Pfizer, Celgene-backed upstart Arrakis hopes to mine RNA spice

Michael Gilman will split his time as CEO of Arrakis and running another stealth biotech.

In the sci-fi universe of Frank Herbert’s Dune, Arrakis was considered the most valuable (yet desolate and forbidding) planet, given that it was the source of spice (aka melange), a drug that lengthens life span and heightens awareness.

A new upstart has launched today with this planet’s name as its moniker, denoting its desire to mine for potent new meds, although its focus is on a new kind of RNA target.

Industry vet Michael Gilman PhD (and ex-CEO of Padlock Therapeutics) becomes its chief, and tells FierceBiotech: “We view the RNA world as a vast and potentially forbidding source of powerful new medicines for humanity. And we intend to systematically mine the RNA world to find those agents.”

Gilman is not, however, looking to follow in the footsteps of other biopharma RNA players, but forge a new path.

“What’s bold about our approach is that we are using small molecule medicinal chemistry—which has been historically limited to only about 500 protein targets within the vast transcriptome of over 200,000 RNA transcripts—and applying it to target RNA,” Gilman explains.

“Our founders asked: ‘Why not expand the reach of small molecule drugs to RNA in addition to proteins?’ We already know that many approved small molecule antibiotics bind RNA. Recently, drug candidates in Big Pharma pipelines have emerged that exert their activity through RNA rather than proteins.”

These include Novartis’s LM1070, which targets mRNA and is in the clinic for spinal muscular atrophy, and Merck’s ribocil, that acts by binding to a region of a bacterial mRNA. 

Gilman says that, so far, these RNA-targeting molecules have been found by accident, whereas Arrakis is discovering them intentionally. “That’s our pioneering mission to a new frontier—our Arrakis.”

Gilman will be halving his time between Arrakis and his leading role at another, as yet undisclosed stealthy biotech.

Arrakis, which is based in Waltham, Massachusetts, starts life with a $38 million Series A led by Canaan Partners, with help from Advent Life Sciences, Pfizer, Celgene, Osage University Partners, and biotech industry leader (and former Genzyme chief) Henri Termeer. 

That’s a fairly big early raise with some big backing players. “The things that create such a compelling opportunity with Arrakis—that I believe our investors recognized—is that we are taking a systematic and sophisticated approach to targeting RNA with small-molecule medicines and that, in the short time since the company’s founding [Oct. 2015], we have already made significant progress,” Gilman explains.  

“We have hits from our first screens. We have two proprietary platform technologies largely in place. We are geared up and ready to go. What the company has accomplished in such a short time is a real tribute to the great people who founded Arrakis, notably Russ Petters, our CSO [and former exec at Celgene, Biogen, and Sandoz/Novartis], who has been thinking about this problem and driving the platform build for almost two years.”

They have 10 employees that they hope to double over the next year, predominately R&D focused. “This is a highly experienced, formidable group of drug hunters,” Gilman explains. “We’ve seen a lot over the years. However challenging you may think our goal is, I am confident that this team can crack it.”

Everything is still preclinical and the biotech has not as yet disclosed its first target, or a timeline for going into the clinic. 

But Gilman says that its drug discovery and development is focused on three key disease areas: neurology, oncology, and rare genetic disorders. “We chose these disease areas because of the potential impact to patients, because they are rich in targets of interest, and because we think small-molecule drugs will be uniquely effective, relative to other modalities for targeting RNA.”

In terms of its longer-term funding and corporate strategy, Gilman says: “As long as we are advancing powerful science and achieving our milestones, we are confident we will be able to secure the capital we need to build this company and bring multiple programs into the clinic—whether from private investors, public investors, or strategic partners. 

“Our Series A includes an incredibly strong syndicate of investors, including two from pharma, Pfizer and Celgene, who made investments through their R&D organizations. We plan to keep all of our options open.”

It will compete in the biotech RNA space with the likes of Arrowhead, Alnylam and Moderna, although the first two had a series of big trial setbacks last year, with Moderna only in the last two months showing its early-stage hand for its targets.

Arrowhead had been working on what once dubbed a trillion-dollar opportunity for an RNA med to cure Hep B. But last year it, and other meds tied to its EX1 delivery vehicle, were canned after safety concerns were raised from animal testing.

Its once leading drug, ARC-520, used a small interfering RNAs to reduce the levels of HBV proteins and the RNA template used to produce viral DNA, but is now gone given the “time and expense” it would take to sort out the safety issues, with the company having to hit the reset button and go further back in its pipeline.

Alnylam also had some issues last year, with the rival RNAi specialist losing around a half-billion dollars in market cap in trading in late September on the news that it halted development of RNAi liver disease candidate ALN-AAT after a phase 1/2 study resulted in three patients with liver enzyme elevation at the highest dose.

Back in January, the highly secretive, highly cash-rich Moderna finally revealed some of its early targets, saying it has 12 mRNA development candidates that include vaccines and therapeutics across the three therapeutic areas.

Tests are now underway for five of these across the globe, including Moderna’s Zika mRNA vaccine, mRNA-1325, which started phase 1 late last year, and two others against influenza targets, which also started in 2016.