ARCA Discovery Inc. brought in $15 million in its Series A round to complete a new drug application filing for bucindolol, a beta-blocker aimed at treating heart failure in specific patient subpopulations.
Waltham, Mass.-based Atlas Venture led the round. Boulder Ventures, of Boulder, Colo., which provided the company’s original seed money, also participated, along with Pequot Capital Management, of Westport, Conn.
The financing is expected to support the NDA filing for bucindolol, said CEO Michael Bristow, who founded ARCA in 2002 with the aim of developing small-molecule drug therapies against pharmacogenetic cardiovascular targets, meaning the company targets specific subsets as opposed to the entire patient population.
The genetically-targeted approach has "proven to be somewhat slow in coming to the field," he added. "But we believe that we have an ideal candidate that, hopefully, will be the first successful drug developed against a pharmacogenetic target."
ARCA licensed commercial rights to bucindolol from CPEC LLC, a joint venture between Research Triangle Park, N.C.-based Incara Pharmaceuticals Corp. (now Aeolus Pharmaceuticals Inc.) and Lexington, Mass.-based Indevus Pharmaceuticals Inc., in exchange for milestone and royalty payments. Incara, which had been developing bucindolol in heart failure, halted work in 1999 after an interim analysis of a Phase III study showed an efficacy trend in certain subgroups but missed the primary endpoint of mortality reduction across the entire patient population.
After re-examining the data, scientists at ARCA and the University of Colorado discovered a genetic marker that correlates with patients who fail to respond to bucindolol.
"There are two adrenergic receptor polymorphisms that have major functional consequences, and bucindolol interacts with both, one in a positive way and one in a negative way," Bristow told BioWorld Today. "So, by mixing and matching polymorphisms, we were able to identify the subsets with the best response, and identify a subgroup that should not be treated with the drug."
About 89 percent of heart failure patients can be treated with bucindolol, and for half of those, the response is at least as good as any other drug in that indication. For the other half, the drug elicits a hyper response, with an efficacy far above existing treatments. "And that’s the real angle here, to heighten the response by targeting certain genetic subsets." Bristow said.
Baseline genetic testing prior to treatment will identify the patients likely to benefit from bucindolol, and ARCA is developing a genetic test in conjunction with the drug.
At this time, the company has no plans to conduct any additional trials with bucindolol, relying primarily on further analysis of data from earlier studies, including subset data reported in 2003.
"We’ve been invited by the FDA to go ahead and submit an NDA," he said, adding that the first part, expected to be submitted this year, will include the clinical section, allowing ARCA to "get a read on that, in terms of approvability."
Non-clinical information would be sent to the agency next. If all goes as planned, bucindolol could hit the market in two years.
ARCA’s business model is expected to be similar to that of Myogen Inc., the Denver-based company previously founded by Bristow to develop drugs for cardiovascular disorders. Bristow remains a scientific advisor to Myogen, and that firm holds an equity interest in ARCA.
Myogen’s work has involved two initiatives: to in-license late-stage products for development, while also working to develop new compounds from scratch.
"We’re doing the same thing here," Bristow said of ARCA. Beyond bucindolol, "we are attempting to license another pharmacogenetic compound, and we’re continuing to identify additional programs" in collaboration with Bristow’s lab at the University of Colorado.
ARCA has eight employees.
With this financing, Jean Francois Formela, a senior partner with Atlas, will join the company’s board, which also includes: Kyle Lefkoff, of Boulder Ventures; John Zabriskie, former CEO of Upjohn/Pharmacia and NEN Life Sciences; Frank Bullock, former senior vice president of research at Schering-Plough; and Bristow.