When Flagship Pioneering propped up a small research team back in 2017 to study a little-known circular form of RNA, it wasn’t exactly a high-profile project. But with mRNA providing the blueprint, that nascent biotech thinks it may have found the goldmine of all goldmines — and it’s all founded on a quixotic little molecule dubbed “eRNA.”
Laronde, founded on science from Flagship general partner Avak Kahvejian and led by CEO-partner and former Vividion chief Diego Miralles, thinks eRNA could be the future of drugmaking, augmenting or replacing altogether standard drugs. On Monday, the biotech formally launched with a $50 million check from Flagship and some huge ambitions despite its relatively meager pocketbook.
Hear this: By 2031, Laronde believes it can develop and market 100 products for use across a broad range of diseases, effectively replacing the small molecule-biologics diad that has dominated drug development for decades. That’s right — 100.
The story of how eRNA came to be starts with a circular, mysterious class of naturally occurring RNA dubbed lncRNA, or long non-coding RNA. Researchers identified the class decades ago, noting that unlike mRNA, lncRNA doesn’t interact with ribosomes or code for proteins. They do have some effect on epigenetic control, swimming around in both the cytoplasm and nucleus, but that function is still not totally clear.
What captured researchers’ interest was their shape: lncRNA forms in a ring and folds for different functions. That shape allows them to escape enzymes prowling in the cytoplasm and last much longer than mRNA. In 2017, under the leadership of Kahvejian, a former founding CEO at Ring Therapeutics and Rubius Therapeutics, Laronde’s small “exploration” research team was kickstarted to investigate the role of lncRNA in the cell and possible therapeutic applications.
At the same time, as you’ll know, another Flagship startup, Moderna, was busy at work investigating mRNA. The function of mRNA as a therapeutic was fairly obvious — if you could teach a human cell to produce antibodies, proteins, peptides and channels/receptors then you could theoretically solve most diseases — but mRNA are one-hitter quitters in terms of transcription and don’t hang around the cell after they’re transcribed.
That’s when Kahvejian’s team had a breakthrough: What if you could combine the best of both worlds from mRNA and lncRNA? By jamming what’s called an “internal ribosome entry site” — the same mechanism viruses use to hijack ribosomes — onto an lncRNA, Laronde’s researchers could make those non-coding rings translatable in much the same way as mRNA. From that eureka moment came eRNA — “e” for “endless.”
Unlike mRNA, which can only produce proteins that last days, Laronde thinks its in vivo manufacturing machines can produce the same proteins for weeks to months without tripping the innate immune system or exonuclease enzymes over time.
“We see this as a new class of medicines, not just a single biotech company with a handful of products,” Kahvejian said. “We are very convinced that by virtue of having these properties of persistent protein expression and the ability to make any protein in or on cells and inside the body, we can address a really broad range of things for a whole set of different kinds of proteins and many diseases.”
In terms of how the biotech will get to 100? That’s a little complicated.
First, Laronde’s eRNA platform is programmable, they say, allowing the biotech to tweak what it calls “protein-coding cassettes” to produce different complex molecules in vivo. That plug-and-play design, Laronde said, greatly reduces the workload in discovery and development. Instead of hunting rare diseases right away, Laronde is going after biology it says is already highly validated, which could go a long way to taking a big bite out of the 100-drug benchmark.
Then there’s the “Gigabase Factory” that Laronde aims to build, which uses a modular, pod-based approach for manufacturing to maximize scale with the smallest possible footprint. The name borrows from the Tesla playbook — in fact, Miralles mentions Tesla multiple times on our call — which serves as a helpful window into the Laronde team’s psychic influence.
Laronde will be the first tenant at a new Flagship lease in Somerville, MA, for its ever expanding platform, Miralles said, and will establish manufacturing space there for its first clinical studies.
Manufacturing will present a key challenge as Laronde gears up for human trials and beyond, and it’s already brought on its first manufacturing head before launch, Miralles said. But the rapid production of the mRNA vaccines has proven that billions of doses of mRNA can be manufactured in a short timeframe without the standard scale-up needs.
“We’re sitting on the shoulders of giants in the mRNA field,” Miralles said. “In the last 18 months, we’ve gone from mRNA almost as an idea to dosing hundreds of millions of people. That has proven that programmable RNA platforms have changed the game in terms of timelines to bring these drugs to markets and changed the game in terms of scale.”
But here’s the thing: Flagship is footing just $50 million in launch money to get Laronde off the ground, which will put a huge onus on the fledgling firm to bird dog investors to fund its factory scheme as it grows and help hire the 200 employees it wants to bring on board within the first two years. For any other biotech, hiring 200 employees from scratch in 48 months would be enough of a logistical nightmare to make your head spin.
At the root of these huge plans is one thing: belief. Belief in the tech, belief in the magic sauce driving Flagship’s brain trust and belief there’s a better way to do therapeutics. If the Laronde team is right, the payoff could disrupt an industry worth hundreds of billions of dollars and moot decades worth of R&D in antibodies and small molecules that Miralles said don’t work well for patients and are difficult and expensive to access.
“We need to think differently about what these programmable platforms can do,” Miralles said. “This is a completely new class of medicines that can do things we could never do before.”
As for the immense amount of clinical work that would have to go in to bringing 100 products to market in a decade? Laronde is open to considering its options in terms of how best to bring each of its products into the clinic — whether that’s solo, through partnerships, future spinouts or sales. Miralles, a quick talker with the charisma of a big-tent preacher, likens the biotech’s potential to the late 19th century oil boom: Start drilling, no matter where you are, and you may find black gold.
But the whopping size of a potential clinical program isn’t all that important when you consider the translatability of eRNA, Miralles says. Proving eRNA works in one eukaryotic cell should mean efficacy across eukaryotic cells, he said, a big differentiating factor from traditional therapeutics. If you can cut risk out of the clinic, he says, you can spur a major breakthrough in the failure-ridden and lengthy development process.
“There are days that I wake up and I’m like, ‘whoa, we could do this,’” Miralles said. “It’s such a game-changer — truly, this is a game-changer — that in order to understand all the infinite implications of the platform, it really takes a while to adjust to think differently.”