FORE-8394 program

FORE-8394 is an investigational, novel, small-molecule, next-generation, orally available selective inhibitor of mutated BRAF. Its broad inhibition of ERK signaling makes it a strong candidate for the treatment of tumors driven by class I or II BRAF mutants and fusions.

FORE-8394 goes beyond BRAFV600 mutations:
FORE-8394 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 BRAFV600 monomers targeted by first-generation RAF inhibitors, but also disrupts constitutively active dimeric BRAF class II mutants, fusions, splice variants and others.
FORE-8394 is a paradox-breaker:
Unlike first-generation RAF inhibitors, FORE-8394 does not induce paradoxical activation of the RAF/MEK/ERK pathway. As a “paradox breaker”, FORE-8394 could therefore treat acquired resistance to current RAF inhibitors, and, more generally, yield improved safety and more durable efficacy than first-generation RAF inhibitors.
FORE-8394 is a BRAF-specific dimer-breaker:
As a BRAF-specific dimer breaker, FORE-8394 selectively inhibits ERK signaling in tumors driven by dimeric BRAF mutants, including BRAF fusions and splice variants, as well as BRAFV600 monomers, but spares RAF function in normal cells in which CRAF homodimers can drive signaling.
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For more information about the trial:

Fore is running a clinical trial open for BRAF fusions patients and BRAF mutant glioma patients, as detailed in the NCT02428712 study protocol.
For information about the study or to check suitability for enrolling patients, please contact us via the attached form or at trials@fore.bio.