Nobel Prize Winner Basis of Sanofi Deal for RNA Therapy

Barry Greene couldn’t walk down the block last week without someone stopping to congratulate him.

As the JPMorgan Chase & Co. health-care conference was kicking into gear in San Francisco, Greene’s company, Alnylam Pharmaceuticals Inc., announced that pharmaceutical giant Sanofi would pay $700 million for a stake in the biotech firm. The core of the deal: developing treatments targeting RNA, the molecules that translate DNA code to make proteins.

The Jan. 13 announcement put the spotlight on a technology decades in the making. Long overshadowed by DNA, its more famous counterpart, RNA -- or ribonucleic acid -- is now thought to hold the potential to treat diseases from spinal muscular atrophy to hepatitis C to cancer. Alnylam’s agreement capped a year of momentum in the field, from the first major RNA-focused drug’s approval in the U.S. in January to a $100 million collaboration between two other drugmakers in September.

“There’s been a tremendous explosion, especially in the last 18 months,” said Kleanthis Xanthopoulos, chief executive officer of Regulus Therapeutics Inc., another RNA-focused drugmaker, in an interview. “Now it’s firing on all cylinders.”

RNA is the middleman of what Francis Crick, the co-discoverer of the structure of DNA, called the central dogma of molecular biology: RNA transmits genetic information from DNA to make proteins. Proteins are the target of many medicines currently on the market; Herceptin, for example, a breast cancer drug, binds to proteins called Her2 receptors to block signals for tumor growth.

Silencing Proteins

RNA therapeutics go back a step. Alnylam’s technology, called RNA interference, or RNAi, aims to silence the production of problematic proteins, keeping them from ever being created. The company describes its approach as “stopping a flood by turning off a faucet,” versus mopping up water after the fact.

The discovery of RNAi won the Nobel Prize in Physiology or Medicine in 2006, with the committee citing it as the “start of a new research field.” The award went to American scientists Andrew Fire and Craig Mello for their work, which was published in 1998. Alnylam was founded in 2002.

Last week, Paris-based Sanofi said it will pay $700 million for an ownership stake of about 12 percent in Alnylam. The Cambridge, Massachusetts-based biotech company’s shares soared 41 percent on the news, driving its market value to more than $5.3 billion. Alnylam also said last week that it acquired some experimental RNAi drugs from Merck & Co.

Drug Collaboration

Alnylam and Sanofi will collaborate on drugs including patisiran, in the third and final stage of testing in patients with familial amyloidotic polyneuropathy, a rare genetic disease affecting the nerves. Analysts estimate it will draw $565 million in annual sales for Alnylam by 2020.

Alnylam gained 4.1 percent to $90.93 at the close in New York. The shares have quadrupled in the last year.

Progress developing RNA treatments has been halting over the years. Most recently, Prosensa Holding NV, a Dutch company that uses “RNA” as its stock ticker, lost 70 percent of its value after its experimental drug for muscular dystrophy failed to show it helped patients walk better in a clinical trial. The company said last week it’s still pursuing ways to get the drug to market. The technology, called exon-skipping, is also being pursued by another company, Sarepta Therapeutics Inc., in the same disease.

The assets Alnylam acquired from Merck last week had belonged to a company called Sirna Therapeutics Inc., also focused on RNAi, that Merck bought for $1.1 billion in 2006. A few years later, Merck shut down a Sirna research facility in San Francisco and said it was cutting about 50 jobs.

Alnylam plans to do better.

‘Works in Man’

“Alnylam has shown RNAi works in man,” said Greene, 50, the company’s president and chief operating officer, in an interview in San Francisco last week.

Alnylam is paying $175 million in cash and stock for the Sirna assets, with the potential for more plus royalties tied to product success. It joins other companies that have been making recent strides in the field, including Carlsbad, California-based Regulus and Isis Pharmaceuticals Inc. In September, Isis signed a deal with Biogen Idec Inc. for at least $100 million, expanding on three others between the companies in the last two years.

Isis’s first drug, Kynamro, received Food and Drug Administration approval last January to treat homozygous familial hypercholesterolemia, a rare genetic disease characterized by severely high cholesterol. Isis has a deal with Sanofi’s Genzyme unit to sell the drug.

‘Big Milestone’

“That was the big milestone for the field,” said Bruce Booth, a partner at Atlas Venture and co-founder of another RNA company, miRagen Therapeutics.

Kynamro is the first RNA therapeutic to be administered systemically, rather than in a specific location such as the eye, he said.

Delivery methods for other RNA treatments remain a concern. Alnylam has had success working on targets in the liver; Biogen and Isis’s experimental drug for spinal muscular atrophy is injected directly into the spinal fluid.

Still, the opportunities for RNA therapeutics are vast, said Jean-Francois Formela, a partner with Atlas Venture and co-founder of RaNA Therapeutics, a closely held company targeting RNA. In addition to silencing production of bad proteins, Formela said there is potential to turn on specific genes to gain lost function.

“We’re really at the early age of RNA biology,” Formela said.