F2i: Pioneering a new approach to cancer therapy with an FRS2 inhibitor

Building upon my previous work on disrupting oncogenic signaling, I have continued my research into the fibroblast growth factor receptor (FGFR) pathway, a key driver of cancer progression through its adaptor protein FRS2. My latest project focuses on developing F2i, a novel small molecule ligand designed to interrupt this pathway and halt tumor growth in FGFR-driven cancers.

By leveraging pharmacophore-based computational screening, we identified promising small molecule ligands targeting the PTB domain of FRS2, which couples FRS2 to FGFRs. These ligands were validated through biophysical binding assays and functional cell-based assays. In particular, we observed that the lead compound displayed on-target activity, preventing FRS2 activation and disrupting FGFR signaling. This resulted in significant inhibition of cancer cellinvasion in multiple cancer models both in vitro and in vivo.

Following this groundwork, we advanced the development of F2i into the ‘lead optimization’ phase by the conclusion of our initial seed financing round. F2i has successfully passed the ‘target validation’ and ‘Hit to Lead’ stages and has demonstrated remarkable efficacy in inhibiting cancer cell invasion across multiple FGFR-driven models, including bladder, lung, ovarian, brain, stomach, and colorectal cancers. F2i inhibits 80% of cancer cell invasion in all tested models and shows strong binding affinity for the target with favorable drug-like properties. In vivo pharmacokinetic studies using Pk / PD mouse models demonstrated that F2i can be safely administered via oral gavage. In vivo xenograft studies with F2i exhibited a substantial reduction in tumour growth (as monotherapy) across FGFR-driven ovarian, colorectal, and gastric cancer models, outperforming the established FGFR inhibitors

With promising results from the preclinical models, F2i advanced to CMC, toxicity, and safety studies, which led to the successful submission of the IND to the FDA. F2i is now in the early phases of clinical development at Pharmazz, in collaboration with LabConnect based in USA