Only days after the first gene therapy finally cleared regulatory hurdles in Europe, Cambridge, Mass.-based gene therapy firm bluebird bio closed a $60 million Series D financing round.

The timing, however, was merely coincidental.

"I'd love to be able to say I have that much control over the system, but it was just happenstance," said CEO Nick Leschly, who called the Series D, disclosed Wednesday morning, "an opportunistic financing" for bluebird, which is gearing up to start what it hopes will be a registrational trial for a lead program in rare disease adrenoleukodystrophy (ALD).

Nevertheless, last week's nod – on the fourth try – by the European Medicines Agency for uniQure BV's Glybera (alipogene tiparovec) in lipoprotein lipase (LPL) deficiency is "a big step forward for the field," Leschly acknowledged.

While Amsterdam, the Netherlands-based uniQure still has to convince the FDA of the merits of its LPL treatment, European approval of the first gene therapy product was a much-needed victory, not least for Glybera's developer, Amsterdam Molecular Therapeutics, which after struggling following the earlier rejections, agreed to liquidate in February, selling its assets to uniQure. (See BioWorld Today, Feb. 22, 2012, April 23, 2012, and July 23, 2012.)

For bluebird, the road so far has been smoother, thanks in large part to continued support from its investors. "They've really taken a mature approach," Leschly told BioWorld Today.

The Series D round included new investors Deerfield Partners, RA Capital, Ramius Capital Group and two undisclosed blue chip public investment funds, as well as existing investors ARCH Venture Partners, Third Rock Ventures, TVM Capital and Forbion Capital Partners. Dublin, Ireland-based pharma firm Shire plc also joined the round as a strategic investor.

Prior to the latest round, bluebird had raised about $77 million in venture capital, including a $30 million Series C closed last year. (See BioWorld Today, April 20, 2011.)

Funds remaining from the previous round combined with the new capital should carry bluebird into 2015, allowing it to conduct a pivotal program in ALD, advance into late-stage development with a second program in beta-thalassemia and expand a third program in sickle cell disease.

bluebird's treatment approach involves the use of stem cells harvested from a patient's bone marrow. Using a lentiviral vector, a functional version of the disease-causing gene is inserted into the stem cells, which are grown in culture and then delivered back into the patient.

It's basically an "enzyme replacement system," Leschly said. In other words, rather than continually replacing a missing enzyme via chronic treatment, bluebird's gene therapy enables the body to function properly on its own. And, because the treatment involves autologous cells, it eliminates the risk of complications such as graft-vs.-host disease.

For the lead program in ALD, a patient's hematopoietic stem cells are transduced with the lentiviral vector encoding ABCD1 cDNA, the gene that provides transport function in brain cells for clearing up fatty acids. The buildup of those acids causes damage to the myelin sheath in ALD patients. When bluebird's gene-modified cells are delivered back into the patient, they differentiate into glial cells that are able to clear the fatty acids.

Last month, the firm received orphan designation in both the U.S. and Europe for the ALD program and is aiming to start a Phase II/III study next year. "Our objective is to make it a registrational trial," Leschly said, though "at the end of the day, it comes down to the data."

The recent Glybera approval could help bluebird as it reaches agreement on upcoming trial size and design. One of the sticking points in Europe for Glybera was the small number of patients treated – a total of 27 in the file altogether – but Glybera developers cited the rare disease as well as the nature of the gene therapy itself.

Going into ALD, a disease estimated to affect one in every 21,000 boys worldwide, bluebird will be "looking for endpoints that are pretty dramatic," Leschly said. "So you don't need a whole lot of patients" to show that the treatment is having a clear effect on the disease.

The advent of gene therapy in the marketplace also marks a paradigm shift in terms of pricing because it's a one-time treatment vs. a chronically administered drug. Upon Glybera's approval, uniQure CEO Jörn Aldag declined to speculate on the product's commercial potential, though he told BioWorld Today pricing should be at least some multiple of marketed enzyme replacement therapies, which costs patients between $180,000 and $540,000 per year.

That sounds high, but the one-time treatments would offer substantial cost savings to the health care system overall, compared to the expenses of treating, hospitalizing and sustaining patients suffering from those types of rare genetic diseases.

"The economics around that are very favorable," Leschly pointed out. "So I'm very confident that the business model will follow, that the commercial profile will evolve."

Beyond ALD, bluebird is working in beta-thalassemia, with a second U.S.-based Phase I/II trial slated to start next year, and has an earlier program in sickle cell disease. Proceeds from the financing also will support manufacturing, clinical and commercial infrastructure.

In other financings news:

• CoDa Therapeutics Inc., of San Diego, said it raised an additional $20 million from RusnanoMedInvest, a subsidiary of Rusnano, in a second closing of its Series B financing round. The transaction is the first investment agreement between Rusnano and Domain Associates inked in March, which they set up as a $760 million joint fund. The latest investment brings CoDa's Series B to nearly $40 million. All current investors, including Domain, GBS Ventures and BioPacificVentures, participated. Proceeds will support clinical trials of Nexagon, CoDa's lead candidate based on gap junction modulation for treating chronic wounds, including venous leg ulcers and diabetic foot ulcers. Trials will be conducted in the U.S. and Russia, where Rusnano is based. CoDa currently is conducting a 300-patient Phase IIb study in patients with venous leg ulcers and a 160-patient diabetic foot ulcer trial. (See BioWorld Insight, March 12, 2012.)

• Nanosphere Inc., of Northbrook, Ill., said it closed its public offering of 12.1 million shares priced at $2.40 each for gross proceeds of about $29 million. Net proceeds of $26.9 million will be used for general corporate purposes and working capital. Nanosphere develops a molecular diagnostics platform for life-threatening infections and cardiovascular diseases. Piper Jaffray & Co. acted as the sole book-running manager, and Roth Capital Partners acted as co-manager.

• Relmada Therapeutics Inc., of Blue Bell, Pa., said it raised $3 million in an initial closing of its Series A financing for which Laidlaw & Co. (UK) Ltd. is the exclusive placement agent. Noteholders BioAdvance and Ben Franklin Technology Partners of Southeastern Pennsylvania, as well as equity investor Wonpung Mulsan Co. Ltd., have converted their existing liens into the Series A convertible preferred stock. Proceeds will be used to continue the development of LevoCap, a once-a-day extended-release dosage form of opioid levorphanol in a tamper-resistant delivery system, and for general corporate purposes.

• Zogenix Inc., of San Diego, said it priced a public offering of 32.5 million units – each unit consisting of one share of common stock and a warrant to purchase 0.45 of a share – at $2 per unit. Net proceeds will be about $60.7 million and will allow the specialty pharma firm to repay all amounts outstanding under its amended and restated loan and security deal with Oxford Finance LLC and Silicon Valley Bank. Funds also will be used to support pre-approval and pre-commercialization activities for pain product Zohydro ER (hydrocodone bitartrate), the ongoing commercialization costs for migraine drug Sumavel DosePro (sumatriptan injection) and for working capital and other general corporate purposes. Stifel Nicolaus Weisel and Wells Fargo Securities LLC are acting as joint book-running managers, with Leerink Swann LLC serving as lead co-manager and Oppenheimer & Co. Inc. and William Blair & Co. LLC acting as co-managers. Shares of Zogenix (NASDAQ:ZGNX) closed Tuesday at $2.14, up 2 cents.