Insilico Doses First Patient in GENESIS-IPF-3, the First Phase III Trial of a Generative AI-Discovered Drug
核心洞察
Insilico Medicine (搜索) dosed the first patient with Rentosertib (搜索) in the Phase III GENESIS-IPF-3 trial for idiopathic pulmonary fibrosis (搜索) at Peking Union Medical College Hospital.
The 52-week randomized, double-blind, placebo-controlled study will enroll 320 patients across 47 centers in China, with FVC decline as the primary endpoint.
Rentosertib (搜索) is a potentially first-in-class small molecule targeting TNIK (搜索), a fibrosis pathway identified through AI-driven discovery and never previously linked to fibrosis.
Insilico Medicine (搜索) (HKEX: 3696) has dosed the first patient with Rentosertib (搜索) (ISM001-055 / INS018_055) in GENESIS-IPF-3, a Phase III clinical trial (NCT07687459, CTR20262475) in idiopathic pulmonary fibrosis (搜索) (IPF). The first patient was dosed at Peking Union Medical College Hospital, while Shanghai Pulmonary Hospital enrolled its first patient on the same day. The company describes GENESIS-IPF-3 as the world's first Phase III trial of a generative AI-driven innovative drug.
Trial Design and Endpoints
GENESIS-IPF-3 is a prospective, multi-center, randomized, double-blind, placebo-controlled, parallel-group study designed to systematically evaluate the efficacy and safety of once-daily Rentosertib (搜索) administered over 52 weeks. The trial is expected to enroll a total of 320 participants across 47 centers in China.
The primary endpoint is the annual rate of decline in forced vital capacity (FVC) over 52 weeks. The key secondary endpoint is time to first occurrence of any disease progression event. According to Insilico, the trial is intended to assess whether Rentosertib (搜索) can provide clinically meaningful benefit in a larger patient population and over a longer treatment period than the Phase IIa study.
The study is led by Professor Zuojun Xu of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, as Leading Principal Investigator, with Academician Nanshan Zhong of the Chinese Academy of Engineering and President Chang Chen of Shanghai Pulmonary Hospital serving as Co-Leading Principal Investigators.
Validating Phase IIa Findings Over 52 Weeks
Professor Zuojun Xu framed the dosing milestone in the context of the program's origins: "TNIK (搜索), the target driven by AI, had never previously been linked to fibrosis. This perhaps indicates that AI is carving out a path distinct from traditional research paradigms in target discovery for complex diseases."
He added that preliminary findings in the 12-week Phase IIa study showed promising results, including improvements in lung function among patients with IPF, and that the Phase III study is designed to validate those findings in a larger cohort treated for a longer duration of 52 weeks. On timelines, he noted that "from initiating Phase III to obtaining final regulatory approval, it will take three to four years under favorable conditions."
Carol Satler, MD, PhD, Senior Vice President for Clinical Development, Non-Oncology at Insilico Medicine (搜索), said: "I believe Rentosertib (搜索) will be transformative to patient care in the field of IPF, and AI has enabled this breakthrough with higher speed and reduced cost, which could make a lot of difference in the future of drug discovery." She added that with the first patient dosed, the company hopes to "further validate the favorable findings observed in Phase IIa study, and to witness the rapid translation of a scientific concept into potential patient benefit in record time."
Mechanism and Regulatory Status
Rentosertib (搜索) is a potentially first-in-class small molecule targeting TNIK (搜索) developed utilizing generative AI. In IPF, activation of TNIK drives pathological fibrosis in the lungs, contributing to the progressive decline in lung function. By inhibiting TNIK, Rentosertib aims to halt or reverse fibrotic processes, offering a disease-modifying treatment for patients with IPF. The U.S. Food and Drug Administration (搜索) granted Orphan Drug Designation to Rentosertib for IPF in February 2023. The drug remains investigational and has not been approved by any regulatory authority.
The program's discovery-to-clinic development was published in Nature Biotechnology, its Phase IIa clinical results in Nature Medicine, and its medicinal chemistry in the Journal of Medicinal Chemistry. In 2024, a Nature Biotechnology publication demonstrated the AI-driven early discovery process of Rentosertib (搜索); in 2025, a Nature Medicine study reported Phase IIa results demonstrating a promising dose-dependent efficacy trend. Most recently, in 2026, a Nature Biotechnology study revealed a consistent reduction in biological age after Rentosertib dosage across six independent biological aging clocks.
Disease Burden and Unmet Need
IPF is a chronic, scarring lung disease characterized by a progressive and irreversible decline in lung function. It affects approximately 5 million people worldwide and carries a poor prognosis, with a median survival of 3 to 4 years. Current approved treatments, including antifibrotic drugs, can slow disease progression but do not stop or reverse it, leaving a significant unmet need for more effective, disease-modifying therapies.
Pipeline Productivity and Commercial Momentum
Insilico nominated nine development candidates within nine months of 2026 as of late August, setting a new company record for annual pipeline productivity, and achieved eight clinical milestones across its proprietary and co-developed programs. The company also launched a comprehensive set of benchmarks allowing foundation models to be evaluated across all tasks needed for drug discovery, alongside state-of-the-art foundation models that outperformed other models and internal tools in benchmarks.
Commercially, Insilico reported total revenue of approximately $106 million in the first half of 2026, a 287% year-over-year increase, and achieved its first profitable half-year since listing, with an adjusted net profit exceeding $51 million. The company attributed the milestone to out-licensing, co-development, and R&D collaborations with global partners including Eli Lilly, Servier, Takeda, SK Biopharmaceuticals (搜索), Qilu Pharmaceutical (搜索), Hygtia Therapeutics (搜索), CMS, and Tenacia (搜索). Total contract value of transactions announced in 2026 reached approximately $7.3 billion, pushing the cumulative contract value of its major collaborations since 2021 to approximately $11 billion. Insilico listed on the Main Board of the Hong Kong Stock Exchange on December 30, 2025.