Moderna (NSDQ: MRNA), a Boston-area mRNA company, reported positive early data from a Phase I trial of its coronavirus vaccine. After two doses, the first four patients in each of two mRNA-1273 arms showed blood levels of binding antibodies at levels similar to patients who have recovered from COVID-19. There were no major side-effect problems in the two levels, though Moderna did stop testing a higher dosing cohort. Moderna said it expects to start a Phase III trial as soon as July.

In a preclinical mice study, mRNA-1273 prevented viral replication in the lungs of animals who were exposed to SARS-CoV-2. The levels of neutralizing titers in the mice were similar to those of the subjects in the Phase 1 trial.

According to Moderna, immunogenicity data are currently available for the 25 µg and 100 µg dose level (ages 18-55) after two doses (day 43) and at the 250 µg level (ages 18-55) after one dose (day 29). Dose dependent increases in immunogenicity were seen across the three dose levels, and between prime and boost within the 25 µg and 100 µg dose levels. All participants ages 18-55 (n=15 per cohort) across all three dose levels seroconverted by day 15 after a single dose.

At day 43, two weeks following the second dose, at the 25 µg dose level (n=15), levels of binding antibodies were at the levels seen in convalescent sera (blood samples from people who have recovered from COVID-19). At the higher dose, levels significantly exceeded convalescent sera.

Moderna’s vaccine injects messenger RNA that codes for the virus’s Spike (S) protein. The patient’s cells then manufacture the S protein, which triggers the body’s immune system to recognize the virus itself.

So far, neutralizing antibody data are available only for the first four participants in each of the 25 µg and 100 µg dose level cohorts. Consistent with the binding antibody data, mRNA-1273 vaccination elicited neutralizing antibodies in all eight of these participants, as measured by plaque reduction neutralization (PRNT) assays against live SARS-CoV-2. The levels of neutralizing antibodies at day 43 were at or above levels generally seen in convalescent sera.

Based on the interim Phase 1 data, the Moderna Phase II study will be amended to study two dose levels, 50 µg and 100 µg, with the aim of selecting a dose for pivotal studies. The NIAID-led Phase I study is being amended to include a 50 µg dose level cohort across each of the three age groups. Moderna anticipates the dose for the Phase III study will be between 25 µg and 100 µg.

“These interim Phase I data, while early, demonstrate that vaccination with mRNA-1273 elicits an immune response of the magnitude caused by natural infection starting with a dose as low as 25 µg,” said Tal Zaks, MD, PhD, Chief Medical Officer at Moderna. “When combined with the success in preventing viral replication in the lungs of a pre-clinical challenge model at a dose that elicited similar levels of neutralizing antibodies, these data substantiate our belief that mRNA-1273 has the potential to prevent COVID-19 disease and advance our ability to select a dose for pivotal trials.”

“With today’s positive interim Phase I data and the positive data in the mouse challenge model, the Moderna team continues to focus on moving as fast as safely possible to start our pivotal Phase III study in July and, if successful, file a BLA,” said Stéphane Bancel, CEO at Moderna. “We are investing to scale up manufacturing so we can maximize the number of doses we can produce to help protect as many people as we can from SARS-CoV-2.”

Funding from the Biomedical Advanced Research and Development Authority (BARDA), a division of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the US Department of Health and Human Services (HHS), supported the planning for the Phase II and Phase III studies of mRNA-1273. They will also support the trials themselves and scale-up of mRNA-1273 manufacturing both at Moderna's facilities and those of its strategic collaborator, Lonza Ltd.

Moderna currently has nine development candidates in its prophylactic vaccine portfolio, including:

Vaccines against respiratory infections
• Respiratory syncytial virus (RSV) vaccine for older adults (mRNA-1777 and mRNA-1172 or V172 with Merck)
• RSV vaccine for young children (mRNA-1345)
• Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) vaccine (mRNA-1653)
• Novel coronavirus (SARS-CoV-2) vaccine (mRNA-1273)
• Influenza H7N9 (mRNA-1851)

Vaccines against infections transmitted from mother to baby
• Cytomegalovirus (CMV) vaccine (mRNA-1647)
• Zika vaccine (mRNA-1893 with BARDA)
Vaccines against highly prevalent viral infections
• Epstein-Barr virus (EBV) vaccine (mRNA-1189)

To date, Moderna has demonstrated positive Phase 1 data readouts for seven prophylactic vaccines (H10N8, H7N9, RSV, chikungunya virus, hMPV/PIV3, CMV and Zika). Moderna’s CMV vaccine is currently in a Phase II dose-confirmation study. Its investigational Zika vaccine (mRNA-1893), currently in a Phase 1 study, was granted FDA Fast Track designation in August 2019.

See our other articles on Moderna.

Disclosure: none.