Next-generation, refrigerator-stable COVID-19 vaccine candidate, mRNA-1283, has dosed first participant in its Phase 3 trial

Company expects to file for approval of its investigational RSV vaccine candidate, mRNA-1345, this quarter

Company's first influenza candidate, mRNA-1010, did not accrue sufficient cases at the interim efficacy analysis to declare early success in the Phase 3 Northern Hemisphere efficacy trial and the independent DSMB recommended continuation of efficacy follow-up

Preliminary immunogenicity analysis from the Northern Hemisphere trial showed mRNA-1010 demonstrated titers consistent with superiority against influenza A strains (H1N1, H3N2) and non-inferiority against influenza B strains (B/Victoria, B/Yamagata) versus the licensed comparator

Moderna announces new development candidates against Lyme disease, the Company's first bacterial vaccine, and norovirus, an enteric virus

Company establishes 2027 financial framework for the Respiratory Franchise

CAMBRIDGE, MA / ACCESSWIRE / April 11, 2023 /Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced clinical and program updates demonstrating expansion and advancement of its mRNA pipeline. The updates include advancements in the Company's respiratory and latent virus portfolios, new vaccine candidates, and commercial and financial framework announcements for the respiratory vaccines business.

"Our mRNA platform has changed medicine and will continue to have a major impact on global health. Today we are excited to announce multiple new vaccine candidates, including for enteric viruses, such as norovirus, and targeting Lyme disease, our first bacterial vaccine," said Stéphane Bancel, Chief Executive Officer of Moderna. "With mRNA-1010, our first investigational vaccine against seasonal flu, we are encouraged by the consistently strong immunogenicity results against influenza A, and titers consistent with non-inferiority against influenza B strains in the most recent Phase 3 trial. With our mRNA platform and technology, as well as our agile manufacturing capabilities, we are confident that we can quickly develop safe and effective vaccines to address critical unmet needs."

Portfolio Overview

The vaccine portfolio seeks to address infectious diseases that cause considerable health burdens, including those due to respiratory viruses, latent viruses, global health threats, and now norovirus and Lyme disease.

Respiratory Portfolio

Moderna's approach to ease the global burden of respiratory infections includes vaccine candidates against major causative pathogens, including SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV). Respiratory infections are a top cause of death globally 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 against RSV and influenza, and a next-generation COVID-19 candidate. The pipeline includes four additional influenza vaccines with expanded antigens (Phase 1 - Phase 2), vaccines against other respiratory pathogens (e.g., hMPV, PIV3), and five combination vaccine programs (preclinical - Phase 2).

COVID-19

Despite the success of vaccination in reducing the burden of SARS-CoV-2, COVID-19 remains a leading cause of severe illness and mortality throughout the world.

Moderna expects to continue to meet the evolving needs of the endemic COVID-19 market including through multi-valent boosters and 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.

Moderna's next-generation, refrigerator-stable COVID-19 vaccine, mRNA-1283, has demonstrated encouraging results in multiple clinical studies and recently began dosing participants in a Phase 3 trial.

Influenza (Flu)

Worldwide, influenza leads to 3-5 million severe cases of flu and 290,000-650,000 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, the influenza A viruses lead to most flu-related hospitalization in older adults, including more than 95% of hospitalizations in the most recent flu season.

The Company has five influenza vaccine candidates in clinical development.

• mRNA-1010 a seasonal quadrivalent vaccine using strains recommended by the World Health Organization (WHO)
• mRNA-1011/1012, aseasonal penta-/hexa-valent vaccine candidate that includes more hemagglutinin antigens (e.g. H3, H1) to expand strain matching
• mRNA-1020/1030, a seasonal vaccine candidate that includes neuraminidase antigens to target more conserved regions of the virus

mRNA-1010

The Company's first vaccine candidate against influenza is mRNA-1010, which is being developed in adults. mRNA-1010 is currently being evaluated in two Phase 3 trials. The first Phase 3 trial (P301) was conducted in the Southern Hemisphere to evaluate safety and non-inferior immunogenicity compared to a licensed flu vaccine. The previously announced interim results from the P301 trial indicated that mRNA-1010 demonstrated superiority in geometric mean titers (GMT) for A/H3N2 and non-inferiority in GMT for A/H1N1. mRNA-1010 did not meet non-inferiority for both influenza B/Victoria- and B/Yamagata-lineage strains. mRNA-1010 demonstrated an acceptable safety and tolerability profile in the trial, and the independent Data and Safety Monitoring Board (DSMB) for P301 did not identify any safety concerns.

The second Phase 3 trial (P302) is being conducted in the Northern Hemisphere to evaluate safety and non-inferior efficacy compared to a licensed flu vaccine. The independent DSMB has completed the first interim analysis of efficacy and informed the Company that mRNA-1010 did not meet the statistical threshold necessary to declare early success and recommended that the trial continue with efficacy follow-up towards the next analysis. The DSMB did not identify any safety concerns. Blinded follow-up for safety and efficacy is ongoing in this trial.

A preliminary analysis of immunogenicity from a subset of participants in the P302 trial has also been completed. In this analysis, mRNA-1010 demonstrated geometric mean titer ratios consistent with superiority against both influenza A strains (A/H1N1, A/H3N2) and consistent with non-inferiority against both influenza B strains (B/Victoria, B/Yamagata) relative to the licensed comparator. The P302 study did not pre-specify success criteria for immunogenicity endpoints.

The Company has developed an update to mRNA-1010 that is expected to have improved immunogenicity against influenza B strains and announced plans to initiate a confirmatory Phase 3 trial this month.

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. Annually, there are approximately two million medically attended RSV infections and 58,000 to 80,000 hospitalizations in children younger than 5 years old in the U.S. And in the U.S., each year there are up to 160,000 hospitalizations and 10,000 RSV-related deaths in adults aged 65 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 old.

Moderna is advancing RSV candidates to address the areas of greatest need, including candidates for older adults and pediatric populations, and combination vaccines to target RSV along with flu and COVID-19.

mRNA-1345

mRNA-1345, Moderna's RSV vaccine candidate, is in an ongoing Phase 2/3, randomized, observer-blind, placebo-controlled case-driven trial (ConquerRSV) in adults aged 60 years and older. In this study, 35,541 participants from 22 countries were randomized 1:1 to receive one dose of mRNA-1345 or placebo.

Following review by an independent Data and Safety Monitoring Board (DSMB), the primary efficacy endpoints have been met, including vaccine efficacy (VE) of 83.7% (95.88% CI: 66.1%, 92.2%; p