Advancing a Pipeline of Targeted Oncology Therapeutics

Our lead RAF program, exarafenib (KIN -2787), is a small molecule kinase inhibitor targeting specific classes of BRAF kinase alterations (Class II and Class III) that characterize subsets of melanoma, lung cancer, and other solid tumors. As a pan-RAF kinase inhibitor, exarafenib inhibits CRAF, a critical effector of oncogenic signaling in NRAS-mutant melanoma. While three BRAF targeted kinase inhibitor drugs targeting the Class I BRAF alterations have been approved by the FDA, no targeted therapies have been approved for Class II or Class III BRAF alteration-driven cancers or NRAS-mutant driven melanoma Patients with Class II or Class III BRAF alterations and NRAS-mutant melanoma do not respond to existing approved targeted therapies, have few treatment options available to them, and consequently have a poor prognosis. Initially, we plan to develop exarafenib for the treatment of patients with melanoma and non-small cell lung cancer (NSCLC) subpopulations with Class II or Class III BRAF alterations that include specific BRAF point mutations (other than BRAF V600E), BRAF insertions/deletions (indels) and BRAF gene fusion events as well as for the treatment of patients with NRAS-mutant melanoma. We expect that exarafenib may provide substantial clinical benefit to these cancer patients who are inadequately served by current therapies. We are currently evaluating the safety and tolerability of exarafenib in a first-in-human dose-escalation study in adults with BRAF-mutated advanced or metastatic solid tumors and NRAS-mutated advanced or metastatic melanoma both as a monotherapy and in combination with binimetinib for NRAS-mutant melanoma (KN-8701). More information can be found on ClinicalTrials.gov at: https://www.clinicaltrials.gov/ct2/show/NCT04913285

Our FGFR program, KIN-3248 is a small-molecule kinase inhibitor that target cancer-associated alterations in FGFR2 and FGFR3 genes, which are among the most commonly identified oncogenic drivers detected in solid tumor cancers. KIN-3248 aims to address the primary driver-alteration and clinically observed and predicted FGFR 2/3 mutations that drive resistance to current FGFR2- and FGFR3-targeted therapies in intrahepatic cholangiocarcinoma (ICC) and urothelial carcinoma (UC). In preclinical studies, we have observed inhibitory activity across a broad range of clinically relevant mutations that drive acquired resistance. We believe that by addressing these mutations and broadly covering FGFR isoforms, we may be able to meaningfully increase the duration of response (DoR). We are currently evaluating the safety and tolerability of KIN-3248 in a first-in-human dose-escalation study in adults with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations. More information can be found at ClinicalTrials.gov at: https://clinicaltrials.gov/ct2/show/NCT05242822.