Following the publication of its latest study in Nature Biotechnology, Insilico Medicine founder and CEO Alex Zhavoronkov, Ph.D., took the stage at Sorbonne University during the Nature AI Conference on Redefining Healthcare in the Age of AI to deliver a detailed presentation of the breakthrough findings.

Addressing an audience of global research leaders, clinical investigators, and biopharma innovators, Zhavoronkov detailed how the company’s AI-driven novel drug candidate, rentosertib (ISM001-055), achieved a unanimous reversal of biological age across six independent proteomic aging clocks in a Phase IIa clinical trial.

Inside the Nature Biotechnology Findings

Introduced during the conference’s AI and Drug Discovery session, Zhavoronkov presented the newly published Nature Biotechnology study, describing it as "probably the most important paper in my life so far". The presentation expanded on key findings from the 12-week Phase IIa trial in idiopathic pulmonary fibrosis (IPF) patients.

The clinical evaluation centered on longitudinal serum proteomic data collected from 42 idiopathic pulmonary fibrosis (IPF) patients across 2,841 proteins. Six proteomic aging clocks—including ProtAge, OrganAge, PAC, ipfP3GPT, and PAOPAC, independently developed by academic groups at Harvard, Oxford, Peking University, and Insilico—unanimously confirmed that patients treated with rentosertib experienced a significant reduction in predicted biological age compared to placebo. Peak age reversal occurred at Week 4 in the 30 mg twice-daily cohort, demonstrating an average biological age reduction of three to four years, with specific clocks recording reversals of up to six years.

The presentation also highlighted a key biological insight: rentosertib’s geroprotective effects operate partially independent of its primary disease indication. While the 60 mg once-daily dose yielded the highest numerical improvement in Forced Vital Capacity—reversing lung function decline with a mean increase of +98.4 mL compared to a -20.3 mL decline in placebo—the 30 mg twice-daily regimen produced the strongest age-reversal signal. Mechanistically, rentosertib acts as a potent senomorphic agent, downregulating key senescence drivers such as MMP10, MMP13, SPP1, and growth factor pathways including RTK–PI3K and RAS–ERK.

Redefining Dual-Purpose Therapeutics

Addressing the commercial and regulatory bottlenecks in longevity research, Zhavoronkov outlined Insilico’s core business model: developing dual-purpose therapeutics. By targeting fundamental aging pathways to treat severe, highly regulated clinical indications (such as IPF, fibrosis, and oncology), Insilico secures patent protection and regulatory clarity while simultaneously advancing geroprotective medicines.

"Rather than repurposing old generic drugs where there’s no commercial incentive to invest, we use AI to discover novel, on-patent molecules that address age-related diseases first, while evaluating their potential to combat aging at a systemic level," Zhavoronkov explained.

To support scientific transparency and future research, the team has deposited all trial proteomic data at the China National Center for Bioinformation (CNCB accession: OMIX008341) and released the underlying analytical pipeline code as an open-source Python library on GitHub. This work establishes a standardized blueprint for embedding geroscience endpoints into disease-focused clinical trials aligned with FDA Biomarker Qualification and NIH BEST guidelines.

"Aging-First" Business Model & Commercial Scale

Insilico's dual-purpose therapeutic strategy is also proving its viability as a sustainable commercial model.

Recently, 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. This milestone was driven by a series of out-licensing, co-development, and R&D collaborations with global partners, including Eli Lilly, Servier, Takeda, SK Biopharmaceuticals, Qilu Pharmaceutical, Hygtia Therapeutics, CMS, and Tenacia. As of the latest practicable date, the total contract value of transactions announced by Insilico in 2026 reached approximately $7.3 billion, pushing the cumulative contract value of its major collaborations since 2021 approximately $11 billion.

On the AI-driven R&D front, Insilico nominated nine development candidates within nine months of 2026 as of late August, setting a new company record for annual pipeline productivity and achieving eight clinical milestones across its proprietary and co-developed programs. Leading this progress is rentosertib (ISM001-055), the world's first drug candidate discovered and developed using generative AI, which has advanced to a Phase III trial evaluating for idiopathic pulmonary fibrosis (IPF).

In addition, Insilico Medicine launched a comprehensive set of benchmarks that allow foundation models to be evaluated in all tasks needed for drug discovery and launched state of the art (SOTA) foundation models outperforming other models and even internal tools in benchmarks. Using this new capability Insilico hopes to expand and accelerate longevity drug discovery and development both in terms of scale, therapeutic modalities, and indications.

Reference

[1] Zhavoronkov, A., Galkin, F., Chen, S. et al. Integration of proteomic aging clocks in a phase 2a clinical trial supports simultaneous geroprotective assessment. Nat Biotechnol (2026). https://doi.org/10.1038/s41587-026-03286-y

[2] Ren, F., Aliper, A., Chen, J. et al. A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models. Nat Biotechnol 43, 63–75 (2025). https://doi.org/10.1038/s41587-024-02143-0

[3] Xu, Z., Ren, F., Wang, P. et al. A generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial. Nat Med 31, 2602–2610 (2025). https://doi.org/10.1038/s41591-025-03743-2

Rentosertib is a potentially first-in-class small molecule targeting TNIK, developed using Insilico Medicine's generative AI platform Pharma.AI. TNIK was identified through AI-powered target discovery as a gene involved in six hallmarks of aging, making it a dual-purpose target for both aging biology and idiopathic pulmonary fibrosis (IPF). The drug's discovery, design, preclinical validation, and Phase I results were published in Nature Biotechnology in March 2024. Phase IIa results were published in Nature Medicine in June 2025. Rentosertib has entered Phase III clinical development in China.

Idiopathic Pulmonary Fibrosis is a chronic, scarring lung disease characterized by progressive and irreversible decline in lung function. Affecting approximately 5 million people worldwide, IPF carries a poor prognosis with a median survival of 3–4 years. Current approved treatments can slow disease progression but cannot stop or reverse it, leaving a significant unmet need for disease-modifying therapies.

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