image: The drug candidate is co-developed with Fosun Pharma (600196.SH, 02196.HK) for the treatment of advanced malignant tumors.
Credit: Insilico Medicine
Insilico Medicine ("Insilico"), a generative artificial intelligence (AI)-driven clinical-stage biotechnology company, today announced that the company has initiated the first in patient dose for ISM8207, a potential first-in-class small molecule inhibitor targeting QPCTL. The drug candidate is co-developed with Fosun Pharma (600196.SH, 02196.HK) for the treatment of advanced malignant tumors.
This open-label, multicenter Phase I clinical trial conducted in China aims to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of ISM8207 in patients with lymphoma and other advanced solid tumors (CTR20240727). The dose-escalation Phase I clinical trial will not only explore the recommended dose for the extended study, but also focus on evaluating the safety and efficacy of ISM8207 in patients with lymphoma and other advanced solid tumors.
Glutaminyl-peptide cyclotransferase-like protein (QPCTL) plays a crucial role in the post-translational modification of the "don't eat me" signal protein CD47 which interacts with the signal regulatory protein alpha (SIRPα) on macrophages, helping cancer cell evade immune surveillance. Besides that, QPCTL also post-translationally modifies several chemokines which are associated with immune-suppressive tumor microenvironment.
ISM8027 is a novel, potent, orally bioavailable QPCTL inhibitor. In the early drug discovery stage completed, Insilico Medicine together with Fosun Pharma proposed an oncology target hypothesis and designed the compound with favorable druggability by leveraging Pharma.AI, its generative AI-driven platform. In preclinical studies, ISM8207 demonstrated a significant synergistic anti-tumor effect, as a combination agent, against multiple solid tumor and hematologic malignancy models. It also exhibits a favorable in vitro ADME and in vivo PK profile. The promising data support the further clinical development of ISM8207.
“To our knowledge, ISM8027 is the pioneer QPCTL inhibitors to advance to clinical stage and be dosed in patients with solid tumors or lymphoma.” says Feng Ren, PhD, co-CEO and Chief scientific Officer of Insilico Medicine. “Compared to current strategies that interfere with the CD47-SIRPα signaling pathway, ISM8027 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, holding great promise for the development of novel therapeutics for patients.”
“AI, as a revolutionary tool for discovering innovative drugs, is continuously deepening and expanding its innovation empowerment in the medical field. We are pleased to see the first dosing of ISM8207 in a patient, the first anti-tumor candidate drug jointly developed with Insilico Medicine. This is an important milestone in our collaborative development for innovative medicine,” says Xingli Wang, MD, PhD, CEO of Global R&D Center, and Executive President of Fosun Pharma. “ISM8207 is the First-in-class drug candidate targeting the QPCTL protein. As an innovation-driven pharmaceutical company, Fosun Pharma is committed to addressing unmet medical needs and improving the patient accessibility of safety and effective drugs through continuous innovation and joint efforts with our partners.” Through this collaboration, Fosun Pharma is developing more AI-powered drug candidates against novel targets based on patient needs.
In January 2022, Insilico Medicine announced a strategic collaboration with Fosun Pharma to proceed generative AI-driven drug discovery programs globally. The QPCTL inhibitor is one of the most advanced programs in the framework of the collaboration. In July 2023, ISM8207 received IND approval from CDE with joint efforts from both companies.
Powered by proprietary generative AI platform Pharma.AI, Insilico has nominated 18 preclinical candidates since 2021 in its comprehensive portfolio of over 30 assets, seven molecules of which have received IND approvals. In March 2024, the Company published a paper in Nature Biotechnology that discloses the raw experimental data and the preclinical and clinical evaluation of its lead drug – a potentially first-in-class TNIK inhibitor for the treatment of idiopathic pulmonary fibrosis discovered and designed using generative AI currently in Phase II trials with patients.
About Insilico Medicine
Insilico Medicine, a global clinical-stage biotechnology company powered by generative AI, connects biology, chemistry, and clinical trial analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques for novel target discovery and generating novel molecular structures with desired properties. Insilico Medicine is developing breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system diseases, infectious diseases, autoimmune diseases, and aging-related diseases. www.insilico.com
About Fosun Pharma
Founded in 1994, Shanghai Fosun Pharmaceutical (Group) Co., Ltd.* ("Fosun Pharma"; stock code: 600196. SH, 02196. HK) is a global innovation-driven pharmaceutical and healthcare industry group. Fosun Pharma directly operates businesses including pharmaceuticals, medical devices, medical diagnosis, and healthcare services. As a shareholder of Sinopharm Co., Ltd., Fosun Pharma expands its areas in the pharmaceutical distribution and retail business.
Fosun Pharma is patient-centered and clinical needs-oriented. The company continuously enriches its innovative product pipeline through independent research and development, cooperative development, license-in, and in-depth incubation. Fosun Pharma improves the research and clinical development capabilities of FIC (First-in-class) and BIC (Best-in-class) new drugs as well as accelerates the R&D and launch of innovative technologies and products. Fosun Pharma’s innovative products mainly covered core therapeutic areas such as tumors (solid tumors and hematologic tumors), immunology, central nervous system, and chronic diseases (liver disease/metabolism/kidney disease).
Guided by the 4IN strategy (Innovation, Internationalization, Intelligentization, and Integration), Fosun Pharma will uphold the development model of “Innovation Transformation, Integrated Operation and Steady Growth", with the mission of creating shareholder values through strengthening its independent R&D and external cooperation and enriching its product pipelines, as well as promoting the global networks and enhancing operational efficiency. Fosun Pharma will actively promote key business and rapidly enhance operational and asset efficiency, and is committed to becoming a first-class enterprise in the global major pharmaceutical and healthcare market.
For more information, please visit our official website: www.fosunpharma.co