Moderna Announces Clinical Progress from its Industry-Leading mRNA Vaccine Franchise and Continues Investments to Accelerate Pipeline Development
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
Vaccines Day to be held on
“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
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).
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.
“I am encouraged by these interim Phase 1 data showing the ability of mRNA-1345 to elicit a strong neutralizing antibody response,” said
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
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
A second approach, mRNA-1574, is being evaluated in collaboration with the
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
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
In 10 years since its inception,
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.
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
Director, Corporate Communications
Senior Vice President & Head of Investor Relations