Vividion Therapeutics has secured exclusive worldwide rights to develop and commercialize VVD-214 (RO7589831), the only clinical-stage covalent inhibitor of Werner helicase (WRN) in development worldwide. The acquisition strengthens the Bayer subsidiary's oncology pipeline with a first-in-class therapeutic targeting microsatellite instability-high (MSI-high) cancers.
VVD-214 was originally discovered and developed under an exclusive collaboration between Vividion and Roche initiated in 2020. Preliminary data from a first-in-human study presented at the recent American Association for Cancer Research (AACR) Annual Meeting demonstrated that the compound is well tolerated and shows promising signs of activity.
Targeting Synthetic Lethality in MSI-High Cancers
WRN is a DNA repair enzyme that represents a highly sought-after synthetic lethal target for treating cancers with microsatellite instability. By inhibiting WRN, VVD-214 aims to cause lethal DNA damage specifically in cancers with high microsatellite instability while minimizing harm to healthy cells.
The therapeutic approach addresses a significant unmet medical need. Treatment options for patients with MSI-high solid tumors are currently limited, and a majority will relapse or become refractory to immune checkpoint inhibitors.
"Bringing VVD-214, the only clinical-stage covalent inhibitor of WRN in development worldwide, into our portfolio marks an incredibly exciting moment for Vividion," said Aleksandra Rizo, M.D., Ph.D., Chief Executive Officer of Vividion. "We are eager to progress development of this compound, building on the encouraging clinical data we've seen to date, as part of our mission to transform treatment for patients with cancer and other serious diseases."
Phase I Clinical Development
The ongoing Phase I clinical trial (NCT06004245) is evaluating VVD-214 both as a monotherapy and in combination with pembrolizumab for patients with solid tumors displaying high MSI or deficient mismatch repair (dMMR). The study includes patients with colorectal, endometrial, ovarian, and gastric cancers, among other tumor types.
Initial data presented at AACR by Timothy Yap, M.B.B.S., Ph.D., clinical investigator and professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, showed early signals of efficacy for VVD-214 across a range of solid tumor types with high MSI.
Expanding Oncology Pipeline
Christian Rommel, Ph.D., Global Head of Research and Development at Bayer's Pharmaceuticals Division, emphasized the compound's potential impact: "VVD-214 is showing promising potential to improve treatment options for patients suffering from MSI-high cancers, a population with high unmet medical need. It underscores the ability of Vividion's chemoproteomics technology to identify and advance new treatment opportunities for challenging and intractable diseases."
Beyond VVD-214, Vividion maintains an active clinical pipeline with ongoing Phase I trials evaluating an oral KEAP1 activator in solid tumors, an oral STAT3 inhibitor in solid and hematologic malignancies, and an oral RAS-PI3Kα inhibitor in advanced solid tumors. The company continues advancing multiple drug discovery programs leveraging its proprietary chemoproteomic platform to target traditionally undruggable proteins in oncology and immunology.
