Vividion Therapeutics, a wholly owned and independently operated subsidiary of Bayer AG, has dosed the first patient in a global Phase 2 clinical trial evaluating VVD-214, an investigational oral Werner helicase (WRN) inhibitor, in patients with advanced Microsatellite instability-high (MSI-high) or deficient Mismatch Repair (dMMR) colorectal cancer.

The randomised trial will compare VVD-214 in combination with pembrolizumab against pembrolizumab alone as a first-line treatment for patients with these forms of advanced colorectal cancer. The study marks an expansion of VVD-214's clinical development into an earlier stage of treatment, where additional therapeutic options are needed.

According to Vividion, approximately 15 percent of colorectal tumours are MSI-high, representing a significant patient population that may benefit from targeted treatment approaches.

The global Phase 2 trial is planned to enrol approximately 140 patients at clinical sites across around 21 countries in North America, Latin America, Europe and Asia. The primary endpoint is the six-month progression-free survival rate. Secondary endpoints include objective response rate, disease control rate, duration of response, overall survival and safety.

VVD-214 is an investigational oral small-molecule inhibitor targeting WRN, a DNA repair enzyme considered a synthetic lethal target in MSI-high and dMMR cancers. The drug is designed to inhibit WRN and selectively induce lethal DNA damage in cancer cells while limiting harm to normal cells.

Vividion is also evaluating VVD-214 in an ongoing Phase Ib trial (NCT06004245), which is investigating the drug in combination with bevacizumab in patients with MSI-high or dMMR colorectal cancer whose disease has progressed following previous lines of treatment.

Preliminary findings from the Phase 1a study, presented at the American Association for Cancer Research (AACR) 2025 Annual Meeting and published in Nature Medicine, indicated that VVD-214 was well tolerated, with early signs of clinical activity.

Aleksandra Rizo, President and Chief Executive Officer of Vividion Therapeutics, said progress in the programme had supported the company's decision to investigate the drug in first-line treatment. She highlighted the need for effective and better-tolerated therapies for patients with advanced colorectal cancer.

Christian Rommel, Global Head of Research and Development at Bayer's Pharmaceuticals Division, said the clinical evidence generated so far had encouraged the company to expand the programme and evaluate VVD-214's potential as a treatment option for patients with MSI-high or dMMR colorectal cancer.

Beyond VVD-214, Vividion is advancing Phase 1 clinical programmes evaluating an oral KEAP1 activator in advanced solid tumours and a RAS-PI3Kα inhibitor targeting RAS-driven cancers.