Tekmira Tackles RNAi Delivery Challenge, With Alnylam, Roche Putting It to the Test

Xconomy Seattle — 

The people at Cambridge, MA-based Alnylam Pharmaceuticals are widely recognized as leaders in the field of RNA interference, but they are quick to acknowledge they don’t do it all themselves. They lean on partners, including one important one in the Northwest, Vancouver, BC-based Tekmira (TSX: TKM).

This Canadian company’s reputation as a key player in the field of RNAi is growing, especially since it agreed to license its drug delivery technology for $50 million this month to Roche, the Swiss pharmaceutical giant. I decided it was time to learn more, which was pretty easy. It turns out that Tekmira CEO Mark Murray lives in Seattle, and divides his time between here and Vancouver.

RNAi is one of the hottest concepts in biotech, especially since its discoverers won the Nobel Prize in 2006, but actual drugs built on this science need help to get delivered in the body. These drugs are thought to have the advantage of being able to specifically hit targets on cells that other drugs can’t, and to silence the genetic root cause of disease. The problem is that small interfering RNA drugs can get chewed up by enzymes in the body, or flushed through the kidneys long before they ever get to the diseased cells. Some leading RNAi companies, like Alnylam (NASDAQ: ALNY), have tried to work 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. Tekmira’s approach uses lipid nanoparticle capsules (sort of like little grease balls) are designed to protect the drug in the body until it gets to the diseased cells.

“There’s no such thing as an RNAi drug without the technology like this from Tekmira,” Murray said. “You can’t do it. It’s an enabling, game-changing technology for RNAi.”

Tekmira has gone through a few corporate iterations over the years that I won’t bore you with, as well as older versions of the technology that offered only marginal benefit to delivery of chemotherapies. Suffice to say it traces roots to liposomal chemistry work by Pieter Cullis at the University of British Columbia, and parts of the technology have evolved through companies like Inex Pharmaceuticals and Protiva, before it all came together under the Tekmira banner a year ago.

The company, which has about 80 employees now, has rallied around three important scientific principles, Murray says. The lipid nanoparticles have to pull some delicate maneuvers. They have to protect the RNAi drugs and keep them stable throughout the bloodstream, allow them to be delivered to the target diseased cells, and be nimble enough to allow the RNAi molecules to be released into the cytoplasm of cells so they can go to work, Murray says.

Last month, Alnylam started the first significant clinical trial in 55 patients, for an RNAi drug that can circulate throughout the body, built on Tekmira’s delivery technology. The drug, ALN-VSP, is designed to treat liver tumors by blocking two critical genes for that type of malignancy. Alnylam has run tests in mice that show its drug can suppress the intended genes, shrink tumors, and help the cancerous animals to live longer. ALN-VSP also passed safety tests in rats and monkeys, Alnylam says.

Tekmira stands to gain milestone payments for every drug candidate Alnylam or its partners advances using its lipid nanoparticle delivery technology, plus royalties on sales if they ever become marketed products.

That could generate some income to mitigate the company’s need to burn through its cash, but Murray says it’s only part of Tekmira’s business strategy. It hopes to keep some of the delivery technology in-house for its own drugs, including one RNAi drug to block a protein called ApoB that carries the so-called “bad” LDL cholesterol in the blood.

This drug—which hasn’t yet entered clinical trials—aims to be a competitor to Genzyme and Isis Pharmaceuticals’ mipomersen, which uses a different technology to block ApoB. That drug is years ahead in development, as those companies have said they aim to seek FDA approval in the second half of 2010.

There are plenty of competitors looking to solve the RNAi delivery problem. London-based Silence Therapeutics, Seattle-based PhaseRx, and Palo Alto, CA-based Intradigm are a few companies with different technology approaches to the problem, Murray says.

Like I do with every company without a product on market, I had to ask how Tekmira’s cash is holding out. The company had about C$30 million in the bank at its last financial update, which is enough to run into mid-2011, Murray says. The market gave the company a lift when it announced the Roche deal, but now investors want to see promising Phase I data. The company deserves a valuation of more than $75 million, Murray said, but he didn’t sound whiny about it.

“If we continue to put products into the clinic and build value there, we’ll be sustainable,” he says.

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