Vividion and Bayer Advance First-in-Class WRN Inhibitor VVD-214 for Solid Tumors

Vividion Therapeutics and Bayer are advancing VVD-214, the world’s only clinical-stage covalent WRN inhibitor, for MSI-high cancers including colorectal, endometrial, ovarian, and gastric tumors. Preliminary Phase I data show VVD-214 is well tolerated and active, offering hope for patients resistant to immune checkpoint inhibitors. This reinforces Vividion’s pipeline and chemoproteomics platform for oncology innovation.

Vividion Therapeutics, a clinical-stage biopharmaceutical company and an independently operated subsidiary of Bayer AG, is further reinforcing its oncology pipeline with the clinical-stage Werner helicase (WRN) inhibitor, VVD-214. This first-in-class, covalent inhibitor is the only one of its kind in clinical development worldwide, marking a significant step forward in targeting cancers characterized by high microsatellite instability (MSI).

VVD-214 was discovered and developed under a global collaboration initiated between Vividion and Roche in 2020. It exemplifies Vividion’s approach of harnessing advanced chemoproteomics and precision small-molecule therapeutics to tackle difficult-to-drug targets in cancer and immune disorders.

A Broader Vision for Oncology Innovation

“VVD-214 is showing promising potential to improve treatment options for patients suffering from MSI-high cancers, a population with high unmet medical need,” said Christian Rommel, Global Head of Research and Development at Bayer’s Pharmaceuticals Division. “It underscores the ability of Vividion’s chemoproteomics technology to identify and advance new treatment opportunities for challenging and intractable diseases, and will be a valuable addition to the company’s portfolio.”

Targeting WRN in MSI-High Tumors

WRN, a key DNA repair enzyme, has emerged as a synthetic lethal target for tumors with high MSI or deficient mismatch repair (dMMR). Inhibiting WRN can cause lethal DNA damage in cancer cells with these genetic vulnerabilities, while sparing normal cells. This approach offers a promising therapeutic strategy, particularly for cancers such as colorectal, endometrial, ovarian, and gastric cancers—where treatment options remain limited and many patients ultimately relapse or develop resistance to immune checkpoint inhibitors.

The acquisition of exclusive worldwide rights to VVD-214 underscores Vividion’s commitment to expanding therapeutic options for patients with intractable diseases. Dr. Aleksandra Rizo, CEO of Vividion, highlighted the significance of this milestone, stating: “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.”

Preliminary data from the Phase I clinical trial (NCT06004245) were recently presented by Dr. Timothy Yap at AACR 2025 Annual Meeting. The results showed that VVD-214 is well tolerated and exhibits encouraging signs of antitumor activity across a range of solid tumors with high MSI. The trial is evaluating VVD-214 both as a monotherapy and in combination with pembrolizumab, aiming to address the critical need for effective treatments in this patient population.