Lynch Syndrome: Exploring the Potential of mRNA in Cancer Prevention
We recently received authorization from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for our Phase 1/2 clinical study evaluating mRNA-4194, an investigational mRNA-based vaccine for people with Lynch syndrome, an inherited condition that increases the risk of cancer.
While we anticipate the first trial participant to be dosed sometime this summer, this is the first step toward advancing a novel mRNA approach that aims to shift care from treating cancer after its diagnosis to preventing cancer from occurring. By applying mRNA technology earlier in the patient journey, the goal is to harness the immune system when it could have the greatest impact.
I sat down for an episode of IR Insights to provide an overview of this innovative program and Moderna’s research in the cancer prevention vaccine space:
What is Lynch syndrome?
Lynch syndrome is one of the most common hereditary cancer predisposition conditions, affecting approximately 1 in 300 people worldwide.1 Our cells have exquisite proof-reading ability to correct small errors that occur during cell division when DNA is copied.2 Patients with Lynch syndrome have alterations in genes responsible for repairing DNA, known as DNA mismatch repair (MMR) genes, causing these errors to accumulate over time.3 This can contribute to the transformation from normal cells to precancerous lesions, and eventually to cancer.4
Patients with Lynch syndrome have about an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and an increased risk for other cancer types such as ovarian, gastric, prostate and pancreatic cancer.5 These cancers are more likely to develop at earlier ages, often before the age of 50.6
People typically only discover they have Lynch syndrome after they or a family member develop cancer at a relatively young age, which raises suspicion and leads to genetic testing.7 It is recommended that those with a family history of early-onset cancer or Lynch syndrome discuss genetic testing with their healthcare provider to understand their options.
Once diagnosed with Lynch syndrome, these people typically undergo intensive surveillance, with regular medical visits and procedures such as colonoscopies, aimed at detecting early signs of cancer.8
A shift toward prevention
mRNA-4194 reflects a broader ambition at Moderna: to push the boundaries of what is thought to be possible in medicine. Understandably, much of modern oncology has focused on treating cancer once it occurs. At Moderna, our oncology research to date has similarly focused on helping the immune system recognize and attack tumors that already exist. Now, we’re venturing into the preventative arena — can mRNA technology be applied to not only treat cancer after its diagnosis, but also to prevent cells from being a cancer growth, particularly for high-risk individuals?
mRNA technology works by instructing cells to produce specific proteins that can train the immune system to recognize and respond to disease. In the case of Lynch syndrome and mRNA-4194, we are investigating whether similar principles could train the immune system, specifically T cells, to detect and eliminate cells that carry these abnormal mutations before they grow into tumors.
We are just at the beginning of this journey, and there will be important insights along the way, deepening our understanding of Lynch syndrome and the potential of mRNA technology to address this high unmet need. We are deeply grateful to the participants and collaborators who make this work possible.
Forward-Looking Statements
This post and accompanying video contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: the potential of mRNA to address Lynch syndrome and prevent cancer from occurring; and Moderna’s Phase 1/2 clinical study evaluating mRNA-4194. In some cases, forward-looking statements can be identified by terminology such as "will," "may," "should," "could," "expects," "intends," "plans," "aims," "anticipates," "believes," "estimates," "predicts," "potential," "continue," or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this post are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna's control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading "Risk Factors" in Moderna's Annual Report on Form 10-K for the fiscal year ended December 31, 2025, filed with the U.S. Securities and Exchange Commission (SEC), and in subsequent filings made by Moderna with the SEC, which are available on the SEC's website at www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this post in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna's current expectations and speak only as of the date of this post.