Rentosertib shows lower predicted biological age across six proteomic aging clocks

Summary

Insilico Medicine announced the publication of a study in Nature Biotechnology showing that its AI-discovered idiopathic pulmonary fibrosis drug candidate rentosertib produced reductions in predicted biological age across six independently developed proteomic aging clocks. The research analyzed longitudinal serum proteomic data collected during a Phase IIa clinical trial of rentosertib in idiopathic pulmonary fibrosis, or IPF. The analysis included 42 patients and measurements covering 2,841 proteins. Researchers applied six independently developed proteomic aging models, including ProtAge, OrganAge, PAC, ipfP3GPT and PAOPAC. Despite differences in model architecture, training data and methodologies, all six indicated a trend toward lower predicted biological age among rentosertib-treated patients compared with placebo. The strongest signal was observed at Week 4 among participants receiving 30 mg of rentosertib twice daily. The study reported an approximately three- to four-year reduction in predicted biological age across certain measures and as much as six years according to one aging clock. The findings remain exploratory and do not establish that rentosertib extends lifespan or reverses human aging. The study instead evaluates changes in proteomic biomarkers that have been developed to estimate biological aging. The work is notable because rentosertib was developed from the outset using artificial intelligence to identify both its therapeutic target and the molecule itself rather than being a previously approved drug repurposed for aging research. Insilico used its AI-powered target discovery platform to identify TNIK as a target associated with both fibrosis and aging biology. The company said TNIK scored highly across six hallmarks of aging, leading researchers to investigate it as a dual-purpose target for IPF and aging-related biological processes. Insilico subsequently used its generative chemistry platform Chemistry42 to design rentosertib, also known as ISM001-055, as a small-molecule inhibitor targeting TNIK. The program progressed from target identification to preclinical candidate nomination in approximately 18 months. Preclinical research on the program was published in Nature Biotechnology, followed by Phase IIa clinical results in Nature Medicine in 2025. The Phase IIa study met its primary safety endpoint and showed a dose-dependent effic…