On September 13, 2021 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate"), a biopharmaceutical company focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers, reported results from preclinical studies evaluating its lead Fibroblast Growth Factor Receptor (FGFR) inhibitor candidate, KIN-3248 (Press release, Kinnate Biopharma, SEP 13, 2021, View Source [SID1234587665]). These findings were presented during a virtual poster session at the joint JCA-AACR Precision Cancer Medicine International Conference that took place September 10-12, 2021.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
KIN-3248 is a next-generation, irreversible, small molecule pan-FGFR inhibitor designed to target cancer-associated FGFR2 and FGFR3 gene alterations, which are common oncogenic drivers seen in human cancers. KIN-3248 was developed to address both primary FGFR2 and FGFR3 oncogenic alterations and those predicted to drive acquired resistance to current FGFR-targeted therapies, including gatekeeper, molecular brake, and activation loop mutations observed in cancers such as intrahepatic cholangiocarcinoma (ICC) and urothelial carcinoma (UC). Kinnate anticipates filling an Investigational New Drug (IND) application for KIN-3248 with the U.S. Food and Drug Administration (FDA) in the first half of 2022.
"We are very pleased with the progress of our FGFR program, and these positive preclinical data are an important indicator of the potential anti-tumor activity of KIN-3248," said Eric Martin, Ph.D., SVP, Translational Research and Medicine at Kinnate. "In preclinical studies, we have demonstrated inhibitory activity across a wide range of clinically relevant mutations that drive primary disease and acquired resistance. We believe that by addressing these mutations and broadly covering multiple FGFR isoforms, KIN-3248 may be able to overcome challenges associated with currently approved FGFR inhibitors and provide a meaningful increase in the duration of response."
The poster presentation, delivered by Aleksandra Franovic, Ph.D., Senior Director of Translational Medicine at Kinnate, highlights data which show that in biochemical and cellular assays, KIN-3248 exhibited nanomolar potency against all four wild-type FGFR family members but not against other non-FGFR kinases. Importantly, KIN-3248 was active against mutations associated with resistance to FGFR inhibitors both in the clinic and in experimental models, including the FGFR2 and FGFR3 gatekeeper (V565X and V555M, respectively), molecular brake (N550X and N540X, respectively), and activation loop (L618V and K650M, respectively) mutations with less than a five-fold difference in IC50 values relative to corresponding wild-type receptors. In addition, dose-dependent inhibition of FGFR2- and FGFR3-driven human in vivo xenografts, including one with an acquired gatekeeper mutation, was attained with once-daily KIN-3248 treatment and was well tolerated. This efficacy was accompanied by both pharmacodynamic biomarker modulation and downstream pathway inhibition.
Kinnate’s poster presentation, titled "The next-generation FGFR inhibitor, KIN-3248, is active against acquired FGFR2 and FGFR3 gatekeeper and molecular brake drug resistance mutations," is available for on-demand viewing and can be accessed via: View Source