyses confirmed Rentosertib’s mechanism of action:
- Significant reductions in profibrotic proteins (e.g., COL1A1, MMP10, FAP)
- Increased levels of anti-inflammatory marker IL-10
- Protein changes correlated with improvements in FVC
“These findings validate TNIK as a novel target and Rentosertib’s disease-modifying potential in IPF,”
- Dr. Zuojun Xu, Professor, Peking Union Medical College and Lead Investigator.
Clinical and Industry Significance
IPF affects ~5 million people globally, with a median survival of 3–4 years. Current treatments only slow disease progression. Rentosertib may offer a first-in-class, disease-modifying therapy that not only slows but potentially reverses fibrosis.
“IPF remains a major unmet medical need. Rentosertib offers real hope for meaningful improvement in patients' lives,”
- Dr. Zuojun Xu, Professor, Peking Union Medical College and Lead Investigator.
Insilico is now engaging with global regulatory agencies to initiate larger Phase IIb/III trials.
Insilico’s AI Pipeline: Efficiency Redefined
From 2021–2024, Insilico nominated 22 preclinical candidates in 12–18 months each, far surpassing industry norms of 2.5–4 years. Its success rate from PCC to IND-enabling studies stands at 100%, with only 60–200 compounds synthesized per program.
About Rentosertib (ISM001-055)
A TNIK inhibitor discovered through generative AI, Rentosertib interrupts fibrotic signaling in the lungs. It may halt or reverse fibrosis progression. Its discovery and preclinical development were detailed in Nature Biotechnology (March 2024).
About Idiopathic Pulmonary Fibrosis (IPF)
IPF is a chronic, progressive lung disease marked by irreversible lung scarring. Approved therapies offer limited benefit, underscoring the urgent need for novel, disease-modifying agents.
About Insilico Medicine
Insilico Medicine is a global clinical-stage biotechnology company that integrates AI with biology, chemistry, and medicine. It leverages cutting-edge platforms for novel target discovery, molecular design, and clinical development across oncology, fibrosis, neurology, infectious and age-related diseases.
