From The Editor | November 26, 2024

Commercializing mRNA: 3 "Action Items" To Turn Promising Science Into Real-World Impact

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By Anna Rose Welch, Editorial & Community Director, Advancing RNA

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Over the past few months, I’ve been publishing articles centered on a topic that certainly seems miles and miles down the road for the RNA therapeutics space: Commercialization. However, having spent a few years in the biosimilar space, as well as the cell & gene therapy space prior to the mRNA world, I’ve become increasingly sensitive to the ways history tends to repeat itself across modalities.

As I’ve articulated in several articles prior to this one, launching a drug goes well beyond presenting safe and differentiated clinical data at a price point that promotes access. At any one point in a drug’s journey, there is a mess (yes, a mess) of factors and influences that dictate the “when and why” of our products. This is why I was immensely happy to hear that such concerns are also top of mind across the industry.

The recent Alliance for mRNA Medicines’ inaugural Ascent conference provided us with a lot of great updates on the mRNA industry’s progress. But throughout each of these specific conversations, there was a shared underlying question: How can we become a less esoteric industry? Though we as members of the industry know that mRNA/RNA has a lot to offer the world, it goes without saying that, to succeed, mRNA/RNA’s value must also be understood and recognized from outside of our company walls and mRNA conference halls.

Obviously, there are many stakeholders, and how each stakeholder defines “value” will be different. But there were three “action items” that stood out over the two days that stand to solidify RNA’s value in the biologics and advanced therapies space and which will make our products even more relevant to the provider/patient communities.

Let The Science Catch Up

In the year immediately following the accelerated launch of the world’s first mRNA vaccines, our conversations were often rooted in how we could keep the Operation Warp Speed efficiency alive. Four years later, we’ve returned to some state of pre-pandemic development and regulatory normalcy. However, as was nicely articulated by Pfizer’s Jane True, we aren’t entirely where we need to be scientifically as an industry to realize the benefits of warp-speed-like development.

“The promise of mRNA to treat a lot of different diseases is there,” she explained. “We have a desire to accelerate in certain areas and move as quickly as everybody was able to during the pandemic. But at the same time, we must let [the science] catch up and mature to allow this efficiency to happen.”

Obviously, clinical data will be one of the most important sources of knowledge about our mRNA molecules/products. In fact, as I’ve heard in numerous end-of-year interviews, 2025 is positioned to be an important year for mRNA as we continue/begin to see proof of concept data. As Danaher’s Sadik Kassim reaffirmed, 2024 has already delivered some great clinical data demonstrating “the fungibility and flexibility of mRNA beyond vaccines” (namely gene editing & mRNA-based CARTs).

However, though clinical data is much needed, there is still a lot of foundational knowledge we have yet to glean about our RNA molecules’ structure. For example, I was struck by another remark from Kassim, emphasizing just how limited (or nonexistent) our data on the structure of mRNA/RNA is compared to that of protein structure.

“The Nobel Prize this year went to David Baker and the AlphaFold team for their ability to define protein structure,” he explained. “We now know the structure of hundreds of millions of proteins. Meanwhile, data on the relationship between sequence and the folding of secondary RNA structures, for example, and then the RNA’s subsequent functionality, whether in in vitro cell culture models, mouse models, or in humans, is completely absent.”

As he went on to emphasize, investigating and sharing sequencing and structure data will be an essential step toward more efficient preclinical development and more precise mRNA molecule design. Though these advancements will strengthen our scientific knowledge and development efforts, it’s also important to think beyond the lab. Such innovations will ultimately help us expand our mRNA therapeutics into a broader array of indications, and, in turn, make mRNA a much more meaningful and relevant molecule/therapeutic offering in more patient communities.

Be Smart About Selecting Our Indications

There were a few different conversations throughout AMM Ascent that raised the importance of answering the question: “Why is mRNA technology best suited for treating this indication, in particular?”

As I’ve written before, there are a few important factors to consider when deciding the indications our mRNA therapies will be best suited to treat. These factors include a patient population’s risk tolerance to changing treatments; the competitive dynamics of current standards of care (i.e., what payers may be more inclined to reimburse); and in which specific pockets of each community there are still unmet needs. And, by the way, let’s not forget: A patient doesn’t end up on a therapy without their physician. So, understanding physician prescribing practices in each indication is equally — if not even more — important.

There are a lot of moving parts and influences that will dictate patients’ and providers’ choices and access to our therapies. However, demonstrating a differentiated clinical profile will, of course, be one of the most important influences. To achieve this differentiation, BioNTech’s Andreas Kuhn emphasized the importance of incremental or stepwise scientific improvements — for example making the RNA 20% better and/or making the formulation 50% better. As Pfizer’s True went on to acknowledge, these seemingly “incremental” scientific improvements could translate to exponentially meaningful commercial improvements.

However, as Andy Tran of Matrix Capital Management reminded us all, the scientific and the commercial realm each has its own definition for and reaction to “incremental innovations.” In fact, on the commercial side, the phrase “incremental innovation” may not exactly translate into what an investor or the market considers to be “a unique and differentiated” enough offering to unseat or compete against an indication’s standard(s) of care. As Tran went on to clarify, “Though we like to focus on the science and data, ultimately, if the product doesn’t make sense from the commercial and reimbursement angle, you’re going to have a really tough time.”

Create mRNA “Fans”

I’ve gone long on the importance of telling mRNA’s story “differently” in previous articles. I’ve also strived to “put my money where my mouth is” by launching my own creative video series in which I compare mRNA to the worlds of Harry Potter, The Game of Risk, and fly fishing, to name a few. This is why I was exceptionally thrilled to hear my passion matched — if not exceeded — by Strand Therapeutics’ Jake Becraft, who argued we need to be in the business of creating “fans.” And the only way we can do that is by changing the ways we communicate about what we do.

“Why do we watch the Super Bowl and not just read the score after the game is over?” Becraft asked. “It’s the pursuit. Why do people give a shit about what Space X does? Because they fail in public. They inspire you to hope for their success. The mRNA industry has a real opportunity here to inspire people — and this won’t happen just by selling our successes via a drug ad people see during a TV program. We need to create educational materials that get people excited about the pursuit of curing diseases, and when they see the successes, they will feel like they were part of it. That’s how you create fans.”

This is only just the start of my coverage from the AMM Ascent conference. Stay tuned for future panel summaries/editorial capturing my learnings in the weeks/months ahead.