FORE Biotherapeutics Announces Oral Presentation at SNO 2023 Reporting Updated Phase 1/2a Results for Plixorafenib in BRAF V600 Advanced Solid Tumors, Including Novel Data for Patients with BRAF V600 Primary CNS Tumors

FORE Biotherapeutics today reported updated safety and efficacy data from the Phase 1/2a clinical trial evaluating plixorafenib (FORE8394; PLX8394), a novel, investigational, small-molecule, next-generation, orally available selective inhibitor of BRAF alterations. The results continue to demonstrate promising single-agent activity against BRAF V600-mutated tumors, including primary central nervous system tumors (PCNSTs), as presented at the Society for Neuro-Oncology (SNO) 2023 Annual Meeting, being held November 15-19, 2023, in Vancouver, Canada.

"The updated data from our Phase 1/2a study continues to reinforce plixorafenib's differentiated clinical profile in patients harboring BRAF V600 mutations," said Stacie Shepherd, MD, PhD, and Chief Medical Officer of FORE. "The data presented today at SNO 2023 demonstrate deep and durable confirmed responses in MAPK inhibitor-naïve patients, including a 67% overall response rate in patients with primary central nervous system tumors. I look forward to further elucidating plixorafenib's potential in our ongoing, global Phase 2 FORTE study."

"These results continue to demonstrate that plixorafenib has a favorable safety and efficacy profile compared to the currently approved BRAF/MEK inhibitors and investigational pan-RAF inhibitors," shared Macarena de la Fuente, MD, Associate Professor and Chief of Neuro-oncology at the University of Miami Sylvester Comprehensive Cancer Center. "I am excited to share these data today with the medical community and I look forward to the further study of plixorafenib to address the high unmet need of patients living with these difficult to treat cancers."

Key Findings from the Phase 1/2a Study

Safety and Tolerability

As of the data cutoff date of September 6, 2023, 113 patients have received plixorafenib under continuous dosing until disease progression and are included in the safety population.

• Plixorafenib continues to demonstrate a favorable tolerability profile with a low frequency of symptomatic treatment emergent adverse events (TEAEs) relative to approved BRAF/MEK inhibitors
• The safety profile in patients with PCNSTs (N=22) was consistent with that observed in the overall population
  • Headache was the only symptomatic Grade ?3 treatment emergent AE occurring in >5% of patients
• At the recommended Phase 2 dose (plixorafenib 900mg QD with PK booster: cobicistat 150mg QD), dose optimization maximizes dose intensity early in treatment with:
  • No DLTs
  • Most common laboratory abnormality TEAEs are predominantly Grade 1-2
  • Symptomatic TEAEs were almost all Grade 1

Efficacy

• Among the 9 MAPKi-naïve patients with V600-mutated PCNSTs, 6 achieved a response for an ORR of 66.7% (95% CI: 29.9, 92.5), all of which were confirmed responses
  • mDOR was 13.9 months (range: 3.7, 32.3) with 4/6 (67%) of responders having DOR of 6 months or longer
  • mPFS was not yet reached in patients with low grade glioma and glioneuronal tumors (range: 1.6, 27.8+ months; n=4) and 6.7 months (range: 2.8, 34.1 months; n=5) in high grade gliomas
• Among the 24 MAPKi-naïve patients with V600-mutated advanced solid tumors, 10 had a response for an ORR of 41.7%, all of which were confirmed responses
  • mDOR was 17.8 months (range: 3.7, 59.2)
• Median time to response was 3.5 months in patients with V600-mutated solid tumors, including those treated with prior MAPK inhibitor

About Plixorafenib (FORE8394; PLX8394)

Plixorafenib 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, plixorafenib does not induce paradoxical activation of the RAF/MEK/ERK pathway. As a "paradox breaker," plixorafenib could therefore treat acquired resistance to current RAF inhibitors and, more generally, yield improved safety and more durable efficacy than first-generation RAF inhibitors.

Plixorafenib was granted Orphan Drug Designation by the U.S. Food and Drug Administration in March 2023 for the treatment of primary CNS malignancies. In September 2022, the Agency granted plixorafenib Fast Track Designation for the treatment of patients with cancers harboring BRAF Class 1 (V600) and Class 2 alterations (including fusions) who have exhausted prior therapies.

Plixorafenib is currently being evaluated in Phase 1/2a clinical trial in patients with advanced solid tumors (including brain and spinal cord tumors) with activating BRAF alterations. Interim clinical data presented at ESMO 2022, ASCO 2023 and SNO 2023 provided evidence of durable anti-tumor activity in patients with BRAF-altered cancers.

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 plixorafenib (FORE8394; PLX8394) 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 Bio research and development 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.