Celladon, a company founded on a unique UC San Diego enzyme replacement technology, has the distinction of receiving the first “breakthrough therapy” designation from the Food and Drug Administration for a gene therapy for heart disease. The treatment has the potential to extend millions of lives and reduce the strain and expense of multiple hospital stays for heart patients.
Clinical trials testing the company’s MYDICAR treatment, which improves the heart’s ability to pump blood, demonstrated an 88-percent reduction in hospitalizations for acute heart failure and improvement in mortality rates. “We are using a gene therapy technology to improve the enzymes in the heart that make its muscles contract,” said Krisztina Zsebo, Ph.D., President and CEO. “There are no other therapies approved that do anything like that. We’re at the forefront of technology in this area.”
The idea of introducing the SERCA2a gene directly into heart muscle to stimulate calcium cycling, which is often weak or damaged in heart patients, came from UC San Diego endocrinologist Wolfgang Dillman, M.D., Helen M. Ranney Professor and Chair of the Department of Medicine. That innovation was in-licensed by Kenneth Chien, M.D., Ph.D., who was then Director of the UCSD Institute for Molecular Medicine, into Celladon. Celladon was later launched with co-founder Roger Hajjar, M.D., of the Mt. Sinai School of Medicine.
For help in setting up the company, Chien approached Enterprise Partners Venture Capital, a San Diego venture firm established in 1985 to match large institutional investors with predominately Southern California start-ups. Zsebo, a UC Berkeley-trained biochemist with a stellar track record in biomedical and pharmaceutical start-ups, was a venture partner at Enterprise Partners when Chien’s proposal came in. She quickly grasped the value of using gene therapy to target pathways for heart failure, and after helping put together Series A financing along with Venrock for the new firm, she left Enterprise Partners to join Celladon as its founding chief executive. The company went public in January 2014.
“Celladon was the first company to take a gene therapy approach to treating heart failure,” said Zsebo. “It’s as innovative a technology as I’ve ever worked on.”
MYDICAR works by correcting deficiencies in the enzyme SERCA2a, which controls the flow of calcium ions in and out of cardiac cells. In failing heart cells, the genetic code for SERCA2a is not efficiently translated into the enzyme. Celladon devised a way to attach the SERCA2a gene to a benevolent vector for delivery to the interior of the heart. Repairing this molecular defect in preclinical studies reversed the disease and restored cardiac function, clearing the way for clinical trials.
Celladon’s April 2014 announcement of the FDA designation garnered worldwide headlines, and the agency’s decision cleared the way for expedited development and review of the MYDICAR therapy. In August 2014, the company began a clinical trial to assess MYDICAR’s potential to treat advanced heart failure patients who must rely on a left ventricular assist device. “The initiation of this trial highlights the potential for MYDICAR to positively impact a wide range of cardiovascular conditions,” said Zsebo. That same month, Celladon secured s $25-million credit facility from Hercules Technology Growth Capital, a leading biotech finance company as well as a $43-million public offering.
Looking back on Celladon’s first decade, Zsebo credits the company’s success to its ability to chart its own course. “The biggest challenge can be confronting the dogma in science and medicine that certain things have to be done in certain ways,” she said. “Much of that turns out not to be true. You have to do your own groundwork and find your own path.”
11988 El Camino Real Suite 650, San Diego, CA 92130
Tel: (858) 366-4288
Krisztina Zsebo, Ph.D. – President and CEO
Kenneth Chien, M.D., Ph.D. – Co-Founder
Roger Haijar, M.D. – Co-Founder
Wolfgang H. Dillmann, M.D.
Helen M. Ranney Distinguished Professor and Chair of the Department of Medicine,
Division of Endocrinology and Metabolism