Moderna Announces Positive Initial Booster Data Against SARS-CoV-2 Variants of Concern

• Single booster dose of 50 µg of mRNA-1273 or mRNA-1273.351 increased neutralizing titers against SARS-CoV-2 and two variants of concern (B.1.351, P.1) in previously vaccinated clinical trial participants
• Booster dose of mRNA-1273.351, a strain-matched candidate, achieved higher titers against B.1.351 than a booster dose of mRNA-1273
• mRNA-1273.351 and mRNA-1273 booster doses were generally well tolerated
• Evaluation of a multivalent vaccine booster candidate, mRNA-1273.211, is ongoing; data expected shortly

Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced initial data from its Phase 2 study showing that a single 50 µg dose of mRNA-1273 or mRNA-1273.351 given as a booster to previously vaccinated individuals increased neutralizing antibody titer responses against SARS-CoV-2 and two variants of concern, B.1.351 (first identified in South Africa) and P.1 (first identified in Brazil). A booster dose of mRNA-1273.351, the Company’s strain-matched booster, achieved higher neutralizing antibody titers against the B.1.351 variant of concern than a booster dose of mRNA-1273. A manuscript describing these preliminary results has been submitted as a preprint to bioRxiv and will be submitted for peer-reviewed publication upon completion of the multivalent mRNA-1273.211 booster arm.

“As we seek to defeat the ongoing pandemic, we remain committed to being proactive as the virus evolves. We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants. The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory,” said Stéphane Bancel, Chief Executive Officer of Moderna. “Our mRNA platform allows for rapid design of vaccine candidates that incorporate key virus mutations, potentially allowing for faster development of future alternative variant-matched vaccines should they be needed. We look forward to sharing data on our multivalent booster candidate, mRNA-1273.211, which combines mRNA-1273 and mRNA-1273.351 in a single vaccine, when available. We will continue to make as many updates to our COVID-19 vaccine as necessary to control the pandemic.”

The initial data is from an ongoing Phase 2 study in which three strategies for boosting neutralizing titers in previously vaccinated participants are being evaluated: mRNA-1273.351, a booster candidate based on the B.1.351 variant first identified in the Republic of South Africa, mRNA-1273.211, a multivalent booster candidate which combines a 50-50 mix of mRNA-1273, Moderna’s authorized vaccine against ancestral strains, and mRNA-1273.351 in a single vaccine, and a 50 µg booster dose of mRNA-1273. Today’s update includes preliminary data two weeks following administration of a booster dose of mRNA-1273 or mRNA-1273.351. Evaluation of additional samples collected at later timepoints after the booster, the Company’s multivalent vaccine candidate, mRNA-1273.211, and a lower dose of mRNA-1273.351 are ongoing and data is expected shortly.

Participants in the Phase 2 study were tested for pseudovirus neutralization (PsVN) titers prior to boosting approximately 6 to 8 months after their primary vaccination series. Although titers versus the wild-type SARS-CoV-2 virus remained high, with 37 of 40 participants having detectable titers, titers against the variants of concern (B.1.351 and P.1) were much lower, with approximately half of participants having titers below the assay limit of quantification prior to boosting. Two weeks after receiving either mRNA-1273 or mRNA-1273.351, PsVN titers were boosted in all participants and all variants tested. Following boost, geometric mean titers (GMT) against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination¹.

mRNA-1273.351 appeared to be more effective at increasing neutralization titers against the B.1.351 variant when compared to mRNA-1273, as evidenced by higher mean GMT levels already at 15 days following booster dose (GMT = 1400 for mRNA-1273.351; GMT = 864 for mRNA-1273). The relative decrease in neutralizing titers between the wild-type (D614G) and B.1.351 assays also improved with mRNA-1273.351 booster, from a 7.7-fold difference prior to boost to a 2.6-fold difference 15 days after boost, suggesting a potentially more balanced immune response against the tested variants.

Safety and tolerability profiles following third dose booster injections of 50 µg of mRNA-1273 or mRNA-1273.351 were generally comparable to those observed after the second dose of mRNA-1273 in the previously reported Phase 2 and Phase 3 studies. A review of solicited adverse events indicated that the vaccine boosters were generally well tolerated. The majority of adverse events were mild or moderate in severity. The frequency of any Grade 3 solicited local or systemic adverse events was 15% after the third dose of mRNA-1273 and 10.5% after the third dose of mRNA-1273.351. There were no Grade 4 solicited local or systemic adverse events. The most common solicited local adverse event was injection site pain in both groups. The most common solicited systemic adverse events after the third dose of mRNA-1273.351 or mRNA-1273 were fatigue, headache, myalgia and arthralgia. In general, mRNA-1273.351 had a lower reactogenicity profile than mRNA-1273 in this study.

In parallel, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) is conducting a separate Phase 1 study of mRNA-1273.351.