Lead Cardiology Candidate — Zemiva™ for Detecting Cardiac Ischemia

Zemiva is our lead molecular imaging pharmaceutical product candidate under development for the diagnosis of cardiac ischemia, or insufficient blood flow to the heart. Zemiva is based on I-123-BMIPP, a known chemical compound which has been commercially available in Japan under the name Cardiodine and used in the non-acute setting for over 10 years. Zemiva is a radiolabeled fatty acid analog, which is a fat-like molecule that allows doctors to visualize the heart’s use of fats as an energy source. Visualizing the changes in the use of fats by the heart can provide doctors with important information about the state of health of heart tissue, including the diagnosis of cardiac ischemia.

Clinical Need
We believe that Zemiva potentially enables improved diagnosis and management of heart disease in a more timely and cost-effective manner and thus offers significant potential medical and economic advantages over the current standard of care in both the emergency department and non-acute settings.

• Emergency Department. Currently available imaging agents are considered effective only when used during ongoing symptoms or within two hours after cessation of symptoms. After this period, a time consuming and expensive series of diagnostic tests is required, including a stress test after the patient has been stabilized. Clinical trial results to date suggest that Zemiva enables the detection of cardiac ischemia without a stress test up to 30 hours following an ischemic episode. If these results are confirmed in large-scale clinical trials, we believe that Zemiva will significantly expand the “imaging window” resulting in more timely, convenient and cost-effective diagnosis of cardiac ischemia compared to the current standard of care.


• Non-Acute Setting. While myocardial perfusion stress tests are generally effective in terms of diagnosis, the manner in which they are conducted is inconvenient, time consuming and expensive because of the inherent limitations of current imaging agents. With currently available imaging agents such as Cardiolite and Myoview, stress tests typically require three to four hours, and may require up to 24 hours in certain cases. Based on research to date, we anticipate that a stress test using Zemiva can be completed in approximately one hour. If confirmed by further research as required by the FDA, we believe that the reduced testing time offered by Zemiva will offer increased patient throughput and convenience at a lower overall cost to the healthcare system.

Clinical Profile and Development
We have completed two multi-center Phase 2 clinical trials for Zemiva, which were designed to assess safety and efficacy. We currently have a Phase 2 clinical trial underway to develop a database of normal Zemiva images of the heart using SPECT camera imaging. This Normals trial is designed to include approximately 120 patients. We intend to commence a pivotal Phase 2 clinical trial for Zemiva in the first half of 2007, comprised of approximately 600 to 700 patients. The pivotal Phase 2 trial, if successful, will be followed by a similar sized confirmatory Phase 3 registration trial. A Phase 3 clinical trial is a stage of drug development for an experimental drug in which the safety and efficacy is ascertained in a larger number of patients than the Phase 2 clinical trials. We believe that these two trials will form the basis for our submission of a new drug application, or NDA.

If approved for marketing by the FDA, we believe that Zemiva has the potential to enable improved diagnosis and management of heart disease in a more timely and cost-effective manner to provide significant advantages over the current standard of care in both the emergency department and nonacute settings. The current standard of care to detect acute coronary syndrome, or ACS, an umbrella term that refers to both cardiac ischemia and myocardial infarction (heart attack), results in an estimated $6 billion per year in inpatient expenses that we believe could be avoided with improved disease detection. In 2002, over nine million nuclear stress tests were performed in the United States to evaluate cardiac ischemia. We believe there is a substantial unmet need for an improved imaging pharmaceutical that will shorten the time required to perform stress tests, which typically amounts to three to four hours and up to 24 hours in certain cases. By reducing this period, we believe that patient convenience and throughput will be increased and overall costs will be reduced.

Future Indications
We believe that the data from successful completion of these anticipated clinical trials, along with the data from our previous clinical trials as well as that derived from the use of I-123-BMIPP in Japan, will provide a basis for us to file for regulatory approval in the United States.