The companies will combine their research expertise to develop BGB-3245, an investigational, oral, selective small molecule inhibitor of monomer and dimer forms of activating B-RAF mutations including V600 BRAF mutations, non-V600 B-RAF mutations, and RAF fusions.
BeiGene and SpringWorks Therapeutics joined forces to launch a new company, MapKure, LLC, that will focus on the development of an oncology asset.
The companies will combine their research expertise to develop BGB-3245, an investigational, oral, selective small molecule inhibitor of monomer and dimer forms of activating B-RAF mutations including V600 BRAF mutations, non-V600 B-RAF mutations, and RAF fusions. These mutations and fusions have been identified in a number of solid tumors to be drivers of cancer growth, including in non-small cell lung cancer, colorectal cancer, thyroid cancer and brain tumors, the companies said this morning when announcing the launch of MapKure. BGB-3245 was discovered by BeiGene scientists and is currently in preclinical development. In addition to its intended use as a monotherapy in several genetically defined solid tumor types, BGB-3245 also has the potential to be used in rational combination therapies in the future.
The formation of MapKure sprang from a collaboration the two parent companies formed in the fall. In September, BeiGene and SpringWorks teamed up to develop therapeutics targeting advanced solid tumors that contain RAS mutations, as well as other MAPK aberrations. The collaboration centered on BeiGene’s investigational RAF dimer inhibitor, lifirafenib (BGB-283) and SpringWorks Therapeutics’ investigational MEK inhibitor, PD-0325901.
BeiGene and SpringWorks plan for MapKure to initiate an adaptive Phase I dose-escalation and expansion study of BGB-3245 in solid tumor patients harboring specific B-RAF driver mutations and RAF fusions. The trial will also include patients who have developed resistance to first-generation BRAF inhibitors. MapKure intends to enter into service agreements with both BeiGene and SpringWorks to enable the execution of this study and to perform other activities to support MapKure operations. Subsequent clinical development efforts with BGB-3245 may also include rational combination therapies, including with MEK inhibitors such as PD-0325901, which is being developed by SpringWorks.
Under terms of the agreement between the companies, SpringWorks has made an equity investment into MapKure and BeiGene has contributed an exclusive royalty and milestone-bearing license to develop and commercialize BGB-3245 in Japan and outside of Asia, in exchange for a majority stake in the fledgling company. MapKure will form a joint steering committee that will oversee clinical development and operations for BGB-3245 and will also announce a board of directors. The steering committee and the board will include members from BeiGene, SpringWorks and MapKure’s chief executive officer. Lusong Luo, head of external innovation at BeiGene, will be acting CEO of MapKure. Further terms of the agreements were not disclosed.
Neal Rosen, the founding member of the MapKure Scientific Advisory Board, touted the preclinical data pf BGB-3245. He said the treatment could potentially address a significant unmet medical need for patients with non-V600 B-RAF mutations or RAF fusions that are presently unaddressed with approved B-RAF-directed therapies.
“BGB-3245 has demonstrated antitumor activity in a variety of preclinical cancer models, including those driven by mutations for which there are currently no approved therapies,” Luo said in a statement. “I look forward to advancing BGB-3245 into human trials in hopes of providing a treatment for these patients.”
