2022 was a Pivotal Year
In 2022, we matured to a company with multiple products on the market, and an extensive research pipeline across multiple modalities. Indeed, after 12 years of hard work on the science, we reached the most important pivot point in our company’s history.
We delivered again in the fight against COVID with two authorized Omicron-targeting bivalent vaccines, mRNA-1273.214 and mRNA-1273.222, bringing the latter to market in less than two months. Today, our COVID-19 vaccines have been approved in more than 70 countries as we continue to build our respiratory franchise.
Our platform technology also delivered the world’s first-ever mRNA cancer treatment to show efficacy in a randomized Phase 2 study. By making an individualized medicine for each unique patient, we are pioneering a new frontier in the fight against cancer with cancer treatments. And in another important advancement this year, we are seeing early promise in two rare disease programs.
Additionally, with the announcement of our Global Public Health strategy in 2022, we expanded our portfolio with a commitment to develop vaccines against priority pathogens that threaten global health including HIV, tuberculosis, malaria and neglected tropical diseases. We will continue to transparently report on our progress in our ESG Report, the first of which published last June.
To support our accelerated growth and to further deliver on our mission, we have stood up operations in 17 countries and we are building manufacturing plants around the world. At the same time, we are entering into partnerships with overseas governments, including a recently announced 10-year strategic partnership with the UK, to bring pandemic response capabilities as well as mRNA research, development and manufacturing to their broader health and science ecosystem.
We brought on new leaders in 2022 who will help us scale during our next phase of growth as we prepare for several upcoming new product launches. The Moderna team is now approximately 3,900 strong, all working together to positively impact human health globally.
Reflecting on our 2022 strategic priorities, we set out to advance our pan-respiratory booster vaccine; develop first-in-class vaccines against the most important latent viruses; bring to market therapeutics based on mRNA-encoded proteins; and bring to market innovative therapeutics based on mRNA-encoded gene editing enzymes. Our team has made important progress on these priorities to deliver on our mission for patients and create value for our shareholders, our employees, our communities and our partners.
Moderna is at an exciting stage with a growing mRNA platform, including three Phase 3 trials ongoing for new drugs, upcoming proof-of-concept data in rare diseases, significant commercial momentum and a strong financial position.
Looking ahead, we will continue to lead with our Values, our Mindsets and a deep sense of purpose embedded in everything we do. Our focus is to use our mRNA platform and the infrastructure we have built to address infectious and serious diseases. We will measure our success on the impact we make on improving human health.
Evolving Our Mission
When we set out in 2010, our Mission was “to deliver on the promise of mRNA science to create a new generation of transformative medicines for patients.” Just as our company evolves in this new age of medicine, so too must our mission.
Moderna has delivered on the promise of mRNA science.
Our team is using this knowledge to bring new drugs to the clinic and our platform is coming to life with multiple investigational drugs within modalities. Now we possess the necessary data, experience and expertise needed to quickly develop innovative medicines that continue to perpetually deliver on the promise of mRNA science.
With this, we can continue to build Moderna into the company we want it to be. We are harnessing the power of mRNA to create a new category of medicines and a company that maximizes its impact on human health. Our new Mission:
Deliver the greatest possible impact to people through mRNA medicines.
Delivering the Greatest Possible Impact through mRNA Medicines
Now that we know our mRNA medicines can have a profound impact on human health, we will continue to focus on relentless execution of our goals. I will share a few highlights of our recent progress and anticipated milestones in this letter and you can learn more from our September 2022 R&D Day announcement.
Respiratory Vaccines
As we build our respiratory franchise, we are applying our experience and using our mRNA platform to develop medicines that can help prevent hospitalizations and deaths from the top respiratory viruses. By pursuing combination products to protect against a range of diseases, we can potentially help decrease morbidity and mortality from respiratory disease, lower healthcare costs and increase health security globally. Our late-stage respiratory vaccine pipeline continues to progress. The Phase 3 immunogenicity and safety study of one of our seasonal influenza vaccine candidates in the Southern Hemisphere is fully enrolled with approximately 6,000 participants. We also initiated a Phase 3 efficacy trial in the Northern Hemisphere to test the vaccine’s efficacy compared to a currently licensed seasonal influenza vaccine.
The Phase 3 study of our RSV vaccine candidate in adults over 60 years of age has enrolled more than 36,000 of the 37,000-participant target. The study has been designed to provide an efficacy readout expected in the 2023 winter season. Since RSV also imposes a significant disease burden on children, we are studying our RSV vaccine candidate in an ongoing Phase 1 trial in pediatric populations.
We are also progressing several combination respiratory vaccine candidates. A Phase 1/2 study of our combination vaccine candidate targeting SARS-CoV-2 and influenza is fully enrolled and ongoing. We further initiated a clinical trial for a combination vaccine candidate targeting SARS-CoV-2, influenza, and RSV this year.
Latent Vaccines
Once a human is infected by a latent virus, the virus remains in the body and can lead to lifelong medical complications. We are committed to developing a portfolio of vaccine and therapeutic candidates against latent viruses, including cytomegalovirus (CMV), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV) and varicella-zoster virus (VZV). To date, we have enrolled approximately 40 percent of anticipated participants in the Phase 3 study of our CMV vaccine candidate and enrollment is ongoing in the U.S. and internationally.
Public Health Vaccines
We have also focused on developing a global health vaccine program since our inception and with our recently announced Global Public Health Strategy, we are expanding our work to develop vaccines against 15 priority pathogens that threaten global health by 2025. We are committed to bringing the full force of our mRNA vaccine platform to combat infectious diseases of public health concern and we look forward to working with global partners to prevent future pandemics and help millions of people worldwide.
Therapeutics
Cancer
Personalized cancer vaccines target an individual patient’s unique tumor mutations to selectively treat their cancer. Moderna’s personalized cancer vaccine program is being developed in partnership with Merck and is designed to stimulate an immune response by boosting T cells, which are believed to be necessary for recurrence-free survival.
Recent primary data from our Phase 2 study showed that the investigational personalized cancer vaccine in combination with KEYTRUDA® (pembrolizumab) can improve recurrence-free survival in patients with resected melanoma at high risk of recurrence, compared to KEYTRUDA alone. Adjuvant treatment with mRNA-4157/V940 in combination with KEYTRUDA reduced the risk of recurrence or death by 44 percent.
For the first time ever, we have demonstrated the potential for mRNA to have an impact on outcomes in a randomized clinical trial in melanoma. We will begin additional studies in melanoma and other forms of cancer with the goal of bringing truly individualized cancer treatments to patients.
Rare Diseases
In rare diseases, our programs aim to deliver mRNA into target organ cells as a therapeutic approach for diseases caused by a missing or defective protein. We are excited about several clinical trials in this therapeutic area that have the potential to help improve quality of life for young patients and their families.
The Phase 1/2 Paramount study of our propionic acidemia program is ongoing and the first two groups of patients are fully enrolled. Encouraging early data have shown a decrease in the number of metabolic decompensation events (MDEs) among participants and initial discussions with regulators are supportive of MDE as a primary endpoint for a pivotal study. We are optimistic that we will have clinical impact so that we can finalize the dose in early 2023. The Phase 1/2 study of our methylmalonic acidemia candidate is ongoing and we are recruiting participants in the United Kingdom, Canada, and the U.S. with preliminary data expected to be available in 2023.
We are also evaluating the safety, tolerability and pharmacology of a single IV dose of our therapeutic candidate for glycogen storage disease 1a (GSD1a) in adult participants in a Phase 1 study. Enrollment is ongoing and initial data are expected in 2023.
Based on proof-of-concept data and leveraging our learnings from our rare disease programs, we recently announced a new development candidate for ornithine transcarbamylase (OTC) deficiency, which uses the same lipid nanoparticle (LNP) as our GSD1a program. This is our sixth rare disease candidate.
Cardiovascular
We are excited to develop novel mRNA medicines to address the significant unmet medical needs of heart failure patients, joining our existing clinical candidates in infectious diseases, oncology and rare diseases. In December 2022, we dosed the first patient in our relaxin Phase 1B clinical trial, which is an important step in advancing a potential new treatment for cardiovascular disease.
Our drug candidate is designed to produce the naturally occurring cardioprotective hormone relaxin and uses similar technology as our investigational treatment for propionic acidemia. Longer duration relaxin and repeated infusions could allow for improved outcomes with a treatment that matches the time course of the pathophysiology of heart failure, which large pharmaceutical companies have been unable to show in previous trials.
At the end of 2021, we saw early positive data from the AstraZeneca-led Phase 2 EPICCURE study evaluating the use of an mRNA therapeutic that encodes for VEGF-A in patients undergoing coronary artery bypass grafting. We continue to push new boundaries in the treatment of cardiovascular and other ischemic vascular diseases to address serious unmet needs with the goal of improving patients’ lives.
Inhaled Pulmonary
At the end of 2021, we announced our first program in a new modality with “inhaled pulmonary therapeutics.” Since then, GLP toxicology studies for the Cystic Fibrosis (CF) program Vxc-522 have been ongoing in partnership with Vertex. In December 2022, the U.S. FDA cleared the Investigational New Drug application for Vxc-522, our first inhaled mRNA candidate. With this new development candidate moving to the clinic, this marks our seventh modality going into human studies.
Gene Editing
Next on the horizon are innovative therapeutics based on mRNA-encoded gene editing enzymes. Moderna Genomics is our effort to expand the use of our platform to create more innovative drugs to help patients with new cures for diseases. Our vision is to be a leader in large, complex genomic editing, and our strategy is to invest internally and to set up strategic partnerships with next-generation gene editing companies.
Acting Responsibly
Today, we are guided by our unwavering belief that Moderna's mRNA platform can solve the world’s greatest health challenges—from diseases impacting millions to medicines personalized down to the individual patient. As part of our Global Public Health Strategy, we launched our new mRNA Access program to create a community of global scientists who can access our mRNA vaccine technology from anywhere in the world. The world needs novel, innovative approaches to address both known and emerging infectious diseases and we know that we can't go it alone.
We are also committed to maintaining a great work environment for our employees, as exemplified by our eighth consecutive year ranked as a best company to work for by Science in 2022. Being our best also means building a company that is responsible and minimizes our impact on the planet, and I am proud of our progress toward setting a baseline for our greenhouse gas emissions and establishing science-based targets.
