CAMBRIDGE, Mass., July 7, 2026
Insilico Medicine has announced the initiation of its Phase III clinical trial evaluating Rentosertib, a potentially first-in-class oral TNIK inhibitor developed using the company’s generative artificial intelligence (AI)-powered Pharma.AI platform for the treatment of Idiopathic Pulmonary Fibrosis (IPF). The late-stage trial marks a significant milestone not only for Insilico but also for the broader AI-driven drug discovery industry, as Rentosertib represents one of the first investigational medicines to progress into Phase III after an AI-discovered target, AI-designed molecule, and AI-supported clinical development pathway. The decision follows encouraging Phase IIa GENESIS-IPF data demonstrating favorable safety, tolerability, and promising improvements in lung function, while the program’s complete discovery-to-clinic journey has been documented in Nature Biotechnology and Nature Medicine. The initiation of Phase III strengthens the growing role of artificial intelligence in accelerating pharmaceutical innovation and advancing precision therapies for patients with severe age-related fibrotic diseases.
AI-Driven TNIK Inhibitor Advances into Global Late-Stage Development
The Phase III study is a prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial expected to enroll 320 patients with Idiopathic Pulmonary Fibrosis across 47 clinical centers in China. Participants will receive once-daily oral Rentosertib for 52 weeks, allowing investigators to comprehensively evaluate the therapy’s long-term efficacy, safety, and disease-modifying potential. The study’s primary endpoint is the annual rate of decline in Forced Vital Capacity (FVC), the most widely accepted clinical measure of lung function in IPF, while important secondary endpoints include time to disease progression and overall clinical outcomes.
Rentosertib targets Traf2- and Nck-interacting kinase (TNIK), a previously underexplored signaling protein involved in fibrosis, inflammation, extracellular matrix remodeling, and aging-related cellular pathways, including Wnt, TGF-β, Hippo/YAP-TAZ, JNK, and NF-κB signaling. Unlike existing antifibrotic therapies that primarily slow disease progression, Rentosertib was specifically designed to intervene earlier in the biological mechanisms responsible for fibrosis, offering the potential for a more meaningful therapeutic benefit.
Phase II Success Reinforces AI-Powered Drug Discovery Platform
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The launch of Phase III follows positive findings from the GENESIS-IPF Phase IIa clinical trial, a randomized, placebo-controlled study involving 71 patients across 22 clinical sites. The trial successfully met its primary objective of demonstrating manageable safety and tolerability, while the 60 mg once-daily treatment group achieved a mean Forced Vital Capacity improvement of +98.4 mL after 12 weeks, compared with a decline of 20.3 mL in the placebo group. Exploratory biomarker analyses further supported Rentosertib’s anti-fibrotic and anti-inflammatory activity, consistent with TNIK pathway inhibition. Rentosertib represents one of the most advanced examples of end-to-end AI-enabled drug development, with PandaOmics identifying TNIK as a novel therapeutic target through multi-omics and aging biology analysis, Chemistry42 generating the optimized small-molecule inhibitor, and Medicine42 supporting clinical development strategies.
Idiopathic Pulmonary Fibrosis remains one of the most devastating chronic lung diseases, affecting approximately five million people worldwide and carrying a median survival of only three to four years following diagnosis. Current approved therapies can delay disease progression but cannot reverse fibrosis, highlighting the urgent need for innovative treatment approaches. If successful, Rentosertib could become the first AI-designed TNIK inhibitor to reach regulatory approval, demonstrating the transformative potential of generative AI in discovering novel targets, designing differentiated medicines, and accelerating development for complex diseases with high unmet medical needs.
Source: Insilico Medicine press release
