Moderna Announces Positive Interim Phase 1 Data for mRNA Flu Vaccine and Provides Program Update

Phase 1 study of quadrivalent flu vaccine (mRNA-1010) successfully boosted titers against all four strains in older and younger adults, even at lowest dose; no significant safety concerns were observed

Phase 2 dose-confirmation study was fully enrolled in November (N=500); preparation for Phase 3 study underway

Seasonal flu program now moving beyond quadrivalent: announcing mRNA-1011 & mRNA-1012 development candidates

Conference call to be held today at 8:00 a.m. ET

Moderna, Inc., (Nasdaq: MRNA) a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced the first positive interim data from the Phase 1 study of the Company’s quadrivalent seasonal flu vaccine candidate, mRNA-1010. In the study, mRNA-1010 successfully boosted hemagglutination inhibition (HAI) assay geometric mean titers against all strains 29 days after vaccination at all doses tested in both younger and older adults. The Company also announced that the Phase 2 study of mRNA-1010 is now fully enrolled and preparation for the Phase 3 study is underway. Moderna also provided an update on its seasonal flu vaccine program including the announcement of two beyond quadrivalent seasonal flu development candidates (mRNA-1011 and mRNA-1012).

“Even before the COVID-19 pandemic, approximately three million people died each year due to respiratory infections, and many more are hospitalized or become ill as a result of these viruses. At Moderna, our goal is to limit this suffering with an annual pan-respiratory single dose booster vaccine that is adapted to the circulating strains of SARS-CoV-2, seasonal influenza and RSV,” said Stéphane Bancel, Chief Executive Officer of Moderna.

“The positive interim results from our Phase 1 quadrivalent flu vaccine candidate, mRNA-1010, are an important milestone toward achieving that goal. It is encouraging to see that participants in the study who received the 50 µg dose, including older adults, achieved robust increases in geometric mean antibody titers against H1N1 and H3N2, the strains responsible for the vast majority of morbidity and mortality in this age group. We believe our mRNA platform is well-positioned to address the significant unmet need in seasonal flu as evidenced by our new beyond quadrivalent candidates, mRNA-1011 and mRNA-1012, which we believe will expand strain coverage and provide more options for public health officials,” Stéphane Bancel continued.

Quadrivalent mRNA-1010 encodes for the hemagglutinin (HA) protein from four seasonal influenza viruses based on the recommendations of the World Health Organization (WHO), including seasonal influenza A/H1N1, A/H3N2 and influenza B/Yamagata- and B/Victoria-lineages. In the Phase 1 study, mRNA-1010 was evaluated at 50 µg, 100 µg and 200 µg dose levels in younger adult (age 18-49) and older adult (age 50+) cohorts. No significant safety findings were observed through day 29. Adverse reactions (ARs) were generally reported more frequently in younger adults compared to older adults, and at higher dose levels. The most common solicited local ARs for both age groups included pain and axillary swelling/tenderness. The most common solicited systemic ARs for both age groups included fatigue, arthralgia, myalgia and headache.

At the lowest dose level (50 µg) in younger adults, Day 29 geometric mean titers (GMT) against influenza A strains were 538 (H1N1) and 530 (H3N2); GMT against influenza B strains were 467 (B/Yamagata) and 261 (B/Victoria). Geometric mean fold-rises (GMFR) above baseline for influenza A strains were approximately 10-fold (H1N1) and 8-fold (H3N2), and approximately 3-fold for B/Yamagata and 2-fold for B/Victoria. Minimal dose response was observed between the 50 µg, 100 µg and 200 µg dose levels, suggesting the potential to explore even lower doses.

At the lowest dose level (50 µg) in older adults, Day 29 GMT against influenza A strains were 310 (H1N1) and 263 (H3N2); GMT against influenza B strains were 305 (B/Yamagata) and 215 (B/Victoria). GMFR for influenza A strains were approximately 6-fold (H1N1) and 6-fold (H3N2), and approximately 3-fold for B/Yamagata and 2-fold for B/Victoria. Minimal dose response was observed between the 50 µg, 100 µg and 200 µg dose levels.

Update on Phase 2 and Phase 3 studies of mRNA-1010

The Phase 2 study of mRNA-1010 was initiated in November to confirm dose across three dose levels, including a lower 25 µg dose level, and the two lowest dose levels from Phase 1 (50 µg and 100 µg) with approximately 150 participants per arm. The Phase 2 study also includes an approved flu vaccine comparator arm (N=50). The Phase 2 study was fully enrolled in November (N=500), and interim analysis is expected in early 2022. Preparation for the Phase 3 study for mRNA-1010 is already underway, including manufacturing. The Company is seeking guidance from global regulatory agencies on the Phase 3 program.

Moving Beyond Quadrivalent in Seasonal Flu: Two New Development Candidates

Today, Moderna announced two beyond quadrivalent development candidates which the Company believes offer the opportunity to expand strain coverage and enhance tools available to public health authorities when selecting antigens. mRNA-1011 will have one additional hemagglutinin (HA) antigen and mRNA-1012 will have two additional HA antigens. Separately, the Company previously announced that it is also developing two next-generation flu candidates that incorporate neuraminidase antigens to broaden immunity beyond hemagglutinin (mRNA-1020, mRNA-1030).

Moderna’s Pan-Respiratory Annual Booster Vaccine

Respiratory infections are a top cause of death globally, accounting for approximately three million deaths annually. Approximately one million of these deaths occur annually due to respiratory infections in high and upper middle-income countries and respiratory infections are responsible for more deaths than colorectal cancer in high income countries¹. The burden of disease from respiratory viruses is greatest in children under five years, adults older than 65 years and in the high-risk population, including those who are pregnant, immunocompromised or have cancer².

One pillar of Moderna’s product strategy is to develop a pan-respiratory annual booster vaccine, which the Company plans to continuously customize. The Company believes that it could be first to market with a COVID + Flu + RSV booster vaccine. Moderna’s RSV vaccine candidate (mRNA-1345) demonstrated positive Phase 1 results and the Company’s Phase 2/3 study is ongoing. A pan-respiratory annual single booster vaccine to cover multiple viruses could create value for the healthcare system through compliance, convenience to the customer (one vs. three injections), and reduction in vaccine administration cost.

Conference Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on Friday, December 10, 2021. To access the live conference call, please dial 866-922-5184 (domestic) or 409-937-8950 (international) and refer to conference ID 8748887. A webcast of the call will also be available under “Events and Presentations” in the Investors section of the Moderna website at investors.modernatx.com. The archived webcast will be available on Moderna’s website approximately two hours after the conference call.

About Seasonal Influenza

Seasonal flu (influenza A and influenza B) epidemics occur seasonally and vary in severity each year, causing respiratory illnesses and placing substantial burden on healthcare systems. The WHO estimates approximately 3-5 million severe cases of flu occur each year globally³ with 290,000-650,000 flu-related deaths annually. Approximately 8% of the U.S. population experiences symptoms from flu each year². In the U.S., the estimated average economic burden of flu is approximately $11 billion per year⁴.

Current flu vaccines are only approximately 40-60% effective and their formulation is decided 6-9 months before the vaccines are intended to be used. Egg-based vaccine production, the process used for the majority of currently licensed influenza vaccines, also has the potential to cause unintended antigenic change to the vaccine virus.

About Moderna

In 10 years since its inception, Moderna has transformed from a science 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 both clinical and commercial production at scale and at unprecedented speed. 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 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.

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 potential to combine different vaccines into a single dose and the potential benefits from such combinations; the timing for interim analysis data from the Company’s Phase 2 study of mRNA-1010; determination regarding the regulatory pathway with respect to mRNA-1010; and the potential market opportunity for a pan-respiratory booster vaccine. 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.

¹ https://www.cdc.gov/flu/about/keyfacts.htm

² Jackson, Michael et al. “Incidence of Medically Attended Acute Respiratory Illnesses Due to Respiratory Viruses Across the Life Course During the 2018/19 Influenza Season,” Clinical Infectious Diseases (16 Feb. 2021), 2021; https://doi.org/10.1093/cid/ciab131

³ https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal)

⁴ https://pubmed.ncbi.nlm.nih.gov/29801998

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