4 Biotech Companies Working On RNA Therapies

The COVID-19 messenger RNA (mRNA) experimental vaccine from Moderna MRNA 0.53% is one of the most promising vaccine candidates for the disease.

Its success could serve as a proof-of-concept for several other mRNA projects at other publicly-traded companies, such as Pfizer PFE 2.07%, BioNTech BNTX 2.04%, CureVac CVAC 3.49% and Translate Bio TBIO 1.95%.

What Is Messenger RNA (mRNA)?

Our genetic information is stored in DNA molecules in the nuclei of our cells. DNA contains encoded instructions for making various proteins used in the creation or maintenance of cells.

But the ribosomes — the cell organelles which make proteins — can’t actually read DNA. They can only read mRNA, an intermediary form of nucleic acid, which transcribes genetic information from DNA and carries it throughout the cell.

In recent years, scientists have started to experiment with using mRNA as a vector to transmit genetic information to cells, which can teach them how to fight a virus.

In other words, they’ve been looking to use mRNA as a vaccination method.

According to the University of Cambridge’s PHG Foundation, mRNA vaccines could be faster, cheaper and safer to produce than conventional vaccines - which typically contain weakened or modified forms of a pathogen which the patient’s immune system uses as “target practice.”

Moderna’s COVID-19 mRNA Vaccine Candidate

There are currently no mRNA vaccines approved for human use in the U.S. Moderna is looking to change that with MRNA-1273, its mRNA-powered COVID-19 vaccine candidate.

MRNA-1273 is widely viewed as the frontrunner in the race for a COVID-19 vaccine. Moderna reported last week that it has completed enrollment for its 30,000-participant late-stage trial of the vaccine candidate. And unlike Johnson & Johnson JNJ 1.1% or AstraZeneca AZN 0.92%, it has not yet had to halt trials over safety concerns.

If Moderna successfully brings a mRNA vaccine to market — especially if it’s among the first COVID-19 vaccines available to the public — it could bring a surge of interest to mRNA technology in general.

And it’s not the only biotech company working on an mRNA-based project. There are at least three other publicly-traded firms offering investors exposure to this emerging technology.

Pfizer PFE 2.07% And BioNTech’s BNTX 2.04% COVID-19 Vaccine Candidate

Moderna isn’t even the only company working on a COVID-19 vaccine candidate which uses mRNA technology.

Pfizer and BioNTech are also developing BNT162, a mRNA-based COVID-19 vaccine candidate which is currently in global Phase 2/3 trials.

BNT162b2 isn’t quite as far along in the drug development process as MRNA-1723. But it received Fast Track designation from the U.S. Food and Drug Administration (FDA) in July, making it a strong contender to be the second or third mRNA-based vaccine on the market.

CureVac CVAC 3.49% Is Developing Vaccines For Rabies And COVID-19

CureVac is also working on a mRNA-based COVID-19 vaccine, as well as a mRNA-based vaccine for rabies.

The biotecg company has been working on an unnamed mRNA-based COVID-19 vaccine platform along with the nonprofit Coalition for Epidemic Preparedness Innovations (CEPI) since the virus’s genome was published in early January. It is currently in Phase 2 clinical trials.

It developed that platform based on positive early data from its mRNA-based rabies vaccine candidate, CV7202, which is currently in Phase 1 trials.

Translate Bio TBIO 1.95% Is Working On A mRNA-Based Cystic Fibrosis Drug

A new cystic fibrosis drug candidate from Translate Bio provides an example of a non-vaccine drug built on mRNA technology.

Translate Bio recently presented data from its MRT5005 drug candidate at the 34th Annual North American Cystic Fibrosis Conference (NACFC). It’s a mRNA-based gene therapy which seeks to help patients’ malformed lung cells produce essential proteins correctly.

MRT5005, which is currently in Phase 1/2 clinical trials, has also won Orphan Drug, Fast Track and Rare Pediatric Disease designations from the FDA.

https://www.benzinga.com/general/biotech/20/11/18128283/4-biotech-companies-working-on-rna-therapies

Pfizer Analyst's 3 Possible Coronavirus Vaccine Readout Scenarios

The first Interim data from an ongoing, late-stage coronavirus trial by Pfizer Inc. PFE 2.07% is expected sometime after the U.S. presidential elections, according to an analyst at Cantor Fitzgerald.

The Pfizer Analyst: Louise Chen has an Overweight rating and $53 price target for Pfizer shares.

The Pfizer Thesis: Pfizer plans to report the results if they are definitive — achieving 76.9% or more efficacy in 32 total number of cases, or if the vaccine fails, Chen said in a Monday note.

The potential stock reaction to a vaccine readout will in part hinge on macro factors and competing vaccines and treatments, the analyst said.

She discussed three possible scenarios for the vaccine readout and outlined how Pfizer's stock could trade under each one. 

If Pfizer reports positive data at the first interim analysis, the company's shares will trade higher, with all else being equal, Chen said.

If the vaccine candidate becomes a worldwide, recurring revenue stream for Pfizer, it will likely augment net present value by about $5 per share, the analyst said. 

Under the second scenario of Pfizer reporting positive efficacy data and the vaccine being only a one-time benefit for the company, $2 per share will accrue to the net present value, she sad.

A one-time benefit means that once everyone is vaccinated, then there is no longer a recurring revenue stream to the company, Chen said. 

Under the third scenario of the vaccine candidate failing, Pfizer shares would lose about $4, the analyst said.

"This is because FactSet consensus already has $1.4B of sales for PFE's COVID-19 vaccine in 2020, $8.7B in 2021 and ~$2.1B annually, thereafter."

https://www.benzinga.com/analyst-ratings/analyst-color/20/11/18170499/a-pfizer-analysts-3-possible-coronavirus-vaccine-readout-scenarios

FDA shows signs of cold feet over emergency authorization of Covid-19 vaccines

There are serious signs the Food and Drug Administration is getting cold feet over the notion of issuing emergency use authorizations to allow for the widespread early deployment of Covid-19 vaccines.

Instead, it appears the agency may be exploring the idea of using expanded access — a more limited program that is typically used for investigational drugs — in the early days of Covid vaccine rollouts.

Whereas a few weeks ago the agency’s concern was to protect against the possibility that unproven vaccines would be pushed out prematurely due to pressure from President Trump, now the fear is that early authorization of vaccines could squander a one-time chance to determine how well the various vaccines work and which work best in whom.

Marion Gruber, director of the FDA’s office of vaccines research and review, put the issue on the table when members of the Vaccines and Related Biological Products Advisory Committee began to discuss a series of questions FDA staff posed at the end of a grueling day-long virtual meeting Thursday.

“We are concerned about the risk that use of a vaccine under an EUA would interfere with long-term assessment of safety and efficacy in ongoing trials and potentially even jeopardize product approval,” Gruber said. “And not only the first vaccine, but maybe even follow-on vaccines.”

The acting chair of the committee, Arnold Monto, from the University of Michigan, who has decades of experience studying the efficacy of vaccines, put it in more dire terms during the discussion. The maker of a Covid-19 vaccine that is given an EUA might not be able to generate enough additional data to ever successfully apply for a full license, Monto said.

The problem stems from thorny ethical questions about whether — once a vaccine has been cleared for use by the FDA — the people who were randomly assigned to receive a placebo in its clinical trial must be informed and offered vaccine. Vaccinating the people who received placebo injections — the trial’s control arm — would end the ability to continue to compare the two groups after what would have been a short trial.

Pfizer and BioNTech, the collaboration expected to be first to apply for an emergency use authorization — sometime in mid-November — have indicated they plan to unblind their trial and offer people in the placebo arm vaccine. (When a trial is blinded, participants don’t know if they received vaccine or a placebo injection.)

Early unblinding of these trials actually runs counter to the FDA’s advice. The agency is urging vaccine manufacturers to keep their trials blinded as long as possible, to collect as much data as they can.

The EUA could trigger another related problem. People in clinical trials might choose to pull out and try to get the vaccine that has been authorized for emergency use, especially if they are in a high-risk group that is likely going to be at the front of the line when vaccines begin to become available. Enrollment in the vaccine trials for other Covid vaccines might slow as people decide they don’t want to risk being randomized to receive a placebo, and instead wait for their turn to get vaccine cleared under an EUA.

If they are stopped too early, the trials, which were structured to come up with quick answers as to whether Covid vaccines prevent symptomatic Covid-19 infections, might fail to answer additional, important questions needed to figure how to best use the various vaccines that have been produced, if — as expected — multiple vaccines prove to work.

For most of the vaccine trials, the “primary endpoint” is showing they prevent symptomatic Covid-19 disease in at least 50% of vaccinees. But there are also “secondary endpoints.” Secondary endpoints include whether the vaccines reduce the number of severe Covid cases, and how well they work in important subsets of the population such as the elderly or people of color, who have been disproportionally hit by the pandemic. Trials that end after reaching their primary endpoint will leave gaping knowledge gaps, a number of experts warned.

“We may have limited and in some instances no information about some of the secondary endpoints,” said Stephanie Schrag, an epidemiologist from the Centers for Disease Control and Prevention who made a presentation at the meeting. “This would be particularly true in the instance of an early EUA because many of these secondary endpoints require longer time than the primary to accrue events.’’

Jesse Goodman, a former FDA chief scientist who listened to the meeting, concurs with the agency’s concerns. Answers about how well these vaccines work, how long they work, and which work best for which segment of the population will always be clearer if they are generated by randomized controlled trials — the gold standard of clinical trials.

“Let’s say one of these vaccines has, you know, 60% efficacy and another one has 80%. Or one of them, the efficacy waned after four months, and the other lasts a last year. It’s going to benefit people to find that out now rather than three years later from crummy observational data,” Goodman told STAT.

Using expanded access rather than emergency use authorizations would be a more cumbersome process and create some challenges. People who were to be vaccinated would have to sign informed consent forms, which requires a discussion of risks and benefits during vaccine administration; safety data from vaccinees also would have to be gathered. But Goodman, who actually suggested expanded access as an option in a commentary he co-wrote in JAMA in July, said that this route might better ensure the continuation of the clinical trials.

Members of FDA’s advisory committee appeared to share the concerns of the agency staff who were asking for their guidance.

Sheldon Toubman, a lawyer from New Haven, Conn., who is the consumer representative on the panel, said it would be his preference that the vaccines not be deployed under emergency use authorizations. Toubman said the public fears politics, not science, is driving the approvals process and EUAs won’t dispel those views.

A number of polls, including one published Monday by STAT and the Harris Poll, have shown that the public is cooling to the idea of Covid vaccines. The declining percentage of Americans who say they are willing to be vaccinated is thought to be linked to the politicization of the vaccine approvals process, which Trump has attempted to fast-track in the weeks leading up to the election.

Toubman’s position was echoed by representatives of the HIV Medical Association and the Infectious Diseases Society of America during a public comment section of the hearing.

Emily Martin, an assistant professor of infectious diseases epidemiology from the University of Michigan who studies vaccines effectiveness, urged the committee to advise the FDA that EUAs should not allow companies to halt their clinical trials early.

“Without complete and full randomized trial data, we will lack the evidence base needed to monitor and adapt vaccination strategies as needed over the many years these vaccines will be in use,” Martin said. “Ending these trials early will irrevocably hamper our ability to optimize the effective use of the vaccines going forward.”

Goodman agreed that an early EUA could actually leave a manufacturer with too little data to persuade the FDA to issue a full license, though he thought that was not the likeliest of scenarios.

“I think more likely than that, but really, as concerning from a public health point of view would be if … we don’t get adequate enough information to understand how these vaccines compare with each other and perform in terms of their safety and efficacy, we don’t know how to use them in a public health context,” he said. “Which could end up hurting far more people at the end of the day.”

https://www.statnews.com/2020/10/23/fda-shows-signs-of-cold-feet-over-emergency-authorization-of-covid-19-vaccines/