Companies are deploying a range of technologies in the complex realm of RNA drugs.
After several years of waning enthusiasm for an approach to drug-making that was once called revolutionary, interest in RNA medicines is suddenly on the upswing, and Boston area start-ups in the U.S. are at the front of the resurgence.
The field got a high-octane boost last week when Watertown start-up Dicerna Therapeutics Inc. — a company developing drugs using a gene-silencing technology called RNA interference — became the first Massachusetts biotech to go public this year.
Its shares surged a stunning 207 per cent on the first day of trading.
Companies are deploying a range of technologies in the complex realm of RNA drugs. But the goal of all of them is to battle diseases such as cancer and rare genetic disorders by turning on and off the genes that regulate proteins in people’s cells.
From research successes
Making that happen has long proved elusive. But some recent research successes — and an increased flow of money into local biotechs doing the work, such as Cambridge-based Alnylam Pharmaceuticals Inc. and Moderna Pharmaceuticals Inc. — has generated new optimism about bringing RNA therapies to the market.
At the J.P. Morgan Healthcare Conference in San Francisco last month, several firms drew attention by disclosing investments and positive data from clinical trials. One study by Sarepta Therapeutics Inc. of Cambridge found its experimental RNA drug to treat a form of muscular dystrophy in young boys helped them retain their ability to walk.
“‘You can see all of the RNA stocks trending up,” said Bruce Booth, partner in the life sciences group at Atlas Venture, a Cambridge venture capital firm that has invested in RNA start-ups. “We’re finally seeing the signal that RNA can open up new therapeutic pathways.”
The successful initial public offering of Dicerna, whose technology blocks disease-causing overproduction of protein in cells, shows investor appetite for RNA drug companies is high. A decade after the mapping of the human genome, scientists are finally gaining the “molecular understanding” to produce “precision medicines,” said Christoph Westphal, a partner in the Boston venture firm Longwood Fund, which has bankrolled RNA research.
Work with RNA molecules, which long ago surrendered the spotlight in the field of genetics to the better-known DNA, has been the talk of the biopharmaceutical world in recent weeks. On the eve of the J.P. Morgan event, Cambridge-based Genzyme said its French parent company, Sanofi SA, paid $700 million to buy a chunk of Alnylam, a leader in RNA interference.
Under the deal, Genzyme took a 12 per cent stake in Alnylam and won the rights to eventually market several of its drugs being developed to treat rare blood disorders such as haemophilia and porphyria. Alnylam separately said it was plunking down $175 million in cash and stock to acquire San Francisco biotech Sirna Therapeutics Inc. and its pipeline of RNA drug candidates from pharmaceutical giant Merck & Co.
Venture-backed Moderna also joined in by pocketing a $125 million investment from Alexion Pharmaceuticals Inc. of Cheshire, Conn., to deploy a different technology, messenger RNA, which seeks to battle rare diseases by stimulating protein growth.
Moderna promptly spun out its cancer-fighting messenger RNA research programme into a separate company, Onkaido Therapeutics, which will work on 15 experimental drugs. Onkaido will start out wholly owned by Moderna, but Moderna may soon seek to partner with other investors or larger drug makers to speed its progress.
Chief executive Stephane Bancel said Moderna is creating a technology “platform,” akin to an operating system, that can help multiple business partners develop medicines. The partners include Anglo-Swedish drug maker AstraZeneca plc, with which Moderna has a collaboration on RNA drugs to fight cardiovascular, metabolic, and kidney disorders.
Mr. Bancel and others in the field say RNA therapeutics offer advantages over traditional small molecule drugs or biotech medicines grown from organic materials.
“We can do hundreds, if not thousands, of drugs the biotechnology industry can’t do, by injecting messenger RNA into cells,” Mr. Bancel said. The messenger RNA contains instructions telling cells how to make protein and whether to leave it in the cell or carry it into the bloodstream. As for companies working in RNAi research, such as Alnylam, he said, “We see them as collaborators. We’re doing the opposite of one another, but we’re working in the same field.”
Another local company, Atlas-funded RaNA Therapeutics Inc. of Cambridge, is working on a technology called long non-coding RNA to create a class of targeted medicines that can selectively activate protein in cells.
Even the largest Massachusetts biotech, Cambridge-based Biogen Idec Inc., secured a foothold in the emerging RNA space last year by striking a partnership with Isis Pharmaceuticals Inc. of Carlsbad, Calif., which is pioneering yet another RNA technology, called antisense, to combat neurological disorders.
“‘RNA is hot,” said Chris Garabedian, chief executive of Sarepta, which also works on antisense technology, using “splice switching” to move a gene’s coding around and let it regulate protein levels. “We are hitting the RNA space at a unique time. Several companies over the past year and a half have started to turn the corner with some very compelling 1/8clinical3/8 data.”
Mr. Garabedian moved the company to Cambridge from Bothell, Wash., outside Seattle, two years ago because he concluded it would be easier to attract RNA research talent in the Boston area. Sarepta is building a new lab near Kendall Square. He, too, sees the small cluster of RNA drug companies in the area less as rivals than as partners in an emerging field. “‘We can play in anybody’s sandbox,” he said.