September 12, 2019
By Stéphane Bancel
Chief Executive Officer
Today, we hosted Moderna’s annual R&D Day in New York City during which we announced two eagerly awaited, critical positive data readouts — Phase 1 studies of our cytomegalovirus (CMV) vaccine (mRNA-1647) and our antibody against chikungunya virus (mRNA-1944).
Both trials were designed to answer important scientific questions, and we knew—no matter what the data showed—that our learnings would help inform our future efforts and advance our understanding of the potential of mRNA to become a new category of medicines. I’m incredibly proud of our team as these results are a testament to their dedication and validate the scientific and technological foundation upon which we built the company.
Addressing unmet needs
Moderna is pioneering mRNA therapeutics and vaccines to create a new generation of medicines to address unmet medical needs. Our prophylactic vaccines modality is an important part of this effort, as we believe the world needs novel, innovative approaches to address both known and future infectious disease threats. From our beginning, we’ve been working to advance a new approach—mRNA vaccines and therapeutics for the prevention and treatment of a wide range of diseases. This includes infectious diseases such as influenza, CMV, respiratory syncytial virus (RSV) and Zika.
We talked about that unmet need and the opportunity to help people around the world at this morning’s event. CMV can be transmitted during pregnancy and is the leading infectious cause of birth defects in the United States.[i] Chikungunya is a mosquito-borne virus that can cause debilitating joint pain and has led to outbreaks around the world.[ii] Additionally, both CMV and chikungunya are complex viruses that have eluded many previous attempts to develop vaccines that could protect against infection.
Sixth positive Phase 1 data readout of a Moderna prophylactic vaccine
These strong CMV human data mark the sixth positive Phase 1 readout from the Moderna vaccine platform, an important area for our future growth. Additionally, these results underscore the ability of our platform to translate therapeutically relevant pharmacology from preclinical species to humans in clinical trials—making our CMV vaccine a technical breakthrough.
Each vial of our CMV vaccine contains six mRNAs (five encoding the subunits of the pentamer complex and one encoding the glycoprotein B target antigen). I give a lot of credit to our technical development teams for their relentlessness in building our capabilities to manufacture this at clinical GMP scale.
Large commercial opportunity for CMV
mRNA-1647 is wholly owned by Moderna, and we believe it has the potential to be a blockbuster commercial opportunity. Our team understands the urgent need for a preventative vaccine. As a result, we have been working for several quarters to ensure this program can transition to a dose-confirmation Phase 2 study in the near term, while preparing for a pivotal Phase 3 study in parallel.
Our ultimate goal is to eradicate CMV. As we generate more clinical data over time, we see three potential waves of indications to get us closer to this goal: women of child-bearing age, adolescents and infants. We believe this is possible because unlike many viruses, the CMV virus can only survive in humans. Thus, spread of the virus occurs between people - between a child and parent, or between a pregnant woman and her developing fetus. People who are immune to CMV, through infection or by an effective vaccine, would be protected from a new infection and serve as a barrier to further spread of the virus. Once enough people become immune to CMV, it would be very difficult for the virus to find new, vulnerable hosts. At a certain point, no new infections would occur and the virus would become eradicated. A real-world example of this is Rubella, which is no longer endemic in the U.S. because of pediatric MMR immunization.
mRNA-1647 is designed to provide this protective seropositivity or immunity, not only protecting them against infection but preventing spread of the virus that they might otherwise cause. Currently the greatest unmet need is preventing congenital transmission—women who may become pregnant should be immunized so they can reduce the chance of their baby being born with birth defects as a result of congenital infection. As we learn more about the ability of mRNA-1647 to protect against CMV infection, we hope to expand its use in other key populations and ultimately provide widespread immunity.
Breakthrough scientific achievement: first systemic mRNA therapeutic to show production of a secreted protein in humans
Today, we presented chikungunya Phase 1 data that we believe represent a significant scientific breakthrough: for the first time, we showed the ability to generate therapeutic levels of a complex protein (monoclonal antibody) in humans through systemic administration of mRNA.
You can read our president Stephen Hoge’s blog post from February to learn more about the scientific significance of mRNA-encoded antibodies. He also discusses why we selected chikungunya—and the antibody discovered by Vanderbilt scientists—to test this technology. mRNA-1944 is being developed in collaboration with DARPA, as they see the potential for this technology to be able to respond rapidly to future pandemics.
Additionally, these data are significant because the same lipid nanoparticle (LNP) formulation is being used in our first rare disease program: mRNA-3704 for methylmalonic acidemia (MMA). This program is now recruiting in a Phase 1/2 study.
Reflecting on progress to date
The data presented at Moderna’s annual R&D Day are just one part of our advancing pipeline, and they are an important part. These findings help to validate the scientific foundation of our work and also lay the groundwork for significant commercial opportunities.
It is defining moments like these that cause me to reflect on our progress. We took calculated risks and made early investments in our platform and our manufacturing infrastructure that have now put us in the position to advance and produce investigational mRNA medicines and vaccines at our Norwood manufacturing site. We have the flexibility to manufacture commercial product there as well.
We have now demonstrated a total of 10 positive interim Phase 1 data readouts.
Our platform investments in research, manufacturing and clinical development have enabled 16 investigational medicines to start clinical trials in the last three and a half years. And now, across five modalities, we have shown that our development candidates have an acceptable safety profile and are generally well-tolerated[iii], result in consistent protein expression, encode functional proteins at well-tolerated doses and translate from preclinical models to humans.
As a result, we’re thrilled to be progressing additional investigational mRNA therapies into Phase 2 and to be preparing for our first Phase 3 trial with our CMV vaccine.
I continue to feel excited about Moderna’s scientific leadership in the mRNA space. Our team thrives on embracing the unknown and is driven by our mission to help patients. I look forward to generating more data as we keep investing in and advancing our science, technology and pipeline with the goal of creating a new class of medicines to prevent or treat a wide range of diseases.
If you are curious and would like to learn more about these scientific breakthroughs, please have a look at the R&D Day webcast.
[iii] Common Adverse Events by Modality - Prophylactic Vaccines: injection site pain, myalgia, and fatigue; Cancer Vaccines: for PCV, the most common grade 2 adverse events were fatigue, soreness at the injection site, colitis, and myalgias; Intratumoral Immuno-Oncology: for OX40L, multiple grade 2 and a single grade 3 transient reversible injection related reactions; Localized Regenerative Therapeutics: for VEGF-A, mild injection-site reactions; and Systemic Secreted Therapeutics: for antibody against chikungunya virus, none of the participants treated with mRNA-1944 at the low or middle doses experienced significant adverse events; three of the four participants at the high dose had infusion related adverse events, with the highest grade by subject being Grade 1 (n=1), Grade 2 (n=1) and Grade 3 (n=1).