Gilman buckles in as Arrakis raises $75M, gains momentum

Arrakis is focusing on cancer because it has well-known, well-validated targets that have been considered undruggable. (Arrakis Therapeutics)

Biotech veteran Michael Gilman “failed at retirement.” He sold his company Padlock Therapeutics to Bristol-Myers Squibb in early 2016 and contemplated calling it quits. Yet he found himself on the boards of two new biotechs, Obsidian Therapeutics and Arrakis Therapeutics, and eventually wound up in the CEO chair of both. 

Now, as both companies are ramping up, Gilman is buckling in at Arrakis as its full-time CEO. The company raised $75 million in its series B round to advance its work in RNA-targeting drugs, a mission many thought to be crazy—or simply impossible. Gilman has stepped down from his post at Obsidian, a company working on cell and gene therapies, where Paul Wotton—another industry vet who has helmed many a biotech—will take over. 

Arrakis raised the series B from a laundry list of investors—including venBio and Nextech Invest, which led the round—and existing backers Advent Life Sciences, Canaan Partners, Celgene, Osage University Partners, Pfizer Ventures and the estate of Henri Termeer. Newcomers Alexandria Venture Investments, GV, HBM Healthcare Investments, Omega Funds and WuXi AppTec Venture Fund also pitched in. 

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The company will use the proceeds to advance a pipeline of RNA-targeting small molecules (rSMs), as well as to keep improving its discovery platform. It has identified four programs it wants to take forward, three in oncology and one cardiovascular target. All four take aim at RNAs that code for proteins that are undruggable. 

“Three are cancer targets. One is a bit of an oldie but a goodie oncogene—that's MEK—and another is a transcription factor that has long been associated with cancer,” Gilman said. “The third is a synthetic lethal gene.” 

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Arrakis is focusing on cancer because it is deeply studied. 

“We know a lot about how cancer cells tick and how cancer cells interact with host functions like the immune system... There’s no question about the role of oncogenes in cancer, just some of them are completely out of reach,” Gilman said. 

As for its drug discovery platform, Arrakis was able to modify some existing tools used in protein-based drug discovery to work for RNA. But other tools it had to build from scratch, including its target identification engine, because, as Gilman told FierceBiotech last year, no one really knew what constitutes a druggable site in RNA. 

“We had to rethink the problem from scratch relative to proteins because RNAs are just different. They don’t have active sites, they’re not enzymes and they go about their business in a very different way from proteins,” he said. 

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“We have built an end-to-end platform for the discovery of rSMs by creating or adapting tools that allow us to predict and validate the structure of RNA targets, locate druggable pockets, identify drug-like hits, and conduct medicinal chemistry programs to improve potency, selectivity, and safety. We are now operating this platform at scale to create a pipeline of utterly novel rSM medicines,” he said in a statement. 

Though the platform is up and running, Gilman said there are “clearly opportunities” to make it even better. Its No. 1 priority is what Gilman calls the front end of the process: “identifying druggable structures in RNA that have function.” Most of it is computational—that is, using algorithms to predict RNA structure. 

“There is a lot of room to improve those algorithms and one of the advantages I think we have for doing that is the fact that we are collecting all of this data on how RNAs are folded inside cells. No one knew that before. People could predict these structures all day long, but had no way to validate that those structures were actually correct,” Gilman said. 

Arrakis is checking those predictions by working with RNAs in the lab. It hopes to be able to feed those data back into the algorithms to make them smarter. 

“It’s a classic machine learning opportunity,” Gilman said. 

Arrakis, which numbered about 26 staffers last summer, has grown to “somewhere between 35 and 40.” It will think carefully about how it proceeds from here until it has a better understanding of what kind of talent it needs, Gilman said. It’s probably got enough people working on the platform, though, and future hires will be driven by its therapeutic programs as they mature. 

Though Gilman kept tight-lipped on the four programs, the company is getting ready to take off. As Gilman put it in a blog post, Arrakis has achieved escape velocity—the speed at which it needs to travel to break free of Earth’s gravity.