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Insilico Medicine Announces Advancement of Its Preclinical Candidate for USP1 Synthetic Lethality Target to IND-enabling Studies for Various Oncological Disorders


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Insilico Medicine

13 Apr, 2022, 15:00 GMT

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Insilico Medicine Nominates Its USP1 Small Molecule Inhibitor as a Preclinical Candidate for Tumors with Homologous Recombination Deficiency

NEW YORK, April 13, 2022 /PRNewswire/ -- Insilico Medicine ("Insilico"), a clinical-stage end-to-end artificial intelligence (AI)-driven drug discovery company today announced that the company completed the experimental validation of AI-designed molecules with the desired properties and nominated the preclinical candidate (PCC) for anti-cancer therapies targeting ubiquitin-specific protease 1 (USP1), a known synthetic lethality target.

Synthetic lethality is a promising area of cancer therapy, it is a well-established genetic approach to exploit vulnerabilities in tumor cells to induce tumor cell death while sparing normal cells. It opens a new path for the development of cancer treatment for patients with cancer-specific mutations by targeting synthetic lethal targets.

Insilico's candidate compound is an orally available and selective small molecule inhibitor of USP1, which plays an essential role in the cellular response to DNA damage by deubiquitinating specific proteins in the Fanconi Anemia (e.g., FANCD2) and Translesion Synthesis pathways (e.g., PCNA). In homologous recombination deficient-(HRD) tumors, USP1 inhibition could induce cell cycle arrest and cell apoptosis. The synthetic lethality between USP1 and HRD is due to persistent monoubiquitinated PCNA/FANCD2.

Insilico's PCC molecule demonstrated potential when targeted against a broad range of tumor lineages with HRD backgrounds. In vitro data showed potent anti-proliferation activity of the compound in BRCA-mutant tumor cells with excellent selectivity. In vivo efficacy studies in CDX and PDX models showed strong anti-tumor activity and robust, durable tumor regression both in monotherapy group and when combined with Olaparib. Insilico has initiated  Investigational New Drug (IND) enabling study of the compound to advance this internally developed program to the clinical stage.

"We are glad to see our AI engine enabled the rapid discovery of a preclinical candidate for the USP1 program, and this achievement again demonstrated the power of AI in drug R&D," said Feng Ren, Ph.D., Chief Scientific Officer of Insilico Medicine. "We will continue to utilize our AI platform to further strengthen our pipelines in synthetic lethality in both compound generation, novel target identification and validation."

The company launched its AI-designed program targeting USP1 in June 2021, relying on the synergy between its powerful AI platform and strong internal drug discovery expertise enabled Insilico to achieve the PCC nomination in only 9 months with less than eighty compounds synthesized and tested starting from the project initiation. The novel structure of the compound was designed and optimized through Insilico's proprietary AI platform, Chemistry42, which utilizes generative adversarial network (GAN) technology to advance small molecule generation.

"The nomination of the preclinical candidate for USP1 synthetic lethality target strengthens our growing oncology pipeline,"  said Alex Zhavoronkov, PhD, Founder and CEO of Insilico Medicine. "There are very few promising molecules targeting USP1 and our AI-designed molecule is highly differentiated with many desired properties embedded during the generation stage, which were confirmed experimentally. We are very happy to see how the Chemistry42 next-generation AI platform, which we provide to our partners, accelerates our own drug discovery efforts."

Insilico has rapidly developed its portfolio of AI-discovered therapeutics of novel targets with novel structures and AI-designed therapeutics of known targets with desired properties.In the past 12 months, Insilico has delivered six preclinical candidates discovered and designed using its AI platform including one for the QPCTL immuno-oncology target in partnership with Fosun Pharma. It also successfully completed a Phase 0 microdose trial and entered a Phase I clinical trial with its first internally developed program for fibrosis.

About Insilico Medicine

Insilico Medicine, a clinical stage end-to-end artificial intelligence (AI)-driven drug discovery company, is connecting biology, chemistry, and clinical trials 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 to discover novel targets and to design novel molecular structures with desired properties. Insilico Medicine is delivering breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system (CNS) diseases and aging-related diseases.

For more information, visit www.insilico.com.

For media inquiries, please contact media@insilicomedicine.com.

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