Washington Editor

Adamas Pharmaceuticals Inc., which has flown under the radar since its founding in 2002, landed a contract with the U.S. Navy to jointly develop the company's triple combination antiviral drug (TCAD) therapy against influenza A viruses, including the 2009 novel H1N1 swine-origin flu virus.

The privately held Emeryville, Calif.-based firm, which is developing ADS-8902, its lead TCAD therapy for the flu, and drugs to treat symptoms of Parkinson's disease and dementia, also boosted its cash position with a $40 million Series D financing.

The Cooperative Research and Development Agreement (CRADA) with the Naval Health Research Center (NHRC) in San Diego - which played a key role in identifying the emergence of the H1N1 swine flu virus - is for preclinical studies evaluating Adamas' TCAD flu therapy, which includes the firm's investigational proprietary fixed-dose oral combination of amantadine and ribavirin, administered adjunctively with a neuraminidase inhibitor, such as Roche AG's Tamiflu (oseltamivir).

NHRC is conducting comparative tests of the TCAD therapy against various strains of the influenza A virus, including the H1N1 and H3N2 seasonal flu strains, the H5N1 avian flu and the 2009 H1N1 virus, to assess the in vitro activity of combination therapy against the flu strains. NHRC also is comparing the in vitro activity of the TCAD therapy to other pharmaceutical agents when used alone or in double combination.

Data from the experiments will be used to advance the development of the TCAD therapy as a potential broad-spectrum antiviral therapy for serious infections caused by influenza A viruses.

No financial details about the CRADA were disclosed, but Adamas CEO Gregory Went said his firm has had an ongoing relationship for the past year with the NHRC prior to signing the agreement.

"For us, it represents a collaboration with probably the top surveillance and mechanistic understanding group in the U.S. government for looking at influenza and influenza pandemics," he told BioWorld Today.

It was NHRC scientists who helped the Centers for Disease Control and Prevention and the local health department in San Diego identify the first two cases of the H1N1 swine flu in two California children, which the CDC first made public on April 21 in an online posting of its Morbidity and Mortality Weekly Report.

The military has long been engaged in flu surveillance, because armed forces historically have been disproportionately affected by the flu, most notably during the 1918 and 1957 pandemics, Went said.

Prior to the identification of the H1N1 swine flu virus, Adamas had been working with the NHRC, but the pandemic outbreak "gave us the opportunity to get the Navy more actively involved in our development of TCAD for severe influenza. We are really pleased to have them on board," Went said.

He noted that the naval commander in charge of the CRADA program with Adamas, CDR Patrick Blair, has been involved for years in surveillance of flu strains, including the H5N1 in Indonesia.

"His interest arises from experience and a fairly deep scientific understanding that if you are going to treat something like influenza, in particular, severe influenza, you have to recognize that historically, to treat a virus, a rapidly mutating pathogen, it takes more than one drug," Went said.

He noted that other pathogens, like HIV, hepatitis C and tuberculosis, have all become resistant to monotherapy treatments and now are treated with combination therapies.

"Resistance develops very quickly against monotherapy in a rapidly mutating pathogen," Went said.

Adamas, he said, has found a way to "restore the activity of the resistant drugs to drug-resistant strains and thereby create a broad-spectrum treatment option" against influenza, which shifts and moves seasonally from year to year.

Went noted the A/Brisbane/59/2007 (H1N1)-like virus is resistant to Tamiflu and the A/Brisbane/10/2007 (H3N2)-like virus is resistant to amantadine, the two main antivirals used to treat flu.

The novel 2009 H1N1 swine flu virus also appears to be resistant to amantadine, he added.

Went said his firm was founded on the idea that there were a lot of problems that could be solved by combinations of existing drugs precisely calibrated to the strength and release profile to optimize the efficacy-safety ratio, which he called advantage therapeutics.

"Flu was of interest to us immediately from a health economic standpoint, and we worked our way backward from there to identify mechanistically, how many drugs it would take to treat flu and overcome both background and treatment-induced resistance," Went said.

There currently are no drugs available to treat severe influenza, mostly because trials for such a drug are "very difficult and time-consuming," Went said.

With more than 200,000 people in the U.S. hospitalized annually with seasonal influenza, it would be difficult to recruit patients who are spread out across thousands of hospitals, he said.

Adamas is conducting a Phase II trial of its TCAD flu therapy, which is designed to inhibit viral replication at multiple points in the virus proliferation pathway, in the Southern Hemisphere, where the H1N1 pandemic is active, and is preparing to initiate a clinical study of the therapy in North America during this upcoming flu season, Went said.

While the emergence of the novel H1N1 flu strain is an exacerbation of a major health economic problem, it also is "a great opportunity to conduct large clinical trials in a shorter period of time than normal," he said.

"So we mobilized our investor base, got a couple of new folks interested very quickly and closed" on the Series D round a few weeks ago, he said.

The round, which is primarily being used for the flu studies, was led by new Aeris Capital AG and DAG Ventures, joined by returning investors MDV-Mohr Davidow Ventures and Northgate Capital.

In other financings news:

• AdvanDx, of Woburn, Mass., has closed another $8 million in financing from existing stockholders, SLS Venture and LD Pensions. The additional investment is part of a series C round of financing, the first part of which was closed in September 2007, and will be used to fund the expansion of AdvanDx's molecular diagnostics product offering as well as its international sales and marketing activities.

• Clavis Pharma ASA, of Oslo, Norway, has completed an offering of 650,000 shares, raising $1.2 million, in addition to the $20.1 million it raised in an offering in June. In total, the private placement and subsequent offering brought in $22.3 million to fund the further development of its pipeline of novel anticancer drug candidates.

• Kolltan Pharmaceuticals Inc., of New Haven, Conn., has raised an additional $5 million to close its Series A preferred stock financing at $40 million. Participants include Purdue Pharma LP, HBM BioCapital LP, the Pritzker/Vlock family and other substantial private life science investors.

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