By Allison Proffitt 

July 8, 2026 | Insilico Medicine is launching a phase III clinical program for rentosertib, its potentially first-in-class oral small-molecule inhibitor of TNIK (TRAF2- and NCK-interacting kinase) for the treatment of idiopathic pulmonary fibrosis (IPF), a progressive, age-related fibrotic lung disease with high unmet medical need. It is the next step in making AI-discovered drugs a reality for patients.  

“It’s a major milestone for the company and my life as well,” CEO Alex Zhavoronkov told press assembled for a briefing yesterday. “If we outperform the standard of care and show a disease modifying effect with this drug, it’s going to be the first and only of its kind.”  

Rentosertib was discovered and designed through Insilico’s Pharma.AI platform. In a Nature Biotechnology (DOI: 10.1038/s41587-024-02143-0) paper, TNIK was reported as the top-ranked candidate in the protein and receptor kinase discovery scenario, representing a previously underexplored target class for IPF compared with the receptor tyrosine kinase biology addressed by existing antifibrotic drugs. Later, phase IIa clinical results were published in Nature Medicine (DOI: 10.1038/s41591-025-03743-2) and presented at the American Thoracic Society (ATS) 2025 International Conference. 

“Usually AI helps you significantly to accelerate preclinical R&D to go from zero to developmental candidate. Our records are 9-18 months to go from zero to this developmental candidate,” Zhavoronkov said. “But after that, you’re moving with the speed of traffic.”  

Stepping into Traffic 

For all of Insilico’s innovation in AI target identification, generative chemistry, and robotics laboratories, the phase III clinical trial is surprisingly traditional. Carol Satler, Vice President of Clinical Development at Insilico, joined the company in late 2024 to advance non-oncology programs. In the briefing yesterday, she described the phase III program as a “randomized, double-blind, placebo-controlled parallel group study.”  

The study will run 52 weeks with 320 patients who are older than 40 years, have been diagnosed with idiopathic pulmonary fibrosis (IPF), and have restricted lung volume as measured by force-vital capacity.  

Insilico sketched out a timeline that included first patient enrolled by September 2025, last patient enrolled by November 2028, with initial results expected by December 2029, a potential NDA by March 2030 and approval by September 2030. Patients in the study who would like to continue on the drug past 52 weeks would have the option for a long-term open label extension trial until NDA.  

Satler predicted about 50 sites would be needed to fully enroll the trial.  

Gateway Indications to Aging Biology 

The drug’s initial indication, IPF, is a chronic, progressive lung-scarring disease that disproportionately affects older adults. As fibrosis accumulates, lung tissue becomes stiff and scarred, making breathing increasingly difficult and leading to irreversible decline in lung function. The median survival after diagnosis is commonly reported at approximately two to four years, and there remains a substantial need for disease-modifying treatments that can meaningfully alter the clinical course. 

Zhavoronkov calls this the “gateway indication” for rentosertib. “Our hope is that if we get the drug approved in a specific area, it may be expanded in terms of indications into other disease,” he explained “For TNIK, we identified this target at the end of 2019, prioritized it for IPF, but we saw IPF as a window into many other diseases and now we have a portfolio of therapeutics with different molecular properties targeting this specific protein.”  

Zhavoronkov’s ultimate indication is aging on the whole. Insilico starts with disease biology of aging to identify targets tied to “aging clocks” including methylation, proteomics and transcriptomics. TNIK is one of those targets, and Zhavoronkov predicts it could be implicated in more than 60 indications. “It looks like a longevity target to us, but in order to prove the point we need to perform multiple experiments.”  

Many of those experiments will be in silico, but the IPF phase III study will also gather proteomic data from enrolled participants both to reveal how rentosertib is working and also to show what other indications are likely to be available for this specific drug and target. “If we win this particular race, we’ll would be able to expand into many, many indications,” Zhavoronkov said.