SAN DIEGO, Calif., and BERLIN, Germany, October 15, 2026
Vividion Therapeutics, Inc., a clinical-stage biopharmaceutical company and a wholly owned, independently operated subsidiary of Bayer AG, announced that the first patient has been dosed in a global Phase 2 clinical trial of VVD-214 in advanced colorectal cancer. The randomized study will evaluate the investigational oral Werner helicase (WRN) inhibitor in combination with pembrolizumab against pembrolizumab alone as first-line treatment for patients with microsatellite instability-high (MSI-high) or deficient mismatch repair (dMMR) colorectal cancer. The trial expands VVD-214’s clinical development into the first-line setting, complementing an ongoing Phase 1b study evaluating the candidate with bevacizumab in patients whose disease has progressed following previous treatment. The Phase 2 study is planned to enroll approximately 140 patients across about 21 countries in North America, Latin America, Europe and Asia. Its primary endpoint is the six-month progression-free survival rate, with secondary measures covering response, disease control, response duration, overall survival and safety. Vividion said the program builds on preliminary clinical findings that supported further investigation of WRN inhibition in MSI-high and dMMR cancers.
Phase 2 Study Expands VVD-214 into First-Line Treatment
The new Phase 2 trial will assess whether adding VVD-214 to pembrolizumab can provide clinical benefit compared with pembrolizumab alone in patients receiving first-line treatment for advanced MSI-high or dMMR colorectal cancer. The randomized design will allow investigators to compare outcomes between the combination regimen and the pembrolizumab-only group. According to Vividion, approximately 15% of colorectal tumors are MSI-high, representing a substantial population within the broader MSI-high cancer setting. The company is pursuing the program in an area where additional treatment options remain needed. Vividion President and Chief Executive Officer Aleksandra Rizo, M.D., Ph.D., said progress in the VVD-214 program had encouraged the company to expand its investigation into earlier-line treatment. She cited early clinical data and investigator interest as factors supporting the move into Phase 2. The study is registered as NCT07811193. Its primary endpoint is the six-month progression-free survival rate, which measures the proportion of patients who remain alive without disease progression at the specified time point. Secondary endpoints include objective response rate, disease control rate, duration of response, overall survival and safety. These measures are intended to characterize treatment activity and tolerability. The trial remains investigational, and its design does not establish whether the combination will outperform pembrolizumab alone.
WRN Inhibition Targets DNA Repair Vulnerabilities
VVD-214 is an investigational oral small-molecule inhibitor of Werner helicase (WRN), a DNA repair enzyme that Vividion identifies as a synthetic lethal target in MSI-high or dMMR cancers. The therapeutic approach is designed to exploit a vulnerability in cancer cells by inhibiting WRN and inducing lethal DNA damage selectively in susceptible tumor cells while minimizing harm to normal cells. MSI-high and dMMR tumors have defects associated with DNA mismatch repair, creating a biological context in which targeting additional DNA repair mechanisms may offer a therapeutic opportunity. Vividion reported that preliminary Phase 1a data presented at the American Association for Cancer Research 2025 Annual Meeting and published in Nature Medicine showed that VVD-214 was well tolerated, with early signals of activity. The company is using these findings to support continued clinical evaluation, including the new first-line combination study. Bayer’s Global Head of Research and Development for its Pharmaceuticals Division, Christian Rommel, Ph.D., said the clinical evidence generated to date supported broadening the program into the first-line setting. However, the preliminary observations do not establish definitive efficacy, and further studies are needed to determine the candidate’s safety and clinical benefit in larger patient populations. The Phase 2 trial will provide additional evidence on the potential role of WRN inhibition in combination with immune checkpoint therapy.
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Development Strategy and Broader Pipeline
The new trial complements Vividion’s ongoing Phase 1b study of VVD-214 with bevacizumab in patients with MSI-high or dMMR colorectal cancer whose disease has progressed after prior lines of therapy. Together, the studies are intended to examine the candidate in different treatment settings. The company is also advancing other precision-medicine programs emerging from its proprietary chemoproteomics platform. These include Phase 1 studies of an oral KEAP1 activator for advanced solid tumors and a RAS-PI3Kα inhibitor designed to target RAS-driven cancers. Vividion uses its discovery platform to identify functional pockets on proteins that may be suitable for selective small-molecule targeting, including targets historically considered difficult to drug. The company is developing a pipeline spanning oncology and immunology and operates as a wholly owned, independently operated subsidiary of Bayer AG. Bayer’s broader business focuses on healthcare and nutrition. The approximately 140-patient VVD-214 Phase 2 study across 21 countries represents a further step in Vividion’s clinical development strategy. The results will be important in determining whether combining WRN inhibition with pembrolizumab provides sufficient evidence of safety and activity to support later-stage development. Until clinical results become available, VVD-214 remains investigational for this indication.
Source::Vividion Therapeutics press release
