Wednesday, January 18, 2012

RaNA Therapeutics emerges from stealth with $20.7M Series A round

By Lori Valigra

Article updated as of 12:45 p.m., Jan. 18, 2012.

RaNA Therapeutics Inc., a secretive company that is developing technology licensed from Mass General Hospital (MGH), said it has completed a $20.7 million Series A round co-led by Atlas Venture, SR One, and Monsanto Co., with participation from Partners Innovation Fund.  
 
The Cambridge-based company is developing a platform that can enable selective activation of target genes and expression of therapeutic factors by targeting a type of regulatory RNA called long non-coding RNA (lncRNA), according to information provided by the company.

"Our platform is based on a new therapeutic approach to selectively up-regulate gene expression,” Dr. Arthur Krieg, RaNA’s president and CEO, told Mass High Tech. He said the company already has conducted in vitro (“test tube”) and in vivo (“inside the body”) experiments that indicate the technology would have broad therapeutic uses.

The company has come up with a short list of 20 diseases, he said, and it will choose one to move forward itself and talk to collaborators for other projects. Krieg said he hopes to have a collaboration by the end of the year, and also to have Investigational New Drug-enabling safety studies in that timeframe as well.

Currently housed in the offices of Atlas, the company is looking to move in the next month or two into about 9,000 square feet of space somewhere in Cambridge, he said. RaNA has about a dozen employees.

The company last November raised $2.66 million of the initial funding, according to federal documents. In connection with the completed financing, Brian M. Gallagher, Jr., a partner at SR One, and Stephen Padgette, vice president at Monsanto, have joined RaNA’s board of directors. The board also includes Dr. Jean Francois Formela, a partner at Atlas Venture as chairman; Dr. Ankit Mahadevia, a principal at Atlas Venture; and RaNA CEO Krieg.

The company uses technology developed in the laboratory of scientific founder Dr. Jeannie Lee, a Howard Hughes Medical Institute Investigator at Massachusetts General Hospital, and is exclusively licensed from the hospital. Lee co-founded RaNA with Atlas and Krieg.

About 2 percent to 3 percent of the genome consists of genes that encode proteins. The rest had been considered “junk DNA” with no role. That was until recently, when it was discovered that it is actively transcribed into lncRNA that serve a critical epigenetic gene-regulating function, Krieg said. These regulatory lncRNAs control the process of development and can lead to disease when aberrantly expressed. By regulating these regulators, RaNA said it may be able to correct defective gene expression and restore health.
 
The company was seed-funded by Atlas last year. The Series A funds will be used to accelerate R&D efforts across various diseases, expand RaNA’s intellectual property in lncRNA, and expand the core team, the company said.

Lee and her co-workers discovered a large number of lncRNA regions that interact with a regulatory complex called PRC2, and showed it is possible to activate single gene expression by specifically blocking this interaction.

“Most drugs to date, such as antibodies, inhibit activity,” said Formela. “We aren’t inhibiting, we are activating the expression of a protein to enhance the gene.”

He said the company is in the process of narrowing down the diseases it will focus on, but likely areas include genetic diseases or any indication of biotechnology. “We’d like to address genetic disease, such as haploinsufficiency,” he said. That condition occurs when there is only a single functional copy of a gene that is not making enough protein, and the other gene is no longer expressing the correct protein. RaNA’s approach is to activate or enhance the expression of protein in the good gene.

Because the RaNA therapies could theoretically be made inside the body, there also is a potential 10-times or higher savings over traditional methods of making drugs in bioreactors, Formela said.

The company has filed several patents, some of which are very broad, such as on the existence and method of use of thousands of lngRNA targets, he added.

RaNA also is being supported by partner Monsanto, which last year formed a partnership with Atlas to look for life sciences investments. Formela said the duo are looking at a number of technologies, and expect another joint seed investment this year.

“Monsanto is a leader in plant genetics and epigenetics, and improving plant properties,” added Krieg. “We think we can contribute to that.”

Krieg sees a broader ripple to his company’s activities. “I think oligonucleotides are on the cusp of being recognized as the third leg of drug development,” he said. Oligonucleotides are drugs made of DNA or RNA, and include RaNA’s lncRNA approach. Historically, the first two waves of drug development were small molecule chemistry, and then in protein therapeutics/biotechnology in the 1980s. “Oligonucleotides are a rich platform for drug development, and they are about to get a lot higher profile.” He said there are currently 8-9 oligonucleotide-based drugs in Phase 3 clinical trials.

But it could take another 10-20 years before oligonucleotides mount a serious challenge to protein and small molecule therapeutics, said Detlef Rethage, president of Milford-based Avecia Biotechnology Inc., a contract manufacturer that claims to make more than half of the outsourced oligonucleotides in the world.

“There are pretty high expectations in the industry, and the mood is very positive,” he said. “But it may take more time than 5-10 years.” He likens the situation to the hype that surrounded small interfering RNA (siRNA) technology over the past decade, saying the disappointment that had been expressed about that oligonucleotide technology was premature, as it needed more years to get it into the clinic.

Another challenge before RaNA will be if it goes after central nervous system diseases, because oligonucleotides do not cross the blood-brain barrier on their own. “That would now limit an lncRNA-based drug in a central nervous system treatment, unless it was administered via injection into the spine,” RaNA’s Krieg said. Avecia’s Rethage said it may be a matter of time until that challenge is met.