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Insilico Medicine Initiates Phase I Clinical Trial for Novel QPCTL Inhibitor

Insilico Medicine, a biotechnology company specializing in generative artificial intelligence, has begun dosing patients in the first clinical trial for ISM8207, a small molecule inhibitor targeting QPCTL. This drug candidate, co-developed with Fosun Pharma, is being tested for its efficacy in treating advanced malignant tumors.

The Phase I clinical trial, taking place in China, is an open-label, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ISM8207 in patients with lymphoma and other advanced solid tumors. The trial, registered under CTR20240727, aims to establish the recommended dose for future studies while assessing the drug’s safety and effectiveness.

ISM8207 is designed to inhibit Glutaminyl-Peptide Cyclotransferase-Like Protein (QPCTL), a protein involved in the post-translational modification of the “don’t eat me” signal protein CD47. This modification allows cancer cells to evade the immune system by interacting with signal regulatory protein alpha (SIRPα) on macrophages. QPCTL also modifies chemokines that contribute to an immune-suppressive tumor microenvironment. By inhibiting QPCTL, ISM8207 may disrupt these modifications, thereby enhancing the immune system’s ability to recognize and attack cancer cells.

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Developed using Insilico’s generative AI platform, Pharma.AI, ISM8207 has shown promising preclinical results. These studies demonstrated significant synergistic anti-tumor effects when used in combination with other therapies against multiple solid tumors and hematologic malignancies. The drug also displayed favorable in vitro ADME (absorption, distribution, metabolism, and excretion) and in vivo pharmacokinetic (PK) profiles.

Dr. Feng Ren, co-CEO and Chief Scientific Officer of Insilico Medicine, highlighted the significance of ISM8207’s progression to clinical trials.

“Compared to current strategies that interfere with the CD47-SIRPα signaling pathway, ISM8207 potentially provides a better margin of safety. It not only can enhance immune recognition and attack against cancer cells, but also potentially enhance the anti-cancer efficacy of various standard-of-care therapies.”

The collaboration between Insilico Medicine and Fosun Pharma began in January 2022, focusing on AI-driven drug discovery. ISM8207, which received Investigational New Drug (IND) approval from the Chinese Center for Drug Evaluation (CDE) in July 2023, is one of the most advanced projects under this partnership.

Insilico Medicine has a robust pipeline powered by its Pharma.AI platform, with 18 preclinical candidates nominated since 2021. Seven of these molecules have received IND approvals. In March 2024, the company published a paper in Nature Biotechnology detailing the experimental data and evaluations of its lead drug, a TRAF2- and NCK-interacting kinase (TNIK) inhibitor for idiopathic pulmonary fibrosis, which is currently in Phase II trials.

Novel Therapeutics