Common use of Rationale and justification Clause in Contracts

Rationale and justification. BL-1040 Myocardial Implant presents a novel, safe and non-surgical therapy that directly addresses the stability and structural integrity of myocardial tissue in this patient population. BL-1040 potentially prevents post infarction remodeling primarily via limiting left ventricle (LV) dilation, while the untreated patient LV will continue to dilate or enlarge. BL-1040, by creating a scaffold, may stabilize the AMI and limit post AMI expansion manifested as LV dilation. There are currently no other available medical and/or surgical interventions that directly address the stability and structural integrity of myocardial tissue damaged as a result of AMI. In the setting of an AMI, an inflammatory response triggers the degradation of the extracellular matrix, thus weakening of the collagen cross-link structure or structural “backbone” of the myocardium. Degradation of the extracellular matrix leads to infarct expansion manifested by myocardial wall thinning and often, aneurysmal dilation with subsequent ventricular enlargement. This process results in progressive LV remodeling and increased LV wall stress. The latter can increase myocardial oxygen consumption, a condition that the infarcted and/or failing LV can ill afford and one that can contribute to increased long-term mortality and morbidity. LV dilation is the predominant cause for morbidity and mortality in congestive heart failure [2], demonstrated that patients with LV end systolic volume smaller than 95 mL showed a 94 % survival after 5 years while LV patients with LV end systolic volume greater than 130 mL showed a 52 % survival after 5 years. Both diastolic and systolic were the main predictors for mortality. Patients with end-stage ischemic heart failure presenting dilated LV with an akinetic/dyskinetic region over 35% and with left ventricular end systolic index >60 mL/m2 are offered LV reconstruction or surgical ventricular restoration (SVR) in order to reduce LV volume and to restore normal LV shape. Overall, in a large number of studies performed using SVR, there is strong evidence that SVR is safe and effective, showing significant reduction in mortality and readmission levels together with significant improvement in ejection fraction as well as in LV end systolic/diastolic index.

Rationale and justification. BL-1040 Myocardial Implant presents a novel, safe and non-surgical therapy that directly addresses the stability and structural integrity of myocardial tissue in this patient population. BL-1040 potentially prevents post infarction remodeling primarily via limiting left ventricle (LV) dilation, while the untreated patient LV will continue to dilate or enlarge. BL-1040, by creating a scaffold, may stabilize the AMI and limit post AMI expansion manifested as LV dilation. There are currently no other available medical and/or surgical interventions that directly address the stability and structural integrity of myocardial tissue damaged as a result of AMI. In the setting of an AMI, an inflammatory response triggers the degradation of the extracellular matrix, thus weakening of the collagen cross-link structure or structural “backbone” of the myocardium. Degradation of the extracellular matrix leads to infarct expansion manifested by myocardial wall thinning and often, aneurysmal dilation with subsequent ventricular enlargement. This process results in progressive LV remodeling and increased LV wall stress. The latter can increase myocardial oxygen consumption, a condition that the infarcted and/or failing LV can ill afford and one that can contribute to increased long-term mortality and morbidity. LV dilation is the predominant cause for morbidity and mortality in congestive heart failure [2], . demonstrated that patients with LV end systolic volume smaller than 95 mL showed a 94 % survival after 5 years while LV patients with LV end systolic volume greater than 130 mL showed a 52 % survival after 5 years. Both diastolic and systolic were the main predictors for mortality. Patients with end-stage ischemic heart failure presenting dilated LV with an akinetic/dyskinetic region over 35% and with left ventricular end systolic index >60 mL/m2 are offered LV reconstruction or surgical ventricular restoration (SVR) in order to reduce LV volume and to restore normal LV shape. Overall, in a large number of studies performed using SVR, there is strong evidence that SVR is safe and effective, showing significant reduction in mortality and readmission levels together with significant improvement in ejection fraction as well as in LV end systolic/diastolic index.. Annotated Protocol incorporating Amendment 1, Amendment 2, Amendment 3, and Amendment 4 01 December 2008 Protocol BL-1040.01, Version 5.00 Safety and Feasibility study of BL-1040 Final CONFIDENTIAL 2 Study Objectives The objectives of this study are: · to evaluate the safety of the BL-1040 myocardial implant in patients after MI at high risk for LV remodeling and CHF, and · to provide feasibility data in order to initiate and conduct a pivotal clinical study evaluating the safety and efficacy of the BL-1040 implant in patients following myocardial infarction. Annotated Protocol incorporating Amendment 1, Amendment 2, Amendment 3, and Amendment 4 01 December 2008 Protocol BL-1040.01, Version 5.00 Safety and Feasibility study of BL-1040 Final CONFIDENTIAL