Molecular Insight Pharmaceuticals Announces Publication of Phase 2a Zemiva(TM) (BMIPP) Trial Results in Circulation; Data Provide Proof-of-Concept for Imaging Cardiac Ischemia at Rest, 30 Hours After Cessation of Chest Pain.

CAMBRIDGE, Mass. -- Molecular Insight Pharmaceuticals, Inc. today announced the publication of a Phase 2a study demonstrating that its lead molecular imaging candidate, Zemiva(TM) (iodofiltic acid I 123, previously known as ((123)I)-BMIPP), can detect areas of decreased fatty acid metabolism at rest that parallel defects in cardiac blood flow during stress. The correlation with stress perfusion imaging was noted for up to 30 hours after the stress study was completed and blood flow had normalized. The study, published today in the on-line edition of the journal Circulation, provides clinical proof-of-concept for the use of Zemiva(TM) in diagnosing cardiac ischemia. Zemiva(TM) is an experimental fatty acid linked to a radioisotope that Molecular Insight is developing initially for use in triaging patients who enter the emergency room due to chest pain. The compound is expected to enter Phase 3 development in the first half of 2006.

"Fatty acids are normally the primary fuel source for heart cells," said Vasken Dilsizian, M.D., Professor of Medicine and Radiology, University of Maryland School of Medicine, and the study's lead author. "However, when an ischemic event such as a heart attack or unstable angina interrupts blood flow, heart cells begin to metabolize glucose rather than fatty acids. Our findings indicated that these metabolic disturbances also occur in the setting of transient, exercise-induced ischemia and persist for up to 30 hours, as evidenced by a decreased BMIPP uptake. This suggests that BMIPP may enable the detection of myocardial ischemia long after blood flow to the heart muscle is restored."

"These data support the concept that BMIPP imaging can successfully identify the metabolic imprint, or ischemic memory, of a stress-induced ischemic episode many hours after the cessation of chest pain symptoms," said John Babich, Ph.D., President and Chief Scientific Officer of Molecular Insight and a study author. "Based on this study and on other clinical data, Molecular Insight has initiated a clinical program to test BMIPP in emergency room patients, a setting where an increased window for imaging and diagnosing cardiac ischemia has the potential to dramatically improve patient care and treatment."

Study details

The Phase 2a study was an open label, within-patient comparative trial involving 32 patients with documented exercise-induced myocardial ischemia. Each patient underwent a clinically indicated treadmill stress test with thallium (Tl-201), an approved blood flow imaging agent. Within 30 hours of the treadmill-induced ischemia and while at rest, the patients were injected with BMIPP. SPECT imaging was performed 10 minutes after the injection and again at 35-60 minutes post injection. Image acquisition times were approximately 10 minutes and 20 minutes, respectively.

The BMIPP images were compared with the thallium images by a panel of three expert nuclear cardiologists. In analyzing the images, the readers were blinded to the patients' clinical data as well as to their thallium and BMIPP data. The BMIPP and thallium analyses were also conducted approximately four weeks apart.

The investigators found that the overall agreement between the BMIPP and thallium studies was 91 percent for the initial images for both the presence or absence of an abnormality, and 95 percent for the images acquired 35-60 minutes after BMIPP was injected. In addition, there were no statistically significant differences between images acquired the same day as the stress-induced ischemia or those acquired the day after. For the 21 patients studied the same day as the stress test, with both thallium and BMIPP, the agreement between the two agents was 95 percent with both sets of images. For the 11 patients studied the day after the stress test the agreement was 82 percent for the early images and 91 percent for the later images.

The data also suggested that the extent and severity of the metabolic defect detected by BMIPP was similar to that identified by thallium blood flow imaging. "Long after restoration of blood flow at rest, BMIPP images showed regional defects that reflected the extent and severity of exercise-induced thallium defects," Dr. Dilsizian noted.

In addition to Drs. Dilsizian and Babich, the study authors included Timothy M. Bateman, M.D., Cardiovascular Consultants; Steven R. Bergmann, M.D., College of Physicians and Surgeons of Columbia University; Robert Des Prez, M.D., Oklahoma Heart Institute; Martin Magram, M.D. University of Maryland Hospital and School of Medicine; Anne E. Goodbody, Ph.D., Molecular Insight Pharmaceuticals; and James E. Udelson, M.D., Tufts-New England Medical Center and Tufts University School of Medicine. Molecular Insight Pharmaceuticals funded the trial.

Background on Zemiva(TM)

Zemiva(TM) (iodofiltic acid I 123, also known as ((123)I)-BMIPP), an iodine-123 labeled fatty acid analog, is a molecular imaging pharmaceutical that enables the detection of cardiac ischemia based on changes in cardiac cell metabolism. While several published studies have demonstrated that imaging of acute chest pain patients admitted to the emergency room yields meaningful medical and economic benefits, its use is limited by the inherent constraints of current blood flow imaging agents. One constraint is that the efficacy of these agents is confined to a 2 hour window after the cessation of chest pain symptoms. Zemiva(TM), in contrast, has demonstrated in clinical studies the ability to identify ischemia through sustained alterations in cardiac cell metabolism up to 30 hours after an ischemic event. This 30-hour window may enable the widespread adoption of imaging in the acute setting to improve cardiac disease management and contain healthcare costs. In addition to acute cardiac ischemia, Molecular Insight is exploring the potential of Zemiva(TM) imaging for other indications, including coronary artery disease screening and acute heart failure.

About Molecular Insight Pharmaceuticals, Inc.

Molecular Insight Pharmaceuticals is focused on becoming a leader in the rapidly emerging field of molecular medicine through the development and commercialization of innovative pharmaceuticals that utilize highly specific targeting technologies designed to meaningfully improve patient diagnosis, treatment and management. The company is leveraging synergies in functional molecular imaging and targeted radiotherapeutics to create a new model for integrated healthcare. Molecular Insight's lead product candidate, Zemiva(TM) (iodofiltic acid I(123)), has completed Phase 2b clinical development for use in triaging emergency room patients with suspected acute coronary syndrome, a situation that results in over six million emergency room visits annually in the United States. The company's first radiotherapeutic candidate, Ultratrace(TM) MIBG (MIP-120T), for the evaluation and treatment of neuroendocrine tumors, is in late preclinical development. Molecular Insight's pipeline leverages proprietary technologies for targeting, visualizing, treating, and monitoring disease in cardiology, oncology and neurology. Molecular Insight Pharmaceuticals is based in Cambridge, Massachusetts; its Web site address is: www.molecularinsight.com.