Cardiokine was founded in Philadelphia in early 2004 by a team of talented executives: Dr. Arthur M. Feldman, a leading expert in heart failure and Chairman of Medicine at Jefferson Medical College; James Mervis, a co-founder of Barrier Therapeutics and Michael Juliano, a co-founder of Myogen.

In April 2004, the company announced a $37 million Series A financing and the in-licensing of the early phase drug lixivaptan from Wyeth. This enabled the initiation of development work. In May 2006, a $50 million Series B financing followed.

In February 2008, the companies announced the initiation of a 650-patient Phase III trial of lixivaptan in patients with congestive heart failure who suffer from hyponatremia (low blood levels of sodium). Lixivaptan may help some patients eliminate excess water while sparing sodium and other electrolytes. Data from the aforementioned study and other Phase III studies will form the basis of the clinical information needed to submit a NDA for lixivaptan.