What You Should Know:
- InSilico Medicine, a clinical-stage company utilizing generative artificial intelligence (AI) for drug discovery, reveals the development of an orally bioavailable preclinical candidate compound. This compound targets KIF18A and aims to treat advanced solid tumors characterized by TP53 mutation.
- The development is particularly significant for high-grade serous ovarian cancer (HGSOC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC).
Advancing Cancer Therapeutics with Innovative AI-Driven Strategies
Chromosomal instability (CIN) is a defining characteristic of cancer, resulting from persistent errors in chromosome segregation during cell division. KIF18A, a motor protein essential for mitosis, has emerged as a potential target for therapeutic intervention in CIN-related cancers. ISM9682, a highly selective inhibitor of KIF18A developed by InSilico Medicine, demonstrates promising preclinical efficacy. Through the utilization of Chemistry42, InSilico’s generative chemistry engine, ISM9682 was identified from a series of novel macrocyclic structures.
Preclinical studies reveal ISM9682’s broad anti-tumor activity across HGSOC, TNBC, and NSCLC CIN cell lines, along with favorable pharmacokinetic properties and safety profile. InSilico plans to explore combination therapies with DNA repair inhibitors like Olaparib and expand into wider indications. Leveraging AI and human expertise, InSilico has established a robust pipeline, with 17 preclinical candidates nominated since 2021 and five progressing to clinical stages. The company has also secured major global out-licensing agreements, including partnerships with Exelixis and Menarini in 2023. Furthermore, InSilico introduced significant updates to its Pharma.AI platform in November 2023, featuring the innovative Copilot feature, enhancing the synergy between large language models and proprietary AI frameworks.
“Targeting KIF18A to inhibit CIN cancers is an emerging therapeutic strategy in drug discovery with broad clinical prospects,” said Feng Ren, PhD, co-CEO and Chief Scientific Officer of Insilico Medicine. “It is exciting that our team discovered a distinct molecule with desirable safety and promising efficacy using Chemistry42. As the IND-enabling study progresses, we are looking forward to identifying the best indication and advancing the program to the clinical stage.”
