BDTX-4933

The therapy is undergoing Phase I clinical development. Credit: Alex_Traksel/Shutterstock. Servier and Black Diamond Therapeutics have signed a licensing agreement for a targeted therapy, BDTX-4933, to treat solid tumours. Servier will be responsible for the development and the global commercialisation of the therapy for several indications. The focus will initially be on non-small cell lung cancer (NSCLC), with the possibility of extension to other solid tumour types. Servier will pay Black Diamond $70m upfront, along with up to $710m in potential milestone payments based on development and commercial sales, plus royalties. The small molecule targets alterations in RAS (rat sarcomas) and RAF (rapidly accelerated fibrosarcomas) present in solid tumours. BDTX-4933 is undergoing Phase I clinical development. The ongoing first-in-human trial is assessing the therapy’s tolerability, preliminary antitumour activity and safety, and determining the recommended dose for Phase II. The study includes adults with advanced or metastatic cancers that exhibit mutations in the B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF), CRAF or neuroblastoma RAS viral oncogene homolog. Servier research and development executive vice-president Claude Bertrand stated: “Our partnership to develop BDTX-4933 is an important opportunity in targeted cancer therapies, as we believe we can serve more people by helping the right patients find the right treatment, at the right time. “We look forward to accelerating the development of this therapy as a potential best-in-class treatment for cancer patients.” Black Diamond develops MasterKey therapies engineered for targeting a wide range of oncogenic mutations, aiming to overcome resistance, reduce toxicity in non-mutated cells and penetrate the brain to address central nervous system conditions. Alongside BDTX-4933, the company is also progressing a brain-penetrant BDTX-1535 in a Phase II trial for NSCLC.

Servier sees BDTX-4933 as a potential best-in-class targeted therapy.\n Black Diamond Therapeutics has found a partner for its deprioritized solid tumor candidate. Five months after cutting support for BDTX-4933, the biotech has licensed the RAF inhibitor to Servier for $70 million upfront and up to $710 million in milestones. In October, Black Diamond concluded its attempt to push two cancer drugs through the clinic was stretching resources too thin and deprioritized BDTX-4933. The biotech, like many companies forced to make such decisions, said it would seek partners for the deprioritized candidate. Unlike many companies, Black Diamond actually found a taker.Servier has secured a global license in return for the aforementioned upfront fee and development and sales milestones, plus royalties. Black Diamond began a phase 1 trial in patients with KRAS, BRAF and select RAS/​MAPK mutation-positive cancers in 2023 but stopped enrollment in the study in October.The deal tees Servier up to kick-start development and advance BDTX-4933 across multiple indications, including non-small cell lung cancer. Through the first-in-human study, the French drugmaker could find the preliminary recommended phase 2 dose and generate early evidence of the safety, tolerability and efficacy of the candidate in patients with cancers that harbor BRAF, CRAF or NRAS mutations. Servier sees BDTX-4933 as a potential best-in-class targeted therapy that is uniquely designed to target RAS and RAF alterations in solid tumors. Aberrant activation of RAF-RAS signaling can induce tumors, leading many drug developers to target the pathway. Despite the activity, Black Diamond identified a need for a highly CNS-penetrant RAF inhibitor that targets a broad spectrum of oncogenic conformations.Paris-based Servier will now show whether BDTX-4933 can meet that need. The prospect will slot into a pipeline that skews toward oncology, a therapeutic area that accounts for almost 70% of Servier’s R&D spending. Servier had 16 solid tumor and blood cancer projects in clinical development prior to its latest deal.