Cypros Pharmaceutical Corp. to begin Phase II trials of its cytoprotective drug CPC-111.

CARLSBAD, Calif.--(BUSINESS WIRE)--Dec. 12, 1994--Cypros Pharmaceutical Corp. (NASDAQ:CYPR) Monday announced that patient recruitment for its Phase II trial of CPC-111 will begin this week.

The multicenter trial will examine dose-response and duration of effect of CPC-111 in 96 patients suffering from decompensated congestive heart failure. Phase 1 trials of CPC-111 have previously been waived by the U.S. Food and Drug Administration because of pre-existing human data on its safety.

In commenting on the announcement, Anthony W. Fox, M.D., Ph.D., the company's vice president of drug development, said: "This is the first of several Phase II studies with CPC-111 to be conducted under our IND in a variety of ischemic disorders covered by our four patents on CPC-111. Soon, there will be further Phase II studies in sickle cell crisis, acute syndromes during angioplasty, and myocardial performance after cardioplegia.

"These indications, and probably others that we select from the many available options with this small-molecule drug, all have a sound pre-clinical basis for investigation in patients."

CPC-111 is a small-molecule natural substance which has already been shown in a number of published studies under physicians' INDs to be very well tolerated when administered intravenously to humans. More than 1.5 million Americans per annum suffer heart attacks or heart failures each year, resulting in more than 500,000 deaths and $50 billion in rehabilitation costs.

Normally, thrombolytic agents, angioplasty and bypass graft procedures are used to restore myocardial blood flow in these patients. These therapies, while useful in ending ischemia, do not address the issue of both ischemia- and reperfusion-induced myocardial injury since they are not cytoprotective, i.e., do not have direct effects on cell viability or survival.

Current approaches to minimize this injury include calcium channel blockers to improve the efficiency of heart muscle function, nitrates to reduce the load on the heart and beta blockers to decrease endogenous catecholamine stimulation of the heart. While beneficial, these drugs are not directly cytoprotective, but simply reduce the amount of work the heart has to perform.

CPC-111 acts to maintain high levels of adenosine triphosphate (ATP), the universal fuel of all cells, which it can do without an oxygen supply. As ischemia-induced excess levels of lactic acid block the normal process of metabolism, CPC-111 enters the anaerobic pathway after the block, and is directly metabolized, generating ATP. Cypros is the first company to file a commercial IND and initiate GCP clinical trials on CPC-111.

Fox stated: "Because of its action on fundamental cellular function, CPC-111 is the only compound that is known to act on multiple processes which contribute to the toxic ischemic cascade. For example, in addition to its ability to generate ATP, CPC-111 has been shown to increase red blood cell deformability, to decrease blood viscosity and to inhibit the oxygen burst and superoxide generation which usually occurs during post-reperfusion injury by free radicals.

"This coupled with the lack of CPC-111 side effects should make this a useful cytoprotective strategy."

Cypros is a Carlsbad-based company currently in clinical trials on two small-molecule drugs, CPC-111 and CPC-211, that facilitate a process called anaerobic glycolysis, which is the body's ability to generate metabolic energy under ischemic (low blood flow) conditions.

CONTACT: Cypros Pharmaceutical Corp., Carlsbad

David W. Nassif, 619/929-9500