- Following positive Phase IIa results for the oral formulation of Rentosertib in the GENESIS-IPF study, which demonstrated good tolerability, favorable pharmacokinetic (PK) profile, and a dose-dependent efficacy trend, the inhaled formulation of Rentosertib has also received IND approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA), paving the way for clinical-stage studies.
- The nebulized inhaled formulation of Rentosertib is designed for direct pulmonary delivery, aiming to achieve faster onset of action and higher local bioavailability at lower doses, while reducing systemic exposure and associated side effects.
- The nebulized inhaled formulation of Rentosertib is the 13th project in Insilico Medicine’s AI-driven pipeline to receive IND approval, further demonstrating the scalability of innovative molecules discovered by the Pharma.AI platform as they advance from preclinical to clinical validation.
The nebulized inhaled formulation of Rentosertib is the 13th project in Insilico Medicine’s AI-driven pipeline to receive IND approval, further demonstrating the scalability of innovative molecules discovered by the Pharma.AI platform as they advance from preclinical to clinical validation.
This IND approval pertains to an upcoming Phase I clinical study designed to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of the nebulized inhaled formulation of Rentosertib. The study consists of two parts: Part 1 is a randomized, double-blind, placebo-controlled trial in healthy subjects, including single ascending dose (SAD) and multiple ascending dose (MAD) cohorts; Part 2 is a non-randomized, open-label assessment in patients with idiopathic pulmonary fibrosis (IPF). A total of approximately 80 subjects are expected to be enrolled.
First ‘AI Drug’ Combines Formulation Innovation: Insilico Medicine’s Rentosertib Inhaled Formulation Receives Clinical Trial Approval
Dr. Feng Ren, Co-CEO and Chief Scientific Officer of Insilico Medicine, stated, “We are pleased that the IND application for the nebulized inhaled formulation of Rentosertib has been approved by the CDE. In previous clinical studies, the oral formulation of Rentosertib demonstrated good tolerability, a favorable PK profile, and a dose-dependent efficacy trend, which further strengthens our confidence in its mechanism of action and clinical potential. We look forward to the nebulized inhaled formulation of Rentosertib again showing positive clinical results in both healthy subjects and patient populations. The inhaled formulation is designed for targeted pulmonary delivery, aiming to achieve higher lung exposure and faster onset of action at lower doses, while reducing systemic exposure and optimizing the benefit-risk ratio. At the same time, we are continuing to advance the clinical development of the oral formulation of Rentosertib, with the Phase III clinical trial still expected to commence in the second half of this year as planned.”
Inhalation administration is an innovative and complex drug delivery method that requires the combination of drug and device, presenting high technical barriers. Inhaled formulations are considered one of the most effective routes of administration for chronic respiratory diseases, delivering drugs directly to the target organ via steam or aerosol through specialized devices, offering advantages such as rapid onset, high bioavailability, low effective dose, fewer side effects, non-invasiveness, and strong targeting.
The preclinical inhaled candidate developed by Insilico Medicine delivers Rentosertib directly to the lungs, thereby reducing the required drug amount and consequently lowering potential side effects, achieving rapid and effective therapeutic effects at the lesion site. In preclinical studies, the nebulized inhaled formulation of Rentosertib achieved high lung exposure and low systemic exposure, and demonstrated anti-fibrotic and anti-inflammatory efficacy in animal models. Additionally, the nebulized inhaled formulation of Rentosertib showed a favorable PK and safety profile, as well as good stability.
Dr. Alex Zhavoronkov, Founder and CEO of Insilico Medicine, stated, “This CDE clinical approval for the nebulized inhaled formulation of Rentosertib once again validates Insilico Medicine’s sustainable, scalable, and reproducible drug discovery innovation driven by our proprietary AI technology. It not only efficiently covers the entire process from target discovery to clinical development but also transcends formulation types and geographical boundaries. To date, we have successfully nominated 30 preclinical candidate compounds (PCCs), with the latest one originating in the UAE, a region where no innovative drug development had previously occurred. At the same time, Insilico Medicine has initiated three Phase II clinical trials and received IND approvals for 13 projects, covering areas such as fibrosis, oncology, immunology, and central nervous system disorders.”
Insilico Medicine has established AI-driven drug discovery collaborations with several leading international companies, including Eli Lilly, Hengtai Biotechnology, Qilu Pharmaceutical, Kangzhe Pharmaceutical, TaiGen Biotechnology, ASKA Pharmaceutical, YuanYi Biologics, Fosun Pharma, and Sanofi, achieving significant R&D milestones in multiple collaborations. By deeply integrating advanced generative AI with automation technology, Insilico Medicine has significantly improved the efficiency of early-stage drug R&D in practical applications, setting a benchmark for AI-driven drug discovery. Compared to the traditional early-stage drug R&D cycle, which typically takes 4.5 years, Insilico Medicine nominated over 20 preclinical candidate compounds between 2021 and 2024, with an average time of 12–18 months from project initiation to PCC nomination, synthesizing and testing approximately 60–200 molecules per project.
About IPF
Idiopathic pulmonary fibrosis is a chronic, progressive pulmonary fibrotic disease characterized by progressive and irreversible decline in lung function. IPF affects approximately 5 million people worldwide and has a poor prognosis, with a median survival of only 3 to 4 years. Current treatments include anti-fibrotic drugs, which can slow disease progression but cannot halt or reverse the disease process, highlighting the urgent need for more effective disease-modifying therapies.
About Rentosertib
The early drug discovery and development of Rentosertib was completed in just 18 months, with fewer than 80 molecules synthesized and tested. Supported by AI-powered target identification and molecular design, its early discovery phase was significantly shortened compared to traditional drug R&D cycles. This AI-driven workflow was published in Nature Biotechnology in March 2024. More importantly, Rentosertib achieved positive results in the GENESIS-IPF Phase IIa clinical trial, marking the world’s first proof-of-concept for efficacy in AI-driven drug discovery, with the results published in Nature Medicine in June 2025.
About Insilico Medicine
Insilico Medicine is a global pioneer biotechnology company dedicated to integrating artificial intelligence and automation technologies to accelerate drug discovery and drive innovation in the life sciences, empowering people to live longer, healthier lives. On December 30, 2025, the company was listed on the Main Board of the Hong Kong Stock Exchange under the stock code 03696.HK.
Utilizing its proprietary Pharma.AI platform and advanced automated biology laboratories, Insilico Medicine is providing innovative drug solutions for unmet medical needs in areas such as fibrosis, oncology, immunology, pain, obesity, and metabolic disorders. Additionally, Insilico Medicine continues to expand the application of Pharma.AI to diverse fields, including advanced materials, agriculture, nutritional products, and veterinary medicine. For more information, please visit the website www.insilico.com.