Moderna Inc.’s chief medical officer, Tal Zaks, said that the results in hand “give us great confidence that we've got the right dose range for phase III” work slated to begin this summer with COVID-19 vaccine prospect mRNA-1273. A regulatory filing could come as early as 2021.

Shares of the Cambridge, Mass.-based firm (NASDAQ:MRNA) shot up $13.31, or 20%, to close May 18 at $80, and indexes rose across the board as Wall Street greeted interim phase I outcomes in eight patients from an experiment led by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).

Data for the 25-µg and 100-µg dose level (in patients ages 18 to 55) after two doses (day 43) and at the 250-µg level (in patients ages 18 to 55) after one dose (day 29) show dose-dependent drops in immunogenicity across all three levels, as well as between prime and boost within the 25-µg and 100-µg dose levels. All participants ages 18 to 55 (n=15 per cohort) across levels seroconverted by day 15 after a single dose, Moderna said.

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 (i.e., blood samples from people who have recovered from COVID-19) tested in the same assay. At the 100-µg dose level (n=10), levels “significantly exceeded” the levels seen in convalescent sera. Samples are not yet available for remaining participants, Moderna said.

Neutralizing-antibody findings 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 brought about neutralizing antibodies in all eight participants, as measured by plaque reduction neutralization assays against live SARS-CoV-2. The levels at day 43 reached or surpassed “levels generally seen in convalescent sera,” the company said. Roth analyst Yasmeen Rahimi said in a report that “although medical consensus doesn't allow us to put a pin on the quantitative definition of ‘levels generally seen in convalescent sera,’ we believe the NIAID-led analysis of the antibody titers was not randomly chosen and likely is in the range of levels cited by the NIH in its guidance,” she wrote.

The vaccine was generally safe and well-tolerated, with a safety profile like that seen in previous Moderna infectious disease vaccine studies. The sole incidence of a grade 3 adverse event (AE) in the 25-µg and 100-µg dose cohorts involved a participant at 100 µg who experienced redness around the injection site. So far, the most notable AEs turned up at the 250-µg dose level, where three subjects exhibited grade 3 systemic symptoms, only following the second dose. All AEs have been transient and self-resolving, Moderna noted. Researchers chalked no grade 4 events or serious AEs.

Preclinical results from a viral challenge study in mice showed replication blocked in the lungs, and neutralizing titers in phase I participants at the 25-µg and 100-µg dose levels lined up nicely with those protective in the animal model. Based on the interim phase I results, the Moderna-led phase II study will be amended to study two dose levels, 50 µg and 100 µg, so that a dose can be chosen for pivotal studies. The NIH-led phase I effort is being amended, too, so that it will include a 50-µg dose level cohort across each of the three age groups. The phase II aims to enroll 600 healthy volunteers into two cohorts of adults, ages 18 to 55 and older than 55. Moderna has partnered with Lonza Group AG, of Basel, Switzerland, to increase vaccine manufacturing capacity up to 1 billion doses per year, “which could provide Moderna with annual mRNA-1273 revenues of $10 billion,” Piper Sandler analyst Edward Tenthoff speculated in a report.

Risks lessening, ‘it works’

“We're talking a matter really of weeks before we hope to be launching the phase III [and] there will continuously be data coming out of this phase I,” Zaks said during a conference call with investors. “Of course, we'll do our best to accelerate any learnings we have from the emerging phase II” experiment. Moderna figures the phase III dose will land between 25 µg and 100 µg and aims to launch the late-stage work in July. While many players crowd the field in the push for a COVID-19 vaccine, J.P. Morgan analyst Cory Kasimov likes Moderna’s progress with mRNA technology, even as he acknowledged “a long way to go and plenty of risk to navigate. The path forward is littered with potential potholes, but we think all signs point to the next key anticipated update – phase I safety and immunogenicity data – being a favorable one,” he wrote in a report. If all goes well, the company could seek approval in 2021, “a rather remarkable accomplishment in the context of historical vaccine development,” he noted. Moderna went public in late 2018, pricing its IPO at the midpoint of its proposed range of $22 to $24 and upsizing by about 20% to offer 26.3 million shares at $23 apiece, collecting $604 million. “We could debate for days the ultimate value of a COVID-19 vaccine to a company,” Kasimov added. “In our view, it’s almost unquantifiable at this stage, as there as so many economic and scientific unknowns. However, to the extent that directionally positive updates continue for one of the more closely watched clinical developments in recent memory (and potentially our lifetimes), we expect a valuation-agonistic momentum trade to continue as well.”

CEO Stéphane Bancel credited his firm’s platform for the fast development of mRNA-1273. The technology imitates the operating system on a computer that can “plug and play” interchangeably with programs. Moderna’s figurative program is the mRNA sequence that codes for a particular protein. “We still believe we're in the early days of mRNA science, we still believe we have a lot to learn, and we still believe we are the best company positioned in this space to keep growing and keep learning,” he said.

Zaks said “the biggest risk, as I see it, is actually in being able to see enough cases” to show statistical significance in the ongoing research. Outcomes as they stand, though, “take off the table the risk of not being immunogenic or the risk of the antibody type being wrong,” he said. “No, it works.”

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