Dr. Li Xing was invited to present at 2024 ESMO Targeted Anticancer Therapies Congress

The 2024 ESMO Targeted Anticancer Therapies Congress was successfully held in Paris, France, on February 26-28, 2024,hosted by the European Society of Medical Oncology (ESMO), focusing on the most cutting-edge oncology research and discovery, and is one of the most influential oncology conferences in the world. Dr. Li Xing, founder and CEO of LexBio, was invited to attend the conference and presented “HIGHLYPOTENT AND SELECTIVE RET INHIBITORS THAT OVERCOME ADAPTIVE DRUG RESISTANCE” in the ESMO TAT 2024, it’s the first time that LexBio had disclosed the preclinical trial data of the next generation RET inhibitors.

We discovered this inhibitor by leveraging the AI platform KINET, which was independently developed by LexBio. We employ the synergistic advantages of domain expertise and modern technology to accelerate early stage drug discovery. On our deep learning (DL) centric AI platform, extensive scientific computing supports large scale virtual screening, generative design, drug property prediction and multi-objective lead optimization. On the KINET platform, only the optimized candidate compounds are passed along for synthesis and testing to save time and cost.

In cell proliferation assays, our compound effectively inhibited KIF5B-RET Ba/F3 WT, V804M, G810S, G810R, V804M-G810S with IC50 values of 0.4 nM, 1.3 nM,   1.1 nM, 3.4 nM, 6.3 nM, respectively, demonstrating significant improvement over selpercatinib in the range of several hundred fold in activities. Importantly, the compound is highly selective against VEGFR, an off-target responsible for cardiovascular adverse effects in the non-selective RET inhibitors. The superior cellular potencies translated consistently into animal models. In Ba/F3 KIF5B-RET-G810R xenograft model, treatment of 25 mg/kg bid resulted in >90% TGI and 100% survival of mice bearing the Ba/F3 KIF5B-RET-G810R tumors. The compound showed favorable pharmacokinetic properties. Preclinical safety evaluations in rats exhibited good tolerance margin.