Kinnate Biopharma Inc. Presents Preclinical Data on its Lead FGFR Inhibitor Candidate at the JCA-AACR Precision Cancer Medicine International Conference
KIN-3248 demonstrates highly-selective, potent, and broad-spectrum activity against mutations in both the FGFR2 and FGFR3 kinase domains – including acquired gatekeeper, molecular brake, and activation loop resistance mutations
SAN FRANCISCO and SAN DIEGO, Sept. 13, 2021 (GLOBE NEWSWIRE) -- 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, announced results from preclinical studies evaluating its lead Fibroblast Growth Factor Receptor (FGFR) inhibitor candidate, KIN-3248. 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.
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: https://www.c-linkage.co.jp/jca-aacr2021.
Kinnate is focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers. Kinnate’s mission is to expand the reach of targeted therapeutics by developing products for underserved populations. Kinnate utilizes its deep expertise in structure-based drug discovery, translational research, and patient-driven precision medicine, which it refers to as the Kinnate Discovery Engine, to develop targeted therapies. Based in San Francisco and San Diego, California, the Kinnate team is composed of drug discovery experts supported by a distinguished group of scientific advisors. For more information, please visit www.kinnate.com.
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