Company Category: Pharmaceuticals

Fore Biotherapeutics is a precision oncology company dedicated to developing innovative treatments that provide a better outcome for patients with cancer. Our lead candidate is plixorafenib (PLX-8394; FORE-8394), an investigational novel, selective BRAF inhibitor with activity against BRAF Class I (V600) and II (non-V600) alterations. Plixorafenib does not induce paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway, and avoids certain side effects, secondary malignancies, and some mechanisms of resistance that have been described with earlier generation BRAF inhibitors. Importantly, this also avoids the need for a second anticancer agent, such as a MEK inhibitor, to suppress paradoxical MAPK pathway activation. In a phase 1/2a multi-center, single-arm study of 113 participants with BRAF-altered solid tumors (NCT02428712), plixorafenib showed good tolerability and promising antitumor activity. Adverse events included primarily low-grade liver function test abnormalities, and the most common symptomatic adverse events were grade 1 in severity. Prolonged tumor responses and disease control were observed across various solid tumors including those with BRAF V600 mutations and BRAF fusions. In this heavily pretreated population, a preliminary analysis showed an objective response rate (ORR) of 30% was observed for participants with BRAF V600 tumors (42% ORR for those patients with no prior MAPK inhibitor therapy), with a duration of response of 17.8 months. The Forte clinical trial, a phase 2 basket study (NCT05503797) of plixorafenib for participants ≥8 years old with BRAF-altered cancers, consists of four sub-protocols: A. Participants with solid tumors and BRAF fusions who have received or are not eligible for standard of care therapy. Patients should not have received prior therapy targeting the MAPK pathway, with the exception of pediatric low-grade gliomas that have not progressed on such therapy. B. Participants with recurrent primary CNS tumors with BRAF V600 mutations who have received standard-of-care therapy and have not received prior therapy targeting the MAPK pathway. C. Participants with BRAF V600-mutated solid tumors excluding primary CNS tumors, CRC, PDAC, and more common BRAF-mutated solid tumors (non-small cell lung cancer, melanoma, and anaplastic or papillary thyroid carcinoma). D. Participants with advanced primary CNS and other solid tumors with BRAF V600 mutations who are not eligible for enrollment in sub-protocols B and C, including cutaneous melanoma, differentiated thyroid cancer, non-small cell lung cancer, and participants previously receiving therapies targeting the MAPK pathway. For more information about Fore Biotherapeutics and our Forte clinical trial, please visit us at https://Fore.Bio.