Plixorafenib

PHILADELPHIA--(BUSINESS WIRE)--FORE Biotherapeutics, a registration stage biotherapeutics company dedicated to developing targeted therapies to treat patients with cancer, today announced a $38 million Series D-2 financing. For this initial close of the Series D-2, leading healthcare dedicated investors participated, including SR One, Medicxi, OrbiMed, HBM Healthcare Investments, Wellington Management, Novartis Venture Fund, Cormorant Asset Management, and 3B Future Health Fund. This $38 million adds to the $75 million raised as part of the earlier Series D and D-1 financings, for an aggregate total to date of $113 million for this Series D financing. “At SR One, our mission is to invest in companies that we believe have the ability to innovate and advance transformational new therapies in areas of high unmet medical need,” said Simeon George, M.D., Chief Executive Officer and Managing Partner at SR One. “Fore Bio is focused on resetting the standard in BRAF driven tumors with a potential first in class paradox breaker with compelling early clinical data that support the potential of plixorafenib monotherapy to address the well-known treatment gaps oncologists face with first- and second-generation BRAF inhibitors. We are impressed with the team’s progress to date, excited about the multiple near term data readouts, and are proud to support the continued advancement of plixorafenib.” “This financing is a testament to the hard work of our team in developing plixorafenib, a differentiated, rationally designed BRAF inhibitor for both V600 and non V600 mutations that has already generated compelling data to date. We believe plixorafenib has the potential to overcome the limitations of currently available BRAF inhibitors, representing a multi-billion-dollar market opportunity,” said William Hinshaw, Chief Executive Officer of Fore. “We are grateful for the continued support of this highly regarded investor syndicate and their confidence in both the Fore Bio team and plixorafenib. With their backing, we are well positioned to continue our capitally efficient execution and make significant strides in delivering the ongoing FORTE Master Protocol as we look to multiple anticipated interim analyses and clinical data supporting potential registration under the accelerated approval pathway with FDA submissions potentially at the end of next year.” Proceeds from the financing will be used to advance the registration-intended FORTE Master Protocol, a global Phase 2 clinical trial which includes four sub-protocol baskets evaluating plixorafenib in distinct patient populations. The three monotherapy indications currently under evaluation are BRAF V600 Recurrent Primary Central Nervous System (CNS) Tumors, Rare BRAF V600 Mutated Solid Tumors and Solid Tumors with BRAF Fusions. 2025 Strategic Objectives and Anticipated Milestones Fore Bio is anticipating interim analyses to occur in 2025 across three monotherapy indications being evaluated in the FORTE Master Protocol: BRAF V600 Primary Recurrent CNS Tumors: In this cohort, up to approximately 50 patients with BRAF V600 primary recurrent CNS tumors will be treated with plixorafenib. The primary endpoints of the study are overall response rate (ORR) and median duration of response (mDOR). An interim efficacy analysis from the first 25 evaluable patients is anticipated to be conducted in the third quarter of 2025. Pending a positive recommendation from the data monitoring committee, topline data from this trial would be anticipated in the second half of 2026. The company anticipates that this trial, with sufficient demonstration of safety and efficacy, would enable the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) under the Accelerated Approval pathway. In a previously conducted Phase 1/2 study of patients with MAPK inhibitor naïve BRAF V600 primary recurrent CNS tumors (n=9), plixorafenib monotherapy demonstrated a 67% ORR and a mDOR of 13.9 months, along with a favorable tolerability profile. Rare BRAF V600 Mutated Solid Tumors: In this cohort, up to approximately 75 patients with rare BRAF V600 mutated solid tumors will be treated with plixorafenib. The primary endpoints of the study are ORR and median duration of response mDOR. An interim efficacy analysis from the first 25 evaluable patients is anticipated to be conducted in the fourth quarter of 2025. In a previously conducted Phase 1/2 study of patients with MAPK inhibitor naïve BRAF V600 mutated solid tumors (n=24), plixorafenib monotherapy demonstrated a 42% ORR and a mDOR of 17.8 months, along with a favorable tolerability profile. Advanced Solid Tumors with BRAF Fusions: In this cohort, up to approximately 75 patients with advanced solid tumors with non-V600 BRAF fusions will be treated with plixorafenib. The primary endpoints of the study are ORR and median duration of response mDOR. An interim efficacy analysis from the first 25 evaluable patients is anticipated to be conducted in the fourth quarter of 2025. In a previously conducted Phase 1/2 study of adults with advanced solid tumors with BRAF fusions (n=14), plixorafenib monotherapy results in one complete response (with a DOR of 67.4 months), one partial response and 7 stable disease, along with a favorable tolerability profile. Recent and Upcoming Medical Meeting Presentations AACR 2025: In April 2025, Fore presented new circulating tumor DNA (ctDNA) results from a previously completed plixorafenib clinical trial and presented the basket study design for the ongoing global Phase 2 FORTE clinical trial at the American Association for Cancer Research (AACR) Annual Meeting 2025. Results from the plasma ctDNA analysis of over 70 plixorafenib-treated patients demonstrated a high concordance between changes in ctDNA and tissue biopsy of several BRAF mutations. The correspondence shown between changes in ctDNA and tumor size across tumor types suggests that ctDNA may be a viable surrogate marker for monitoring disease. Compared to acquired mutations driving resistance to early generation BRAF inhibitors, no new mutations in MAPK pathway genes were found following plixorafenib treatment, supporting the dimer–breaker property and novel mechanism of action of plixorafenib from the early generation BRAF inhibitors. ASCO 2025: At the upcoming 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30 - June 3 in Chicago, Fore will present the master protocol design of the ongoing global Phase 2 FORTE clinical trial. About FORE Biotherapeutics Fore is a registration stage targeted oncology company dedicated to developing innovative treatments that provide better outcomes for patients with the hardest-to-treat cancers. The Company’s lead asset plixorafenib (FORE8394; formerly PLX8394) is a V600 and non-V600 BRAF inhibitor rationally designed with a first-in-class mechanism to address treatment gaps from 1st and 2nd generation BRAF inhibitors. Plixorafenib has demonstrated single-agent efficacy signals across a variety of tumor types with a manageable safety profile in a Phase 1/2a clinical trial of over 100 patients and is currently enrolling patients in FORTE, a global registrational basket trial to support three distinct indications. 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