image: Insilico managed to achieve additional unique molecules with favorable properties by updating Chemistry42 3.0 with ADMET prediction and reward customization features. In addition, PandaOmics 4.0 was used for expanding indications, discovering potential combination strategies and better patient screening. Following additional preclinical studies, Insilico nominated the novel second-generation inhibitor targeting DGKA for the wholly-owned program in December 2023.
Credit: Insilico Medicine
New York, December 26 2023, Insilico Medicine (“Insilico”), a generative artificial intelligence (AI)-driven clinical-stage drug discovery company, today announced that the company has nominated ISM4525, the second generation of DGKA Inhibitor for the treatment of PD-1/PD-L1 resistance solid tumors, following the nomination of ISM4312A in December 2022 with the support of Pharma.AI, Insilico’s integrated generative AI-driven drug discovery and development platform.
“Although immune checkpoint inhibitors have transformed the treatment landscape for patients with many advanced malignancies, only a part of patients respond, leaving a broad swath of patients who do not derive benefit. ” said Feng Ren, Ph.D. Co-CEO and Chief Scientific Officer of Insilico Medicine. “We are committed to leverage our end-to-end AI platform to discover novel targets to improve therapeutic efficacy in immuno-oncology to address unmet medical needs in cancer.”
In a previous internal study, Insilico utilized the target identification capabilities of PandaOmics, a generative biology software of Pharma.AI platform, to discover that targeting DGKA may be a potentially innovative strategy for overcoming anti-PD-1 resistance and expanding the responder patient population in cancer immunotherapy. The company subsequently designed a series of compounds targeting DGKA with the support of Chemistry42, the generative chemistry software. In December 2022, Insilico nominated the first generation preclinical candidate for the DGKA program after completing multiple in vivo and in vitro preclinical studies.
As the work on the program continues, Insilico managed to achieve additional unique molecules with favorable properties by updating Chemistry42 3.0 with ADMET prediction and reward customization features. In addition, PandaOmics 4.0 was used for expanding indications, discovering potential combination strategies and better patient screening. Following additional preclinical studies, Insilico nominated the novel second-generation inhibitor targeting DGKA for the wholly-owned program in December 2023.
“Chemistry42 3.0 customizable and fully automated software platform integrates generative AI algorithms with computational and medicinal chemistry methods to generate novel molecules with potential drug-like properties, sometimes in a matter of hours. ” said Petrina Kamya, Head of AI Platforms and President of Insilico Medicine Canada, “ Insilico is dedicated to pushing the boundaries of science and technology within the pharma-tech sector. The nomination of a second generation DGKA inhibitor is testament to the capabilities of the advancing generative chemistry and biology AI platforms at Insilico.”
ISM4525 is an orally available DGKA inhibitor with high selectivity in cancer immunotherapy. In preclinical studies, it shows promising anti-tumor in vivo efficacy in multiple syngeneic models with excellent PK and good safety profile. It also displays synergistic effects by combination with immune checkpoint inhibitors that indicates ISM4325 as a potentially effective treatment proposed by Insilico's Pharma.AI platform for non-respondent patients to anti-PD-1/L1 monotherapy. The program is progressing through IND-enabling studies.
“ISM4525 is a wholly owned program developed by Pharma.AI and is currently available for collaboration.” said Michelle Chen, Ph.D. Chief Business Officer of Insilico Medicine, “Pharma.AI has designed first and second-generation DGKA inhibitors efficiently that are structurally novel and have favorable activity and selectivity. In addition, the second generation DGKA inhibitor shows more promising selectivities and significantly improved safety margin in preclinical studies with broad clinical prospects of combination usage."
Driven by generative artificial intelligence, Insilico stands at the intersection of artificial intelligence and state-of-art technologies. The company has developed a comprehensive portfolio of more than 30 pipelines with 5 programs currently in the clinical stage developed using Pharma.AI, an integrated AI-driven drug discovery platform connecting biology, chemistry, and clinical development. The nomination of a second-generation PCC for DGKA program brings the total number of PCCs discovered and developed by Insilico to 16 since 2021.
About Insilico Medicine
Insilico Medicine, a global clinical stage biotechnology company powered by generative AI, 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 for novel target discovery and the generation of 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
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