Insilico Medicine Reports Breakthrough Phase IIa Results for AI-Driven IPF Drug ISM001-055

Insilico Medicine announced promising results from a Phase IIa trial of its AI-designed drug, ISM001-055, for IPF. The trial across multiple sites in China demonstrated significant improvements in lung function. Additionally, the drug showed dose-dependent efficacy and was well-tolerated across all dosing regimens. Therefore, ISM001-055 demonstrates strong potential as a breakthrough treatment for IPF patients.

AI-Powered Approach Revolutionizes IPF Treatment Development

Insilico Medicine, a clinical-stage biotech company, reported positive topline results from its Phase IIa trial of ISM001-055. The novel drug candidate targets IPF and was developed using generative AI. ISM001-055 proved safe, well-tolerated, and showed dose-dependent efficacy in improving forced vital capacity (FVC) at 12 weeks. These findings mark a significant step in addressing the unmet needs of IPF patients.

The study enrolled 71 IPF patients across 21 sites in China. Participants received one of three dosing regimens—30 mg once daily (QD), 30 mg twice daily (BID), or 60 mg once daily (QD)—or a placebo for 12 weeks. Results showed a 98.4 mL mean improvement in FVC at the highest dose. This compared to a mean FVC decline of -62.3 mL in the placebo group. Furthermore, ISM001-055 demonstrated a similar improvement in percent predicted FVC (ppFVC) and meaningful quality-of-life benefits.

Insilico’s generative AI technology identified TNIK (Traf2- and NCK-interacting kinase) as a therapeutic target. TNIK activation contributes to pulmonary fibrosis. ISM001-055’s inhibition of TNIK represents a potential breakthrough in disease-modifying therapies.

“I am very impressed by the positive results observed in IPF patients treated with ISM001-055, particularly the encouraging improvement in FVC. It not only reflects ISM001-055’s potential to slow disease progression but also suggests its capability to stop or even reverse it,” said Zuojun Xu, M.D., Professor of Peking Union Medical College and the principal investigator in the Phase IIa trial of ISM001-055 in IPF patients. “AI, as an advanced technology, is already playing a crucial role in many aspects of medical practice, including drug discovery and clinical research, and we expect to see the real clinical benefits it brings to patients.”

ISM001-055: A Breakthrough AI-Developed Treatment for IPF

IPF is a chronic lung disease that progressively worsens, affecting 5 million people globally. With a median survival of 3-4 years, existing treatments only slow disease progression. This creates a critical need for disease-modifying therapies. ISM001-055, a first-in-class small molecule, was developed using generative AI to target TNIK. TNIK activation drives lung fibrosis in IPF, contributing to worsening lung function. ISM001-055 inhibits TNIK to stop or reverse fibrosis, providing a potential disease-modifying treatment for IPF patients.

The drug’s discovery, design, and development, including in-vitro and in-vivo studies, were published in Nature Biotechnology in March 2024. Additionally, the medicinal chemistry findings were reported in the Journal of Medicinal Chemistry in October 2024. Furthermore, insights on TNIK’s role in age-related diseases appeared in Cell Trends in Pharmacological Sciences in June 2024.

In brief, the research showed that Traf2- and Nck-interacting kinase (TNIK) is a key target for anti-fibrotic therapy. The development of INS018_055 demonstrated significant anti-fibrotic and anti-inflammatory effects in preclinical models. The compound exhibited desirable drug-like properties and favorable pharmacokinetics, leading to successful Phase I clinical trials. Moreover, TNIK’s involvement in metabolic signaling and its emerging role in age-related diseases were highlighted. This paves the way for TNIK-targeting therapeutics in cancer, neurodegeneration, and other age-related disorders.

Now, with the promising results of the Phase IIa trial, Insilico plans to initiate regulatory discussions. The company will pursue a pivotal trial of ISM001-055 for IPF. Finally, Insilico will share full Phase IIa data at upcoming medical conferences and publish it in leading journals.

Generative AI’s Role in Accelerating Drug Development

ISM001-055 is the first drug discovered and developed using generative AI to reach this clinical stage. Insilico’s AI engine, Pharma.AI, integrates biology, chemistry, and clinical trial data to expedite the drug development process. Since its inception in 2016, Pharma.AI has supported the nomination of over 20 preclinical candidates, with nine IND approvals.

Founder and CEO of Insilico Medicine, Alex Zhavoronkov, shared how these results showcase the transformative potential of generative AI. “We are thrilled with the positive results from this Phase IIa clinical trial, which underscore the potential of AI to facilitate the development of innovative therapies and improve patient outcomes,” said Zhavoronkov in a statement. “We aim to set industry benchmarks for drug discovery and development using generative AI and commit to pioneering innovative solutions for complex medical challenges.”

Insilico Medicine works in AI-powered biotechnology. The company combines generative AI, deep learning, and machine learning to discover and develop treatments for cancer, fibrosis, and aging-related diseases. Insilico plans to advance ISM001-055 to pivotal trials while engaging with regulatory authorities. Additionally, full Phase IIa data will be presented at an upcoming medical conference. Meanwhile, competitors like Boehringer Ingelheim and GRI Bio are also making strides in the IPF space. However, ISM001-055’s ability to improve FVC positions it as a unique contender.

Author

Bernice Lottering