Anginera™ Preclinical Studies

Summary

Theregen conducted small and large animal studies to support its Investigational New Drug (IND) application in 2005 to the U.S. Food and Drug Administration.

The results from the Company's mouse heart infarction study provided convincing evidence that allowed our researchers to initiate larger animal model studies to confirm the product's safety and effectiveness at the preclinical level. A canine safety study, designed with input from the FDA, was conducted. Once again, positive safety findings and evidence of a biologic effect provided a compelling rationale for moving into human clinical studies.

Recent work with Dr. Steven Goldman, Chief of Cardiology, SAVAHCS, Veteran's Administration Medical Center, Tucson, Arizona has shown improved heart function in a well-characterized rat model of ischemic heart failure.

SCID Mouse Infarct Model

Title:
Efficacy Study of Anginera for Use as a
Cardiac Treatment in a Mouse Model of
Myocardial Ischemia

Results:
• Anginera stimulated mature blood vessel formation (Kellar et al. Circulation, 2001)

View mouse study histology images

• Anginera prevented loss of left ventricular function after an immediate infarct. Survival, post-infarct, was substantially enhanced along with ejection fraction values (Kellar et al. Tissue Engineering, 2005)

View study heart cross sections

Canine Safety (GLP) Study

A canine safety study, designed with the advice of the U.S. FDA, was conducted in 2003-04 in preparation for Theregen's IND submission to the FDA.

Title:
Safety Study of Anginera for Use as a Cardiac Treatment in a Canine Model of Myocardial Ischemia
Note: no immunosuppression was necessary.

Results:
• Safety was demonstrated at designated time points (30 and 90 days) and dosing levels (1-3 patches)

View photos of patch placement on canine heart

• Echocardiography indicated biologic effect at both time points and dosing levels

• Histologic evaluation confirms angiogenic potential of Anginera in ischemic areas of the heart

View canine heart study histology slide

Rat Myocardial Infarction Study

Results from a recently completed rat heart failure study have provided further proof of Anginera's role in improved heart function.

Title:
Implantation of a three-dimensional fibroblast (3DFC) matrix improves left ventricular function and blood flow after acute myocardial infarction

Results:
• Anginera improved LV systolic function by increasing ejection fraction, improving regional wall motion, and shifting the passive LV diastolic pressure volume relationship toward the to the left all implying improved LV function.

• The 3FDC improved LV remodeling by decreasing LV end-systolic and end-diastolic diameters with no change in LV systolic pressure.

• The 3DFC increased myocardial blood flow to the infarcted anterior wall after MI over threefold.

Rat Heart Failure Study

Results from a recently completed rat heart failure study have provided further proof of Anginera's role in improved heart function.

Title:
Implantation of a 3 dimensional fibroblast matrix improves left ventricular function in chronic ischemic heart failure
• Presentation, S. Goldman, M.D., American Heart Assn. Basic Cardiovascular Conference, 2008

Results:
• Anginera improved myocardial blood flow in animals with heart failure.

• Anginera-treated heart failure animals demonstrated improved systolic displacement.