Moderna, Inc. announced that the first participant has been dosed in the Phase II study of the company's Omicron-specific booster candidate (mRNA-1273.529).

Additionally, Moderna announced the publication of neutralizing antibody data against the Omicron variant six months following a booster dose in The New England Journal of Medicine. While Omicron neutralization had declined 6.3-fold from peak titers at day 29 post-boost, levels remained detectable in all participants. Neutralizing titers against Omicron declined more rapidly than titers against the ancestral strain of the virus (D614G) which declined 2.3-fold over the same time period.

"We are reassured by the antibody persistence against Omicron at six months after the currently authorized 50 µg booster of mRNA-1273. Nonetheless, given the long-term threat demonstrated by Omicron's immune escape, we are advancing our Omicron-specific variant vaccine booster candidate and we are pleased to begin this part of our Phase II study," said Stéphane Bancel, Chief Executive Officer of Moderna. "We are also evaluating whether to include this Omicron-specific candidate in our multivalent booster program. We will continue to share data with public health authorities to help them make evidence-based decisions on the best booster strategies against SARS-CoV-2."

Phase II Study of mRNA-1273.529: This extension of an earlier study will evaluate the immunogenicity, safety, and reactogenicity of mRNA-1273.529 as a single booster dose in adults aged 18 years and older in two cohorts: individuals who previously received the two-dose primary series of mRNA-1273 with the second dose being at least six months ago (cohort 1), or who have received the two-dose primary series and a 50 µg booster dose of mRNA-1273 with the booster dose being at least three months ago (cohort 2). Participants in both cohorts will receive a single booster dose of mRNA-1273.529.Moderna expects to enroll approximately 300 participants into each cohort of this study, which will be conducted at up to 24 sites in the U.S. Additionally, Moderna is evaluating the inclusion of mRNA-1273.529 in its multivalent booster program.

Data on Booster Durability Against Omicron Variant: Moderna previously announced preliminary neutralizing antibody data against the Omicron variant following the Company's booster candidates at 50 µg and 100 µg dose levels. The currently authorized 50 µg booster of mRNA-1273 increased neutralizing antibody levels against Omicron approximately 37-fold compared to pre-boost levels and a 100 µg dose of mRNA-1273 increased neutralizing antibody levels approximately 83-fold compared to pre-boost levels. Today's data includes sera from 20 booster recipients each of mRNA-1273 at the 50 µg and 100 µg dose levels, multivalent candidate mRNA-1273.211 at the 50 µg and 100 µg dose levels, and multivalent candidate mRNA-1273.213 at the 100 µg dose level. Neutralizing antibodies against Omicron were assessed in a pseudovirus neutralization titer (ID50) assay (PsVNA) conducted at laboratories established by the National Institute of Allergy and Infectious Diseases' (NIAID) Vaccine Research Center and Duke University Medical Center.

At seven months post-second dose and before the third booster dose, Omicron neutralization was detected in only 55% of participants. A booster dose of mRNA-1273 at the 50 µg dose level increased Omicron GMTs to 20-fold higher than peak Omicron titers post-dose two. At six months after the third booster dose, Omicron neutralization had declined 6.3-fold from peak titers at day 29 post-boost but remained detectable in all participants. Neutralizing titers against Omicron declined faster after the booster than for the wild-type virus (D614G) which declined 2.3-fold over the same time period.

A 100 µg booster dose of mRNA-1273, mRNA-1273.211 or mRNA-1273.213 resulted in similar Omicron GMTs, with all three boosters leading to neutralizing titers 2.5-2.6-fold higher than neutralizing titers after the 50 µg booster dose of mRNA-1273.

See- Letter: "SARS-CoV-2 Omicron Variant Neutralization after mRNA-1273 Booster Vaccination"-January 26, 2022. DOI: 10.1056/NEJMc2119912.