Cell death can occur through two main mechanisms, apoptosis and necrosis. Apoptosis is a tightly regulated process in the body and many of the intracellular proteins and enzymes involved are well characterized. Necrosis has been viewed in the past as an accidental pathological mode of cell death. Recently, evidence has indicated that some forms of necrotic cell death could be related to intrinsic cellular mechanisms.
Necrosis is the outcome of severe and acute injury. It is involved in many pathological conditions such as, heart attack, brain injuries and stroke, neurodegenerative diseases such as Alzheimer’s, dementia, Lou Gherig’s disease (ALS), septic shock, liver cirrhosis, chronic hepatitis, pancreatitis, muscle necrosis, diabetes mellitus, acute or critical limb ischemia, gangrene, chronic pressure ulcers and many others.
Necrosis occurs following ischemia (shortage of oxygen supply to the tissue due to restriction in blood supply). The only treatment available at present for necrosis is providing oxygen by a high pressure facility. Thus, there is a crucial need to develop drugs for prevention and treatment of this pathology.
Limb ischemia is a chronic condition of severe obstruction of the peripheral circulation that results in severe pain in the extremities. Due to the constriction of blood vessels, especially capillaries, red blood cells are unable to flow through them and this disruption in the microcirculation leads to the deprivation of oxygen, or ischemia. Complications include gangrenous sores and wounds that won’t heal, typically in the legs and feet. If left untreated, these lesions can result in amputation of the affected limb. Lower limb ischemia is a life-threatening complication for patients with poorly-controlled diabetes and affects 10% of the diabetic population. Brem Harold, Tomic-Canic Marjana (2007). Cellular and Molecular basis of wound healing in diabetes. JCI 117 (5): 1219–1222. doi: 10.1172/JCI32169. PMC 1857239. PMID 17476353. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1857239
For decades, oxygen carriers have been developed for perfusion and oxygenation of ischemic tissue None have yet succeeded. These products were either blood-derived elements, synthetic perfluorocarbons or red blood cell modifiers. Several of the Hemoglobin-Based Oxygen Carriers (HBOC), contained nonfunctional methemoglobin impurities. These products failed to secure FDA approval based upon either poor outcomes in clinical trials or poorly formulated product.
Our approach to treatment of ischemic tissue and prevention of necrosis is fundamentally different. Boston Therapeutics’ injectable drug, IPOXYN™ is a New Chemical Entity (NCE) and not a biologic blood substitute. IPOXYN™ is a modified Heme chemical structure. A significant improvement over HBOCs, IPOXYN™ prevents methemoglobin formation associated with the adverse effects of vasoconstriction and myocardial infarction.
Furthermore, because of IPOXYN™’s extremely small molecular size, roughly 1/5,000th the size of a red blood cell, IPOXYN™ is able to perfuse constricted, ischemic capillaries which are inaccessible to red blood cells. This small molecular size has particular significance in treating vascular complications of diabetes since red blood cells may already be enlarged and lower limb vasculature may be compromised.
We also intend to file a registration for IPOXYN™ for veterinary applications under the name OXYFEX™. We are unaware of any drug currently on the market for animals that can deliver oxygen, and there is only limited “blood banking” for animals despite a constant need. OXYFEX™ can serve as the only available oxygen delivery mechanism for animals suffering ischemia or traumatic and surgical blood loss events.
We expect to commence marketing OXYFEX™ for veterinary applications, which we view as a potentially lucrative market in 2014 in various locations around the world. We estimate that there are at least 15,000 small animal veterinary practices in the U. S., another 4,000 mixed animal practices treating small and large animals in the U.S. and approximately 22,000 small animal practices in Europe. We believe that the average veterinary practice treats only a small percentage of canine anemia cases with red blood cell transfusion. The remaining animals receive either cage rest or treatment such as fluid administration, iron supplements, nutritional supplements or inspired oxygen. The FDA Center for Veterinary Medicine approved a bio-similar product to OXYFEX™ named Oxyglobin in 1998 and the European Commission approved Oxyglobin in 1999, in both cases for the treatment of canine anemia, regardless of the cause of the anemia. Oxyglobin is no longer in use. Based upon the prior, limited efforts of the now bankrupt third party that developed Oxyglobin, we believe that the potential veterinary market for OXYFEX™ in the U.S. alone could exceed $250 million in sales annually within a few years after introduction.