The field of RNA-based drugs is moving fast. Isis Pharmaceuticals (NASDAQ: ISIS) has an approved drug, and more potentially on the way. Alnylam Pharmaceuticals (NASDAQ: ALNY) has a slew of them in development, and a few that could be approved in the next few years. Younger entrants with different approaches, like Moderna Therapeutics are raising jaw-dropping amounts of financing.
Now a startup called WaVe Life Sciences is joining the mix, claiming that by doing a specific kind of chemistry work, it can potentially make more potent RNA drugs than its predecessors.
WaVe is a Boston- and Japan-based startup that was formed out of the merger of two small companies: Boston’s Ontorii, and Chiralgen of Japan. The startup has been toiling away in stealth mode for a couple of years—the merger took place in 2013—but it’s coming out of the woodwork today with an $18 million round of funding.
WaVe is calling the round a Series A, even though CEO and president Paul Bolno says the company previously raised a “substantial” amount of cash from founding investor SNBL, a Japan-based CRO. The new round is being led by RA Capital Management and Kagoshima Shinsangyo Sosei Investment; SNBL took part as well. RA Capital founding partner Peter Kolchinsky is joining WaVe’s board as part of the funding.
The name WaVe is an amalgam of the last names of the scientific founders of Chiralgen (Tokyo University of Science professor Takeshi Wada) and Ontorii (Harvard University chemical biologist, and Warp Drive Bio founder Greg Verdine). Both companies were supported financially by SNBL.
What’s come out of the combination of the two is a proprietary chemistry method the company says can create RNA drugs that can last longer in the body and be safer and more potent that those produced by existing synthesis techniques. WaVe isn’t saying yet in what diseases it intends to target with technology, just that it’s looking at a range of options including rare diseases, gastrointestinal disorders, central nervous system disorders, and others. Bolno says WaVe will unveil its first programs this year, and aims to start its first clinical trial in 2016.
So why does WaVe think it can make better RNA drugs? It has to do with what’s known as chirality, chemistry’s version of handedness. Just as the right and left hand have all the same components, but arranged in mirror images of one another, many drug molecules have different versions that are composed of the same atoms but in mirrored arrangements—and it turns out that handedness sometimes has a dramatic effect on the body’s response to the molecule. Thalidomide’s notorious propensity for causing birth defects is due to one version of the molecule, for instance, while its desired sedative effects are produced by the mirrored version.
WaVe’s claim—something it’ll have to prove—is that chirality is important for RNA drugs too. Bolno says that this concept has largely been “ignored” when it comes to nucleic acids and antisense drugs, but that it shouldn’t be, because it limits their potential and potency. What’s more, these molecules are larger and more complex than traditional drugs—with more places along their length for atoms to be attached in a left- or right-handed configuration. Current techniques for synthesizing these molecules don’t control for that, so they produce a mixture of thousands of different versions of a would-be drug—each with “unique pharmacology,” Bolno says.
“That’s been underappreciated,” he says.
For his part, Bolno says this is because the issue was ”not possible to address” before WaVe came along. But the question is whether it matters. WaVe contends that it does, and that the company has developed a way to control the chirality of the RNAs it produces. WaVe is starting out using this to develop antisense compounds—Isis’s specialty—and Bolno contends that the process could be applicable to other RNA drug methods, like exon-skipping, RNA interference, and micro RNAs.
WaVe is using the cash to scale up, and get ready to bring its first drug to clinical trials. It’s got 19 employees as of now: 14 in Boston, 5 in Japan. Bolno says WaVe has seen signs in animal studies that it’s on to something, and that the company has have a research collaboration in place with a large pharmaceutical company—it just can’t disclose the deal. But if the company is going to make waves in the RNA space, it’s going to have to prove—with data in human beings—that there really is a chemistry problem that needs solving.