Symphony Medical's Product Candidate for Cardiac Repair

Despite continuous improvements in prevention, diagnosis, and treatment of cardiovascular diseases, the prevalence of congestive heart failure (CHF) continues to increase worldwide. Ventricular remodeling is a central component in the progression of CHF. This term refers to the pathophysiologic adaptations of the left ventricle in response to a change in loading conditions or to a myocardial injury. The pathologic remodeling leads to slippage of myocytes, wall thinning, increased wall stress and ventricular dilatation, and finally wall disruption and rupture.

The growing insight into the mechanisms involved in ventricular remodeling opens new therapeutic perspectives to halt the pathologic remodeling process and to reconstruct the ventricular walls to normalize heart function. Thus far, pharmacologic approaches have only provided marginal evidence of effectiveness. In constrast, surgical reconstruction seeking to resect non-functioning portions of the ventricular cavity carries significant risks due to its invasive nature. Most recently, numerous investigations have been carried out injecting stem cells from various sources into the myocardium with the hope that they will repopulate the area with healthy muscle tissue. This approach is still in its infancy.

In collaboration with Dr. Randall J. Lee, Associate Professor of the Division of Cardiology, University of California San Francisco, and Dr. Hani Sabbah, Director of Cardiovascular Research at the Henry Ford Hospital System in Detroit and Professor of Medicine at Case Western Reserve and Wayne State Universities, Symphony Medical, Inc. has developed an alternative approach to cardiac repair through the use of biopolymers.

Symphony Medical's approach to cardiac repair consists of injecting pre-determined quantities of a proprietary biopolymer into strategic locations of the left ventricular wall in an effort to restore the original shape of the left ventricular chamber. Acting like architectural rebar or scaffolding, the biopolymers thicken the ventricular wall, reduce the chamber's volume, and reduce wall stress. The expected effects of this intervention are:

• Repair of the left ventricular geometry preserves left ventricular heart function and halts the deleterious chronic remodeling in chronic heart failure (HF) patients.
• Repair can successfully be achieved even in the presence of large infarcts. Based on preclinical observations, re-shaping and reversal of remodeling is possible.
• Based on ongoing preclinical studies, the positive effect of cardiac repair appears to be long-lasting.

At present, Symphony Medical is completing preclinical studies to determine the optimized delivery and the long-term preclinical safety and efficacy of the therapy.

Symphony anticipates that the cardiac repair therapy will be delivered through open chest surgery or through less or minimally invasive cardiac surgery. To illustrate, one of the scenarios consists of using robotically assisted minimally invasive surgery with modified tools that are presently available to cardiac surgeons. In this case, a 3D model of a patient’s heart is generated prior to the procedure to plan and program the location and number of injections to the left ventricular myocardium. When the procedure begins, a robotically-assisted device is deployed through one or more small openings in the patient’s thorax. The device then injects the biopolymer into the predetermined areas.

Considering current project plans, Symphony anticipates to initiate a Phase I safety study in humans in 2008.