Insilico's Rentosertib Inhalation Solution Receives IND Clearance for the World's First AI-Driven Candidate to Enter Direct-to-Lung Clinical Study

• Following positive Phase IIa results for oral Rentosertib in GENESIS-IPF with good tolerability, a favorable PK profile, and dose-dependent efficacy improvements, the inhalation solution has received IND clearance from the CDE.
• The inhalation solution is designed for targeted lung delivery to achieve rapid onset and high local bioavailability at lower doses, while reducing systemic exposure and related side effects.
• Rentosertib inhalation solution is the 13th program from Insilico's AI-driven pipeline to receive IND clearance, further demonstrating how Pharma.AI could reproducibly drive the discovery and development of novel molecules from preclinical development to clinical validation.

CAMBRIDGE, Mass., April 28, 2026 /PRNewswire/ -- Insilico Medicine ( "Insilico", HKEX:3696 ), a clinical-stage, generative AI–driven drug discovery company, today announced that the inhalation solution of Rentosertib (ISM001-055), the company's first-in-class drug candidate with AI-identified novel target and AI-developed molecule structure, received IND clearance from CDE. Notably, Rentosertib inhalation solution is the 13th program from Insilico's AI-driven pipeline to receive IND clearance, further demonstrating how Pharma.AI could reproducibly drive the discovery and development of novel molecules from preclinical development to clinical validation.

The IND clearance supports a Phase I study to evaluate the safety, tolerability, and pharmacokinetic (PK) profiles of Rentosertib inhalation solution. The study will consist of two parts: (1) a randomized, double-blind, placebo-controlled Phase I trial in healthy participants involving single ascending dose (SAD) and multiple ascending dose (MAD) cohorts; and (2) a non-randomized, open-label evaluation in patients with Idiopathic Pulmonary Fibrosis (IPF) receiving multiple doses. Approximately 80 subjects are expected to be enrolled.

"We are pleased to receive CDE IND approval for Rentosertib inhalation solution." says Feng Ren, Ph.D., Co-CEO and CSO of Insilico Medicine. "In prior clinical studies, oral Rentosertib showed good tolerability, a favorable PK profile, and dose-dependent efficacy trend, strengthening our confidence in its mechanism and clinical potential. We look forward to seeing the Rentosertib inhalation solution deliver positive clinical results again in both healthy volunteers and patient populations. The inhalation solution is designed for targeted lung delivery, with the goal of achieving higher pulmonary exposure and faster onset at lower doses while reducing systemic exposure and optimizing the benefit–risk profile. In parallel, we continue to advance the oral Rentosertib program and remain on track to initiate Phase III trials in the second half of this year."

Administration by inhalation is a complex drug delivery technology that requires combining formulation and devices, presenting higher technical barriers. Inhalation solutions deliver treatment as vapor or aerosol through special devices into the respiratory tract (i.e. the target organ), which is considered one of the most efficient routes of drug delivery as it may provide advantages including rapid action onset, high bioavailability, lowered effective dose and reduced side effects with a noninvasive and targeted route of administration.

In preclinical studies, the inhalation solution of Rentosertib was able to achieve higher lung exposure with low systemic exposure and demonstrated antifibrotic and anti-inflammatory efficacy in animal models. Moreover, it showed good pharmacokinetic (PK) and safety profiles, as well as good stability and solubility.

"The CDE IND clearance for the Rentosertib inhalation solution further validates Insilico Medicine's sustainable, scalable, and reproducible AI-driven drug discovery and development workflow." says Alex Zhavoronkov, Ph.D., Founder and CEO of Insilico Medicine. "With our proprietary AI models, we empower the whole process from target discovery to clinical development, expanding into formulation types and geographic areas. To date, we have successfully nominated 30 preclinical candidate compounds (DC/PCC), with the latest emerging from the UAE, a country with no prior history of innovative drug development. At the same time, Insilico Medicine has initiated three Phase II clinical trials and achieved IND clearance for 13 programs across fibrosis, oncology, immunology, and central nervous system disorders."

Insilico Medicine has established AI-driven drug discovery partnerships with global leading companies, including Eli Lilly, Hygtia Therapeutics, Qilu Pharmaceutical, CMS, TaiGen, ASKA Pharma, Tenacia, Fosun Pharma, and Sanofi, and has achieved important R&D milestones across multiple collaborations. By integrating advanced AI and automation technologies, Insilico Medicine has demonstrated significant efficiency improvements in practical applications, setting a benchmark for AI-driven drug research and development. Compared to the typical 4.5 years required in traditional drug discovery, Insilico's 20+ nominated candidate drugs from 2021 to 2024 took only 12–18 months on average to progress from project initiation to nomination of preclinical candidates (PCCs), with each project requiring synthesis and testing of only about 60–200 molecules.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, scarring lung disease characterized by a progressive and irreversible decline in lung function. Affecting approximately 5 million people worldwide, IPF 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.

Rentosertib is a potentially first-in-class small-molecule TNIK inhibitor, discovered and developed with the support of Insilico's proprietary generative AI platform, Pharma.AI. The FDA granted Orphan Drug Designation(ODD) to Rentosertib for the treatment of IPF in February 2023. The CDE granted Breakthrough Therapy Designation (BTD) to Rentosertib in May 2025.

Rentosertib's early drug discovery and development process was completed in 18 months with less than 80 small molecules synthesized and tested. This dramatically shortens traditional R&D timeline through AI-enabled target identification and molecule design. The AI-driven workflow was reported in  Nature Biotechnology in March 2024. More importantly, Rentosertib achieved the world's first proof-of-concept for the efficacy of AI-driven drug discovery with the positive results demonstrated in the GENSIS-IPF Phase IIa trial, and the results were published in Nature Medicine in June 2025.

About Insilico Medicine

Insilico Medicine is a pioneering global biotechnology company dedicated to integrating artificial intelligence and automation technologies to accelerate drug discovery, drive innovation in the life sciences, and extend healthy longevity to people on the planet. The company was listed on the Main Board of the Hong Kong Stock Exchange on December 30, 2025, under the stock code 03696.HK.

By integrating AI and automation technologies and deep in-house drug discovery capabilities, Insilico is delivering innovative drug solutions for unmet needs including fibrosis, oncology, immunology, pain, and obesity and metabolic disorders. Additionally, Insilico extends the reach of Pharma.AI across diverse industries, such as advanced materials, agriculture, nutritional products and veterinary medicine. For more information, please visit www.insilico.com

SOURCE Insilico Medicine