OPK Biotech LLC's Oxygenation Technology

The need for oxygen-carrying solutions was identified in the 1940's in response to soldiers dying in battle from oxygen deprivation caused by blood loss. However, the logistics and costs associated with blood transfusion (e.g., collection, refrigeration, typing, cross matching, etc.) warranted another alternative. Subsequent research efforts through the 1980's had poor results resulting from imperfect purification techniques and a lack of understanding of the physiology associated with oxygen delivery. During the 1980's and 90's, dramatic improvements in purification techniques and a new understanding of how to modify native hemoglobin allowed the Company's researchers to overcome many of the problems that plagued previous HBOC development programs.

OPK Biotech LLC has two oxygen therapeutic products, Hemopure for human use and Oxyglobin for veterinary use, which are similar except for their molecular size. Our products, which are administered intravenously, are defined as therapeutics because they are expected to provide help, or therapy, to oxygen-deprived tissues by transporting oxygen to those tissues. These products consist of hemoglobin that has been taken out of the red blood cells of cattle and then purified, chemically cross-linked for stability and formulated in a balanced salt solution similar to Ringer's lactate. The resulting hemoglobin solutions do not contain any cells.

The average stabilized hemoglobin molecule in Hemopure is less than 1/100,000,000th the size of a red blood cell. Upon infusion into a patient's bloodstream, this stabilized hemoglobin spreads throughout the plasma, the fluid part of blood. Thereby Hemopure increases the oxygen content of the plasma. The plasma containing Hemopure is in continuous contact with blood vessel walls, where oxygen transport to tissues takes place. Plasma flows everywhere that blood ordinarily flows and can also bypass partial blockages or pass through constricted vessels that are too small for the normal passage of red blood cells.

The stabilized hemoglobin molecules in Hemopure can hold the same amount of oxygen as the hemoglobin molecules in red blood cells, on a gram-for-gram basis, and release oxygen more readily than red blood cells. In addition, data from preclinical studies suggest that introducing Hemopure into the bloodstream may help red blood cells to offload more oxygen to the tissues than they otherwise would.

The following chart lists the characteristics of Hemopure insofar as its characteristics may apply to treating anemia and oxygenating tissue in conditions where ischemia could occur:

Characteristic

Hemopure is stable without refrigeration for 36 months (2 degrees to 30 degrees centigrade) and for 18 months at elevated temperature (40 degrees centigrade), and is compatible with all blood types. These properties permit the product to be stocked well in advance of anticipated use. Consequently, when blood is not available, Hemopure could be used to provide temporary oxygen-carrying support to a patient until the needed type and quantity of red blood cells arrive, until the patient can be transported to a hospital or until a patient's body replenishes its own red blood cells. Also, as described above, the product's small molecular size permits it to oxygenate through the plasma and thereby act as a potential therapeutic in ischemic conditions, where red blood cell transfusions are generally not indicated. These factors have contributed to the focus on cardiovascular ischemia and out-of-hospital trauma. Until mid 2004, most of the efforts had focused on developing Hemopure for use as an alternative to red blood cell transfusions in surgical patients.

Hemopure has certain disadvantages when compared to red blood cells. Transfused red blood cells have a longer duration of action and can persist in the body for an estimated 60 to 90 days. Hemopure has an average half-life of 19 hours and, depending on the degree of the patient's anemia, may require repeat administration. In addition, it is anticipated that Hemopure will be more expensive than transfused red blood cells when compared on a unit-to-unit basis. Furthermore, the maximum dose (10 units) of Hemopure studied in clinical trials to date may provide temporary oxygen-carrying support, or an Oxygen Bridge, but may not meet the long-term needs required to completely avoid red blood cell transfusions in patients experiencing massive blood loss.