Roche’s First-in-Class Werner Helicase Inhibitor Shows Early Promise in Phase I Cancer Trial

   

    In a meeting at the American Association for Cancer Research (AACR) Annual Meeting 2025, principal investigator Timothy Yap, M.B.B.S., Ph.D., has published the results of RO758931, a first-in-class drug that inhibits the WRN helicase, a protein essential for survival in certain cancers.

    Although target therapy is the first in a new class of drugs, it is part of a wider group of therapies targeting the DNA damage response for patients with solid tumors and genetic changes known as high microsatellite instability (MSI) or deficient mismatch repair (dMMR). These can occur in many cancer types, and most patients who have these types of solid tumors do not respond to immune checkpoint inhibitors or develop resistance during treatment. Dr, Timothy Yap states:

"RO7589831 appears generally safe and shows promising signals of anti-tumor efficacy. These are encouraging early clinical data, especially because this is a patient population that currently has very limited treatment options. This also further validates Werner helicase as an actionable target, which is exciting because many cancers are highly dependent on it for survival."

    Like other DNA damage response therapies, RO7589831 inhibits the DNA repair enzyme, Werner helicase, preventing it from working properly. This creates a buildup of DNA damage within tumor cells, leading to cell death. However, since normal cells lack MSI, they will not be affected. 

    44 patients were evaluated for safety. Most experienced mild to moderate adverse effects. The most frequent side effects are manageable and similar to those of other treatments. They include nausea, vomiting, and diarrhea. While higher doses are less tolerable, no dose-limiting toxicities were observed. Three randomized dose-level cohorts are underway to establish the optimal recommended dose for the Phase II trial in the future. 

WORKS CITED

 MBT Desk (2025). Roche’s First-in-Class Werner Helicase Inhibitor Shows Early Promise in Phase I Cancer Trial. MedBoundTimes. https://www.medboundtimes.com/biotechnology/roches-first-in-class-werner-helicase-inhibitor-phase-i-cancer-trial

Genentech (2025). A clinical trial to look at how safe and well RO7589831 works at different doses in people with advanced solid tumours, and how the body processes RO7589831. https://genentech-clinicaltrials.com/en/trials/cancer/solid-tumors/a-study-to-evaluate-the-safety--pharmacokinetics--and-a-03859.html