Insilico's rentosertib inhalation solution receives China IND clearance for IPF

Insilico Medicine (HKEX: 3696) [announced](https://www.prnewswire.com/news-releases/insilicos-rentosertib-inhalation-solution-receives-ind-clearance-for-the-worlds-first-ai-driven-candidate-to-enter-direct-to-lung-clinical-study-302755747.html) that China's Center for Drug Evaluation (CDE) has cleared an investigational new drug (IND) application for an inhalation solution formulation of rentosertib (ISM001-055), its small-molecule TNIK inhibitor in development for idiopathic pulmonary fibrosis (IPF). The clearance allows the company to initiate a Phase I study evaluating the inhaled formulation in healthy volunteers and IPF patients, marking a formulation expansion for a molecule that has already generated Phase IIa oral data. IPF is a chronic, progressive fibrotic lung disease affecting approximately 5 million people worldwide. Median survival after diagnosis is three to four years, and the two antifibrotic agents approved by the US FDA in 2014 — Boehringer Ingelheim's nintedanib (Ofev) and Genentech's pirfenidone (Esbriet) — slow the rate of lung function decline without reversing or halting the underlying fibrotic process. Boehringer Ingelheim's nerandomilast (Jascayd), a preferential phosphodiesterase 4B inhibitor, received FDA approval in October 2025, representing the first new mechanism approved for IPF in over a decade. All three approved agents are administered orally and act systemically, carrying tolerability burdens — particularly gastrointestinal toxicity with nintedanib and pirfenidone — that contribute to dose reductions and treatment discontinuations in clinical practice. Rentosertib (formerly [ISM001-055](https://app.allsci.com/drugs/ASC-DR-0000000031322-1.0-1772718717)) targets TNIK, or TRAF2- and NCK-interacting kinase, a serine/threonine kinase that Insilico identified as a potential antifibrotic target using its generative AI platform, Pharma.AI. The molecule was designed and nominated as a preclinical candidate in approximately 18 months, with fewer than 80 compounds synthesized and tested during the discovery phase. TNIK inhibition is mechanistically distinct from the tyrosine kinase inhibition of nintedanib, the TGF-β pathway modulation of pirfenidone, and the cAMP-elevating mechanism of nerandomilast, placing rentosertib in a class not yet represented among approved IPF therapies. The oral formulation of rentosertib completed a Phase IIa randomized trial, GENESIS-IPF, with results published in [Nature Medicine](https://www.nature.com/articles/s41591-025-03743-2) in June 2025. Insilico has described the trial as showing good tolerability, a favorable pharmacokinetic profile, and dose-dependent improvements in forced vital capacity — the standard measure of lung function decline used as the primary endpoint across IPF trials. The US FDA granted rentosertib Orphan Drug Designation for IPF in February 2023, and China's CDE granted it Breakthrough Therapy Designation in May 2025, a designation that carries expedited review implications under China's regulatory framework. The newly cleared IND covers a Phase I study structured in two parts. The first is a randomized, double-blind, placebo-controlled evaluation in healthy participants using single ascending dose and multiple ascending dose cohorts. The second is a non-randomized, open-label multiple-dose evaluation in IPF patients. Approximately 80 subjects are expected to enroll across both parts. The study is designed to characterize the safety, tolerability, and pharmacokinetic profile of the inhaled formulation — standard objectives for a first-in-human study of a new route of administration for a compound with an existing clinical safety database from the oral program. The rationale for pursuing an inhalation solution in IPF is rooted in the pharmacological logic of direct pulmonary delivery. Inhaled administration can, in principle, achieve higher local drug concentrations in lung tissue at lower total doses than oral systemic dosing, potentially reducing the systemic exposure that drives off-target side effects. Insilico has reported that in preclinical studies, the inhalation solution of rentosertib achieved higher lung exposure with low systemic exposure and demonstrated antifibrotic and anti-inflammatory activity in animal models, alongside acceptable pharmacokinetic and safety profiles. No inhaled antifibrotic agent is currently approved for IPF, and if the inhaled formulation of rentosertib can reproduce the efficacy signals seen with the oral program while improving the tolerability profile, it would occupy a distinct clinical position relative to all three approved agents. Insilico has also stated that the oral rentosertib program remains on track to initiate Phase III trials in the second half of 2026, meaning the company is advancing two formulations of the same molecule in parallel — a strategy that, if both prove viable, could offer clinicians and patients flexibility in dosing route depending on tolerability and disease stage. The CDE clearance is the 13th IND clearance from Insilico's AI-driven pipeline, which spans fibrosis, oncology, immunology, and central nervous system disorders. Rentosertib remains its most clinically advanced internal program and the one carrying the most direct evidence for the company's broader thesis that generative AI can reproducibly identify novel drug targets and design molecules that reach clinical validation. *** This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: [https://allsci.com/news/](https://allsci.com/news/) --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/rentosertib-ind-clearance-insilico-medicines-1)