Washington Editor

A relatively new company on the cardiovascular drug development scene, Celladon Corp., has secured $6 million as the first tranche of what will be a rather substantial $30 million in Series B money to push its lead product toward clinical testing.

"Gene therapy has come a long way over the last decade," said Celladon CEO Krisztina Zsebo, noting the technique's new emphasis on targeted delivery "to get the safety and efficacy into the therapeutic index that you really need to make these products work."

Mydicar, the La Jolla, Calif.-based firm's gene therapy product to improve calcium handling in failing hearts, involves the combination of a biologic drug and a device for its delivery. Founded a few years ago, Celladon raised $4 million in Series A funding late last year. Before then, its operations were financed through research funding and grants from academic and government sources.

The new funding will allow the company to complete preclinical testing of Mydicar, after which another tranche of funding would come to advance it toward Phase I/II trials. The financing's third and last payment is based upon early clinical trials, and Zsebo said the full amount would sustain Celladon into 2008.

Recent FDA meetings have given her hope that clinical development will begin late next year, and current plans call for the company to at least establish its clinical proof-of-concept before potentially seeking commercialization partners. Those studies will compare Mydicar to the best available care for these patients.

"The product has demonstrated an ability to reverse the progression of heart failure," Zsebo told BioWorld Today, "which is just unheard of in terms of the current optimal medical management for heart failure through pharmacological agents and devices."

Current treatments to slow down the progression of congestive heart failure include beta-blockers, ACE inhibitors, diuretics, bi-ventricular pacing devices and for later-stage heart failure, left-ventricular assist devices.

Already, studies of Mydicar in large animal models of heart failure have generated encouraging results and support a belief that the product "would have a major impact in the progression of the disease," Zsebo said, "and if intervention is early enough, potentially even reverse some of the symptoms and some of the pathology."

It works by enhancing SERCA2a, which regulates myocardial contractility, forming the scientific roots of the company, which Zsebo said is run "in quasi-virtual mode." Its co-founders include Roger Hajjar and Kenneth Chien, both of whom work these days at Massachusetts General Hospital in Boston.

The target was developed in their labs, and Mydicar's more recent development largely has been in collaboration with several contributing parties. The SERCA2a gene construct is inserted in adeno-associated virus (AAV) vectors, which come to Celladon by way of an AAV-based manufacturing and gene product development collaboration with Seattle-based Targeted Genetics Corp. It is delivered to the heart percutaneously using a closed-loop oxygenated system called V-Focus, for which Celladon is collaborating with The Baker Heart Research Institute in Melbourne, Australia, and V-Kardia Inc., of St. Paul, Minn.

"I think it's this targeting issue that is key for the new generation of gene therapy opportunities," Zsebo said, "in terms of balancing in favor of success as opposed to failure."

While the company continues to contract its pharmacology and toxicology work, a recent internal growth highlight was the recruitment of its chief medical officer, Stephen Grant, a cardiologist who previously had served as the FDA's general medicine team leader in its Office of Cellular, Tissue and Gene Therapies. Other employees also have lengthy backgrounds at the FDA's biological and device divisions, fitting well with Celladon's focus.

Two new investment groups led the round: Kleiner Perkins Caufield & Byers, of Menlo Park, Calif.; and Domain Associates, of Princeton, N.J. As a result, both firms added directors to Celladon's board: Jesse Treu of Domain and Joseph Lacob of Kleiner Perkins, both of whom are likely to consult on future in-licensing opportunities planned for Celladon, Zsebo said.

Additional funds were brought in through Celladon's existing investors, La Jolla-based Enterprise Partners Venture Capital and New York-based Venrock Associates.