Regulus, AstraZeneca Deal Rekindles Interest in RNA
By Catherine Shaffer
Regulus Therapeutics Inc., of La Jolla, Calif., inked another two deals related to its microRNA technology. Its agreement with London's AstraZeneca plc calls for a $28 million up-front cash and equity payment, plus milestones, for development of three microRNA targets.
The selected targets include Regulus' lead product microRNA-33 for cardiovascular and metabolic disease.
Another deal with Biogen Idec Inc. establishes a collaboration to identify microRNAs as biomarkers for multiple sclerosis. Biogen Idec will make an investment in Regulus, in addition to undisclosed up-front and milestone payments.
The deals follow previous alliances with GlaxoSmithKline plc and Sanofi SA, and may signal that pharma is becoming more comfortable with RNA technology, after some high-profile program terminations within the past couple of years.
Under the agreement with AstraZeneca, Regulus will take the lead in preclinical development, receiving certain success-based milestone payments. AstraZeneca would then take over clinical development and commercialization of any resulting programs.
For a product that progresses successfully through development, Regulus is eligible for clinical milestone payments, and also launch and commercial milestone payments and royalties.
Regulus is a joint venture between Alnylam Pharmaceuticals Inc., of Cambridge, Mass., and Isis Pharmaceuticals Inc., of Carlsbad, Calif. Alnylam made an initial investment of $10 million in Regulus as a start-up in 2007, and Alnylam and Isis have each made equity investments in the company.
Regulus established an early track record of funding through partnerships, and it has gained most of its capital through those deals. In 2008, GSK paid $20 million up front in a deal worth up to $600 million. GSK later committed as much as an additional $150 million in a hepatitis C deal.
That partnership is chugging along happily. In July 2011, Regulus reported that it had identified a third microRNA target, triggering a preclinical milestone payment from GSK.
A 2010 deal with Sanofi garnered $25 million up front, plus a $10 million equity investment and research funding for three years, in exchange for access to four programs in the area of fibrosis, including miRNA-21. Potential milestones total up to $650 million, and Regulus is eligible for royalties from that deal as well.
Rodman & Renshaw analyst Michael G. King, Jr., pointed out that the deal be an indication of a positive trend. "We view this deal as another sign of big pharma's growing comfort with RNA technology, whether it be microRNA or single- or double-stranded RNAi approaches," King wrote.
That's welcome news for a field that has had dramatic ups and downs. In 2010, Roche AG terminated a deal valued at up to $1 billion with Regulus's parent company Alnylam, followed shortly thereafter by Novartis AG's decision to pass on an option to extend a high-dollar deal with Alnylam. (See BioWorld Today, Sept. 27, 2010, and Nov. 24, 2010.)
Those high-profile passes cast a shadow on the field, leading to speculation that the potential of RNA technologies had been overblown and that early stage products were not going to fulfill their promise.
Two years later, those fears seem largely unfounded. The year thus far has seen an avalanche of clinical news, albeit still relatively early phase.
For example, RXi Pharmaceuticals Corp., of Worcester, Mass., began a dose-escalating Phase I trial of its RNAi compound RXI-109, which incorporates self-delivering RNAi technology, for skin scarring following trauma or surgery. And Sylentis SA, of Madrid, Spain, a subsidiary of Grupo Zeltia SA, received authorization from Spanish and Estonian regulatory agencies to begin Phase II trials of RNAi therapeutic SLY040012 for ocular hypertension of glaucoma, looking at efficacy for a range of doses.
Alnylam reported Phase I data for ALN-PCS, for severe hypercholesterolemia, and completed enrollment in a Phase I trial of ALN-TTR02, for TTR-mediated amyloidosis, bouncing back after its candidate for syncytial virus, ALN-RSV01, missed its primary endpoint in a Phase IIb trial in lung transplant patients.
Alnylam's Phase I data for ALN-PCS showed significant and durable reduction of PCSK9 plasma levels of up to 84 percent and lowering of LDL-cholesterol by up to 50 percent.
Tekmira Pharmaceuticals Inc., of Vancouver, British Columbia, began enrolling in a Phase I trial of TKM-Ebola, a systemically delivered RNAi therapeutic that uses the company's lipid nanoparticle delivery technology.
There have been some casualties, as well. In June, Marina Biotech Inc., of Bothell, Wash., furloughed 90 percent of its employees and ceased day-to-day operations in an effort to stay afloat when its cash ran out.
Alnylam's stock (NASDAQ:ALNY) bumped modestly, possibly from Regulus's news, gaining 67 cents, to close Wednesday at $17.67.
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