FORE Biotherapeutics Presents Phase 1/2a Plixorafenib Data Demonstrating Prolonged Duration of Effect in BRAF Altered Thyroid Cancers at American Thyroid Association® 2025 Annual Meeting

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PHILADELPHIA--(BUSINESS WIRE)--Sep 12, 2025--

FORE Biotherapeutics, a registration stage biotherapeutics company dedicated to developing targeted therapies to treat patients with cancer, today presented new plixorafenib results from the previously completed Phase 1/2a clinical trial that demonstrate treatment with plixorafenib in patients with BRAF-altered papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) resulted in durable disease control that appears very favorable compared with historical data with standard treatment options. The data also demonstrate an encouraging safety profile consistent with previously reported results following treatment with plixorafenib. The data are being presented at the American Thyroid Association ® (ATA) 2025 Annual Meeting, taking place September 10-14, 2025 in Scottsdale.

“These results presented at ATA 2025 demonstrate durable clinical benefit in both V600 mutated and BRAF fusion thyroid tumors, and durable disease control in patients with stable disease. These new findings continue to support the strong clinical profile of plixorafenib as well as the potential to benefit patients with BRAF-altered thyroid cancers,” said Eric J. Sherman, M.D., Head and Neck Cancer Medical Oncologist at the Memorial Sloan Kettering Cancer Center, and Principal Investigator for the ongoing FORTE Phase 2 plixorafenib study. “Patients with differentiated thyroid cancer, including papillary thyroid cancers which account for about 80% of all thyroid cancers, are in dire need of new treatment options. BRAF V600E alterations occur in approximately 60% of papillary thyroid cancers, underscoring the need for development of a targeted therapy such as plixorafenib that addresses the mechanistic drivers of these tumors along with the compelling clinical efficacy and safety profile demonstrated by treatment with plixorafenib.”

“We are excited to share these data that show additional evidence of strong and durable clinical activity of plixorafenib, in both BRAF V600 mutant and BRAF fusion thyroid cancers,” said Stacie Peacock Shepherd, M.D., Ph.D., Chief Medical Officer of Fore. “The data also demonstrate a high duration of response in MAPKi-naïve patients, highlighting the unique mechanism of action of plixorafenib that avoids paradoxical MAPK pathway activation and delivers differentiated results as a single therapeutic agent in BRAF altered cancers. We continue to advance our ongoing registrational FORTE basket study, which includes BRAF V600 altered thyroid cancers, as we aim to generate further data to inform treatment and help patients with BRAF driven tumors.”

The results presented at ATA 2025 are from 21 patients with thyroid cancer, 16 with PTC and 5 with ATC, treated with plixorafenib in a previously completed Phase 1/2a study that treated a total of 113 patients with advanced, unresectable solid tumors that were intolerant to standard therapy or had no standard therapy available. All 21 patients with thyroid cancer received prior radiation therapy, nearly all underwent prior surgery, and the majority had received prior systemic anticancer therapies. The safety profile of treatment with plixorafenib in patients with ATC or PTC was consistent with previously reported results from the Phase 1/2a study.

Treatment with plixorafenib with and without cobicistat in MAPK-inhibitor naïve patients with a BRAF V600 mutation demonstrated an encouraging clinical benefit with a differentiated duration of response and support plixorafenib’s paradox breaker mechanism of action in BRAF-altered tumors, including a median progression free survival (mPFS) of 63.9 months and a clinical benefit rate (CBR: response or stable disease ≥ 24 weeks) of 85.7% (6 of 7 patients). Four MAPK-inhibitor naïve PTC patients remained on treatment for over 5 years, including one partial response (PR) of 59.2 months (treatment duration=7.6 years) and a second PR of 30.9 months (treatment duration=8.3 years). In four ATC patients with a BRAF V600 mutation, all of whom were MAPK-inhibitor naïve, the mPFS was 16.1 months, with one confirmed PR lasting 17.8 months and two patients reaching stable disease. In the three PTC patients that received prior MAPK inhibition therapy as well as at least one prior BRAF inhibition therapy, all three patients reached stable disease, with a CBR of 33.3%. Clinical benefit was also observed in patients with BRAF fusion PTC, with one of three patients achieving a PR lasting 12.9 months (treatment duration=25 months, continued post-study completion), and one patient with ATC having stable disease.

The results presented at ATA 2025 demonstrate a differentiated and durable clinical benefit in BRAF altered anaplastic and papillary thyroid cancers, compared to historical results of approved and investigational therapies, including BRAF, MEK, and pan-RAF inhibitors. Plixorafenib’s novel mechanism of action does not induce paradoxical activation of the MAPK pathway, thereby not requiring combination with a MEK inhibitor and potentially improving upon safety, efficacy, and durability compared with treatments containing prior generation RAF inhibitors.

FORE is advancing 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 progressive or recurrent primary CNS tumors, rare BRAF V600 mutated advanced solid tumors, including ATC, and solid tumors with BRAF fusions, including PTC and ATC. BRAF v600E alterations occur in 45% of ATC and approximately 60% of PTC, representing a differentiated potential future development opportunity for plixorafenib.

Poster Presentation Details:

Title: Clinical Activity and Safety of Novel BRAF Inhibitor (BRAFi) Plixorafenib (FORE8394; PLX8394) in Advanced Thyroid Cancers (TC) Harboring BRAF Alterations
Lead Author & Presenter: Eric J. Sherman, M.D., Memorial Sloan Kettering Cancer Center
Poster Session: Clinical Thyroid Diseases & Cancer
Date and Time: Friday, September 12, 2025, 3:00 – 4:00 p.m. MT
Poster Number: 300

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 favorable 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.

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SOURCE: FORE Biotherapeutics

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PUB: 09/12/2025 05:00 PM/DISC: 09/12/2025 04:59 PM

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