In an S-1 slid into the SEC on New Year’s Eve, following a confidential filing a month earlier, Dicerna Pharmaceuticals Inc. joined Revance Therapeutics Inc. in seeking to extend biotech’s initial public offering (IPO) window into the new year. (See related story this issue.)

Dicerna is seeking to raise up to $69 million to advance its next-generation RNAi pipeline, based on optimized Dicer substrate siRNA (DsiRNA) molecules. The Watertown, Mass., company, founded in 2006, plans to list on Nasdaq as an emerging growth company under the Jumpstart Our Business Startups Act of 2012 under the ticker “DRNA.” Jefferies, Leerink Swann and Stifel are joint bookrunners on the deal.

Thursday, Dutch firm Uniqure BV became the first biotech of 2014 officially to join the IPO queue, filing for a $75 million offering to advance its gene therapies to treat orphan diseases. The Amsterdam-based company plans to list on Nasdaq as “QURE.” Jefferies, Leerink Swann and Piper Jaffray are joint bookrunners on that deal.

Dicerna is among the leaders in RNAi development, which has bumped along a rocky road since the early 2000s, when the science of silencing genes related to disease triggered a flurry of deals. RNAi pioneer Sirna Therapeutics Inc., for instance, went to Merck & Co. Inc. in 2006 in a $1.1 billion buyout. (See BioWorld Today, Nov. 1, 2006.)

However, the challenges of delivering RNAi therapeutics – primarily because RNAi degrades quickly in the bloodstream – delayed development and prompted Roche AG’s headline-grabbing pullout of the space in 2010, leaving some smaller RNAi firms in a lurch. Unable to raise additional cash, for instance, Marina Biotech Inc. closed up shop and divested its technology. (See BioWorld Today, Nov. 18, 2010, and June 4, 2012.)

Dicerna had more fortuitous timing. The company closed a $25 million Series B in 2010 shortly before the implosion, giving the company breathing room to advance the DsiRNA technology and its delivery platform, Encore, which combines “envelope” and “core,” while waiting for prospects to improve. (See BioWorld Today, Aug. 12, 2010.)

Engineered with 25 or more base pairs, DsiRNAs are longer than most competing siRNAs, an advantage allowing them to engage the Dicer enzyme, which operates early in the gene silencing cascade. Dicerna’s Encore platform incorporates lipid-based nanoparticles to deliver the RNAi payload.

The approach was sufficiently compelling for Dicerna to attract a $60 million Series C in August 2013 – one of last year’s largest private rounds. (See BioWorld Today, Aug. 1, 2013.)

The company’s pipeline includes DCR-PH1 for primary hyperoxaluria and DCR-M1711 for the treatment of various cancers related to the MYC oncogene, with an initial focus on hepatocellular carcinoma. Dicerna has discovery and early development programs focused on additional disease targets in the liver, including antithrombin for clotting disorders and alpha-1 antitrypsin (AAT) for liver disease associated with AAT deficiency.

In 2010, Dicerna partnered with Japanese biopharmaceutical firm Kyowa Hakko Kirin Co. Ltd. to discover, develop and commercialize drug delivery systems and siRNA medications using its Dicer substrate technology for undisclosed oncology targets. The deal – called the biggest in the RNAi space to that point – potentially could garner Dicerna more than $1.4 billion. In 2013, Kyowa moved the second therapeutic oncology candidate in the partnership into development, triggering a $5 million milestone payment. (See BioWorld Today, Jan. 5, 2010.)

Despite cash from the partnership, Dicerna becomes one of a handful of biotechs wooing the public markets before moving a compound into the clinic. In its filing, the company said it will use proceeds from the IPO to fund preclinical studies and to initiate clinical trials for DCR-M1711 in the first half of the year and for DCR-PH1 in 2015.

In the offering, which is not yet priced, the company said certain existing stockholders, including affiliates of its directors, indicated an interest in purchasing an undisclosed number of shares. Dicerna boasts A-list investors, among them Oxford Bioscience Partners, Skyline Venture Partners, Abingworth Bioventures LLP, Domain Associates LLP, Brookside Capital Partners and Deerfield Management.

The company reported cash and equivalents of $54.7 million and an accumulated deficit of $78.7 million as of Sept. 30, 2013, and 10.6 million common shares outstanding prior to the offering.

UNIQURE PREPARES FOR GLYBERA NDA

Uniqure, which also filed as an emerging growth company, disclosed in November that it had confidentially submitted an F-1 registration statement to the SEC. (See BioWorld Today, Nov. 12, 2013.)

Uniqure became a commercial entity in 2012 with the approval of Glybera (alipogene tiparvovec). The world’s first approved gene therapy, based on an adeno-associated viral vector, gained European approval in the ultra-orphan indication lipoprotein lipase deficiency, following an exhaustive and protracted approval process. (See BioWorld Today, Nov. 5, 2012.)

In fact, Uniqure was established earlier in 2012 by Forbion Capital Partners to assume the assets and liabilities of the liquidated Amsterdam Molecular Therapeutics Holding NV after the European Committee for Human Medicinal Products three times voted not to recommend Glybera. (See BioWorld Today, Oct. 24, 2011, and Feb. 22, 2012.)

Following Glybera’s approval, Uniqure inked a $40M deal with Chiesi Famaceutici SpA, of Parma, Italy, to commercialize the drug in Europe, China, Brazil, Mexico, Pakistan, Turkey, Russia and the other members of the Commonwealth of Independent States and China. In the nine months ending Sept. 30, 2013, Uniqure realized €220,000 (US$300,680) in licensing revenues and €1.8 million in collaboration revenues related to the drug, according to the F-1. The commercial launch of Glybera in the European Union is expected in the first half of 2014. (See BioWorld Today, July 10, 2013.)

Uniqure retained rights in the U.S., Canada and Japan, however. In its filing, the company indicated it will submit an investigational new drug application for Glybera in the U.S. in the first half of the year while advancing additional gene therapy products through its pipeline, including treatments for hemophilia B, acute intermittent porphyria, Parkinson’s disease (PD) and the rare liposomal storage disorder Sanfilippo B.

In July 2013, Uniqure advanced its PD therapy into a Phase I study, with company CEO Jörn Aldag personally assisting in the surgery, during which the gene for glial cell line-derived neurotrophic factor was administered directly into the brain. (See BioWorld Today, July 30, 2013.)

In its preliminary prospectus, dated Jan. 2, Uniqure said proceeds from the IPO will be used primarily to complete the build-out of its manufacturing facility in Lexington, Mass., prepare for commercial launch of Glybera in the U.S. and begin a planned Phase I/II trial of AMT-060 in hemophilia B. The company reported cash and equivalents of €31.4 million and an accumulated deficit of €137.7 million.

Uniqure disclosed 61 million shares outstanding prior to the offering, which is not yet priced.