Once thought to be useless junk of the genome, long noncoding RNA is getting some serious attention as a source of druggable targets. And that interest helped RaNA Therapeutics Inc., of Cambridge, Mass., land a $20.7 million Series A financing round led by Atlas Venture, SR One and Monsanto Co. – with participation by Partners Innovation Fund – to get its lncRNA discovery platform off the ground.

Based on technology licensed from Massachusetts General Hospital, RaNA seeks to modulate disease-associated lncRNAs through their interaction with the polycomb repressive complex 2 (PRC2).

"RaNA has been operating in stealth mode until this point, quietly generating data," RaNA CEO Arthur Krieg told BioWorld Today.

The company was formed in July 2011, prompted by interest from Atlas Venture in starting a company around the lncRNA concept.

Krieg brought his experience as chief scientific officer of Pfizer Inc.'s oligonucleotide therapeutics to the project, although initially he said he was not "immediately clear" what the scientific significance of the field was.

The key to developing a drug discovery platform around lncRNA, in this case, was PRC2, the protein complex responsible for X chromosome inactivation. It turned out that PRC2 had a much broader role in gene expression, and that thousands of lncRNAs contain binding regions for it.

The technology was pioneered by founder Jeannie T. Lee, and licensed exclusively from Massachusetts General Hospital.

A drug compound can theoretically activate expression of a gene by disrupting the interaction of an lncRNA with PRC2.

A number of companies are working generally in the area of epigenetics. Examples include Constellation Pharmaceuticals Inc. and Epizyme Inc. However, RaNA is the first to focus on lncRNAs.

The most comparable company was Curna Inc., acquired nearly a year ago by Opko Health Inc. for $10 million. Curna was developing antisense RNA, rather than lncRNA. However, the two companies shared a strategy of up-regulating gene expression in a world where most RNA companies are silencing or knocking genes down. (See BioWorld Today, Feb. 2, 2011.)

Another difference between RaNA's approach and earlier generations of RNA companies is that it is acting at the level of nuclear RNA rather than messenger RNA. RNAi molecules, for example, are double -stranded.

Other types of RNA therapeutics typically require a sophisticated delivery system, as well. Those delivery vehicles usually work best in the liver.

RaNA's delivery strategy is simple subcutaneous injection of the compound in saline solution.

Krieg said that based on in vivo studies in mice, RaNA's oligonucleotides distribute broadly through the body, with function through the lung, kidney, fat tissue, liver, small intestine and most other tissues.

They do not cross the blood-brain barrier. Although that is an advantage for some types of therapies, RaNA's plan for delivery to the central nervous system would involve the use of a catheter.

RaNA has not selected a disease indication yet. That's high on its to-do list now that it has secured financing.

"We had no trouble raising funds," Krieg said. "We had to turn away a number of parties who would have liked to take part."

One of their investors is a bit of an outsider to the biotech venture scene. Monsanto was attracted to the lncRNA field because of its applicability to plant epigenetics. Monsanto is best known as a seed company. It is aware that plants also have a PRC2 and a large number of noncoding RNAs, so any outcome of RaNA's research will be applicable to enhancing crop production.

According to Krieg, Atlas and Monsanto have a strategic alliance around that type of technology and plan to make similar investments in the future.

The current Series A financing follows seed funding by Atlas Venture in 2011. The funds will boost RaNA's research and development efforts and expand the current staff of 12.

"We're struggling with how fast we want to expand," Krieg said. The company also has decisions to make about its partnering strategy. "We probably have bandwidth for one or two target-based collaborations at this point. We're starting to talk to potential partners for that."

In other financings news:

• BioRelix Inc., of New Haven, Conn., received $500,000 from Connecticut Innovations, a quasi-public authority responsible for technology-based economic development. The investment is part of a $4.2 million round of funding for BioRelix, which is developing antibiotics using a new riboswitch-based drug discovery platform.

• Hadasit Bio-Holdings Ltd., of Jerusalem, completed a $1.4 million investment round for Thrombotech Ltd., its portfolio company, at a pre-investment valuation of $5 million. Clal Biotechnology Industries, Ofer Hi-Tech and Hadasit Bio participated in the financing. The proceeds will be used to complete ongoing clinical trials. Thrombotech is also in negotiations with potential global pharmaceutical partners to collaborate on the development of THR-18, its Phase IIa stroke candidate.

• Vitae Pharmaceuticals Inc., of Fort Washington, Pa., obtained a $15 million round of debt financing from Oxford Finance LLC and Silicon Valley Bank. The senior credit facility will be used to advance Vitae's drug pipeline, which includes treatments for chronic kidney disease, diabetes, Alzheimer's disease and atherosclerosis. Vitae's lead compound, VTP-27999, a renin inhibitor, is expected to enter a Phase IIb trial early this year. (See BioWorld Today, June 28, 2011.)

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