Reflecting on Moderna’s Phase 3 CMV Vaccine Readout

Stéphane Bancel

CEO of Moderna

Today, we announced topline results from a Phase 3 pivotal trial evaluating the efficacy of mRNA-1647, our investigational cytomegalovirus (CMV) vaccine. The study did not meet its primary efficacy endpoint of preventing CMV infection in seronegative female participants of childbearing age (16-40 years). With this news, we will discontinue our congenital CMV clinical development program.

Of course, this outcome is disappointing for families and healthcare professionals who have been eagerly awaiting a vaccine to prevent congenital CMV, a leading cause of infectious birth defects. The majority of the data from this trial is still forthcoming, and we will share our full results with the scientific community in hopes that our learnings can contribute to the continued pursuit of a congenital CMV vaccine.

After the pandemic, to diversify from our first COVID vaccine and to drive sales growth, we prioritized the development of an additional 10 investigational products—for 11 prioritized products in total. Eight of those 11 have already achieved proof of concept or are approved. Our CMV vaccine candidate would have been number nine. We continue to await results from mRNA-4359, our investigational therapy designed to elicit T-cell immune responses against tumor and immunosuppressive cells, and mRNA-1403, our norovirus vaccine candidate. While the outcome on the pivotal trial for CMV primary infection is not what we hoped for, our portfolio of eight prioritized products either approved or with established proof of concept remains extraordinary for a company pioneering an entirely new class of medicines.

CMV has long been one of the most difficult vaccine targets. Despite decades of effort across multiple vaccine technologies, no one has yet developed an effective vaccine. This study for mRNA-1647 was particularly challenging in that it was aiming to prevent primary infection from a latent virus, rather than preventing symptomatic disease. This makes this trial unique in our pipeline; it was the only clinical trial in which the prevention of primary infection was a primary endpoint. We believe there is minimal read-through to the broader platform, including other latent viruses.

We are clearly disappointed by the failure to prevent primary infection because it means there is still no vaccine for the prevention of congenital CMV despite the many decades of work by the field. CMV does cause significant disease in other contexts, including reactivation of the latent virus in those undergoing bone marrow transplantation, and we will continue to explore the potential of mRNA-1647 to suppress disease associated with reactivation in those high-risk patients through our ongoing Phase 2 study.

We remain steady on our path, executing on our R&D strategy as our broader pipeline momentum continues:

Our respiratory portfolio is delivering meaningful public health impact, with three approvals this year alone and two more products that have been or will be submitted for approval in 2025.
Our cancer programs are showing promise, including strong proof of concept from intismeran autogene (mRNA-4157) as we await Phase 3 trial results, and encouraging early data from mRNA-4359 with potential proof of concept in 2026.
Our rare disease candidates are advancing in the clinic.

These results reinforce why we built Moderna: to take bold scientific risks in pursuit of breakthroughs that can transform human health.

We do not anticipate any impact to our 2025 financial guidance or our expectation of achieving breakeven in 2028. We anticipated minimal initial revenue contribution from mRNA-1647 given necessary investments in market building and launch, and expected the product to be cash-flow negative in 2028.

In closing, I am tremendously grateful for our dedicated team, our partners at clinical trial sites, and all the trial participants who made this research possible. We are proud to have tried to develop a vaccine for congenital CMV given the unmet medical need. Our work on mRNA-1647 has deepened scientific understanding of this complex virus and advanced what’s possible with mRNA science.

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: Moderna’s 2025 financial guidance and its expectation of achieving breakeven in 2028; the potential of mRNA-1647 for bone marrow transplant patients and Moderna’s ongoing Phase 2 trial; the potential of Moderna’s prioritized portfolio; Moderna’s belief that there is minimal read-through from the mRNA-1647 trial to the broader platform; and anticipated milestones for Moderna’s pipeline programs, including potential regulatory submissions in 2025 and potential proof of concept in mRNA-4359. 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, 2024, 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 presentation 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.