Moderna advancing early stage mRNA prospects to show depth beyond COVID-19 shot

Moderna, sitting on a powder keg of cash after launching a COVID-19 vaccine that's being distributed around the world, is not going to be resting on its laurels anytime soon.

New interim phase 1 data for the biotech's respiratory syncytial virus, or RSV, vaccine candidate called mRNA-1345 showed the treatment was well tolerated in younger adults and increased neutralizing antibodies in patients with the virus. The candidate is based on the same mRNA technology that brought the COVID-19 vaccine to the world.

The Cambridge, Massachusetts-based biotechnology company has 14 different mRNA candidates launched into clinical trials already with plans to further invest in the mRNA platform. Moderna is hosting its second annual Vaccines Day on April 14.

“Moderna has one of the world’s largest and most innovative vaccine development pipelines,” said CEO Stéphane Bancel. “We believe we have a unique opportunity to develop new vaccines against viruses hurting people around the world, at a pace that is radically different from what the industry has previously done.”

The company plans to draw on experience gained in 2020 when the COVID-19 vaccine went from preclinical to launch and manufacture in record time.

The RSV trial is ongoing, with several different cohorts testing the vaccine in a wide range of ages. There is currently no approved vaccine for RSV, which is typically a mild respiratory virus that can be severe in infants and older adults. Moderna intends to investigate combinations of mRNA-1345 with its other vaccine candidates for other respiratory pathogens in children and older adults.

Cold viruses often don’t get much of a look when it comes to R&D; they are annoyances, but ones that usually make us feel miserable for a few days and then clear up.

But some cold viruses can hit vulnerable people much harder, leading to pneumonia and hospitalizations. These are colds caused by RSV, which, in the elderly and in children under 5, can cause serious complications and sometimes can prove fatal.

In younger children, it can cause bronchiolitis (inflammation and congestion of the small airways or bronchioles of the lung), and it sometimes leads to pneumonia in both infants and the elderly. It's thought to cause about 3 million hospitalizations of children under 5 globally, with around 177,000 hospitalizations of older people in the U.S.

There have been several Big Pharma attempts at a vaccine, but the road has been fraught with setbacks and flops. There is a monthly preventive shot from Swedish Orphan Biovitrum's Synagis used against RSV in high-risk infants, but a fully protective vaccine remains elusive.

GlaxoSmithKline is currently well ahead of Moderna in the RSV vaccine race, having last year kick-started a phase 3 trial in pregnant women for the vaccine, to assess whether it can help protect babies after birth. New data on the vaccine, which contains a recombinant subunit pre-fusion RSV antigen (RSVPreF3) and is also in trials for older adults, is slated to see data from next year.

“I am encouraged by these interim phase 1 data showing the ability of mRNA-1345 to elicit a strong neutralizing antibody response,” said Jacqueline Miller, M.D., Moderna’s senior vice president, infectious diseases. The biotech will now hope to be able to show its vaccine can help protect the vulnerable populations RSV hits.

Moderna will also advance a 100-ml dose of mRNA-1647 to a phase 3 clinical trial for cytomegalovirus after a midstage study found the vaccine was well tolerated and created neutralizing antibodies in patients without the virus after a third shot. Patients who were positive for the virus also saw an increase in neutralizing antibodies, although at a lower rate than those who were negative. Cytomegalovirus typically goes undetected or causes mild illness, but can cause serious problems such as hepatitis in people who have weakened immune systems or in babies born with the virus.

Several of Moderna's vaccine candidates are expected to hit the clinic in 2021, including two for HIV and another for seasonal flu. The latter trial is Moderna’s effort to do better than antiquated egg-based vaccines that over half of all Americans receive each year to prevent the flu.

Meanwhile, Moderna continues to deliver the COVID-19 vaccine, contributing to the 192,282,781 doses that have been administered in the U.S. as of April 13. Pfizer and BioNtech and Johnson & Johnson also have vaccines that have been authorized in the U.S. on an emergency basis. Administration of J&J's jab, however, was put on hold on April 13 over blood clot concerns.