Fierce JPM Week: After 'objectively astonishing' progress on mRNA, biotech looks to tinker with winning formula

Messenger RNA (mRNA) technology became a household name so quickly thanks to the COVID-19 vaccines by Pfizer-BioNTech and Moderna, and, now, biotech leaders are taking a moment to reflect on where the field goes from here. 

“When so much progress has been made, as the past two years, which is objectively astonishing, it can be hard to realize that it's also the beginning,” said Geoffrey von Maltzahn, Ph.D., co-founder, and CEO of Tessera Therapeutics, during a Fierce JPM Week panel on "The Next mRNA Wave."

Now, companies that were involved in mRNA before the pandemic have a validated platform on their hands to develop new therapeutics and vaccines, which leads to the inevitable question: What comes next?

“mRNA is not new, but it's still in infancy,” said Jean-Francois Toussaint, Ph.D., head of research and development for Sanofi Pasteur. “There is room to improve it much further down the road, and that's what we are doing.”

mRNAs are essentially copies of genetic instructions that can direct your body to make proteins that can then be used to fight or prevent disease. This technology can be harnessed in multiple ways to create different types of medicines. Tessera, for instance, is combining the idea with genetic medicine to allow modifications to the genome that were previously thought to be difficult or impossible.

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Ultragenyx, meanwhile, is focusing on protein replacement using mRNA as a delivery mechanism, according to Chief Medical Officer Camille Bedrosian, M.D.

Sanofi is focusing its research on vaccines that can be implemented into regular inoculation schedules—think RSV, acne vaccines or potentially chlamydia, according to Toussaint. But where Sanofi really wants to make an impact is on improving the known challenges of mRNA: storage and tolerability.

A known issue with the COVID-19 vaccines has been the side effects a day or so after, when many patients report headaches, chills or even fever. This is absolutely an acceptable outcome in a global pandemic where the need to protect against a deadly disease is so great, but Toussaint said these kinks have to be worked out for the next generation of therapies and vaccines.

“Vaccines are given to people that are healthy people that go to work every day, and of course, you don't want them to miss work; you don't want them to stay in bed for one day because they received a vaccine,” Toussaint said.

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Von Maltzahn remembers just five years ago “more than a few whispers that this would never work.” Just before the pandemic, there were more than a dozen clinical trials underway with mRNA involved in some way, and the modality seemed to have landed on a trajectory toward becoming a major part of drug development someday.

“It's kind of hard to go pre-moon landing and remember all of the challenges that it took to get onto the moon,” von Maltzahn said. But those challenges were plentiful: manufacturing and delivery chief among them.

Now, in the third year of the pandemic, the modality has been accelerated by at least five years to a decade, according to von Maltzahn.

“Lipid nanoparticle compositions have now been administered to probably more people than all biologicals,” he said, referring to the delivery system that underpins the mRNA-based COVID-19 vaccines.  

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As Sanofi tinkers with improving the mRNA model, Toussaint said one key part of the delivery equation could be solving the cold storage requirements that initially limited the launch of vaccines from Pfizer-BioNTech and Moderna to major centers that had the proper equipment.

The COVID-19 vaccines certainly accelerated the field, but, because they were approved via emergency use authorizations that are slowly turning into full approvals, their path to market may not be a great comparison for therapies to come. But there’s one very important way the shots have helped: awareness.

Ultragenyx recently advanced an mRNA therapeutic for glycogen storage disease type III into the clinic, according to Bedrosian. She shared the story of a patient who asked, “When can I get my GST 3 vaccine?”

“mRNA was a foreign concept. It rolls off the tongue of everybody in the country and in the world now,” she said.

Toussaint also suspects regulators will be more comfortable with mRNA therapies and vaccines to come.

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Now that the delivery challenges have been for the most part resolved—with, of course, room to improve and build on the current method—von Maltzahn thinks mRNA is poised to have applications across medicine.

“It's fairly easy to speculate that we're going to open up multiple categories of new medicines as the field advances,” he said.

And on delivery mechanisms, he added, “that's probably an unheralded success in what we've called mRNA vaccines. We might have called them lipid nanoparticle vaccines.”