Alnylam, Tekmira and New Northwest Firm, AlCana, Push Boundaries of RNAi Delivery

Xconomy Boston — 

Alnylam Pharmaceuticals is looking to the frontiers of science for ideas on how to best deliver RNA interference drugs throughout the body, and the Cambridge, MA-based company sounds most jazzed about what it sees emerging from laboratories in Vancouver, BC.

Back in May, I wrote about how Alnylam—one of the richest companies in biotech—was leaning on partners at Vancouver, BC-based Tekmira to deliver an RNAi drug that can circulate through the body. Last week, Alnylam said it is doubling down with its Canadian friends. The company has picked a second drug candidate that uses the same technology, and is sponsoring research at a new company made up of four former Tekmira employees who are pushing further on the leading edge of drug delivery, at Vancouver-based AlCana Technologies.

These are important developments to watch, because while RNAi has been one of biotech’s hot concepts for years, scientists still have plenty of work left to prove these drugs can be efficiently delivered. RNAi treatments are thought to be superior to conventional pills because they specifically hit targets on cells that other drugs can’t, and can silence malfunctioning proteins that cause disease. It sounds great, but when small interfering RNA drugs are injected into the body on their own, they get chewed up by enzymes, or flushed through the kidneys long before they ever get to the desired target on diseased cells. Alnylam has worked around this with locally-delivered drugs that don’t have to circulate through the body, but only a limited number of diseases can be treated that way (and that approach poses challenges too, as I described earlier this week.)

Alnylam, and Swiss pharma giant Roche, see big potential to deliver RNAi drugs through the body using Tekmira’s approach, with lipid nanoparticle capsules (sort of like little grease balls, as Alnylam CEO John Maraganore told me last December) designed to protect the drug in the body until it gets to the diseased cells. This is the approach that Alnylam has implemented with ALN-VSP, an experimental drug for liver cancer that is in clinical trials, and it’s the same technology it plans to use for a second candidate called ALN-TTR, for a rare genetic disease called amyloidosis.

“It’s great technology. It works well, you can manufacture it,” says Maraganore. “It’s ready for prime time.”

But this being the leading edge of biology, what’s prime time today can turn obsolete really quickly. I wanted to know from Maraganore what advantages he sees from this two-year collaboration, in which his company is agreeing to sponsor “a handful” of former Tekmira employees who have set up shop at AlCana Technologies, in a close collaboration with Pieter Cullis, a prominent nanomedicine researcher at the University of British Columbia.

This requires a little background explanation. The existing Tekmira technology, using lipid nanoparticles, has been shown in rodents and primates to deliver RNAi drugs throughout the body at relatively low doses of as little as 0.1 milligrams per kilogram of body weight, and as much as 1 milligram per kilogram of body weight, Maraganore says. By developing much smaller lipids and lipid particles, researchers now believe it’s possible to bring that dose down much further, so drugs are effective at “single-digit microgram per kilogram” territory, Maraganore says. In basic business terms, this is a tantalizing thing. It means you could have a drug that’s equally or more effective, but which requires very little in the way of raw materials for manufacturing—what’s known on income statements as cost of goods sold. If it works, you can charge the same price. That translates directly to higher profit margins.

What may be even more important is that such miniscule drug delivery packages make it possible to deliver RNAi molecules more broadly throughout the body than the current state-of-the-art lipid nanoparticles. The current products are made to circulate through the body, but Maraganore says they tend to accumulate in two tissue types—liver and tumors. That’s why Alnylam is pursuing its first systemically-delivered RNAi drug as a treatment for liver cancer. But Alnylam has a much bigger vision of delivering drugs for other diseases as well. Maraganore pointed out that Alnylam also has an important drug delivery research partnership with MIT.

“Delivery is really a long term technology investment for us,” Maraganore says.

AlCana, at least when I first heard the name, sounded an awful lot like a Canadian subsidiary of Alnylam, but Maraganore says that’s not the case. It’s a new operating business that has agreed to carry out sponsored research for Alnylam on lipid drug delivery, but Alnylam has taken no equity ownership stake in it, Maraganore says. Alnylam is getting exclusive rights to intellectual property that comes from within the terms of the research agreement, but AlCana is free to invent other things and do what it wants with them, Maraganore says.

“They are their own entity,” Maraganore says. “They took some inspiration from our name, which we found flattering. They aspire to be like Alnylam in the future.” He added, with a laugh, “We don’t have a trademark on a company name that starts with the letters A and L. Not yet.”

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