Moderna completes enrollment in ph 2 study of mRNA-1273, ready for ph 3 in 30000 participants

Moderna has finalized the phase 3 study protocol based on feedback from the U.S. FDA. The randomized, 1:1 placebo-controlled trial is expected to include approximately 30,000 participants at the 100 µg dose level in the U.S. and is expected to be conducted in collaboration with NIAID, subject to regulatory approval. Moderna has completed manufacture of vaccine required to start the phase 3 study. With the phase 3 dose at 100 μg, the company remains on track to be able to deliver approximately 500 million doses per year, and possibly up to 1 billion doses per year, beginning in 2021. 

-1273 is an vaccine against *redacted* encoding for a prefusion stabilized form of the Spike (S) protein, which was selected by Moderna in collaboration with investigators from the VRC. The first clinical batch, which was funded by the Coalition for Epidemic Preparedness Innovations, was completed on February 7, 2020 and underwent analytical testing; it was shipped to NIH on February 24, 42 days from sequence selection. The first participant in the NIAID-led Phase 1 study of -1273 was dosed on March 16, 63 days from sequence selection to Phase 1 study dosing. On May 12, the FDA granted -1273 Fast Track designation. 

Moderna highlights diverse research at their third annual science day

At this year’s virtual Science Day, Moderna will present new platform science and preclinical research, including: 

Engineering and Proteins to Improve Therapeutic Properties – advantage of medicines over small molecule drugs is the ease of engineering their properties to achieve desired pharmacology. New research will be presented on efforts to engineer both s and encoded proteins to improve and extend therapeutic effect. At Science Day, Moderna will present a protein engineering workflow by which it has engineered a Moderna T7 RNA polymerase (MT7) that does not produce dsRNA impurities. 

Optimizing Lipid Nanoparticle Technology – the Company will present new research in delivery science to optimize its lipid nanoparticles (LNPs). The presentations will highlight a novel squaramide-based ionizable lipid designed to enhance the interactions between the lipid and . Preclinical data from new LNPs incorporating this novel ionizable lipid show improved protein expression after IV administration, including repeat dosing, and efficient delivery to the liver, as compared to current state-of-the-art Moderna proprietary LNPs. 

Moderna currently has 23 development candidates in its portfolio with 13 in clinical studies. More than 1,900 participants have been enrolled in clinical studies across Moderna’s pipeline. Moderna and collaborators have published more than 45 peer-reviewed papers. 

Encouraging interim data from ph 1 trial of Moderna’s redacted vaccine candidate mRNA-1273

-1273 was generally safe and well tolerated, with a safety profile consistent with that seen in prior Moderna infectious disease vaccine clinical studies. The sole incidence of a grade 3 adverse event in the 25 µg and 100 µg dose cohorts was a single participant at 100 µg who experienced grade 3 erythema (redness) around the injection site. To date, the most notable adverse events were seen at the 250 µg dose level, comprising three participants with grade 3 systemic symptoms, only following the second dose. All adverse events have been transient and self-resolving. No grade 4 adverse events or serious adverse events have been reported.

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 redacted) tested in the same assay. At day 43, at the 100 µg dose level (n=10), levels of binding antibodies significantly exceeded the levels seen in convalescent sera. Samples are not yet available for remaining participants.

At this time, 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, -1273 vaccination elicited neutralizing antibodies in all eight of these participants, as measured by plaque reduction neutralization (PRNT) assays against live redacted. 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-led Phase 2 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 1 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 3 study to be between 25 µg and 100 µg and expects Phase 3 trial initiation in July, subject to finalization of the clinical trial protocol.