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. 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. 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. Indication: 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.

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 high 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.