Moderna Announces Clinical and Program Updates at 3rd Annual Vaccines Day

• COVID-19 vaccine Phase 2/3 study in children 6 months to under 6 years has successfully met its primary endpoint with robust neutralizing antibody titers similar to adults. Moderna is moving forward with global regulatory submissions for mRNA-1273 for primary vaccination of children 6 months to under 6 years of age.
• Moderna has initiated a submission to the FDA for emergency use authorization of mRNA-1273 in children 6 to under 12 years of age; mRNA-1273 is approved for use in this age group in Europe, Canada, and Australia.
• In an interim analysis of a Phase 2 study of influenza vaccine candidate mRNA-1010, no significant safety concerns were identified, and the immunogenicity data is consistent with a potential for superiority to standard dose vaccine for influenza A strains.
• Moderna is advancing vaccine candidates against five viruses that cause latent infections, three of which are in clinical trials. In a Phase 2 study, the CMV vaccine (mRNA-1647) was observed to be generally well tolerated and interim data demonstrates strong immunogenicity.
• Moderna announces an increase in signed Advance Purchase Agreements for 2022 from $19 billion announced on February 24, 2022, to $21 billion.

CAMBRIDGE, MA / ACCESSWIRE / March 24, 2022 / Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messengerRNA (mRNA) therapeutics and vaccines, today announced clinical and program updates demonstrating expansion and advancement of its mRNA pipeline. This announcement reflects the Company's commitment to expanding its portfolio by building on Moderna's experience with Spikevax®, its COVID-19 vaccine. The updates include advancements in the Company's respiratory and latent virus portfolios, updates on its global health programs, and new partnerships formed in the recently launched mRNA Access program.

"We believe our mRNA platform disrupts the traditional vaccines market and as indicated in our Vaccines Day announcements, we expect to bring many more safe and effective vaccines to market. There is an opportunity for Moderna to positively impact public and global health, and with 31 active development programs, 19 of which are in the clinic, we expect to address several critical unmet medical needs with the power of our mRNA platform," said Stéphane Bancel, Chief Executive Officer of Moderna.

"We are pleased to announce advancements across our pipeline and the formation of significant research partnerships intended to accelerate development of vaccines to pathogens that pose the greatest threat to global health," said Stephen Hoge, M.D., President of Moderna. "We are focused on unmet vaccine needs for respiratory viruses, latent viruses, and persistent global health threats. Importantly, we also continue to advance a range of COVID-19 vaccine options for adults, adolescents, and pediatric populations."

Updates on vaccines candidates against respiratory viruses

Moderna is implementing a multi-pronged approach to ease the substantial global burden of respiratory infections with vaccine candidates aimed at the major causative agents, including the SARS-CoV-2 virus, influenza virus, respiratory syncytial virus (RSV), and the four endemic human coronaviruses (HCoVs). Respiratory infections are a top cause of death globally and are particularly impactful to older adults who experience more severe illness and greater mortality than younger adults.

As COVID-19 transitions to an endemic phase, Moderna focuses on defending against SARS-CoV-2 variants, developing multi-valent boosters for the broadest immunity and protection for high-risk individuals, and advancing a next-generation refrigerator-stable vaccine.

COVID-19 Boosters

Moderna is advancing development of several boosters, including the prototype booster, an Omicron-specific booster and a bivalent booster. In the U.S., a Phase 2 study of the Omicron-specific booster candidate (mRNA-1273.529) as a third or fourth dose is fully enrolled. Also in the U.S., enrollment is ongoing in a Phase 2 study of the bivalent booster candidate (mRNA-1273.214), which combines the Omicron-specific booster candidate (mRNA-1273.529) and the prototype vaccine (mRNA-1273).

In the U.K., enrollment is ongoing in a Phase 3 to evaluate Omicron-containing candidates as a third or fourth dose in individuals who received any primary series.

Spikevax®/Moderna COVID-19 Vaccine in ages <18

In adolescents aged 12-17 years, the primary series (2 dose, 100 µg) is authorized/approved in more than 40 countries. Moderna is preparing to submit data for 50 µg COVID-19 boosters in this age group.

In children aged 6-11 years, the primary series (2 dose series, 50 µg) is authorized/approved in Australia, Canada and the EU. Moderna is evaluating 25 µg dose as a primary series and a booster dose in this age group.

The Phase 2/3 KidCOVE study in children 6 months to under 6 years has successfully met its primary endpoint. The interim analysis showed a robust neutralizing antibody response after a 25 µg two-dose primary series of mRNA-1273 along with a favorable safety profile. Based on these data, Moderna will submit a request for authorization of a 25 μg two-dose primary series of mRNA-1273 for children 6 months to under 6 years of age to the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) and other global regulators in the coming weeks.

Similar to adults, Moderna is preparing to evaluate the potential of a booster dose for all pediatric populations, including those age 6 months to under 6 years, 6 to under 12 years, and adolescents.

Next-Generation COVID-19 Vaccine Candidate

Development is underway for a next-generation refrigerator-stable mRNA COVID-19 vaccine (mRNA-1283) that is expected to facilitate distribution and administration by healthcare providers.

In a Phase 1 study of mRNA-1283, preliminary results indicate that when administered as primary series at lower doses levels (10 µg, 30 µg), mRNA-1283 elicits a robust anti-SARS-CoV-2 neutralizing antibody response comparable to the 100 µg mRNA-1273 primary series. The frequency of local and systemic solicited adverse reactions of the mRNA-1283 primary series administered at lower dose levels (10 µg, 30 µg) was overall comparable to mRNA-1273.

Enrollment is complete in a Phase 2 study evaluating booster doses of mRNA-1283, mRNA-1283.211 (SARS-CoV-2/Beta bivalent), and mRNA-1283.529 (Omicron monovalent).

Influenza (Flu)

Worldwide, influenza leads to 3-5M severe cases of flu and 290-650K flu-related respiratory deaths annually. Three main types of influenza viruses (A, B, and C) infect humans. Although influenza A and B viruses cause seasonal flu epidemics, it is the influenza A viruses that lead to >95% of flu-related hospitalization in adults. Influenza A viruses are divided into subtypes based on two surface proteins, hemagglutinin and neuraminidase, which are recognized by the immune system and are capable of triggering an immune response.

Moderna is advancing three influenza vaccine development strategies, each with increasing levels of enhancements aimed at improving immune responses. First, a seasonal quadrivalent vaccine (mRNA-1010) using strains recommended by the World Health Organization (WHO). Second, Moderna is adding more hemagglutinin antigens (e.g. H3, H1) to expand strain matching (mRNA-1011/1012). And third, Moderna is adding neuraminidase antigens to target more conserved surface protein regions and broaden immunologic breadth (mRNA-1020/1030).

In an interim analysis of a Phase 2 study of mRNA-1010, no significant safety concerns were identified, and the immunogenicity data is consistent with a potential for superiority to standard dose vaccine for influenza A strains (which drives the majority of disease in adults). The interim data is consistent with potential for non-inferiority to standard dose vaccine in influenza B strains (primarily a concern in pediatrics).

Respiratory Syncytial Virus

Respiratory Syncytial Virus (RSV) is the leading cause of respiratory illness in young children and older adults are at high risk for severe infections. 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. Each year in the U.S. there are approximately 177,000 hospitalizations in adults age 65 and older due to RSV, and approximately 14,000 deaths.

A Phase 1 RSV trial (mRNA-1345) is ongoing evaluating tolerability, reactogenicity and immunogenicity in children, younger adults, older adults and women of child-bearing age. In an interim analysis, mRNA-1345 boosted RSV neutralizing antibodies and was well-tolerated at all dose levels in younger and older adults.

Also underway is ConquerRSV, a pivotal Phase 3 trial in adults ≥ 60 years of age; expected enrollment is ~34,000 participants in multiple countries.

COVID-19 + Flu

A Phase 1 COVID-19 + Flu vaccine trial (mRNA-1073) in healthy adults aged 18 to 75 years old is expected to begin in 2022.

COVID-19 + Flu + RSV

Moderna launched a respiratory combination vaccine program to target three of the most significant viruses causing respiratory disease in older adults. The new combination respiratory vaccine candidate (mRNA-1230) is envisioned as an annual booster targeting SARS-CoV-2 virus, influenza virus and RSV.

New Program against Endemic Human Coronaviruses

Moderna is introducing a program to develop a vaccine candidate (mRNA-1287) against endemic human coronaviruses (HCoVs). While less-well known than other coronaviruses, HCoVs are a significant cause of respiratory disease worldwide. Four HCoVs (HCoV-229E, -NL63, -OC43, and -HKU1) are endemic globally, accounting for approximately 10% to 30% of upper respiratory tract infections in adults.

Updates on vaccines against latent viruses

Moderna is advancing vaccine candidates against five viruses that cause latent infections, three 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 during times of stress or when immunity is compromised. The capacity for latency is a defining feature of human immunodeficiency virus (HIV) and members of the Herpesviridae family, including Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Varicella-Zoster virus (VZV), and herpes simplex virus (HSV). Moderna is advancing candidates against each of these latent viruses, targeting both the potential short and long-term health impacts of infection.

Cytomegalovirus (CMV)

CMV is the most common cause of congenital infection worldwide and responsible for more than $1B in annual healthcare costs. Possible short- and long-term sequelae of CMV infection include microcephaly, chorioretinitis, seizures, sensorineural hearing loss, cognitive impairment, cerebral palsy, and seizure disorder.

In a Phase 2 study (mRNA-1647), the Company's CMV vaccine was observed to be generally well tolerated and seven-month interim data demonstrates strong immunogenicity in both CMV-seronegative and CMV-positive participants.

CMVictory is a pivotal Phase 3 trial evaluating mRNA-1647 against primary CMV infection in women ages 16-40 years and is expected to enroll up to 6,900 women from approximately 150 clinical sites.

Since birth defects are not the only impacts of CMV, Moderna also plans to evaluate mRNA-1647 against long-term impacts (autoimmune disease, cancer, cardiovascular) in Phase III trials.

Epstein-Barr virus (EBV)

EBV, a globally prevalent herpesvirus, is a major cause of infectious mononucleosis (IM) and an associated risk for several long-term medical conditions. Long term, EBV is associated with certain lymphoproliferative disorders, a higher risk of developing cancers and autoimmune diseases, and an approximately 32-fold increased risk of developing multiple sclerosis (MS).

Moderna is developing mRNA-1189 aimed at preventing IM and is currently conducting a Phase 1 trial that is in expansion phase following a favorable initial safety review. Additionally, a therapeutic vaccine (mRNA-1195) against long-term EBV sequelae, such as MS and post-transplant lymphoproliferative disease (PTLD), is in preclinical development.

Human immunodeficiency virus (HIV)

Human immunodeficiency virus (HIV), the cause of AIDS, continues to have devastating health effects globally, resulting in approximately 700,000 deaths worldwide annually. Moderna is advancing three clinical trials of HIV vaccines with partners. First, enrollment is underway in two Phase 1 trials of mRNA-1644 in collaboration with IAVI and the Bill & Melinda Gates Foundation. mRNA-1644 is designed to elicit broadly neutralizing HIV-1 antibodies (bnAbs), a goal widely considered to be essential for prevention of HIV through vaccination. The immunogens being tested were developed by scientific teams at IAVI and Scripps Research and will be delivered via Moderna's mRNA technology.

Second, dosing is ongoing in a Phase 1 trial (mRNA-1574) designed to evaluate the safety and immunogenicity of experimental HIV trimer mRNA vaccines. The primary hypothesis is that the soluble and membrane-bound HIV envelope trimer mRNA vaccines will be safe and well-tolerated by HIV-uninfected individuals and will elicit autologous neutralizing antibodies. The trial is expected to enroll approximately 100 HIV-negative adults, aged 18 to 55 years.

Varicella Zoster Virus (VZV) and Herpes Simplex Virus Type 2 (HSV-2)

Preclinical studies are underway for VZV (mRNA-1468) and HSV (mRNA-1608) vaccine candidates, both members of the Herpesviridae family that establish life-long latent infections.

Primary VZV infection leads to "chickenpox" and then establishes latency. Declining immunity in older adults can lead to reactivation of the virus as herpes zoster (HZ) or "shingles," causing painful and itchy lesions. Herpes zoster occurs in 1 out of 3 adults in their lifetime. Moderna's vaccine candidate against herpes zoster/shingles generated a similar anti-gE immune response compared to an adjuvanted subunit gE vaccine (proxy for Shingrix^TM) in mice and nonhuman primates.

HSV-2 establishes life-long latent infections within sensory neurons from which it can reactivate, leading to genital herpes. Moderna's HSV-2 vaccine candidate induces strong immune responses in preclinical animal studies at levels comparable to, or higher than, those induced by natural infection in healthy adults.

Global health vaccines & mRNA Access

Moderna is advancing its global public health strategy with three new initiatives aimed at advancing mRNA vaccines. First, Moderna has announced a commitment to advance vaccines targeting 15 priority pathogens into clinical studies by 2025. Moderna will prioritize HIV, Tuberculosis (TB), Malaria, neglected tropical diseases, and priority pathogens of the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI).

Second, Moderna launched mRNA Access, a program that offers researchers use of Moderna's mRNA technology to explore new vaccines against emerging or neglected infectious diseases. mRNA Access will also allow researchers to explore novel vaccine designs against prototype viral families in preparation for "Disease X." Disease X was named by the WHO to represent the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease. mRNA Access research partners currently include The University of Queensland, The Peter Doherty Institute for Infection and Immunity, Institute Pasteur (Paris and Tunisia) and McGill University.

Third, Moderna has expanded its pledge to never enforce its patents for COVID-19 vaccines against manufacturers in 92 low- and middle-income countries in the Gavi COVAX Advance Market Commitment (AMC), provided that these vaccines are manufactured solely for use in these countries. Outside of the AMC-92, supply is no longer a barrier to access. Moderna remains willing to license its technology for COVID-19 vaccines to manufacturers in these countries on commercially reasonable terms.

Commercial updates

Spikevax® Commercial Outlook

Advance purchase agreements (APAs) for 2022 are at ~$21 billion and options (probability weighted) are at ~$0.5 billon. 2023 purchase agreements are in place with United Kingdom, Canada, Taiwan, Kuwait, and Switzerland. Discussions for additional 2022 and 2023 orders are ongoing with countries from around the world, including with the U.S.

About Moderna

In over 10 years since its inception, Moderna has transformed from a research-stage company advancing programs in the field of messenger RNA (mRNA), to an enterprise with a diverse clinical portfolio of vaccines and therapeutics across seven modalities, a broad intellectual property portfolio in areas including mRNA and lipid nanoparticle formulation, and an integrated manufacturing plant that allows for rapid clinical and commercial production at scale. Moderna maintains alliances with a broad range of domestic and overseas government and commercial collaborators, which has allowed for the pursuit of both groundbreaking science and rapid scaling of manufacturing. Most recently, Moderna's capabilities have come together to allow the authorized use and approval of one of the earliest and most effective vaccines against the COVID-19 pandemic.

Moderna's mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, and has allowed the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases and auto-immune diseases. Moderna has been named a top biopharmaceutical employer by Science for the past seven years. To learn more, visit www.modernatx.com.

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.

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 regarding: the anticipated timing of regulatory submissions to the U.S. FDA, EMA and other global regulators for authorization of mRNA-1273 for primary vaccination of children 6 months to under 6 years of age; Moderna's submission to the U.S. FDA for emergency use authorization of mRNA-1273 in children 6 to under 12 years of age; the potential for mRNA-1273 to provide protection from COVID-19 in vaccine recipients down to 6 months of age; the safety and tolerability of mRNA-1273 in pediatric populations; Moderna's plans to evaluate the potential of a booster dose for all pediatric populations and adolescents; the potential for superiority of mRNA-1010 to standard dose vaccine for influenza A strains and non-inferiority to standard dose vaccine in influenza B strains; anticipated vaccine deliveries under advance purchase agreements and options in 2022 and the associated dollar amounts to be received, which should not be construed as expected 2022 revenue; Moderna's discussions for additional 2022 and 2023 orders with countries from around the world, including with the U.S.; Moderna's ability to expand its portfolio and address critical unmet medical needs with its mRNA platform; the potential for Moderna's mRNA platform to disrupt the traditional vaccines market, and Moderna's ability to bring additional safe and effective vaccines to market; the transition of COVID-19 to an endemic phase; the Company's development of vaccines against COVID-19, including efforts to develop variant-specific and multivalent vaccines and for booster doses; the ability of mRNA-1283 to facilitate distribution and administration by healthcare providers; expected enrollment in ConquerRSV; expected timing for commencement of a Phase 1 COVID-19 + Flu vaccine trial in healthy adults aged 18 to 75 years old; the potential of mRNA-1230 as an annual booster; expected enrollment in CMVictory; Moderna's plans to evaluate mRNA-1647 against long-term impacts in Phase III trials; the potential for mRNA vaccines to elicit autologous neutralizing antibodies in humans, and to be safe and well-tolerated by HIV-uninfected individuals; expected enrollment in the Phase 1 trial of mRNA-1574; Moderna's plans to expand its portfolio of global public health vaccines to 15 total programs, and the timing for advancing these vaccine programs; the potential ability to leverage Moderna's platform to address Disease X; Moderna's mRNA Access initiative to allow researchers access to Moderna's mRNA platform; the Company's commitment not to enforce its COVID-19 patents in the Gavi COVAX AMC 92 low- and middle-income countries; potential licensing of COVID-19 patents to third parties; and Moderna's agreements and ongoing discussions with countries regarding service/subscription contracts. 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 those other risks and uncertainties described under the heading "Risk Factors" in Moderna's most recent Annual Report on Form 10-K 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 press release 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 hereof.

Moderna Contacts

Media:
Mary Beth Woodin
Senior Director, Communications
617-899-3991
Mary.BethWoodin@modernatx.com

Investors:
Lavina Talukdar
Senior Vice President & Head of Investor Relations617-209-5834
Lavina.Talukdar@modernatx.com

SOURCE: Moderna, Inc.