Moderna Charts Fast Track of SARS-CoV-2 Vaccine to Clinical Trials

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Coronavirus Covid-19 Vaccine
Cropped hand wearing a nitrile glove holding a Covid-19 vaccine vial and a syringe

The holy grail of the current pandemic—a vaccine for COVID-19—will not be available next month. It may not even be ready by next year. Regardless, the strides being made are happening at unprecedented speed. One of the companies at the front of the pack is Moderna Therapeutics.

Synbiobeta, the network of the synthetic biology world, has hosted “town halls” for the past few weeks. This week, their guest host was Stéphane Bancel, Moderna’s CEO. Hailing originally from France, Bancel spoke about Moderna’s efforts to make a vaccine for SARS-CoV-2, how Moderna has moved as rapidly as they have, and why he is hopeful that they will continue on this progression.

RNA vaccines

Moderna’s platform is based on injecting mRNA into cells to produce protein in human cells. When he first heard the idea, Bancel admitted, “I thought this was crazy.” RNA, he knew, is both unstable and immunogenic. But, he asserted, there had been some recent scientific breakthroughs where synthetic RNA was making protein in vivo. Also, he noted that after thinking about it, he realized that making a human protein in a human cell is probably not going to be worse than making it in bacteria. “We don’t guess the biology—we use the biology of nature,” he said.

Stéphane Bancel, CEO of Moderna

The system has many advantages, many of which led Moderna to be able to move as rapidly as they did to develop the SARS-CoV-2 vaccine.

RNA is a great molecule to hitch a wagon to, Bancel noted, as it has many dimensions to play with. All of the uridines in Moderna’s mRNAs are modified to evade the normal immune response triggered when toll life receptors—specifically TLR7 and TLR8—recognize uridine and activate an interferon response.

Also, mRNA is very long. For example, the SARS-CoV-2 mRNA is more than 4,000 bp so there is lots of secondary structure to play with.

Another perk is the ability to combine mRNAs. If cells can have 10,000 mRNAs at any given time, Moderna can do the same in a synthetic way.

The mRNA based platform allows them to move very fast and scale quickly. Whether they make mRNA for a flu vaccine or a rare liver disease—it’s the same. It’s the same rooms, same reactors, same people, noted Bancel.

MERS-CoV set the stage

Moderna has been working on multiple viral “first in class” vaccines for years, including cytomegalovirus, Zika virus, respiratory syncytial virus, Epstein Barr virus, Flu H7N9, to name a few.

One of the reasons the SARS-CoV-2 vaccine development has been so fast (for details, see the timeline of events at the bottom of the story) is the work Moderna has done over the past two years in an existing collaboration with the Vaccine Research Center (VRC) of NIAID to develop a vaccine against MERS-CoV.

The rabbit infection data, shown to the left, measures the amount of neutralizing antibodies produced by the rabbits is response to the vaccine. The first dose of Moderna’s vaccine produced neutralizing antibodies in the blood, with production greatly increased upon the second dose—or booster—on day 21.

 

A challenge of the rabbits with MERS-CoV virus at day 46, resulted in a huge reduction of MERS viral load in the nose, throat, and bronchoalveolar lavage (data shown to the right.)

When the company received the SARS-CoV-2 genomic sequences from China on January 11, the stage was already set.

The mRNA vaccine against SARS-CoV-2 (mRNA-1273) was quickly designed, tested for sterility, and shipped to the NIAID for clinical study. The IND was filed on February 21 and, on March 2, FDA gave the green light to start clinical study. The first person was dosed last Monday and the company is currently filing an IND to start Phase II.

When asked to pull out his crystal ball, and predict a timeline, Bancel noted that the most optimistic scenario, “which would require 20 different things to work,” is that they may progress through Phase II and III this year and have a vaccine in 2021. Although that may sound like a long way off, he added that it “would be a world record,” noting that vaccines normally take 10 years to make.

But, he added, it is a very unique situation to be working on a vaccine in the middle of a pandemic. Everyone, he noted, “needs to be aware that the NIH, CDC, FDA, and others are collaborating like nothing I have ever seen before.” He said the amount of email that occurs in the middle of the night is a testament to that.

The biggest reason for Moderna’s progress on this vaccine is because a lot of the work had been done before—given the time and energy they invested into the MERS vaccine. He explained that, without that, they never would have been able to move as fast.

He hopes that they can continue to do this work up front, for the next 10 or 20 viruses that could cause epidemics. Bancel stressed that time is needed in order to do things correctly. “You need to get ahead of things,” he explained, because, “chasing a pandemic is not something that can be done well.”

Timeline of Moderna’s path to the SARS-CoV-2 vaccine

January 11 – the Chinese authorities shared the genetic sequence of SARS-CoV-2

January 13 – the U.S. National Institutes of Health (NIH) and Moderna’s infectious disease research team finalized the sequence for mRNA-1273, the company’s vaccine against the novel coronavirus.

February 7 – the first clinical batch was completed, a total of 25 days from sequence selection to vaccine manufacture. The batch then proceeded to analytical testing for release.

February 24 – the clinical batch was shipped from Moderna to the NIH for use in their Phase I clinical study.

March 4 – FDA completed its review of the Investigational New Drug (IND) application filed by the NIH for mRNA-1273 and allowed to the study to proceed to begin clinical trials.

March 16 – the NIH announced that the first participant in its Phase I study for mRNA-1273 was dosed, a total of 63 days from sequence selection to first human dosing. The open-label trial is expected to enroll 45 healthy adult volunteers ages 18 to 55 years over approximately six weeks.

March 23 – Moderna filed a Current Report on Form 8-K which included, among other things, information regarding the potential timing of the availability of a vaccine against COVID-19. The company reported that the Phase I study is proceeding in accordance with the protocol under the direction of NIAID. Moderna further reported that while a commercially-available vaccine is not likely to be available for at least 12–18 months, it is possible that under emergency use, a vaccine could be available to some people, possibly including healthcare professionals, in the fall of 2020. Any emergency use would be subject to authorization by the appropriate regulatory agencies, based on the emergence of clinical data for mRNA-1273 that would support use of the vaccine prior to licensure. In addition, Moderna confirmed that it is scaling up manufacturing capacity toward the production of millions of doses per month, in the potential form of individual or multi-dose vials. As has previously been disclosed, the ability of the company to make millions of doses per month is contingent on investments in the scale up and further buildout of the company’s existing manufacturing infrastructure.

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