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. For more information, please visit www.fore.bio or follow us on X and LinkedIn.

PHILADELPHIA--( BUSINESS WIRE )--FORE Biotherapeutics, a registration stage biotherapeutics company dedicated to developing targeted therapies to treat patients with cancer, today highlighted its recent pipeline achievements and provided its key strategic objectives for 2025. William Hinshaw, Chief Executive Officer of Fore Biotherapeutics, will detail progress and discuss anticipated milestones in a presentation at the 43 rd Annual J.P. Morgan Healthcare Conference. The presentation will take place on Tuesday, January 14, 2025, at 5:30 p.m. PT in San Francisco, CA. “ 2025 will be an exciting year at Fore, with multiple value-creating catalysts anticipated in the near-term across our trials. Our focus in 2025 will be continued execution of our differentiated monotherapy development of plixorafenib, which represents a multi-billion dollar opportunity, and the potential for expansion into developing plixorafenib as a combination agent. Plixorafenib’s unique mechanism of action supports the potential to reset the standard for patients with BRAF driven tumors, which have been underserved and underpenetrated due to the limitations of current agents. Plixorafenib is designed to inhibit not only the constitutively active BRAFV600 monomers targeted by first-generation RAF inhibitors, but also disrupt constitutively active dimeric BRAF class II mutants, fusions, splice variants and others, which differentiates it from current approved therapies. We are encouraged by the compelling safety and efficacy profile we have seen and the progress in our registrational trials,” said William Hinshaw, Chief Executive Officer of Fore. 2024 Achievements Strengthened Leadership Team: In 2024, Fore strengthened its leadership team with the appointment of William Hinshaw as Chief Executive Officer, Michael Byrnes as Chief Financial Officer and Payman Darouian, as Senior Vice President, Corporate Development, Strategy and Commercial. The new management team brings extensive experience from large pharmaceutical companies and multiple high-growth, publicly traded biotechnology companies adding to the strong existing capabilities of the team. Continued Execution of FORTE Master Protocol: The FORTE Master Protocol is a global clinical trial which includes 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. Advanced Plixorafenib in BRAF V600 Recurrent Primary Central Nervous System Tumors: Continued enrollment in registration-intended basket in up to 50 patients with BRAF V600-mutated recurrent primary CNS tumors. This BOP2 design trial enrolls patients who are naïve to MAPK pathway inhibitor (MAPKi) treatment. Major efficacy endpoints include overall response rate (ORR) and duration of response (DOR). The study builds upon a previous clinical trial of plixorafenib in which six out of nine, or 67%, of MAPKi naïve adults with recurrent BRAF V600-mutated primary CNS tumors demonstrated a partial response (PR) with a median DOR (mDOR) of 13.9 months. Advanced Plixorafenib in Rare BRAF V600 Mutated Solid Tumors: Initiated enrollment in registration-intended basket in up to 75 patients with rare BRAF V600-mutated solid tumors. This BOP2 design trial enrolls patients who are naïve to MAPKi treatment. Major efficacy endpoints include ORR and DOR. The study builds upon a previous clinical trial of plixorafenib in which 42% of MAPKi naïve adults with BRAF V600-mutated solid tumors demonstrated a PR with a mDOR of 17.8 months. Advanced Plixorafenib in Solid Tumors with BRAF Fusions: Continued enrollment in registration-intended basket in up to 75 patients with BRAF fusion advanced solid tumors. This BOP2 design trial enrolls patients with tumors harboring BRAF fusions, excluding those with prior treatment with MAPK inhibitors as well as patients with colorectal or pancreatic ductal adenocarcinoma. The primary endpoint is ORR, as determined by RANO criteria or RECIST v1.1 for primary CNS tumors or other solid tumors, respectively. The study builds upon a previous clinical trial of plixorafenib that demonstrated promising single agent activity including one complete response with a DOR of 66.7+ months, one PR with a DOR of 9.2+ months, and seven stable disease, out of 14 adults evaluable for efficacy. Reported Supportive Nonclinical Data at AACR 2024: Fore reported nonclinical data at AACR 2024 demonstrating that plixorafenib in combination with binimetinib, a MEK inhibitor, is more potent than other BRAF and pan-RAF inhibitors combined with binimetinib, as well as the synergistic activity of plixorafenib with MEK inhibition across all BRAF alterations tested. Reported Supportive Safety and Efficacy Data at International Symposium on Pediatric Neuro-Oncology (ISPNO 2024): Fore reported safety and efficacy data at ISPNO 2024 building on the existing evidence of plixorafenib in children and adults with BRAF-altered recurrent primary CNS tumors. Reported Supportive Safety and Efficacy Data in Ovarian Cancer at 15 th Biennial Ovarian Cancer Research Symposium (OCRS): Fore reported safety and efficacy data at OCRS 2024, including durable partial responses in three out of three patients with BRAF V600-mutated ovarian cancer, who were all heavily pre-treated. 2025 Strategic Objectives and Anticipated Milestones Continued Execution of the FORTE Master Protocol with Interim Analyses in Three Monotherapy Indications Anticipated in 2025 BRAF V600 Primary Recurrent Central Nervous System Tumors: 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. Rare BRAF V600 Mutated Solid Tumors: An interim efficacy analysis from the first 25 evaluable patients is anticipated to be conducted in the fourth quarter of 2025. Advanced Solid Tumors with BRAF Fusions: An interim efficacy analysis from the first 25 evaluable patients is anticipated to be conducted in the fourth quarter of 2025. 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 1 st and 2 nd 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. For more information, please visit www.fore.bio or follow us on X and LinkedIn .