Watch out Moderna: John Maraganore, ARCH and Beam are hatching a platform play ‘to lead the future of RNA therapies’

Giuseppe Ciaramella joined Moderna in 2014, back when the mRNA specialist only employed about 70 people. There, as CSO of the infectious disease division, he helped build the initial mRNA vaccine pipeline and steered Moderna’s first vaccine program toward an IND.

He left for Beam Therapeutics four years later, before a wildly successful Covid-19 vaccine propelled Moderna to the biotech hall of fame.

After immersing himself in base editing for the past several years, the biotech vet is making a return to the RNA world — and, with the backing of ARCH, a16z and Newpath Partners, he wants to build the next big thing.

John Maraganore is coming on board as a co-founder of Orbital Therapeutics. The Alnylam founder and former CEO told Endpoints News in an email that he started getting involved soon after becoming a venture partner at ARCH last year. Notably, while Ciaramella believes Orbital has put together the most complex and comprehensive toolbox in the RNA space, it’s conspicuously steering clear of RNA interference — the field Alnylam made its name in.

“My vision for Orbital is to lead the future of RNA therapies (outside of RNAi),” Maraganore wrote.

Kristina Burow

ARCH’s Kristina Burow and Carol Suh are also playing a part in putting the company together, while Ciaramella brought together a quartet of star researchers to be his scientific co-founders: Stanford’s Howard Chang and Ravi Majeti; Drew Weissman at the University of Pennsylvania; and Gene Yeo out at UC-San Diego.

Ciaramella isn’t leaving Beam. In fact, Beam is providing the tools, infrastructure and even personnel to bootstrap Orbital — including the know-how for making, purifying and characterizing linear RNA as well as the lipid nanoparticles to deliver it. Some of the top leadership at Beam will also double as Orbital execs. Ciaramella is serving as Orbital’s interim CEO while continuing his day job as Beam’s president and CSO; Beam CFO Terry-Ann Burrell will also assist while CEO John Evans is on Orbital’s board.

The discussions with ARCH started, he said, as Beam realized that as it worked on its core promise of making therapies out of base editing — the gene editing technique where scientists can chemically change DNA one letter at a time — the biotech was developing a whole host of complementary technologies that can potentially be applied broadly outside gene editing.

Orbital is grabbing rights to all of that, with certain areas mapped out for exclusivity. In exchange, Beam will grab an equity stake in Orbital and access to the newer technologies Orbital has introduced from its scientific co-founders, such as circular RNA and virus-like particles.

“The idea is really to take the state-of-the-art of what is currently available as far as delivery and RNA technology and put them all under one roof,” Ciaramella said. “And the reason why that, we think, is really essential is because it creates, first of all, a critical mass of technologies that are needed to realize the full potential of RNA medicine. This is basically behind the foundation of Orbital — it’s really to finally achieve the potential that RNA has always had since the very beginning. But some technical limitations were preventing this from happening.”

One of those limitations, he added, was a short half-life that prevented companies from making protein replacement therapies out of RNA, akin to what’s currently done with one-shot gene therapies. From autoimmunity to blood disorders to regenerative medicines, he sees Orbital making medicines that have “never been possible to make before.”

If you think about it, the beauty of RNA is its programmability. The same chemical can actually make many different proteins. And so potentially you can combine, let’s say a cytokine with a receptor or an intracellular protein, which will be very, very difficult to do with traditional technology. Imagine a drug product that binds maybe a peptide or cellular component or a receptor — it’s very difficult to manufacture. In this case, it’s always the same thing. So you manufacture exactly the same polymer, which is the RNA, you can potentially even co-formulate it in the same LNP. And now you’re instructing the body to really manipulate a disease system in a very sophisticated and complex way. And so you’re not just relying on a single point of intervention, but potentially — imagine if there is a signaling cascade, modulated at the beginning or at the end, you can really now develop therapeutic modalities that it’s never been possible to do before. And that was the dream of RNA and I think the technology that is emerging is providing line of sight to doing that. And that’s why you really need that critical mass of all of the available technology.

With some of the newer tools, Ciaramella would go so far as to say Orbital’s technology suite is probably competitive with what Moderna has now, at least based on publicly available information. And just like Moderna, he envisions Orbital to be a platform company that will push forward multiple projects simultaneously.

The deal with Beam provides Orbital access to its tech exclusively for vaccines and protein replacement therapies, and non-exclusively for other uses. For Beam, the exclusive terms are limited to gene editing and conditioning for transplants, while the rest is all non-exclusive.

At this stage of the company build, Ciaramella is reluctant to go into timelines. But with a funding round on the horizon — to be unveiled soon — he wants to stay on the faster side of an IND by identifying some programs that are relatively quick to the clinic. The goal is not only to generate buzz on the tech, but also to train the organization.

“Really what we want to create is what I call momentum,” he said.

The company’s headcount is at 15 now, and Ciaramella pointed to Beam — which is five years into launch and has about 500 employees — as a reference point for the speed and scale he’s shooting for. A fellow Moderna vet, Gilles Besin, will soon jump from Affinivax to become Orbital’s CSO.

So you can expect plenty of cash for the showdown at a time the whole field is bubbling with excitement.

“Having spent 20 years advancing RNAi therapeutics as a whole new class of medicines, I’m a huge believer in the potential of RNA-based therapies as one of the most important frontiers of medicine,” Maraganore wrote. “Excluding RNAi and ASOs, RNA therapies are in the 1st few innings of their potential for disease impact.”

therapeutics
vaccines
gene editing
biotech