CMV 7-month data shows all GMT measures at or above CMV seropositive baselines; pivotal Phase 3 study of at least 8,000 participants expected to begin in 2021

First interim analysis of Phase 1 RSV vaccine candidate (mRNA-1345) shows >11- fold increase in RSV neutralizing antibodies in younger adults (ages 18-49 years); both 50 μg and 100 μg dose levels generally well-tolerated

Phase 1 clinical study of mRNA flu vaccine candidate expected to begin in 2021

Phase 1 study evaluating HIV mRNA vaccines with novel strategy expected to begin in 2021

Company provided update on its COVID-19 Vaccine program on April 13

Vaccines Day to be held on Wednesday, April 14 at 8:00 a.m. ET

Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, is today hosting its second annual Vaccines Day, with presentations highlighting the advantages of mRNA vaccines. The Company is also announcing new positive interim Phase 1 data from its Respiratory Syncytial Virus (RSV) vaccine candidate (mRNA-1345) and new 7-month interim Phase 2 data from its cytomegalovirus (CMV) vaccine candidate. Building on its COVID-19 vaccine clinical development experience, the Company plans to invest resources and continue to leverage the power of its mRNA platform to accelerate the development of its mRNA vaccine pipeline.

“Moderna has one of the world’s largest and most innovative vaccine development pipelines. We believe we have a unique opportunity to develop new vaccines against viruses hurting people around the world, at a pace that is radically different from what the industry has previously done,” said Stéphane Bancel, Chief Executive Officer of Moderna. “We are working to further increase our vaccine pipeline and accelerate these important programs. With our mRNA vaccines, we believe we have an opportunity to have a profound impact on human health.”

The vast majority of human viruses do not have a commercially available vaccine. This gap includes many long-known viruses causing a spectrum of long-term sequelae, such as cytomegalovirus (CMV) (discovered in 1956), Zika (1952) and Epstein-Barr virus (EBV, 1964), but also includes many emerging novel viruses. Since 1980, an average of two novel viruses that infect humans have been discovered each year. Examples of these novel viruses include HIV 1 (discovered in 1983), Hepatitis C (1989), H1N1 (2009), and SARS-CoV-2 (2019).

To date, Moderna has entered 14 different mRNA vaccine candidates into clinical trials. Clinical data demonstrate that Moderna’s proprietary vaccine technology has been generally well-tolerated and can elicit durable immune responses to viral antigens. The Company has demonstrated the ability to attain high biological flexibility with the ability to develop mRNA vaccines against complex antigens and combination vaccines while leveraging mRNA as a platform with a flexible manufacturing infrastructure to advance a large portfolio quickly and efficiently.

On Tuesday, April 13, the Company provided an update on its COVID-19 Vaccine program.

Interim Phase 1 data for Respiratory Syncytial Virus (RSV) vaccine candidate (mRNA-1345)

mRNA-1345 is a vaccine against RSV encoding for a prefusion F glycoprotein, which elicits a superior neutralizing antibody response compared to the postfusion state. RSV is the leading cause of respiratory illness in young children. Older adults (65+) are at high risk for severe RSV infections. mRNA-1345 uses the same lipid nanoparticle (LNP) as Moderna’s authorized Covid-19 vaccine and contains optimized protein and codon sequences. The Phase 1 study of mRNA-1345 to evaluate the tolerability and reactogenicity of mRNA-1345 in younger adults, older adults and children is ongoing. All four cohorts of younger adults (ages 18-49 years) are fully enrolled. Dosing in the older adult cohort (ages 65-79 years) is ongoing. The age range of toddlers in this de-escalation Phase 1 study is 12-59 months.

Today, the Company is sharing the first interim analysis of the Phase 1 study of mRNA-1345, through 1-month post-vaccination, of the younger adult cohorts. A single mRNA-1345 vaccination of 50 μg (N=19) or 100 μg (N=20) was generally well-tolerated in younger adults (ages 18-49 years). Ten participants received placebo. The most common local solicited adverse reaction was injection site pain, and the most common systemic solicited adverse reactions were headache, fatigue and myalgia. The majority of solicited adverse reactions occurred within 1-3 days after vaccination and resolved after 1-4 days. There were no deaths, no severe adverse events, no study discontinuations due to adverse events, and no adverse events that led to a study pause.

mRNA-1345 was shown to increase RSV neutralizing antibodies in seropositive younger adults. Neutralizing antibodies were confirmed to be present at baseline in all participants, as expected. A single vaccination of mRNA-1345 at the 50 or 100 μg dose level boosted neutralizing antibody titers against both serotypes of RSV-A and RSV-B with no apparent dose response. At month 1, the geometric mean fold rise in neutralizing antibody relative to baseline was at least 20.5 for RSV-A and at least 11.7 for RSV-B.

At the 100 μg dose level, the geometric mean fold rise (95% CI) in RSV-A neutralizing antibody titer at month 1 relative to baseline was 2.7 (2.1, 3.4) with mRNA-1777, the Company’s previous RSV vaccine candidate, compared to 21.0 (13.9, 31.8) with mRNA-1345. Both mRNA-1777 and mRNA-1345 encode for the prefusion RSV-F.

The Company also intends to evaluate the potential of combinations of mRNA-1345 with its vaccines against other respiratory pathogens in children and separately in older adults. There is no approved vaccine for RSV. Moderna owns worldwide commercial rights to mRNA-1345.

“I am encouraged by these interim Phase 1 data showing the ability of mRNA-1345 to elicit a strong neutralizing antibody response,” said Jacqueline Miller, M.D., Senior Vice President, Infectious Diseases, Moderna. “We will continue to pursue RSV vaccines to protect the most vulnerable populations – young children and older adults – where reducing RSV infection is also a significant unmet need. We will also be evaluating possible combinations of mRNA-1345 with other respiratory virus vaccines.”

Interim Phase 2 data for CMV vaccine (mRNA-1647) at 7 months

mRNA-1647 is a vaccine combining six mRNAs in a single vial, which encode for two antigens located on the surface of CMV: five mRNAs encoding the subunits that form the membrane-bound pentamer complex and one mRNA encoding the full-length membrane-bound glycoprotein B (gB). Both the pentamer and gB are essential for CMV to infect barrier epithelial surfaces and gain access to the body. mRNA-1647 is designed to produce an immune response against both the pentamer and gB for the prevention of CMV infection.

Today, the Company is sharing interim, seven-month data from the Phase 2 study of mRNA-1647 at the 50 μg, 100 μg and 150 μg dose levels. mRNA-1647 was generally well tolerated. The most common solicited local adverse reaction (AR) was injection site pain and the most common solicited systemic ARs were headache, fatigue, myalgia, arthralgia and chills. Rates of Grade 3 solicited ARs after the 3rd vaccination were similar to, or lower than the rates of Grade 3 solicited ARs after the 2nd vaccination.

In CMV-seronegative participants in mRNA-1647 treatment groups after the third vaccination:

• Neutralizing antibody geometric mean titers (GMTs) against epithelial cell infection were at least 20-fold higher than the baseline GMT of the CMV-seropositive group
• Neutralizing antibody GMTs against fibroblast infection approximated the baseline GMT of the CMV-seropositive group

In CMV positive participants in mRNA-1647 treatment groups after the 3rd vaccination:

• Neutralizing antibody GMTs against epithelial cell infection increased to at least 6.8-fold over baseline
• Neutralizing antibody GMTs against fibroblast infection increased to approximately 2-fold over baseline

Plans for Phase 3 study of CMV vaccine candidate (mRNA-1647)

Based on the interim analysis of the Phase 2 study, the 100 μg dose has been chosen for the Phase 3 pivotal study, which will evaluate the prevention of primary CMV infection in seronegative women ages 16-40 years. The Company plans to enroll approximately 8,000 participants from approximately 150 sites across the U.S., Europe and Asia-Pacific into the Phase 3 study, which is expected to begin in 2021. Moderna owns worldwide commercial rights for mRNA-1647.

Update on clinical development of HIV vaccine candidates (mRNA-1644 & mRNA-1574)

mRNA-1644 is a novel approach to HIV vaccine strategy in humans designed to elicit broadly neutralizing HIV-1 antibodies (bNAbs) and is being developed in collaboration with the International AIDS Vaccine Initiative (IAVI) and the Bill and Melinda Gates Foundation (BMGF). A Phase 1 study for mRNA-1644 will use iterative human testing to validate the approach and antigens and multiple novel antigens will be used for germline-targeting and immuno-focusing.

A second approach, mRNA-1574, is being evaluated in collaboration with the National Institutes of Health (NIH) and includes multiple native-like trimer antigens. The Company expects to begin phase 1 clinical trials for both mRNA-1644 and mRNA-1574 in 2021.

Dr. William Schief is presenting new data from the Phase 1 study of the IAVI G001 HIV vaccine candidate, which established the proof-of-principle for germline-targeting vaccine design in humans. This Phase 1 study confirms that vaccines can induce broadly neutralizing antibodies, a necessary strategy to develop an HIV vaccine. The development is expected to require multiple iterative human clinical trials. Moderna’s mRNA technology may have promise in HIV vaccine development. Three Phase 1 trials studying HIV vaccine concepts delivered by Moderna mRNA are expected to launch in 2021. The speed and cost advantages of Moderna’s mRNA vaccine technology have enabled Moderna’s collaborators to develop these trials rapidly.

Phase 1 clinical study of mRNA flu vaccine candidate (mRNA-1010) expected to begin in 2021

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

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

The Company plans to explore potential combination vaccines against flu, SARS-CoV-2, RSV and human metapneumovirus (hMPV). The Company’s first-generation flu program will evaluate multiple candidates comprising multiple antigen combinations against the four seasonal viruses recommended by the WHO. The Company expects to begin a Phase 1 clinical trial for the program in 2021.

Vaccines Day Today

Moderna is hosting its Vaccines Day today, Wednesday April 14, beginning at 8:00 a.m. ET. A live webcast will be available under “Events and Presentations” in the Investors section of the Moderna website at investors.modernatx.com. A replay of the webcast will be archived on Moderna’s website for one year following the presentation.

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 six 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. Today, 24 development programs are underway across these therapeutic areas, with 13 programs having entered the clinic. Moderna has been named a top biopharmaceutical employer by Science for the past six 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 statements regarding: the Company’s investments to accelerate the development of its mRNA vaccine pipeline; the safety profile and tolerability of the Company’s vaccines and the potential of these vaccine candidates to trigger an immune response; the Company’s ability to develop vaccines with complex antigens and combination vaccines, and the speed and flexibility of the Company’s development platform; the potential for the Company’s RSV vaccine (mRNA-1345) to elicit neutralizing antibodies in different age cohorts; the safety and tolerability profile for mRNA-1345; the potential incorporation of mRNA-1345 in a combination vaccine; the potential for the Company’s CMV vaccine (mRNA-1647) to elicit neutralizing antibodies; the safety and tolerability profile for mRNA-1647; plans for future clinical studies of mRNA-1647; the Company’s plans to develop vaccine candidates against HIV (mRNA-1644 and mRNA-1574) and coordination efforts with third parties and strategic partners; plans for the launch of clinical trials for the Company’s HIV vaccine candidates; the Company’s development of vaccine candidates against seasonal influenza and the timing for clinical trials of those vaccine candidates; and plans to pursue combination vaccines for respiratory diseases. 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: the fact that there has never been a commercial product utilizing mRNA technology approved for use; the fact that the rapid response technology in use by Moderna is still being developed and implemented; the safety, tolerability and efficacy profile of the Moderna COVID-19 Vaccine observed to date may change adversely in ongoing analyses of trial data or subsequent to commercialization; the Moderna COVID-19 Vaccine may prove less effective against variants of the SARS-CoV-2 virus, or the Company may be unsuccessful in developing future versions of its vaccine against these variants; despite having ongoing interactions with the FDA or other regulatory agencies, the FDA or such other regulatory agencies may not agree with the Company’s regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted; Moderna may encounter delays in meeting manufacturing or supply timelines or disruptions in its distribution plans for the Moderna COVID-19 Vaccine; whether and when any biologics license applications and/or additional emergency use authorization applications may be filed in various jurisdictions and ultimately approved by regulatory authorities; potential adverse impacts due to the global COVID-19 pandemic such as delays in regulatory review, manufacturing and clinical trials, supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy; and 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20210414005347/en/