Neuromed Pharmaceuticals Inc. closed a $53.3 million Series E financing, bringing the company's running total of venture capital raised to date to more than $126 million.

Christopher Gallen, Neuromed's president and CEO, said the money should last "well into the second half of 2008" and will allow Neuromed to pursue its "fusion" business model, which combines high-risk, high-reward drug discovery with lower-risk but less-revolutionary specialty pharmaceuticals.

On the discovery side, Neuromed's Vancouver, British Columbia-based labs will continue to focus on preclinical work with novel N-type and T-type calcium channel blockers for pain. Meanwhile, Neuromed's clinical group in Conshohocken, Pa., is preparing to kick off two Phase III trials with NMED-1077, a once-daily formulation of the widely available Schedule II opioid analgesic, hydromorphone.

Gallen said the hope is that specialty pharmaceutical products like NMED-1077 will allow Neuromed to gain a foothold in the pain marketplace and eventually provide non-dilutive funding to support the discovery programs.

Neuromed acquired U.S. rights to NMED-1077, formerly known as OROS Hydromorphone, from Johnson & Johnson subsidiary ALZA Corp. The product previously failed a Phase III trial and received an approvable letter, but Gallen attributed that to trial design and said a single, positive Phase III trial should be sufficient for approval. (See BioWorld Today, April 25, 2007.)

Although just one trial is needed, Neuromed is conducting two: one in low-back pain and one in osteoarthritis pain. Gallen said both trials are expected to end in the second half of 2008, so both likely will be used in the regulatory filing, providing a "more complete data package." The filing is expected in the first half of 2009, with an approval and launch following in the second half if all goes well.

Neuromed currently is working with the FDA to open an investigational new drug application and finalize a special protocol assessment for the low-back pain trial, which is expected to begin in the fall. The trial will use a randomized withdrawal design in which about 400 patients will be enrolled and transitioned from their existing opiate to NMED-1077. Once the dose is optimized, about 300 patients with adequately controlled pain will be randomized to continue NMED-1077 or switch to placebo.

"Arriving at the right dose for each individual patient is just as important in clinical trials as in clinical practice," Gallen said. He added that dosing is especially important in pain trials, since each individual's pain is different. The randomized withdrawal design was previously used to support approval of the oxymorphone-based pain product Opana ER, launched by Endo Pharmaceuticals Inc. last year.

Although most of the Series E financing is earmarked for the NMED-1077 trials, Gallen said Neuromed is "quite active" in pursuing acquisitions of additional specialty pharmaceutical products. The company also is moving forward with its N-type and T-type calcium channel blockers.

Neuromed licensed its N-type program to Merck & Co. Inc. last year in a deal that could be worth up to $475 million. But earlier this month, Merck discontinued development of the lead compound in the program, the Phase II-stage MK-6721 (previously NMED-160). Although no safety issues were identified, the compound was deemed to have less-than-ideal pharmaceutical properties. (See BioWorld Today, March 21, 2006, and Aug. 9, 2007.)

Merck, of Whitehouse Station, N.J., and Neuromed are working to identify second- and third-generation N-type calcium channel blockers. "My gut sense of it is that this is progressing very well," Gallen said, adding that he is on board with Merck's desire to find a best-in-class compound.

Merck is funding the research, but Gallen noted Neuromed is investing its own resources as well to accelerate the program - and for good reason, as the deal is back-end loaded so the sooner a product is launched, the sooner Neuromed starts raking in hefty milestone payments.

Neuromed already has received $25 million up front from Merck, which Gallen said was invested into the T-type calcium channel blocker program. Multiple compounds are in advanced preclinical studies, and Gallen said a lead compound should be in the clinic in 12 to 18 months.

The lead investor in the Series E financing was not disclosed, nor were the names of the new investors in the round. Gallen said only that "most of the investment came from existing investors," including MPM Capital, James Richardson & Sons Ltd., Neuro Discovery LP, GrowthWorks Capital, BDC Venture Capital, Canadian Medical Discoveries Fund Inc. and the Royal Bank of Canada.

The Series E follows a $25 million Series D raised in February 2006, a $32 million Series C raised in October 2003, a $13.5 million Series B raised in December 2000 and a $3.2 million Series A raised in November 1998.