Insilico's TNIK inhibitor posts +98.4 mL FVC edge, advances to Phase III in IPF
GENESIS-IPF's Phase IIa readout on rentosertib cleared its safety bar and showed a FVC signal versus placebo, and Insilico has now moved the once-daily oral drug into a 320-patient Phase III trial.
Executive Summary
- A completed Phase IIa trial of Insilico Medicine's oral TNIK inhibitor rentosertib in idiopathic pulmonary fibrosis cleared its safety endpoint and showed a lung-function difference against placebo, and the company has now advanced the drug into Phase III.
- The study was designed and registered to measure treatment-emergent adverse events, not lung function, so the efficacy comparison driving the Phase III decision comes from a secondary measure in a small trial.
- No other industry program combines this target with this indication, leaving the asset without an in-class comparator, while the broader IPF field remains built on antifibrotics that slow but do not reverse disease progression.
- The company has committed to a larger, randomized, placebo-controlled trial with a lung-function primary endpoint, which will be the first test of whether the Phase IIa signal holds under a design built to detect it.
The readout
Insilico Medicine disclosed results from its completed GENESIS-IPF Phase IIa study of rentosertib (also known as INS018_055) on July 7, 2026, reporting that the 60 mg once-daily arm showed a mean forced vital capacity (FVC, a measure of lung volume) change of +98.4 mL at 12 weeks, versus -20.3 mL for placebo. The trial, registered as NCT05938920, enrolled 71 adults with idiopathic pulmonary fibrosis (IPF) and FVC between 40% and 80% of predicted normal, and completed in China in September 2024. The company's release calls the drug a first-in-class oral small-molecule TNIK inhibitor and says the discovery-to-clinic path was published in Nature Biotechnology, with the Phase IIa results published separately in Nature Medicine. Insilico+1Insilico Initiates Phase III Clinical Trial for Rentosertib, Its AI-Empowered TNIK Inhibitor for Idiopathic Pulmonary FibrosisJul 7, 2026Study Evaluating INS018_055 Administered Orally to Subjects With Idiopathic Pulmonary Fibrosis (IPF)NCT05938920
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What the trial actually measured
The registered primary endpoint for NCT05938920 was the percentage of participants with at least one treatment-emergent adverse event, a safety measure, not a lung-function comparison. The FVC changes cited in Insilico's release, both the +98.4 mL and -20.3 mL figures, come from a secondary endpoint (relative and absolute change in FVC from baseline), assessed by standardized spirometry across four arms: three dose levels of rentosertib and a placebo group. The study's own posted results describe safety across all four arms as broadly comparable, with one death recorded in the 30 mg twice-daily arm and none in the 60 mg once-daily or placebo arms. Insilico characterizes the overall safety and tolerability as manageable and consistent with the drug's known profile. NCT05938920+1Study Evaluating INS018_055 Administered Orally to Subjects With Idiopathic Pulmonary Fibrosis (IPF)NCT05938920Insilico Initiates Phase III Clinical Trial for Rentosertib, Its AI-Empowered TNIK Inhibitor for Idiopathic Pulmonary FibrosisJul 7, 2026
The Phase III commitment
Insilico has now initiated a prospective, randomized, double-blind, placebo-controlled Phase III trial expected to enroll 320 patients with IPF across 47 centers in China, with an annual rate of FVC decline over 52 weeks set as the primary endpoint. That endpoint structure, a direct lung-function measure over a full year, is the design that will test whether the secondary-endpoint signal from the 71-patient Phase IIa holds up when the trial is built specifically to detect it. Professor Zuojun Xu of Peking Union Medical College Hospital will lead the study, with Academician Nanshan Zhong and Shanghai Pulmonary Hospital President Chang Chen as co-leading investigators. China's Center for Drug Evaluation granted Rentosertib Breakthrough Therapy Designation for IPF in May 2025, ahead of this disclosure. InsilicoInsilico Initiates Phase III Clinical Trial for Rentosertib, Its AI-Empowered TNIK Inhibitor for Idiopathic Pulmonary FibrosisJul 7, 2026
Where it sits in the field
No other industry trial currently pairs the TNIK target with idiopathic pulmonary fibrosis, and rentosertib's own Phase III trial is the only Phase 3 program built around that target in this indication. IPF's existing landscape includes antifibrotics such as pirfenidone and nintedanib, which target different mechanisms (TGF-beta and VEGFR pathways, respectively) and are already established as approved therapies that slow disease progression without reversing it. The absence of an in-class comparator for a TNIK inhibitor in IPF means the Phase III trial will generate the first direct evidence on whether this mechanism can move lung-function decline in a design powered to measure it, rather than a safety-first study reporting a secondary efficacy signal.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.