It’s Tough to Find Drugs to Bind to RNA: Arrakis Nabs $75M to Help

Xconomy Boston — 

Arrakis Therapeutics has been scouting elusive pharmaceutical quarry: small molecules able to “drug” RNA, the molecular messengers that carry the genetic instructions for proteins. Most drugs in use today act on proteins. But CEO Michael Gilman says targeting the genetic blueprints could prevent RNA from translating those instructions into disease-causing proteins in the first place.

Waltham, MA-based Arrakis is now ramping up to turn its discoveries into potential drugs and it has $75 million to support its work. The Series B round of funding announced Thursday was co-led by venBio and Nextech Invest. Gilman (pictured above) says Arrakis could reach clinical trials in the next two years.

“We want to step on the gas and build out the pipeline,” he says.

For many years, the conventional wisdom in biotech held that RNA was undruggable, or at least very difficult to drug, Gilman says. Small molecule drugs bind to a protein to block its activity. But RNA does not have active sites, which are the typical binding sites for molecules. RNA structures are also “floppier,” Gilman adds, making them harder for molecules to bind to.

Despite those challenges, signs emerged showing that drugging RNA with small molecules can work. Gilman says research has shown that some commonly used antibiotics were not binding to proteins, but were instead binding to ribosomal RNA in bacteria. He adds that Novartis (NYSE: NVS) and Roche have made progress researching small molecules that bind to RNA to treat the muscle disease spinal muscular atrophy.

Arrakis was founded in 2015 by Jennifer Petter, the company’s chief scientific officer. Gilman says that while decades of industry research built tremendous knowledge about the structure of proteins, little was known about the 3D structures of RNA. To understand those structures, Arrakis used a publicly available research technology called SHAPE, which was developed in the laboratory of Kevin Weeks, a University of North Carolina at Chapel Hill chemistry professor. Arrakis expanded on Weeks’ technology, building the company’s own bioinformatics tools and other software to support its drug discovery work.

The growing knowledge about RNA has led to a number of companies researching RNA-targeting small molecule drugs. SHAPE research at UNC led to the formation of Durham, NC-based Ribometrix, which raised $30 million in Series A funding last November. Others developing small molecule drugs to that target RNA include Skyhawk Therapeutics, Accent Therapeutics, and Gotham Therapeutics.

Gilman is well aware that other companies are working on RNA-targeting drugs. But he says that while some of those companies are focusing on particular diseases, Arrakis could potentially address multiple therapeutic areas.

“We have explicitly opted to take a very broad approach,” Gilman says. “We want to have a platform that can target any RNA, any kind of structure, in any part of the body.”

Arrakis aims to work on between five and 10 programs with the new cash, Gilman says. Those programs will be in diseases where there is ample validation about what to target, but the targets have so far proven to be undruggable. Cancer is the company’s initial focus, he says.

Arrrakis raised $38.5 million in a 2017 Series A financing. The company’s latest funding round added new investors Omega Funds, HBM Healthcare Investments, GV, WuXi AppTech Venture Fund, and Alexandria Venture Investments. Earlier investors Canaan Partners, Advent Life Sciences, Pfizer Ventures, Celgene (NASDAQ: CELG), Osage University Partners and the estate of Henri Termeer also participated in the financing.

In addition to the new capital, Arrakis also announced that Gilman will expand his role and work for the company full time. He had been splitting his time between Arrakis and Obsidian Therapeutics, a Cambridge, MA, company where he was also chief executive. Gilman says he knew he would eventually need to choose.

Obsidian, which is researching how to improve cell therapy by developing ways to control the behavior of these engineered cells, has reached the point where it needs someone who knows that space better, Gilman says. Obsidian has named Paul Wotton, the founder and former CEO of Sigilon Therapeutics, as Gilman’s full-time successor. Gilman will remain on Obsidian’s board. He’ll also continue as chairman of the Arrakis board.