DUBLIN – Nasdaq continues to put out the welcome mat for European drug development companies, with Ascendis Pharma A/S becoming the latest in a lengthening roster of firms to take up residence on the New York-based exchange.

Ascendis received a particularly warm reception. The Hellerup, Denmark-based specialty pharma priced its initial public offering (IPO) at $18 per share, at the top of the indicative range of $16-$18 it set at the outset of the book building process. It grossed $108 million from the sale of 6 million shares, having initially planned to issue just 5 million shares. After expenses, about $96.4 million will flow onto its balance sheet. The IPO price implies a market capitalization of $412.8 million.

Shares in the company began trading Wednesday, under the ticker symbol ASND, generating volume of more than 3.2 million and reaching almost $22 before trailing off to close at $18.83 for a gain of about 4.6 percent on the day.

Total gross proceeds from the IPO could swell to $124.2 million, if the underwriters exercise an option to subscribe for an additional 900,000 shares. Assuming that were to happen, the company would have upward of $165 million in cash, having exited 2014 with €50.2 million (US$57 million) on hand.

It's a rapid and sizable return on investment for its series D syndicate, which invested €48 million, priced at about €8.06 or $9.78 per share, in a deal disclosed on Dec. 1, 2014.

That syndicate came together quickly, according to Rafaèle Tordjman, managing partner at Paris-based Sofinnova Partners and an original member of the Ascendis board of directors. The Sofinnova team knew Jan Mikkelsen, the co-founder, president and CEO of Ascendis, from previous ventures and took him at his word when he described the company's technology as "really quite exceptional," Tordjman told BioWorld Today in an interview following the oversubscribed series D.

Ascendis was established in 2006 but did not commence operations until December 2007, when it acquired Heidelberg, Germany-based Complex Biosystems GmbH, the company that developed its Transcon drug delivery technology, which combines prodrug and sustained-release technologies in patentable therapeutics that have superior activity profiles to their unmodified counterparts.

Transcon is so called as it transiently conjugates an active drug substance to a carrier via a proprietary linker. The linkers can be tuned to ensure that the drug is released in a controlled fashion, depending on physiological conditions, such as pH and temperature. The company claims to be able to control drug release over time scales ranging from a single day to a half year. Its drug carriers also are controllable – they allow for systemic or local drug delivery, depending on the therapeutic objective.

Sofinnova invested at the outset to help Ascendis identify the best target for its technology, Tordjman explained. Nearly eight years later, the company has evolved into a mixed model that includes an internal pipeline and multiple pharma partnerships, attracting broad interest from the venture community. Although the December financing was described as a series D, "it was only the second round," she added.

'WE LOVE COMPANIES THAT AREN'T LOOKING FOR A QUICK FLIP'

Jonathan Silverstein, partner at Orbimed Advisors LLC, told BioWorld Today following the series D that Ascendis possessed two key elements of interest to the health care investment firm, which co-led the round.

"It has a pipeline of products that seem to work and have really impressive data," he said, referring to the company's lead program, a human growth hormone (HGH) prodrug that completed a phase II study in adult growth hormone deficiency (GHD) and is running a phase II study in the indication in children, and a follow-on candidate to treat pulmonary arterial hypertension (PAH). Ascendis owns the rights to both.

Ascendis also has "a real technology platform, which has been validated by multiple pharmaceutical partners in sizable transactions," Silverstein added. These elements, combined with an experienced management team, "got us really excited about the opportunity," he said, noting that the Transcon technology "offers significant advantages to the parent molecule," including more convenient dosing, a clean safety profile and, potentially, better efficacy.

Topline phase II data from the pediatric study of once-weekly Transcon HGH in GHD are due around mid-2015, after which the company aims to move to phase III trials, which will consume most of the IPO proceeds. In December, the company reported six-month interim results from the ongoing study. The analysis consisted of 25 patients, representing approximately 50 percent of the anticipated total enrollment, who completed all six months of treatment. The mean annualized height velocity was achieved by the six-month time point, with mean annualized height velocities among the three dosing levels ranging from 11.9 cm for the 0.14 mg/kg/week dose to 14.5 cm for the 0.30 mg/kg/week dose, compared to 11.5 cm for the active comparator, daily injections of Genotropin (somatropin, Pfizer Inc.) dosed at a 0.21 mg/kg/week.

Ascendis is seeking to overcome a history of failures in the effort to make long-acting HGH, according to Tordjman. Its prodrug releases unmodified growth hormone, thus maintaining the same mode of action as currently prescribed daily growth hormone therapies, raising the prospect of improved compliance with once-weekly dosing.

"Modification of the protein GH doesn't have the efficacy of the native drug," she said.

Earlier this month, Ascendis also began a phase I ascending dose trial of the PAH prodrug, Transcon treprostinil, in healthy volunteers. A synthetic prostacyclin analogue, the vasodilator has been marketed as Remodulin (for infusion), Tyvaso (for inhalation) and Orenitram (oral formulation) by United Therapeutics Corp., of Silver Spring, Md., which had in-licensed and then handed back rights to the Ascendis program. Combined, the United programs accounted for global sales of $930 million in 2013, according to Cortellis Competitive Intelligence. The 2019 sales forecast of $1.47 billion is more telling, since it includes projections for Orenitram, which was approved by the FDA at the end of 2013 but didn't launch until the second quarter of 2014. (See BioWorld Today, Dec. 24, 2013.)

Ascendis has two partnered projects, Transcon insulin, and Transcon ranibizumab, which are licensed to Paris-based Sanofi SA and the Genentech arm of Basel, Switzerland-based Roche Holding AG, respectively. The company has generated €69 million from its licensing agreements and, before the IPO, had raised a total of €72.4 million in equity and debt funding.

"We love companies that aren't looking for a quick flip but want to deliver long-term value to shareholders," Silverstein said, citing Ascendis as a perfect example of that strategy, with a goal to move its candidates through pivotal trials.

"If somebody is interested in these assets, we can have a conversation," he added. "But the focus of this company is to develop its own assets and advance them deep into the clinic and toward approval."