Plixorafenib

PHILADELPHIA--(BUSINESS WIRE)-- FORE Biotherapeutics today announced new nonclinical data related to plixorafenib (FORE8394; formerly PLX8394), the company's novel, investigational, small-molecule, next-generation, orally available selective inhibitor of BRAF alterations, will be presented at the AACR Annual Meeting 2024, taking place April 5-10, 2024, in San Diego and virtually. The data show nonclinical synergistic activity of plixorafenib when combined with MEK inhibition across all BRAF alterations tested. In cells with BRAF V600 or non-V600 mutations or BRAF fusions, the combination of plixorafenib and binimetinib is most potent of the BRAF and pan-RAF inhibitors tested. In plixorafenib resistant cells, these cells can be resensitized with the addition of binimetinib. To date, plixorafenib has demonstrated encouraging efficacy and safety data from the phase 1/2a study; these nonclinical data help build the foundation for potential future development of plixorafenib in combination with a MEK inhibitor. Poster Abstract number: 4609 Poster Title: The paradox-breaker BRAF inhibitor plixorafenib (PLX8394; FORE8394) synergizes with MEK inhibitors (MEKi) in BRAF V600 and non-V600 alterations, with higher potency compared to early generation BRAFi and pan-RAFi Presentation Session Date/Time: April 9, 2024, 9:00 AM - 12:30 PM Poster Session About Plixorafenib 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 alterations while sparing wild-type forms of RAF. Nonclinical and clinical studies have shown that its unique mechanism of action effectively inhibits not only the constitutively active BRAF V600 monomers targeted by first- and second-generation RAF inhibitors but also disrupts constitutively active dimeric BRAF class 2 mutants, fusions, splice variants and others. Unlike earlier-generation BRAF inhibitors, plixorafenib does not induce paradoxical activation of the RAF/MEK/ERK pathway. As a “paradox breaker”, plixorafenib could therefore address acquired resistance to current RAF inhibitors and, additionally, may yield improved safety and more durable efficacy than first-generation RAF inhibitors. Plixorafenib is currently being evaluated in two clinical trials in patients with advanced solid tumors with activating BRAF alterations. Interim clinical data from a Phase 1/2a trial presented at ESMO 2022, ASCO 2023 and SNO 2023 provided evidence of durable anti-tumor activity in patients with BRAF-mutated cancers with a 42% overall response rate and a median duration of response of 17.8 months in MAPK inhibitor-naïve participants with V600-mutated advanced solid tumors. Of the 9 patients with primary central nervous system tumors, 6 had confirmed response (ORR 67%) with a median duration of response of 13.9 months. In addition to the Phase 1/2a trial, plixorafenib is currently being investigated in the ongoing, potentially registrational Phase 2 FORTE study. About FORE Biotherapeutics Fore Bio is a precision 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 with manageable clinical safety and early efficacy signals in an ongoing Phase 1/2a clinical trial. 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 or follow us on X (formerly Twitter) and LinkedIn.

Pictured: A red illustration of a businessman walking through a door/iStock, lerbank Welcome to the second in a regular series of rundowns of people coming and going from executive positions at biopharma companies that BioSpace covers. This column will highlight the hired, fired, retired, promoted or resigning, as well as those personally named in lawsuits. While there were no blockbuster moves in the last two weeks on the scale of the Feb. 21 announcement that CEO Richard Gonzalez will soon retire from AbbVie, some less prominent biopharmas shook up their C-suites and others looked toward the next step of growth. Notably, Sumitomo named a new executive officer as part of a restructuring that will include the closure of its CNS sales department, and Kineta halted the enrollment of a clinical trial and cut most of its small staff as it ponders a sale or even liquidation. Meanwhile, IDRx, a member of BioSpace’s 2023 NexGen class, snapped up two execs from Theseus Pharmaceuticals. Alcanza Clinical Research Research facilities network Alcanza Clinical Research has named James Clark its first-ever chief medical officer. Clinical trials specialist Clark was owner and CEO of Charlottesville Medical Research, a Virginia facility that he sold to Alcanza in 2022. Capsida Biotherapeutics Capsida Biotherapeutics has promoted Rob Murphy to chief manufacturing and quality officer from vice president of technical operations. In this role, Murphy will oversee the gene therapy company’s cGMP manufacturing, process development and analytics as Capsida ramps up production of engineered adeno-associated virus–based treatments. Cellipont Bioservices CDMO Cellipont Bioservices has hired Edwin Beale as chief commercial officer. The firm opened a 76,000-square-foot cell therapy manufacturing plant in The Woodlands, Texas, last week. The facility will house a center of excellence in cryopreservation as part of a collaboration with Evia Bio. IDRx IDRx has hired two former Theseus Pharmaceuticals executives to lead the company. Tim Clackson takes over as CEO and Brad Dahms is the new CFO and chief business officer at the Plymouth, Mass.–based clinical-stage targeted cancer therapy startup, which placed 8th in BioSpace’s 2023 NexGen class. Cofounder Ben Auspitz, who relinquished the top role, has been named IDRx chairman. Moligo Technologies Moligo Technologies has named John Kuijpers chief business officer to lead commercialization of the firm’s long, single-stranded DNA for industrial use. The Swedish company has a collaboration with Nationwide Children’s Hospital in Columbus, Ohio, to support research into gene therapies for cystic fibrosis and related conditions. NeoVac NeoVac, a London-based developer of RNA-lipid nanoparticle vaccines and treatments, has hired Heinrich Haas as CTO. Haas previously was VP of RNA formulation and drug delivery at BioNTech. Sumitomo Pharma As part of a restructuring that will result in the loss of 400 jobs in North America and the dissolution of its CNS sales department, Sumitomo Pharma said that Yutaka Wakemi, current vice president in charge of global corporate strategy, will take over as executive officer on April 1. Three executives, Takuya Taguchi, Myrtle Potter and Armin Szegedi, are scheduled to depart March 31. Sumitomo recently reported disappointing sales of three of its drugs. Velsera Velsera has brought in Jamie Littlejohns as CEO to succeed interim leader Hans Cobben, who has returned to his role as board chairman. Littlejohns joined the computational biology company from McKinsey, where he led the consulting firm’s European healthcare and life science private equity practice. He has served as an external adviser to Velsera since 2022, when the company was formed from the merger of Pierian Dx, Seven Bridges and UgenTec. Anagenex Anagenex, an artificial intelligence–driven data generation company supporting small molecule drug discovery, has named Adrian Schreyer chief technology officer. The firm has a nascent research collaboration with Nimbus Therapeutics. Schreyer is former CTO and a founding employee of Exscientia. OncoNano Medicine OncoNano Medicine has promoted Kartik Krishnan to CEO from president and head of R&D, succeeding Martin Driscoll. The Southlake, Texas–based immune-oncology company also promoted Melissa Paoloni to executive VP and chief operating officer. OncoNano has a Phase I trial underway of its ONM-501 dual-activating polyvalent STING agonist for patients with advanced solid tumors and lymphomas. Fore Biotherapeutics Fore Biotherapeutics has brought in William Hinshaw to serve as CEO and board director. Hinshaw, former president, CEO and board member of Axcella Therapeutics, previously headed the U.S. oncology business of Novartis. Fore’s pipeline includes lead asset plixorafenib, a small molecule selective inhibitor of mutated BRAF that is currently in a Phase I/IIa clinical trial in patients with solid tumors. Ionis Pharmaceuticals Ionis Pharmaceuticals has rehired Kyle Jenne to serve as executive VP and chief global strategy officer as the Carlsbad, Calif.–based company prepares to launch its first commercial products. Jenne is replacing Onaiza Cadoret-Manier as head of global project strategy; Cadoret-Manier will depart March 15 but serve as an advisor to Ionis for an unspecified time period. The firm in December received FDA approval for Wainua (eplontersen), a therapy it codeveloped with AstraZeneca for treatment of adult polyneuropathy of hereditary transthyretin-mediated amyloidosis. Alvotech Biosimilars developer Alvotech announced the departure of Chief Quality Officer Sandra Casaca. She has been replaced on an interim basis by Christina Siniscalchi, who recently held a similar title at Alvogen. Days earlier, Alvotech and partner Teva Pharmaceuticals received FDA approval for Simlandi (adalimumab-ryvk), a biosimilar of AbbVie’s Humira (adalimumab). Kineta Kineta announced that it would eliminate the positions of CEO Shawn Iadonato and General Counsel Pauline Kenny as part of a reduction of seven jobs, or 64% of the company’s workforce. Iadonato and Kenny will stay on through the end of the year as Kineta considers a sale, acquisition, liquidation or other alternative. The firm has also stopped enrolling patients in its VISTA-101 Phase I/II trial for its KVA12123 compound for advanced solid tumors. Corbus Pharmaceuticals Corbus Pharmaceuticals has named Dominic Smethurst CMO to lead clinical development of a portfolio of investigational cancer drugs, including CRB-701, a Nectin-4 antibody-drug conjugate. The firm recently closed a $94.5 million public stock offering. Bexion Pharmaceuticals Bexion Pharmaceuticals has appointed a new CMO, Tariq Arshad, an oncologist who previously led R&D at Qualigen Therapeutics. Bexion is developing biologics to treat solid tumors and chemotherapy-induced peripheral neuropathy. Nicox Nicox fired CEO Andreas Segerros and replaced him with Gavin Spencer on the same day that the French ophthalmology drug company announced a restructuring of its debt to extend its cash runway to November 2024. The firm is concentrating its efforts on landing new financing to complete a Phase III trial of its lead asset, an investigational glaucoma therapy called NCX 470, by generating enough data to New Drug Application with the FDA. Nicox recently inked a partnership with Kowa to develop and commercialize the drug in Japan. Neil Versel is the business editor at BioSpace. You can reach him at neil.versel@biospace.com. Follow him on LinkedIn or X.