September 19, 2020

A vaccine against Coronavirus approved for Phase 1 study

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.

Moderna, Inc., (Nasdaq: MRNA) a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients today announced that it has released the first batch of mRNA-1273, the Company’s vaccine against the novel Coronavirus, for human use.

Vials of mRNA-1273 have been shipped to the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH) to be used in the planned Phase 1 study in the U.S.

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 Therapeutics’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.

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.

I know, it is a lot of technicalities to understand, but there is no simpler way to explain any of it. After all, it is science! Fundamentally, it all means one simple thing that we all care about to know: 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.

From MERS-CoV to SARS-CoV-2

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. In order to use their platform to produce vaccines, the introduced mRNA encodes a viral antigen that is recognized by the immune system and elicits a protective response in the body.

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.

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, which is remarkably fast and probably the fastest ever done.

A Phase 1 open-label study began on March 16 and the first person was dosed on March 23. The positive results opened the doors for the company to advance faster towards Phase 2 this week and NIH just recently expanded the trial to include 60 adults over the age of 56. Some will be tested in Seattle, some in Atlanta at some at the NIH in Bethesda, Maryland.

A Phase 3 clinical trial could begin in fall 2020, but this decision is subject to data from the previous two studies.

Stéphane Bancel, CEO of Moderna

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 2 and 3 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 upfront, 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.

We also suggest you read this article: Possible Paths to COVID-19 Treatment and Prevention

About Moderna’s Prophylactic Vaccines Modality

Moderna recently received $483 million from the Biomedical Advanced Research and Development Authority (BARDA) to bolster COVID-19 vaccine development using the company’s mRNA vaccine candidate.

Moderna scientists designed the Company’s prophylactic vaccines modality to prevent infectious diseases. More than 1,400 participants have been enrolled in Moderna’s infectious disease vaccine clinical studies under health authorities in the U.S., Europe, and Australia. Clinical data demonstrate that Moderna’s proprietary vaccine technology has been generally well-tolerated and can elicit durable immune responses to viral antigens. Based on clinical experience across six Phase 1 studies, the Company designated prophylactic vaccines as a core modality and is working to accelerate the development of its vaccine pipeline.

The potential advantages of an mRNA approach to prophylactic vaccines include the ability to combine multiple mRNAs into a single vaccine, rapid discovery to respond to emerging pandemic threats, and manufacturing agility derived from the platform nature of mRNA vaccine design and production. Moderna has built a fully integrated manufacturing plant that enables the promise of the technology platform.

Moderna currently has nine development candidates in its prophylactic vaccines modality and the company is already planing on hiring nearly 150 new team members in the US this year to accelerate the scale-up. This includes a boost in its skilled manufacturing staff to expand capacity from two shifts per day, five days per week to three shifts per day, seven days per week.

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Julio Marchi