rentosertib (INS018_055) / Insilico Medicine - LARVOL DELTA

Inhaled Rentosertib (ISM018_055), a Selective TNIK Inhibitor, Improves Lung Function and Reduces Fibrosis and Inflammation in Animal Models of Pulmonary Fibrosis (ATS 2026) - No abstract available

Preclinical • Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Inhaled Rentosertib (INS018_055) Achieves High and Specific Pulmonary Exposure in Healthy And Fibrotic Lungs (ATS 2026) - No abstract available

Clinical • Fibrosis

Study Design of a Phase 1, Randomized, Double Blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of Inhaled Rentosertib (INS018_055) (ATS 2026) - No abstract available

Clinical • P1 data • PK/PD data • Interstitial Lung Disease

Inhaled Rentosertib (INS018_055) Exhibits High Safety and Tolerability in Animal Models (ATS 2026) - No abstract available

Preclinical • Interstitial Lung Disease

Artificial intelligence in the development of Rentosertib: A novel TNIK inhibitor for idiopathic pulmonary fibrosis - A letter to editor. (PubMed, Pulm Pharmacol Ther) - No abstract available

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

Leading artificial intelligence-driven drug discovery platforms: 2025 landscape and global outlook. (PubMed, Pharmacol Rev) - "Key developments since 2024 include positive phase IIa results for Insilico Medicine's Traf2- and Nck-interacting kinase inhibitor, ISM001-055, in idiopathic pulmonary fibrosis...In addition, advancement of the Nimbus-originated tyrosine kinase 2 inhibitor, zasocitinib (TAK-279), into phase III clinical trials exemplifies Schrödinger's physics-enabled design strategy reaching late-stage clinical testing...Robotics tightly integrated with AI now enables self-driving laboratories that accelerate design-make-test-learn cycles and improve reproducibility. Together, these advances chart a forward-looking roadmap in which multimodal foundation models, robotics-led platforms, and hybrid physics-AI strategies are poised to accelerate translation, derisk development, and establish trustworthy AI as a cornerstone of modern drug discovery."

Journal • Review • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • TYK2

Study Evaluating INS018_055 Administered Orally to Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: InSilico Medicine Hong Kong Limited | N=60 ➔ 40

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

GENESIS-IPF: PHASE 2A COHORT CHARACTERISTICS AND LUNG IMAGING INDICATE CORRELATES OF RESPONSE TO ISM001-055 (RENTOSERTIB) IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS (CHEST 2025) - P2 | " High-resolution computed tomography (HRCT) was obtained at baseline (week 0) for 69 of 71 participants in INS018-055-003 (NCT05938920), a randomized, double-blind, placebo-controlled Phase 2a study in patients with IPF conducted at 22 clinical sites in China. The enrollment profile and baseline severity of disease in GENESIS-IPF participants and individual treatment arms is typical of the UK IPF patient population. The timing and methods for evaluating lung function is appropriate, as evidenced by the strong correlation between FVC and lung volume, which aligns with the expected physiological relationship. Changes in FVC and ppFVC from baseline to week 12 suggest that the best outcomes may occur in patients with the lowest level of fibrosis and the highest rentosertib treatment dose."

Clinical • P2a data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • COL1A1 • CTNNB1 • IL10 • MMP10 • TGFB1

Artificial Intelligence in Small-Molecule Drug Discovery: A Critical Review of Methods, Applications, and Real-World Outcomes. (PubMed, Pharmaceuticals (Basel)) - "Notable achievements include baricitinib (BenevolentAI/Eli Lilly, an existing drug repurposed through AI-assisted analysis for COVID-19 and rheumatoid arthritis), halicin (MIT, preclinical antibiotic), DSP-1181 (Exscientia, discontinued after Phase I), and ISM001-055/rentosertib (Insilico Medicine, positive Phase IIa results). We provide practical insights for integrating AI into drug discovery workflows, emphasizing hybrid human-AI approaches and the emergence of agentic AI systems that can autonomously navigate discovery pipelines. A critical evaluation of current limitations and future opportunities reveals that while AI offers significant potential as a complementary technology, realistic expectations and careful implementation are crucial for delivering innovative therapeutics."

Journal • Real-world evidence • Review • Immunology • Infectious Disease • Inflammatory Arthritis • Novel Coronavirus Disease • Rheumatoid Arthritis • Rheumatology

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) - P2 | "These results demonstrate that NCT05938920 has recruited patients whose baseline characteristics are representative of the broader IPF population. They provide promise that the positive results of NCT05938920 could be replicated in an ongoing ISM001_055 trial in the USA (NCT05975983)."

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) - "Figure 1: Change from baseline in FVC ± 95% CI after 12 weeks of treatment (excluding outliers*). *n=1 in placebo group and n=1 in 30mg QD group with >600 mL difference between screening and baseline FVC measurements."

Clinical • Idiopathic Pulmonary Fibrosis • Immunology

Traf2- and Nck-interacting kinase inhibitors: a patent review（2008 - 2024）. (PubMed, Expert Opin Ther Pat) - "Despite over 10 patents disclosing multiple scaffolds since 2008, only one inhibitor, INS018_055, has advanced to clinical trials to treat idiopathic pulmonary fibrosis. For the oncology indications, this is largely due to complexities in the relationship between TNIK and oncogenic pathways. Additionally, key characteristics of the molecules, such as kinase selectivity, physicochemical properties and pharmacokinetic profiles, have played significant roles in determining whether the molecules are drug-like enough to advance to clinical trials."

Journal • Review • CNS Disorders • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • CTNNB1

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