Alnylam Pharma gets $10m under Takeda alliance PBR Staff Writer

Alnylam Pharmaceuticals has got $10m from Takeda Pharmaceutical, under the agreement signed between the two parties in May 2008.

The payment triggers from the transferring of Alnylam's RNA interference drug technology to Takeda Pharma for the development of RNAi therapeutics.

Earlier, Alnylam has obtained $140m in upfront and technology transfer payments from Takeda.

Further, Anylam is also entitled to receive milestones and royalties related to the Takeda's advancement of RNAi therapeutic products, and has retained certain product opt-in rights in the US market.

Alnylam president and chief operating officer Barry Greene said they look forward to their continued work with them in developing RNAi therapeutics on a global basis, which includes Alnylam's opt-in right to co-develop and co-commercialize certain Takeda RNAi therapeutic products in the US market.

Alnylam Pharmaceutical's top scientist leaves

CAMBRIDGE, Mass. - Alnylam Pharmaceuticals Inc. said Friday its chief scientific officer, John A. Schmidt Jr., is leaving the company, effective Sept. 30, to pursue other interests.

The company has no immediate plans to replace Schmidt, 58, a spokeswoman said.

However, "we will look opportunistically should an appropriate candidate present him or herself," Alnylam said in a statement.

Shares closed up 80 cents, or 3.6 percent, to $22.92.

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

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

The cure no one saw

Several years ago, a small Cambridge biotechnology firm called Cubist Pharmaceuticals made a surprising business deal. It licensed the rights to a failed drug, called daptomycin.

Though the novel antibiotic showed promise in treating serious bacterial infections, clinical trials suggested it might also cause serious muscle damage - making it too dangerous to give to patients. Eli Lilly & Co., the pharmaceutical giant that originally developed the drug, pulled the plug on the research in the early 1990s. But Cubist executives thought there still might be hope for the compound.

Because the compound originated in soil samples collected at the base of Mount Ararat, the Turkish volcanic cone where some believe Noah's Ark landed, Cubist chief executive Michael Bonney joked, "This is an antibiotic of biblical proportions."

Today, that long shot is paying off many times over. Cubist eventually found a way to adjust the dosage so it didn't cause permanent muscle damage. The drug - now called Cubicin - also turned out to be a powerful weapon in the fight against infections caused by a stubborn form of bacteria called MRSA, for methicillin-resistant Staphylococcus aureus. MRSA has historically been found in hospitals, but has increasingly popped up in day-care centers, prisons, and other settings.

Since winning approval from the US Food and Drug Administration in 2003, Cubicin has generated hundreds of millions of dollars in annual sales and helped transform Cubist into one of the Bay State's best-performing firms. Cubist's revenue leaped 47 percent last year to $434 million. Profit more than quadrupled to $170 million. And its stock finished higher in 2008, even as the market plunged.

And the sales are translating into jobs. Cubist, which moved to Lexington in 2001, recently expanded its headquarters and plans to boost its payroll by 10 percent this year. Cubist now has 554 employees, including 380 in Massachusetts.

The Cubicin story illustrates how the biotech business can often take unpredictable turns. Most promising drugs wind up failing in clinical trials - if not earlier - because they prove to be less effective or safe than hoped. But with a stroke of insight, perseverance, or sheer luck, researchers have occasionally rescued breakthrough therapies from the scrap heap, helping patients and investors alike.

"That's what makes biotech fun," said Leerink Swann & Co. analyst Howard Liang, who has been tracking Cubist for several years. "There are ups and downs."

But Cubicin's tale is particularly dramatic, in part because of its impact on Cubist, which has yet to see another drug approved by the FDA. "There's some question about whether we would exist" without Cubicin, Bonney said.

The potential market for the Cubist product proved far greater than expected. Some analysts underestimated the size of the MRSA threat. Bonney said most predicted the drug might generate up to $250 million in US sales. But this year alone, Cubist predicts, it will take in $520 million to $540 million in the United States.

Cubist still faces challenges, of course, including its reliance on Cubicin. The company faces a potential threat from generic drug makers who hope to make their own versions of the drug. Cubist's patents aren't slated to expire until 2016 and 2019, but Teva Pharmaceuticals, the Israeli generic drug maker, is setting up a legal challenge to them. Bonney said generic drug makers have been successful in challenging patents about 25 to 40 percent of the time. "You certainly can't ignore it," Bonney said. "This is serious stuff."

To diversify its revenue base, Cubist struck an agreement with giant drug maker AstraZeneca to help market another injectable antibiotic, called Merrem IV. And it has invested some of the profits from Cubicin to research new potential drugs, including one to treat Gram-negative bacteria. It also licensed a drug to reduce blood loss during surgery from Dyax Corp. in Cambridge. And it inked a pact with Alnylam Pharmaceuticals of Cambridge in January to help develop a drug to treat a virus called respiratory syncytial.

The Alnylam compound is one of the most advanced potential drugs to use a technique called RNA interference to silence troublesome genes. It's part of the company's continuing effort to bring to market new therapies, the lifeblood and promise of any biotech.

Tekmira Stk Jumps On Licensing Pact With Roche >TKM.T

TORONTO (DOW JONES)--Shares of Canadian biotech Tekmira Pharmaceuticals Corp. (TKM.T) got a boost Monday from a drug-development agreement with pharma giant Roche Holding AG (RHHBY).

As reported, Tekmira is licensing its drug-delivery technology, called SNALP, to Roche for its first two products in the field of RNA interference, or RNAi, a promising new class of drugs that's believed to apply to many types of diseases.

If both products make it to Phase I testing, Tekmira would collect $18.4 million, with potential product-development payments of up to $32 million, plus sales royalties after approval.

In an interview, Tekmira's chief financial officer, Ian Mortimer, said the deal demonstrates that the company has leading technology in an important new field. He noted that Roche, which owns a 4% stake in Tekmira, had been studying the company's technology for about a year before committing to the agreement.

While Tekmira has its own RNAi drug candidates in development, with one expected to begin Phase I in the next couple of months, it's signed licensing deals with pharma companies to help finance development of its own pipeline. "We think there's lots of freedom to operate and lots of room for companies to advance products in the RNAi field," he said, adding that Roche isn't the only company that's taken an interest in Tekmira's drug-delivery technology.

Other companies that have licensed Tekmira's intellectual property include Alnylam Pharmaceuticals Inc. (ALNY), Takeda Pharmaceutical Co. (4502.TO), and Merck & Co. (MRK). Bristol Myers Squibb Co. (BMY) and Johnson & Johnson (JNJ) are evaluating the technology.

Mortimer said the company was in good shape financially before the deal, with enough cash to last through the second half of 2010. The Roche deal will "further strengthen" its balance sheet, and the company plans to give more detailed guidance when it reports quarterly results Wednesday.

In Toronto Monday, Tekmira is up 26 Canadian cents, or 27%, to C$1.23 on 231,000 shares. It traded as high as C$1.30 earlier in the session.