Building the Future of Oncology: From Treatment to Prevention
One of the things that has always inspired me about science is its ability to expand what is possible.
A decade ago, few people viewed mRNA as a technology with potential. Today, mRNA medicines are helping protect millions of people around the world from infectious diseases.
We are applying the same spirit of innovation to one of the most important challenges in medicine: cancer.
At Moderna, our oncology strategy is guided by a simple belief: people living with cancer need better options. They need treatments that improve outcomes and reduce the burden that cancer can place on patients and their families. And, where possible, we should aim to intervene earlier in the course of disease, when the opportunity for long-term benefit may be greatest.
Our oncology portfolio is advancing across a broad range of cancers and disease stages. What excites me most is not only the number of different programs we have in development, but how the flexibility of our platform is allowing us to think differently about the cancer journey—from seeking to reduce the risk of recurrence after surgery, to treating advanced disease, to exploring whether we may one day help prevent certain cancers before they develop.
Starting Earlier in the Cancer Journey
In oncology, many new therapies have historically been developed first in patients with advanced or metastatic disease. These patients have an urgent need for new options, and many important breakthroughs have come from that approach.
Our experience with intismeran autogene (mRNA-4157 or V940), being developed in collaboration with Merck (known as MSD outside of the U.S. and Canada), has followed a different and important path. We began by studying this investigational individualized neoantigen therapy in certain patients with melanoma at risk of recurrence following complete surgical resection—an adjuvant setting where all detectable cancer has been removed, but the risk of recurrence remained significant.
The five-year results from our randomized Phase 2b study in high-risk resected melanoma have been encouraging. The data supports the continued development of an individualized mRNA-based approach in combination with standard of care pembrolizumab, Merck’s anti-PD-1 therapy, with the potential to train the immune system and deliver promising results in an earlier-stage setting. For us, these data are important: mRNA can be used not only to encode information, but also to potentially help generate new cancer-specific T-cell responses while also strengthening existing ones in a highly personalized way against cancer.
This is one of the reasons we are continuing to explore the earlier disease setting. If we can safely activate effective anti-cancer immunity after surgery, before the cancer returns, we may be able to intervene when tumor burden is lower. For this reason, we are excited about our recently announced pivotal trial for intismeran—our first Phase 3 study in certain patients with high-risk Stage 1 non-small cell lung cancer that includes an intismeran monotherapy arm.
Alongside our partners at Merck, our individualized neoantigen therapy program is being explored across multiple solid tumors and disease settings. More broadly, our oncology portfolio also now spans across perioperative, adjuvant and metastatic settings.
The significance of this goes beyond a single program. It reflects a broader ambition: to use mRNA to help redefine where and how we intervene in cancer.
Addressing Metastatic Patients Who Are Not Responding to Immune-Therapy Medicines
When immune-therapy medicines work, they are transformative. Unfortunately, many patients with advanced/metastatic disease (Stage 4), do not respond to checkpoint inhibitors. We are investigating mRNA-4359 in the clinic in patients who are refractory, or do not respond, to immune-therapy medicines. We are encouraged by the recent data showing some early clinical responses of mRNA-4359 in patients with melanoma and are now advancing this investigational medicine through new expansion cohorts.
Building on What We Have Learned to Move Into Liquid Tumors
One of the advantages of being a platform company is that every program teaches us something.
Our work with cancer therapies has strengthened our understanding of antigen selection, immune activation, T-cell responses and the design of medicines that can be tailored to the biology of cancer. These insights are informing the next generation of our oncology programs, including both individualized and off-the-shelf approaches.
Our portfolio also extends beyond solid tumors. In blood cancers, we are advancing mRNA-2808, an investigational multiplexed T-cell engager designed to direct the immune system toward multiple targets expressed in multiple myeloma. This program reflects another strength of our platform: the ability to encode increasingly sophisticated immune therapies in a single mRNA candidate. We believe that mRNA-2808 has the potential to be the first medicine with three T-cell engagers (BCMA X GPR5d X FcRH5) in a single dose.
Together, our investigational individualized cancer therapies, shared-antigen approaches, and mRNA-encoded immune therapies are expanding the ways we can apply our platform across different cancer types and treatment settings.
Moving Toward Cancer Prevention
Perhaps the clearest example of how far this vision can extend is our work in Lynch syndrome, an inherited condition that increases a person’s overall risk of developing cancer, including colorectal, endometrial, ovarian, stomach, pancreatic and prostate cancers.1
Cancer prevention represents one of the most ambitious frontiers in medicine. For people living with Lynch syndrome, which is estimated to affect approximately 1 in 300 people,2 including more than 1 million individuals in the U.S.,3 nearly 2.5 million people in Europe,4 and millions more around the world, the need for new preventive approaches is particularly urgent.
The scientific rationale behind our investigational Lynch syndrome vaccine, mRNA-4194, is compelling. The vaccine is designed around shared frameshift antigens that arise from mismatch repair deficiency—biological signals that are present across many Lynch-associated precancerous lesions and cancers.
The program design encodes 194 frameshift antigen targets selected based on prevalence, immune presentation potential, and relevance across multiple microsatellite instability-high cancers. The team achieved a scientific tour de force, enabling seven mRNA molecules to be included per vial. The goal is to activate antigen-specific T cells capable of recognizing and eliminating abnormal cells before they progress into invasive cancer.
This approach is grounded in a growing understanding of cancer biology. Premalignant lesions may have fewer immune-evasion mechanisms, less heterogeneity and a less suppressive microenvironment than advanced cancers. In other words, there may be advantages to intervening earlier rather than later. The Lynch syndrome program is designed to explore exactly that possibility.
Looking Ahead
When I look at our oncology portfolio today, I see a strategy that is increasingly distinct.
We are studying individualized cancer therapies designed to reduce the risk of recurrence in solid tumors.
We are exploring how the approaches may be used across additional cancer types and disease settings.
We are developing therapies for patients with advanced cancers.
We are advancing new approaches for blood cancers, including mRNA-encoded T-cell engagers.
And we are exploring whether mRNA can help prevent cancer before it starts.
Taken together, these programs reflect a portfolio that spans the cancer continuum.
This evolution reflects a broader vision for Moderna’s future. As our infectious disease portfolio matures, we are increasingly investing in oncology because we believe the opportunity to transform patient outcomes is extraordinary.
Cancer remains one of the world’s greatest medical challenges. We still have much work ahead. Clinical research is inherently uncertain, and every program must earn its way forward with data.
I am encouraged by what we are learning, by the scientists and clinicians driving this work, and by the patients who participate in our studies. Most of all, I am encouraged by the possibility that the future of cancer care may not be defined only by treating cancer after it appears, but increasingly by finding ways to intervene earlier, and perhaps one day, to stop some cancers before they begin.
Forward-Looking Statements
This post contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: mRNA’s potential in oncology, including the potential for cancer prevention; encouraging five-year results from the Phase 2b intismeran study; the potential of mRNA to help generate new cancer-specific T-cell responses; the potential of intismeran as monotherapy; the potential of mRNA-4359; the potential of mRNA-2808; and the potential of mRNA-4194 for individuals with Lynch syndrome. 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.