Moderna Advances Multiple Vaccine Programs to Late-Stage Clinical Trials

• Announces next-generation COVID-19 vaccine candidate as fourth respiratory vaccine to successfully meet its Phase 3 endpoints
• Expects two more Phase 3 readouts in 2024, including combination vaccine against flu and COVID-19, and vaccine against CMV
• Announces positive clinical trial data from three new vaccines against viruses that cause significant burden (Epstein-Barr virus, Varicella-Zoster virus, norovirus) and advances programs toward Phase 3 development
• Anticipates U.S. launch of vaccine against RSV following FDA approval and ACIP recommendation in 2024
• Announces development and commercialization funding agreement with Blackstone Life Sciences for up to $750 million to advance flu program

CAMBRIDGE, MA / ACCESSWIRE / March 27, 2024 / Moderna, Inc. (NASDAQ:MRNA) today announced at its fifth Vaccines Day event clinical and program updates demonstrating advancement and acceleration of its mRNA pipeline. The updates include data readouts in the Company's respiratory and latent and other vaccine portfolios, as well as commercial, manufacturing and financial announcements for its vaccines business.

"Our mRNA platform continues a remarkable track record across our broad vaccine portfolio. Today, we are excited to share that four vaccines in our pipeline have achieved successful clinical readouts across our respiratory, latent and other virus franchises," said Stéphane Bancel, Chief Executive Officer of Moderna. "With five vaccines in Phase 3, and three more moving toward Phase 3, we have built a very large and diverse portfolio addressing significant unmet medical needs. We are focused on execution to further build momentum across our pipeline and business, and to deliver for patients who are impacted by these infectious diseases."

Portfolio Overview

The vaccine portfolio seeks to address infectious diseases that cause considerable health burdens and includes 28 vaccines addressing respiratory, latent and other pathogens.

Latent and Other Vaccine Portfolio

Moderna is advancing five vaccine candidates against viruses that cause latent infections, all of which are in clinical trials. When latent, a virus is present in the body but exists in a resting state, typically without causing any noticeable symptoms. Latent viruses can reactivate and cause clinical symptoms as a person ages, during times of stress or when immunity is compromised. The capacity for latency is a defining feature of members of the Herpesviridae family, including cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) and Varicella-Zoster virus (VZV).

Cytomegalovirus (CMV)

CMV is the most common infectious cause of birth defects in the U.S. and is responsible for several billion dollars in annual healthcare costs. One in 200 babies in the U.S. are born with a congenital CMV infection, and of those affected, one in five will have severe, life-altering health problems. Possible short- and long-term sequelae of CMV infection include microcephaly, chorioretinitis, seizures, sensorineural hearing loss, cognitive impairment and cerebral palsy. There is currently no approved vaccine to prevent congenital CMV.

CMVictory is a pivotal Phase 3 trial evaluating mRNA-1647 against primary CMV infection in women 16 to 40 years of age. The trial is a randomized, observer-blind, placebo-controlled study designed to evaluate the efficacy, safety and immunogenicity of mRNA-1647. The trial is fully enrolled with approximately 7,300 participants from 290 clinical sites globally.

To date, 50 primary infection cases have accrued and are undergoing confirmation. The first interim analysis for the evaluation of vaccine efficacy, which will be triggered when both 81 confirmed per-protocol cases and 12 median months of safety follow-up have occurred, is expected as early as the end of 2024.

Moderna's CMV vaccine candidate mRNA-1647 has advanced to indication expansion studies in adolescents 9 to 15 years of age and adult transplant patients, both of which have begun enrollment.

Epstein-Barr virus (EBV)

EBV is a major cause of infectious mononucleosis (IM) in the U.S., accounting for more than 90% of IM cases annually. Importantly, EBV and IM are associated with a higher lifetime risk of more serious sequelae including certain cancers such as gastric carcinoma, nasopharyngeal carcinoma and multiple types of lymphoma. The lifetime risk of developing multiple sclerosis (MS) is increased by 32-fold after EBV infection. There is currently no approved vaccine to prevent EBV.

Moderna's EBV vaccine candidates are designed to tackle multiple EBV-associated conditions, including prevention of IM (mRNA-1189) and MS and post-transplant lymphoproliferative disorder, a subcategory of lymphoma in solid organ transplant patients (mRNA-1195). The Phase 1 trial for mRNA-1189 was designed to test the safety, reactogenicity and immunogenicity of four different dose levels in participants 12 to 30 years of age in the U.S. The randomized, observer-blind, placebo-controlled study showed mRNA-1189 was immunogenic and generally well tolerated across all dose levels. The Company is advancing mRNA-1189 toward a pivotal Phase 3 trial.

The Phase 1 trial for mRNA-1195 was designed to test the safety, reactogenicity and immunogenicity of two drug products at four different dose levels in healthy EBV seropositive participants 18 to 55 years of age in the U.S. The randomized, observer-blind, placebo-controlled study is fully enrolled.

Herpes simplex virus (HSV)

Herpes simplex virus type 2 (HSV-2) infects approximately 13% of adults globally and is the primary cause of genital herpes. There are an estimated four billion people globally infected with HSV, of which 491 million cases are HSV-2. Recurrent genital herpes causes a reduction in quality of life, which antivirals (current standard of care) only partially restore. Moderna expects that if an HSV vaccine candidate could deliver similar efficacy as a suppressive antiviral treatment, compliance with recommended therapy and associated quality of life would improve. There is currently no approved vaccine to treat HSV-2.

The first in human, fully enrolled Phase 1/2 trial of mRNA-1608 is designed to test safety and immunogenicity and to establish a proof-of-concept of clinical benefit in adults 18 to 55 years of age with recurrent HSV-2 genital herpes. The randomized 1:1:1:1, observer-blind, controlled study is fully enrolled with 300 participants in the U.S.

Varicella-Zoster virus (VZV)

Herpes zoster, also known as shingles, is caused by reactivation of latent VZV, the same virus that causes chickenpox. Declining immunity in older adults decreases immunity against VZV, allowing reactivation of the virus from latently infected neurons, causing painful and itchy lesions. Herpes Zoster occurs in one out of three adults in the U.S. in their lifetime and the incidence increases at 50 years of age. There is potential to reach a growing and underserved patient population.

Moderna's VZV vaccine candidate mRNA-1468 has initial data available from a Phase 1/2 trial, which was designed to test safety and immunogenicity in healthy adults 50 years of age and older in the U.S. The randomized 1:1:1:1:1, observer-blind, active-controlled study of mRNA-1468 elicited strong antigen-specific T cell responses at one month after the second dose and was generally well tolerated. Results of the first interim analysis support the further clinical development of mRNA-1468 for the prevention of shingles. Additional results from the ongoing Phase 1/2 study will be available later this year, including persistence data. The Company is planning for a pivotal Phase 3 trial.

Norovirus

Enteric viruses, including norovirus, are a leading cause of diarrheal diseases, resulting in significant morbidity and mortality worldwide, particularly among young children and older adults. Norovirus is highly contagious and a leading cause of diarrheal disease globally, associated with 18% of all acute gastroenteritis (AGE), resulting in approximately 200,000 deaths per year and substantial healthcare costs. Given the wide diversity of norovirus genotypes, a broadly effective norovirus vaccine will require a multivalent vaccine design. There is currently no approved vaccine to prevent norovirus.

The randomized, observer-blind, placebo-controlled Phase 1 trial was designed to evaluate the safety, reactogenicity and immunogenicity of trivalent (mRNA-1403) and pentavalent (mRNA-1405) norovirus vaccine candidates in 664 participants 18 to 49 years of age and 60 to 80 years of age in the U.S. An interim analysis showed that a single dose of mRNA-1403 elicited a robust immune response across all dose levels evaluated with a clinically acceptable reactogenicity and safety profile. The Company is advancing mRNA-1403 toward a pivotal Phase 3 trial.

Respiratory Vaccine Portfolio

Moderna's approach to ease the global burden of respiratory infections includes vaccine candidates against major causative pathogens, including SARS-CoV-2, respiratory syncytial virus (RSV) and influenza virus. Respiratory infections are a top cause of death in the U.S. and are particularly harmful to the young, immunocompromised, and older adults who experience more severe illness, greater incidence of hospitalization, and greater mortality than younger adults.

Moderna's respiratory pipeline includes Phase 3 trials for investigational vaccines including a next-generation COVID-19 vaccine, an RSV vaccine, a flu vaccine, and a flu and COVID-19 combination vaccine. The pipeline includes three additional flu vaccine candidates with expanded antigen coverage as well as combination vaccine programs.

COVID-19

Moderna continues to address the needs of the endemic COVID-19 market by focusing on public health efforts to increase vaccination coverage rates to reduce the substantial burden of COVID-19 as well as by advancing next-generation vaccines. The Company's mRNA platform can produce variant-matched vaccines on an accelerated time horizon, consistent with recent U.S. Food and Drug Administration (FDA) comments on the timing of potential strain selection for the fall booster season.

A recent announcement of positive interim results from the NEXTCove Phase 3 trial showed that mRNA-1283 elicited a higher immune response against both the Omicron BA.4/BA.5 and original virus strains of SARS-CoV-2 compared to mRNA-1273.222, Moderna's licensed COVID-19 vaccine. mRNA-1283 is designed to be refrigerator-stable and paves the way for a combination vaccine against influenza and COVID-19, mRNA-1083, enhancing the Company's overall respiratory portfolio. This is Moderna's fourth infectious disease vaccine program with Phase 3 data.

Respiratory Syncytial Virus (RSV)

RSV is the leading cause of respiratory illness in young children, and older adults are at increased risk relative to younger adults for severe outcomes. In addition to acute mortality and morbidity, RSV infection is associated with long-term sequelae such as asthma and impaired lung function in pediatric populations, and exacerbation of chronic obstructive pulmonary disease in older adults. Annually, there are approximately two million medically attended RSV infections and 58,000 to 80,000 hospitalizations in children younger than five years old in the U.S. In the U.S., each year there are up to 160,000 hospitalizations and 10,000 deaths in adults 65 years and older due to RSV. Across high-income countries in 2019, RSV caused an estimated 5.2 million cases, 470,000 hospitalizations and 33,000 in-hospital deaths in adults 60 years and older.

mRNA-1345

Moderna's RSV vaccine candidate, mRNA-1345, is in an ongoing Phase 2/3, randomized, observer-blind, placebo-controlled case-driven trial (ConquerRSV) in adults over 60 years of age. In this study, approximately 37,000 participants from 22 countries were randomized 1:1 to receive one dose of mRNA-1345 or placebo.

Based on positive data from the ConquerRSV trial, Moderna has filed for regulatory approvals for mRNA-1345 for the prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) and acute respiratory disease (ARD) in adults over 60 years of age.

The trial met both its primary efficacy endpoints, with a vaccine efficacy (VE) of 83.7% (95.88% CI: 66.1%, 92.2%; p<0.0001) against RSV-LRTD as defined by two or more symptoms, and a VE of 82.4% (96.36% CI: 34.8%, 95.3%; p=0.0078) against RSV-LRTD defined by three or more symptoms. These data were published in the New England Journal of Medicine in December 2023.

A subsequent analysis from the ConquerRSV study with a longer median follow-up duration of 8.6 months (versus 3.7 months in the primary analysis), with a range of 15 days to 530 days, and including subjects from the Northern and Southern Hemispheres was recently presented at the RSVVW'24 conference. In this supplemental analysis, mRNA-1345 maintained durable efficacy, with sustained VE of 63.3% (95.88% CI: 48.7%, 73.7%) against RSV-LRTD including two or more symptoms. VE was 74.6% (95% CI: 50.7%, 86.9%) against RSV-LRTD with ≥2 symptoms, including shortness of breath and 63.0% (95% CI: 37.3%, 78.2%) against RSV-LRTD including three of more symptoms. The stringent statistical criterion of the study, a lower bound on the 95% CI of >20%, continued to be met for both endpoints.

mRNA-1345 has been granted Breakthrough Therapy designation by the FDA for the prevention of RSV-LRTD in adults over 60 years of age. The Company is awaiting regulatory approvals and the U.S. ACIP recommendation in 2024.

Indication expansion studies for mRNA-1345

mRNA-1345 has the potential to protect all vulnerable populations from RSV. Moderna has initiated multiple Phase 3 expansion studies in adults over 50 years of age to evaluate co-administration and revaccination. Additional trials (Phase 1 - Phase 3) have been initiated for high-risk adults, as well as maternal and pediatric populations. Interim data from these studies could be available as early as 2024.

Influenza (Flu)

Worldwide, influenza leads to 3-5 million severe cases of flu and 290,000-650,000 flu-related respiratory deaths annually. Two main types of influenza viruses (A and B) cause seasonal flu epidemics, and the influenza A viruses lead to most flu-related hospitalization in older adults.

The Company has several seasonal influenza vaccine candidates in clinical development. Moderna's seasonal flu vaccine, mRNA-1010, demonstrated consistently acceptable safety and tolerability across three Phase 3 trials. In the most recent Phase 3 trial (P303), which was designed to test the immunogenicity and safety of an optimized vaccine composition, mRNA-1010 met all immunogenicity primary endpoints, demonstrating higher antibody titers compared to a currently licensed standard-dose flu vaccine. In an older adult extension study of P303, mRNA-1010 is being studied against high dose Fluzone HD^®; the trial is fully enrolled. The Company is in ongoing discussions with regulators and intends to file in 2024.

Combination Respiratory Vaccines

Moderna's combination vaccine candidates cover respiratory viruses associated with the largest disease burden in the category. The Phase 3 combination study of the Company's investigational combination vaccine against flu and COVID-19 (mRNA-1083) for adults aged 50 years and older is fully enrolled and data are expected in 2024. mRNA-1083 was granted Fast Track designation by the FDA in May 2023.

Commercial Updates

Respiratory viruses in addition to latent and other viruses represent large unmet or underserved medical needs, and the human and economic costs from these infectious diseases highlight the need for effective vaccines. To help address this need, Moderna expects multiple vaccine product launches in the next few years, each with significant addressable markets.

The 2024 global endemic COVID-19 vaccine market alone is estimated by Moderna to be approximately $10 billion. COVID-19 continues to show a high burden of disease, and while COVID-19 hospitalizations remain high relative to RSV and flu, the risks of Long COVID are also becoming better understood. Moderna is focused on improving education and awareness to increase vaccination rates as Long COVID data suggests even traditionally low-risk groups should be vaccinated. Moderna is also working with health authorities to align the timing of COVID-19 and flu vaccine launches to help improve public health.

For RSV, Moderna estimates the peak annual market to be approximately $10 billion. The Company expects a strong RSV vaccine launch into a large market in 2024. As the only mRNA investigational vaccine with positive Phase 3 data, Moderna's RSV vaccine candidate has a strong profile with consistently strong efficacy across vulnerable and older populations, a well-established safety and tolerability profile, and ease of administration with a ready-to-use, pre-filled syringe formulation, which could relieve some of the burden that falls on pharmacies during the fall vaccination season.

An interim analysis from an ongoing time and motion study evaluating differences in preparation time between a pre-filled syringe (PFS) presentation and vaccines that require reconstitution showed that a PFS presentation could relieve some of the burden that falls on pharmacies during the fall vaccination season. Results from this study suggest that pharmacies may be capable of preparing up to four times as many doses of PFS in an hour compared to vaccines requiring reconstitution.

Moderna estimates flu vaccines represent an approximately $7 billion market in 2024. The market is expected to grow with the rise of more effective vaccines and there is an opportunity to expand the market with next-generation premium flu vaccines as well as combination respiratory vaccines, adding increased value to the health ecosystem.

CMV is expected to be a $2-5 billion annual market. With no vaccine currently on the market and a potential vaccine launch in 2026, Moderna could be the first CMV vaccine in multi-billion-dollar latent vaccine market. In addition, EBV has the potential to address and reduce the burden and cost of EBV infection in multiple populations, while VZV provides the opportunity to enter a large and growing market, which could be $5-6 billion annually. The market for norovirus vaccines is similar to that of rotavirus in pediatrics with opportunity to expand into the adult population, and represents a $3-6 billion annual market.

Moderna's vaccine portfolio targets large addressable markets, with an estimated total addressable market (TAM) of $52 billon for Moderna infectious disease vaccines, which includes a respiratory vaccines TAM of more than $27 billion and a latent and other vaccines TAM of more than $25 billion.

Manufacturing

The Company's manufacturing innovation supports expanding commercialization of a diverse pipeline through efficiency and productivity gains. Its mRNA manufacturing platform enables benefits such as quality, speed, scale and cost efficiency across a footprint that broadly includes the manufacture of plasmid, mRNA, lipid nanoparticles, as well as fill/finish and quality control capabilities.

As the Company continues to build its footprint for the future, it is developing an agile global manufacturing network to meet commercial demand and support its growing pipeline. Pre-clinical through commercial manufacturing occurs at the Moderna Technology Center in Norwood, Massachusetts, which remains central to the Company's network. New facilities being constructed in Australia, Canada and the UK are expected to come online in 2025, and drug product capacity is achieved through a flexible contract manufacturing network. Additionally, the Company has purchased and started build-out of a manufacturing site in Marlborough, Massachusetts, to enable commercial scale of its individualized neoantigen therapy program.

By continuing to pioneer new technologies, including advanced robotics, applying AI and other digital solutions, and driving network and capital efficiency, Moderna's manufacturing network is expected to also drive more predictable cost of sales.

Research and Development Investment Strategy

Today's updates provide further evidence that Moderna's mRNA technology platform is working, and with a rate of success higher than industry standard. Looking ahead, research and development will continue to be the Company's top capital allocation priority.

As Moderna looks to create value through the research and development strategy for its vaccine portfolio, it is taking three prioritization parameters into consideration: pipeline advancement, revenue diversification and risk reduction. As part of its strategy, the funding options Moderna considers are self-funding, project financing and partnerships.

Moderna recently entered into a development and commercialization funding agreement with Blackstone Life Sciences to advance the Company's flu program. As part of the agreement, Blackstone will fund up to $750 million with a return based on cumulative commercial milestones and low-single digit royalties. Moderna expects to recognize the funding as a reduction in research and development expenses and will retain full rights and control of the Company's flu program. This funding does not result in any change to Moderna's 2024 research and development framework of approximately $4.5 billion.

About Moderna

Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.


Moderna's mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.

INDICATION (U.S.)

SPIKEVAX (COVID-19 Vaccine, mRNA) is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older.

IMPORTANT SAFETY INFORMATION

• Do not administer to individuals with a known history of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine.
• Appropriate medical treatment to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of the vaccine.
• Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose. The observed risk is higher among males under 40 years of age than among females and older males. The observed risk is highest in males 18 through 24 years of age.
• Syncope (fainting) may occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting.
• Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished response to the vaccine.
• The vaccine may not protect all vaccine recipients.
• Adverse reactions reported in clinical trials following administration of the vaccine include pain at the injection site, fatigue, headache, myalgia, arthralgia, chills, nausea/vomiting, axillary swelling/tenderness, fever, swelling at the injection site, and erythema at the injection site, and rash.
• The vaccination provider is responsible for mandatory reporting of certain adverse events to the Vaccine Adverse Event Reporting System (VAERS) online at https://vaers.hhs.gov/reportevent.html or by calling 1-800-822-7967.
• Please see the SPIKEVAX Full Prescribing Information. For information regarding authorized emergency uses of the Moderna COVID-19 Vaccine, please see the EUA Fact Sheet.

Spikevax^® is a registered trademark of Moderna.
Fluzone^® is a registered trademark of Sanofi Pasteur.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: the advancement of Moderna's programs under clinical development; the timing for anticipated approvals of vaccine candidates; the efficacy, safety and tolerability of vaccine candidates; the total addressable markets for programs under development; the efficiencies and advantages of Moderna's mRNA platform; future capital allocation and financing efforts; and anticipated spending for R&D in 2024. 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 press release 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, 2023, 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 press release. ​

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Moderna Contacts

Media:
Chris Ridley
Head, Global Media Relations
+1 617-800-3651
Chris.Ridley@modernatx.com

Investors:
Lavina Talukdar
Senior Vice President & Head of Investor Relations
+1 617-209-5834
Lavina.Talukdar@modernatx.com

SOURCE: Moderna, Inc.