Moderna and Oxford plan UK Phase 1/2 test of mRNA-4194 for people with Lynch syndrome

Moderna (NASDAQ:MRNA) said it and the University of Oxford have received UK approval to move forward with the Phase 1/2 INTERCEPT-Lynch clinical trial of mRNA-4194, an investigational mRNA cancer vaccine for people with Lynch syndrome. The trial, aimed at cancer prevention rather than treatment, is expected to begin enrolling participants in spring or summer 2026, according to Oxford’s trial listing.

Lynch syndrome is an inherited condition caused by changes in DNA mismatch repair genes that increases lifetime risk of multiple cancers. It is estimated to affect about 1 in 300 people, and the lifetime risk of colorectal cancer can be as high as 80% depending on mutation and sex, according to summaries from major medical organizations.

The Oxford trial page describes the study’s prevention concept in practical terms: bowel cancer in Lynch syndrome is often preceded by abnormal growths called polyps, which can be detected and removed during colonoscopy. The vaccine is intended to train the immune system to recognize and clear early abnormal cells before they develop into cancer. Oxford says the vaccine works by delivering short-term instructions for the body to make pieces of protein found in those abnormal cells, potentially helping the immune system destroy similar cells later.

Details of the trial design show how safety and immune activity will be evaluated before any longer-term effectiveness readout. The study is an open-label, multicenter Phase 1/2 design using intramuscular (IM) injections, and it includes two parts. Part 1 will enroll up to 30 adults who receive three injections over 12 weeks to help identify a dose that is well tolerated and triggers immune responses. Part 2 will add another 80 to 110 adults, with four injections over about six months and a booster injection after a year, along with blood tests and colonoscopies to monitor changes in bowel lining and polyps.

The investigational product is mRNA-4194, which is administered as an mRNA therapeutic built for tumor specificity, and it will be delivered using lipid nanoparticles, or LNPs, a carrier technology used to protect mRNA and help it enter cells. The trial protocol documentation also states that nonclinical toxicity information draws on prior clinical experience with Moderna’s mRNA-LNP platform using SM-102, and that dosing decisions for later cohorts will be adjusted based on safety and translational indicates.

To measure whether the vaccine has an effect on early disease markers, the trial uses a colonoscopy-based approach focused on mismatch repair deficient tumors, described as MSI-H (microsatellite instability-high). For participants entering Part 2, the protocol calls for at least one adenomatous colorectal polyp between 2 mm and under 10 mm at baseline, with a follow-up colonoscopy 28 weeks after priming to remove retained polyps and assess biological endpoints. The documentation further describes safety assessments using dose-limiting toxicities and adverse events across multiple weeks, while a key secondary outcome tracks percent change in MSI-H polyp burden based on central read after screening and week 28 procedures.

The trial’s timeline and approvals are also defined in UK registration materials. The study period is listed as March 2026 through September 2029, and ethics approval is shown as granted on May 5, 2026, through the North East - York Research Ethics Committee (reference 26/NE/0046). Funding is identified as Moderna, and the site of conduct is the University of Oxford in the UK. Moderna and Oxford have not publicly detailed in the available postings how quickly results from immune or polyp-burden endpoints will be reported, nor do the materials provide any interim efficacy findings.