Fore Biotherapeutics (Fore Bio), a precision oncology company dedicated to developing innovative treatments that provide a better outcome for cancer patients, today announced that the first patient has been dosed in the global Phase 2 FORTE clinical trial evaluating FORE8394 with cobicistat in patients with solid or central nervous system (CNS) tumors with BRAF gene fusions and recurrent primary CNS tumors with BRAF^V600E mutations refractory to standard therapies. The FORTE master protocol trial builds upon the design and interim data of the ongoing Phase 1/2a clinical trial evaluating FORE8394 in advanced solid and CNS tumors with BRAF alterations.

“We are thrilled to have initiated our global Phase 2 trial of FORE8394 in patients with BRAF-mutated tumors who have previously received available treatments and are now in need of alternative therapies,” said Stacie Shepherd, MD, PhD., Chief Medical Officer of Fore Biotherapeutics. “FORE8394, our next-generation BRAF paradox breaker, provides the potential for single agent clinical activity for both BRAF V600 mutations and BRAF fusions without MAPK pathway activation, avoiding the resistance and toxicities observed with the earlier-generation BRAF inhibitors. Advancing this novel therapy to address patients’ needs is the driving force behind our team’s mission to advance FORE8394 through the clinic. The dosing of the first patient is a significant milestone for the entire FORE team. With the FDA’s Fast Track Designation of FORE8394 in the third quarter of this past year, we look forward to continuing to develop FORE8394, working with the FDA and other global regulatory agencies to address the high unmet need for patients suffering from these difficult to treat cancers.”

The FORTE trial is a global, multi-center, single-arm, open-label, Phase 2 master protocol evaluating the safety and efficacy of FORE8394 with cobicistat, a pharmacokinetic booster commonly used with HIV medications, in patients 10 years of age and older with cancer harboring BRAF alterations. The trial will enroll approximately 130 participants in two subprotocols: A) participants with recurrent primary CNS tumors harboring BRAF^V600E mutations (N=50) and B) participants with locally advanced or metastatic solid tumors or recurrent or progressive primary CNS tumors harboring BRAF fusions, excluding colorectal or pancreatic ductal adenocarcinoma (N=80). FORE8394 will be co-administered orally at a dose of 900 mg with cobicistat 150 mg once daily. The primary endpoint of each subprotocol is overall response rate, with duration of response.

The company previously announced interim data from the ongoing Phase 1/2a clinical trial evaluating FORE8394 in advanced solid and CNS tumors with activating BRAF alterations, providing evidence of durable anti-tumor activity in patients with BRAF-mutated (V600+) cancers. The data were presented at the European Society of Medical Oncology Congress (ESMO) in September 2022. Mature data from the Phase 1/2a clinical trial are expected in mid-2023.

About FORE8394

FORE8394 is an investigational, novel, small-molecule, next-generation, orally available selective inhibitor of mutated BRAF. It was designed to target a wide range of BRAF mutations while sparing wild-type forms of RAF. Preclinical studies and clinical trials have shown that its unique mechanism of action effectively inhibits not only the constitutively active BRAF^V600 monomers targeted by first-generation RAF inhibitors but also disrupts constitutively active dimeric BRAF class 2 mutants, fusions, splice variants and others. Unlike first-generation RAF inhibitors, FORE8394 does not induce paradoxical activation of the RAF/MEK/ERK pathway. As a “paradox breaker,” FORE8394 could therefore yield improved safety and more durable efficacy than currently approved RAF inhibitors, without the need for combination with a MEK inhibitor. Co-administration with cobicistat helps slow the metabolism, or breakdown, of FORE8394 in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the cancer. FORE8394 was granted Fast Track Designation by the U.S. Food and Drug Administration for the treatment of patients with cancers harboring BRAF Class 1 (V600) and Class 2 (including fusions) alterations who have exhausted prior therapies.

About Fore Biotherapeutics

Fore Bio is a precision oncology company dedicated to developing innovative treatments that provide a better outcome for cancer patients. Its lead asset FORE8394 is a Class 1 (V600) and 2 BRAF inhibitor with demonstrated clinical safety and early efficacy signals in an ongoing Phase 1/2a clinical trial. Leveraging a proprietary functional genomics platform that can screen a wide range of known mutations for cancer-driving genes, the Fore R&D team is optimizing drug development by identifying existing compounds with known clinical profiles and a clear path through clinical development to advance new medicines for patients without treatment options. For more information, please visit www.fore.bio or follow us on Twitter and LinkedIn.

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