Cultivating A Thriving mRNA Ecosystem: Key Initiatives & Future Directions
By Anna Rose Welch, Editorial & Community Director, Advancing RNA
I first set foot in the Brazilian Amazon in 2018. After spending a few days in Brasilia for work, I decided to “tack on” a few days at an Amazonian eco-lodge that was just a meager “hop” (one flight), a “skip” (a 1.5-hour car ride), and a “jump” (an hour-long boat ride) away.
It was during my first hike in that tiny corner of that enormous rainforest that I became obsessed with the concept of “the garden” or the utopic paradise often known as “Eden.” (As a poet, obsessing over such things comes naturally.) Obviously, this topic is “ripe” for poetry. But as is often the case with my brain, my poetic inspiration tends to leech into my work. This is why I found myself thinking about “gardens” — well cultivated, harmonious ecosystems — while reviewing my notes from the inaugural Alliance for mRNA Medicines Ascent conference last fall.
Throughout that two-day event, there were many conversations about how we can cultivate a successful and sustainable RNA therapeutics industry. But I was particularly struck by a few initiatives and/or conversations that “planted a few seeds,” if you will, as to how we can enable scalable access for personalized medicines, align around suitable global regulatory policies, and educate the public. Overall, I felt that the following initiatives/talking points were demonstrative of the types of creativity and symbiosis that we will need much more of in the near and long-term to foster a healthy and fruitful RNA ecosystem.
A Clinical Trial Initiative To Watch
It’s not unusual to operate under the mindset of “new modality, new problems.” To some extent, this statement holds true — but it’s not always true. As I’ve argued before, there are a lot of lessons we can learn from the ATMPs that have come before us — particularly on the personalized medicine front. Getting all the stakeholders — namely sites of care, patients, manufacturers, and payers — aligned and operating seamlessly remains a big challenge hindering scalable access to autologous CGTs and personalized mRNA cancer vaccines.
So far, we’ve seen several different flavors of multistakeholder models established to help build ecosystems — whether they be national or regional development/treatment hubs for more efficient care and access. On the advanced therapies side, I’m thinking particularly of the Cell & Gene Catapult (or the Catapult system in general) in the U.K., uniting government, academia, research organizations, the biotech industry, and — particularly in the case of the Advanced Therapy Treatment Centers — sites of care to scale access to ATMPs.
Likewise, CTMC based in Houston — an alliance between MD Anderson Cancer Center, Resilience, and cell therapy biotechs — is another prime state-side example of an ecosystem created to co-locate/streamline both development and patient treatment.
This is why I was excited to learn that the mRNA space now has its own fledgling initiative called the NHS Cancer Vaccine Launch Pad (CLVP). The CLVP aims to improve access to personalized mRNA cancer vaccines for patients being treated via the U.K.’s NHS.
The NHS and Genomics England — in partnership with BioNTech, for starters — intends to identify eligible patients for an mRNA cancer vaccine and match them to the appropriate hospital/vaccine trial being carried out under the different NHS trusts across the country. The goal is to treat 10,000 patients by 2030.
As Danaher’s Sadik Kassim explained to those of us at the AMM Ascent conference, “If this pans out within the context of a nationalized healthcare system like the U.K., this will be an important proof point for the universality of mRNA and also with respect to customization, scalability, and affordability.”
A Conversation Worth Listening To/Having
In the past few years, we’ve heard the FDA’s Peter Marks (and the FDA in general) emphasize the role that risk vs. benefit plays in making approval decisions for advanced therapies. We’ve also heard similar discussions emerging in the mRNA space following the advent of the COVID vaccines. As Marks has explained more than once, RNA products that are targeting larger indications (e.g., prophylactic vaccines for the public) will have a different risk vs. benefit profile than a cancer vaccine or a gene editing therapy for a rare disease patient population with no alternative treatment options.
Naturally, we’d like to see future mRNA regulatory guidance take these different risk vs. benefit profiles into account for each therapeutic — the recent release of the MHRA’s draft guidance for mRNA-based personalized cancer vaccines being a great indication that we’re on the right path. However, there were two other areas in which we’re likely to encounter ongoing discussions around risk vs. benefit — the first of which being the FDA’s platform designation. As I’ve written before, I see risk vs. benefit being a core tenet of this designation; however, the fact that international regulators are not currently aligned around the “platform designation” terminology suggests that attaining greater alignment on when to rely on prior knowledge (or platform knowledge) will be a continued topic of discussion/debate.
Another area likely to be influenced by risk vs. benefit — and in which we could stand to see more regulatory alignment and refinement — is around GMP principles for critical raw materials. As Kassim explained, the work we’re starting to do in the personalized therapy and rare disease spaces may ultimately necessitate a more flexible approach to GMP principles.
“As RNA therapies start to span different applications beyond pandemic-level vaccines, the regulatory framework needs to be just as flexible,” he said. “Should full GMP for pandemic-level manufacturing be applicable for an n-of-1 indication in which the timeline for development and treatment is much more compressed, and the benefit of treating the patient is greater than the risk of not treating?”
An Educational Initiative/Experience Worth Copying
In my first takeaway article from the AMM conference, I shared one of my favorite quotes from Strand Therapeutics’ CEO Jake Becraft about creating “fans” to educate and inspire the public about curing disease.
While Becraft pointed to the Super Bowl and SpaceX as prime examples of fan-creating experiences, I was struck by another example Replicate Biosciences’ CTO Andy Geall shared about a business trip he took to Brazil that involved a visit to a vaccine museum. (Yes, we started this article in Brazil, and it would seem we’re also going to end it there…)
“I was expecting [the vaccine museum to be] this dusty old crumbling building,” Geall joked. “But the inside was like something you’d see in Google or SpaceX.”
The museum was full of families and young students on field trips engaging with virtual experiences and computer games teaching them how vaccines were made and how diseases were spread and enabling them to (virtually) inoculate themselves from the different diseases.
“We should have those museums here in the U.S. to educate our kids so they can learn that the work we’re doing is real and we’re only trying to protect them from getting diseases,” Geall concluded.