The Marriage of Science & Strategy: Identifying mRNA Therapeutics' Value Propositions

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

At the end of every year, I sit down with several mRNA/RNA C-suite executives to take stock of the previous year and to discuss predictions for what is yet to come. For those of you who have been following my columns, you’ll know that this year’s interviews turned into a two-part Q&A series that channeled a few ghosts — the Charles Dickens ghosts of mRNA’s past/present and the ghosts of mRNA’s future, to be specific. These RNA/LNP leaders shared their perspectives on the current state of the industry, as well as the advancements and challenges they’re anticipating in the year ahead.
However, as one of the participating executives kindly reminded me, we’re all playing the long game, and a year is hardly a significant amount of time in the grand scheme of things — especially in biotech. If there’s one unifying thread between this year and the years that have come before, it’s the industry’s persistent belief that the best is yet to come for mRNA. But as we are a nascent space, most of us are still in the thick of figuring out how to ensure our products achieve their “personal best” and are competitive and patient centric products when they cross the commercial finish line.
During my conversation with CureVac CEO, Alexender Zehnder, I got a chance to dig into some of his visions for what a successful mRNA product will look like, and how these visions are guiding CureVac’s strategy into 2025. Though it’s not a question we can answer fully yet, in the first of this two-part article, Zehnder starts us down the path of answering a critical question about our RNA therapies: In what ways can and should our mRNA products add value to our patients’ lives?
What Makes mRNA Unique?
Over the past few years, we’ve talked about mRNA as a modality that can do just about anything. I’ve often thought of “her” as a Renaissance molecule — a factor that makes her all the more fun to learn and write about. But as we also know, she’s hardly the only molecule out there with the potential to transform patients’ lives. When it comes to treating diseases, we ultimately want her therapeutic skill set to shine in ways other therapies haven’t in the past or currently don’t.
There’s still a lot to learn about what makes her shine clinically. After 2024, we’ve started to get a better idea of what she can do for patients, particularly in combination with other modalities. For the many of us still fording through discovery and preclinical development, we’ve heard executives advise on the importance of selecting the appropriate indications and prioritizing areas with unmet need to ensure our candidates can stand out clinically in the future. As a trained physician, Zehnder reaffirmed that unmet need has always been at the heart of his strategic decision making. However, as he furthered, there’s another important aspect RNA companies need to think about as they evaluate their value proposition in addressing these unmet needs.
“You can do a lot with mRNA,” he went on to explain. “But if you simply use mRNA to do what another modality can or is already doing without, for example, offering an improvement in efficacy or reducing side effects, there’s no point. We need to marry unmet need and scientific opportunity with the specific technology — in this case, mRNA. It’s important for us to identify where mRNA is unique and to use mRNA to accomplish something that you cannot with another modality, like a mAb or a bispecific antibody.
CureVac’s Strategies For Bringing A Unique mRNA Candidate Into The Clinic
Obviously, entering the clinic will be the sure-fire way to identify mRNA’s therapeutic intricacies and limitations. However, to ensure we’re entering the clinic with the most promising candidate, Zehnder pointed to two strategic considerations in the R&D realms that have proven most helpful in developing CureVac’s infectious disease and cancer vaccine candidates.
The RNA backbone with which we’re working is one important consideration, and it would seem as though there are scientific advancements in this realm daily. In fact, throughout 2024, our drug substances got even more complicated — but in a good way. We started to see more (predominantly preclinical) progress being made on next-gen forms of RNA (saRNA and circRNA), demonstrating long-held hypotheses that these modalities offer improved protein expression and durability.
As Zehnder acknowledged, it’s important to watch these ongoing innovations in the field closely. “We frequently benchmark new technologies in the lab to compare them to our current RNA technology,” he added. “We don’t want to be out-innovated by something else that’s out there.”
For CureVac, twenty years of work has resulted in a second-gen RNA backbone that demonstrated increased antibody production at lower doses compared to BioNTech’s commercialized COVID vaccine. (Interim Ph. 2 results/data were announced last January.)
In addition to prioritizing ongoing R&D work to keep “finetuning” the RNA backbone, Zehnder also pointed to the criticality of developing and advancing the company’s antigen discovery platform, which is particularly important for the development of novel cancer vaccines. Over the past several years, due to the enormous interest in mRNA post-COVID, there’s been great growth in this area, with advancements being made in genome sequencing, -omics, and RNA analytics. However, Zehnder singled out bioinformatics as being an essential technology platform to help further bolster the company’s antigen discovery. CureVac acquired Frame Cancer Therapeutics for its bioinformatics platform in 2022. However, as he acknowledged, he’s keen on further investment to better leverage AI and bioinformatics moving forward.
In fact, as he went on to explain, the foundation the company is building today for more efficient antigen discovery will play an important role in the company’s work on the next generation of mRNA cancer vaccines — products that Zehnder is optimistic will epitomize the all-important marriage of scientific opportunity/unmet need and mRNA’s unique strengths.
My conversation with Zehnder doesn’t end here; please stay tuned for a follow-up piece that will share his and several other executives’ thoughts on the strategies/scientific innovations RNA companies are pursuing to make their mRNA candidates stand out from the crowd therapeutically in the future.