rentosertib (INS018_055) / Insilico Medicine - LARVOL DELTA

Comparison of the baseline clinical and HRCT characteristics of Insilico's ISM001_055 phase 2a trial cohort in China with real-world IPF datasets (ERS 2025) - No abstract available

Clinical • P2a data • Real-world • Real-world evidence • Idiopathic Pulmonary Fibrosis

Rentosertib, a generative AI-discovered TNIK inhibitor improves lung function in IPF patients (ERS 2025) - No abstract available

Clinical • Idiopathic Pulmonary Fibrosis

Insilico Medicine Announces Nature Medicine Publication of Phase IIa Results Evaluating Rentosertib, the Novel TNIK Inhibitor for Idiopathic Pulmonary Fibrosis (IPF) Discovered and Designed with a Pioneering AI Approach (PRNewswire) - P2a | N=71 | GENESIS-IPF (NCT05938920) | Sponsor: InSilico Medicine Hong Kong Limited | "The results demonstrated that Rentosertib exhibited a manageable safety and tolerability profile, with similar rates of treatment-emergent adverse events (TEAEs) observed across all treatment groups, thereby meeting the primary endpoint. Most adverse events (AEs) were mild to moderate in severity, and serious adverse events (SAEs) were rare. Notably, all adverse events resolved following discontinuation of treatment. Promising outcomes were also observed for the secondary efficacy endpoint, with a dose-dependent improvement in forced vital capacity (FVC), the gold-standard metric assessing lung function in IPF patients. Patients receiving 60 mg QD Rentosertib showed the greatest mean improvement in lung function, with a mean FVC increase of +98.4 mL, compared to a mean decline of -20.3 mL in the placebo group."

P2a data • Idiopathic Pulmonary Fibrosis

A generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial. (PubMed, Nat Med) - P2 | "These results suggest that targeting TNIK with rentosertib is safe and well tolerated and warrants further investigation in larger-scale clinical trials of longer duration. ClinicalTrials.gov registration number: NCT05938920 ."

Journal • P2a data • Cough • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Biomarker Analysis Reveals Antifibrotic and Anti-inflammatory Signatures in Idiopathic Pulmonary Fibrosis Patients Treated With INS018_055, an AI-discovered TNIK Inhibitor, in a 12-week Phase 2a Study (ATS 2025) - P2 | " Serum samples were collected from 43 of the 71 participants in INS018-055-003 (NCT05938920), a randomized, double-blind, placebo-controlled Phase IIa study in patients with IPF conducted at 22 clinical sites in China. We identified candidate biomarkers that assess and predict early therapeutic response in patients with IPF treated with INS018_055. These findings suggest dual antifibrotic and immunomodulatory mechanisms of action. Further validation of these biomarkers will be performed in our ongoing Phase 2 study conducted in the US (NCT05975983)."

Biomarker • Clinical • Late-breaking abstract • P2a data • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • COL1A1 • CTNNB1 • CXCL12 • IL10 • IL7 • LTBP2 • LY9 • MMP10 • TGFB1

INS018-055, A Novel Traf2- and NCK-interacting Kinase (TNIK) Inhibitor, Improves Lung Function in Patients With Idiopathic Pulmonary Fibrosis: Results From a Randomized, Double-blind, Placebo-controlled Phase 2a Study (ATS 2025) - P2 | "Patients with % predicted FVC > 40%, FEV1/FVC ratio >0.7 and DLCO ≥ 25% and < 80% were randomized 1:1:1:1 at baseline to receive 30 mg INS018-055 QD (n=18), 30 mg INS018-055 BID (n=18), 60 mg INS018-055 QD (n=18) or placebo (n=17) orally for 12 weeks, with or without background anti-fibrotic therapy (pirfenidone or nintedanib). These results suggested that INS018-055 is well-tolerated in IPF patients and demonstrated a dose-dependent effect in lung function improvement within 12 weeks, supporting further development of INS018-055 in larger Phase 2b trials. Figure 1: Descriptive summary of FVC change from baseline at week 12, box plot, mean (SD)"

Clinical • P2a data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Insilico Medicine Announces Upcoming Presentations at the 2025 American Thoracic Society International Conference (Citybizlist) - "Insilico Medicine...announced the company will present an oral presentation and three scientific posters at the American Thoracic Society (ATS) 2025 International Conference, taking place May 16-21, 2025, in San Francisco, California....All presentations will focus on exploring the potential of rentosertib (INS018_055), a novel TNIK inhibitor developed using Insilico’s generative AI approach, for the treatment of idiopathic pulmonary fibrosis (IPF)."

P2a data • Idiopathic Pulmonary Fibrosis

Insilico Medicine's Class 1 new drug ISM001-055 is planned to be included in the breakthrough therapy category [Google translation] (new.qq.com) - "On April 28, the CDE official website showed that the Class 1 new drug INS018-055 tablets submitted by Insilico Biologics is planned to be included in the breakthrough therapy category for the treatment of idiopathic pulmonary fibrosis (IPF). It is worth mentioning that this drug is the world's first TNIK inhibitor to enter the clinical stage."

Breakthrough therapy • Idiopathic Pulmonary Fibrosis

AI-Driven Robotics Laboratory Identifies Pharmacological TNIK Inhibition as a Potent Senomorphic Agent. (PubMed, Aging Dis) - "These findings reveal TNIK's previously unappreciated role in cellular senescence and INS018_055's senomorphic potential in mitigating processes well-established as driving organismal aging. Thus, TNIK inhibition as a novel senomorphic strategy may inform future therapeutic approaches for diverse aging-related diseases."

Journal • Fibrosis • TGFB1

Insilico Medicine Announces Positive Topline Results of ISM001-055 for the Treatment of Idiopathic Pulmonary Fibrosis (IPF) Developed Using Generative AI (PRNewswire) - P2 | N=71 | NCT05938920 | Sponsor: InSilico Medicine Hong Kong Limited | "The results demonstrate that ISM001-055 is safe, well-tolerated, exhibits a favorable pharmacokinetics (PK) profile, and has encouraging clinical efficacy as measured by improvement in forced vital capacity (FVC) at 12 weeks....ISM001-055 was well-tolerated across all dosing groups. The majority of the drug-related adverse events were mild or moderate in severity. The most common ISM001-055-related adverse events were diarrhea (14.8%) and abnormal liver function (14.8%)....Improvement in quality of life (QoL) and functional measures were also evaluated by change in Leicester Cough Questionnaire (LCQ) score from week 0 to week 12, with a meaningful 2-point improvement in LCQ total score in the highest dose of 60 mg QD group compared to the placebo group by week 12."

P2a data • Idiopathic Pulmonary Fibrosis • Pulmonary Disease • Respiratory Diseases

Discovery of Bis-imidazolecarboxamide Derivatives as Novel, Potent, and Selective TNIK Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis. (PubMed, J Med Chem) - "The lead optimization efforts culminated in the discovery of the recently reported compound 4 (INS018_055), a novel TNIK inhibitor...Results from multiple cell-based and animal models proved that compound 4 exhibits considerable antifibrotic and anti-inflammatory efficacy. Currently, phase II clinical trials of compound 4 are underway for the treatment of idiopathic pulmonary fibrosis (IPF)."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

IPF treatment ISM001-055 safe, improves lung function, data show (Pulmonary Fibrosis News) - P2 | N=71 | NCT05938920 | Sponsor: InSilico Medicine | "The IPF treatment's dose-dependent response in FVC was 'particularly' encouraging, said Toby M Maher, MD, PhD...'Seeing improvements in lung function over just 12 weeks of treatment is a promising indication that ISM001-055 may provide a new therapeutic option for patients,' Maher said."

Media quote • P2a data • Idiopathic Pulmonary Fibrosis • Pulmonary Disease

AI-Driven Drug Discovery Achieves Milestone with Insilico Medicine’s Phase IIa Success in Treating Pulmonary Fibrosis (Unite.AI) - "Leading IPF expert Dr. Toby M. Maher noted, 'IPF is a devastating disease, and seeing improvements in lung function over just 12 weeks of treatment is a promising indication that ISM001-055 may provide a new therapeutic option for patients.'"

Media quote • P2a data • Idiopathic Pulmonary Fibrosis • Pulmonary Disease

Insilico Medicine Reports Positive Phase IIa Results for ISM001-055, a Novel First-in-Class Drug Treatment for Idiopathic Pulmonary Fibrosis (IPF) Designed Using Generative AI (PRNewswire) - "'These results are very encouraging, particularly the dose-dependent response in FVC. IPF is a devastating disease, and seeing improvements in lung function over just 12 weeks of treatment is a promising indication that ISM001-055 may provide a new therapeutic option for patients. Our Phase IIa in the U.S. is actively recruiting patients,' said Toby M. Maher, MD, PhD..."

Media quote • P2a data • Idiopathic Pulmonary Fibrosis

Study Evaluating INS018_055 Administered Orally to Subjects with Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2 | N=71 | Completed | Sponsor: InSilico Medicine Hong Kong Limited | Active, not recruiting ➔ Completed

Trial completion • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Insilico Medicine Reports Positive Phase IIa Results for ISM001-055, a Novel First-in-Class Drug Treatment for Idiopathic Pulmonary Fibrosis (IPF) Designed Using Generative AI (PRNewswire) - P2a | N=71 | NCT05938920 | Sponsor: InSilico Medicine Hong Kong Limited | "Insilico Medicine...announced positive preliminary results from its Phase IIa clinical trial evaluating ISM001-055. ISM001-055 is a first-in-class small molecule targeting TNIK (Traf2- and Nck-interacting kinase) and was designed utilizing generative AI to treat idiopathic pulmonary fibrosis (IPF). The study met both its primary endpoint of safety and its secondary efficacy endpoints, demonstrating dose-dependent response in forced vital capacity (FVC), a critical measure of lung function in IPF patients....A parallel Phase IIa(NCT05975983) clinical trial in the U.S. is ongoing and actively enrolling patients....Complete topline data will be released at the upcoming medical conference and clinical trial results will be submitted for publication in a peer-reviewed journal."

Enrollment status • P2a data • Idiopathic Pulmonary Fibrosis • Pulmonary Disease

Study Evaluating INS018_055 Administered Orally to Subjects With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2 | N=70 | Active, not recruiting | Sponsor: InSilico Medicine Hong Kong Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models. (PubMed, Nat Biotechnol) - P1 | "Using AI-driven methodology, we generated INS018_055, a small-molecule TNIK inhibitor, which exhibits desirable drug-like properties and anti-fibrotic activity across different organs in vivo through oral, inhaled or topical administration...A separate phase I trial in China, CTR20221542, also demonstrated comparable safety and pharmacokinetic profiles. This work was completed in roughly 18 months from target discovery to preclinical candidate nomination and demonstrates the capabilities of our generative AI-driven drug-discovery pipeline."

Clinical • Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Study Evaluating INS018_055 Administered Orally to Subjects With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: InSilico Medicine Hong Kong Limited | Phase classification: P2a ➔ P2

Phase classification • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Study Evaluating INS018_055 Administered Orally to Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: InSilico Medicine Hong Kong Limited | Not yet recruiting ➔ Recruiting | Phase classification: P2a ➔ P2

Enrollment open • Phase classification • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Launch of Insilico’s Phase II Program Highlights Generative AI Momentum (BioSpace) - "INS018_055, a potentially first-in-class anti-fibrotic small molecule inhibitor, is being evaluated to treat idiopathic pulmonary fibrosis (IPF). The first patients have been dosed in the Chinese cohort, while enrollment in the U.S. is expected to begin in the second half of this year with a target of 60 subjects across both countries."

Trial status • Idiopathic Pulmonary Fibrosis • Pulmonary Disease • Respiratory Diseases

Study Evaluating INS018_055 Administered Orally to Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2a | N=60 | Not yet recruiting | Sponsor: InSilico Medicine Hong Kong Limited

New P2a trial • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Study Evaluating INS018_055 Administered Orally to Subjects With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2a | N=60 | Recruiting | Sponsor: InSilico Medicine Hong Kong Limited

New P2a trial • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Phase 1, Evaluate the Safety, Tolerability, and Pharmacokinetics of INS018_055 in Healthy Subjects (clinicaltrials.gov) - P1 | N=78 | Completed | Sponsor: InSilico Medicine Hong Kong Limited | Recruiting ➔ Completed

Trial completion • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Insilico’s AI Candidate for IPF Doses First Patient in Phase II (Genengnews) - "Insilico Medicine has dosed the first patient in a Phase II trial of its lead pipeline candidate INS018_055, a small molecule inhibitor treatment for idiopathic pulmonary fibrosis (IPF) that was discovered and designed using generative artificial intelligence (AI)....Following the cohort studies, Insilico plans to assess INS018_055 in larger populations by recruiting 60 participants with IPF at about 40 sites in both China and the U.S. The company expects to have topline results from the studies available next year."

P2 data • Trial status • Idiopathic Pulmonary Fibrosis • Pulmonary Disease • Respiratory Diseases