Arrakis Therapeutics

(Arrakis Therapeutics)

Mining the RNA world for new medicines

Fierce 15

CEO: Michael Gilman
Based: Waltham, Massachusetts
Founded: 2015 
Clinical focus: Small molecules for currently inaccessible RNA targets 

The scoop: Arrakis launched in February 2017 to develop a new class of medicines: small molecules that target RNAs, a group of macromolecules historically considered undruggable. The Boston-area biotech is building a drug discovery platform, using existing tools where it can and inventing others where needed.  

What makes Arrakis fierce: When Arrakis first set out to drug RNA, most of its prospective investors thought it would be impossible. 

RNAs are difficult targets because they’re small and aren’t stably folded like proteins. And, unlike proteins, which are made of many different amino acids, RNAs all have the same ingredients: the nucleotide bases A, T, G and C. This makes them difficult to selectively target with small molecules. 

Some current drug candidates do it—including Novartis’ spinal muscular atrophy drug LMI070 and Merck & Co.’s ribocil—but so far, these RNA-targeting molecules have been found by accident. Arrakis’ raison d’être is to do so intentionally.

“They thought we were crazy just to try it,” CEO Mike Gilman, Ph.D., said. “But we took it on anyhow, and one of the reasons we did is the management team.”

Most of the leadership team—Gilman, founder and CSO Jennifer Petter, Ph.D., Chief Business Officer Dan Koerwer, SVP of biology James Barsoum, Ph.D., and VP of chemistry Gnanasambandam “Kumar” Kumaravel, Ph.D.—all worked together at Biogen in the early 2000s. And, along with Heather Lounsbury, the VP of business and technical operations, they’ve all logged time at various other biotech and pharma companies too. 

“We’ve been in the drug discovery business for 20, 25—30 years, some of us—and so, we are appropriately curmudgeonly. We’re not going to take on quixotic missions," Gilman said. "We believe this can be done."

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The team also doesn't believe there is a single “magic bullet that will suddenly turn RNA druggable.” Instead, they are drawing on their collective experience to take the existing toolkit for protein-directed drug discovery and “rearchitect” it for RNA. 

The team quite easily adapted the lead optimization toolkit for proteins to RNA. But they had to build their target identification engine from scratch because, as Gilman says, no one really knows what constitutes a druggable site in RNA. 

“[No one knew] how to determine with confidence the structure or structures that an RNA folds into, whether those structures have ‘pockets’ that can be bound by a small molecule, and whether that small molecule binding to that structure will affect the biology of the RNA,” Gilman said. “[Arrakis’ platform is] a combination of computational approaches that allow us to predict what sequences and structures might have biology associated with them and a set of wet lab methods that we use to validate those predictions.” 

The company raised $38 million in early 2017 from a group of marquee investors that included Pfizer and Celgene. Now, about a year and a half later, Arrakis is eager to start identifying hits and leads. And it's planning to raise more capital around the end of the year, Gilman said. 

Arrakis’ headcount is about 26, with a handful of open positions waiting to be filled. Gilman hopes the startup will grow to about 35 by the end of the year and then continue growing “fairly dramatically” after that. 

“It will depend on how many hits we generate, how much money we raise. The usual stuff,” Gilman said. 

Investors: Advent Life Sciences, Canaan Partners, Celgene, Henri Termeer, Osage University Partners, Pfizer 

Arrakis Therapeutics