Oxygen Biotherapeutics' Update on U.S. Army-Funded Preclinical Studies Designed to Support the Safety Profile of Oxycyte PFC Emulsion Currently in Clinical Trials Overseas for Traumatic Brain Injury
Oxygen Biotherapeutics, Inc. (“OBI”) (NASDAQ: OXBT), a development stage biomedical company currently focused on developing its proprietary perfluorocarbon-based intravenous emulsion, Oxycyte®, as a treatment for a variety of emergent ischemic conditions, today reported that the U.S. Army-funded preclinical program that was established to address the U.S. Food and Drug Administration (FDA) questions regarding the product, is well underway with several important milestones complete or nearing completion. Perfluorocarbon emulsions as a class have been shown to cause transient thrombocytopenia in animals and humans and, because of emulsion particle clearance mechanisms, have raised questions regarding their potential impact on normal immune system function. To continue the clinical development of Oxycyte in the United States, the FDA has requested studies to explore in detail the safety profile of Oxycyte with respect to these putative effects. With this preclinical work, OBI has moved several steps closer to addressing the questions posed by the FDA regarding thrombocytopenia, platelet function, and immunocompetence.
Clinical studies of Oxycyte in TBI patients, placed on-hold by the FDA, are being conducted outside the United States. The second cohort of a global Phase IIB study will be launched by the end of the year. Data from the preclinical program may support data collected in patients and provide the company with a regulatory path forward in the United States. Regardless, however, the company is advancing its strategy to allow for licensing the product in any number of countries. If successful, Oxycyte could become an essential element of emergency care for TBI patients by providing fast and effective delivery of oxygen to the brain.
“The majority of the first year of this preclinical program was spent engaging contract research organizations, developing and finalizing study designs and protocols, procuring reviews and approvals from the FDA and Department of Defense for changes to the originally planned studies. In addition, a number of highly technical bioanalytical methods and animal models had to be developed. We are pleased to announce that most of the studies under the program are underway, and we are beginning to review data from recently completed studies,” said Michael Jebsen, President and Chief Executive Officer. “The successful validation of GLP GC/MS bioanalytical methods and the completion of the PK studies was a critical first step to evaluating and interpreting the data generated from the platelet and immune models currently underway.”
Platelet & Thrombocytopenia Studies
Severe TBI is known to cause a significant drop in platelet counts as the body responds to injury. In both animals and humans, administration of Oxycyte has been shown to produce a transient thrombocytopenia. Therefore, the risk of re-bleeding in TBI patients due to this treatment-emergent thrombocytopenia is a concern to the FDA.
OBI recently completed in vitro tests with healthy human blood combined with Oxycyte to determine if Oxycyte alters platelet activation, aggregation or adhesion. These studies will be repeated to evaluate the in vitro effects of Oxycyte on platelet function in blood collected from individuals who have suffered traumatic brain injury.
As noted above, in vitro studies have been completed examining the effects of Oxycyte on platelet function in blood collected from normal, healthy volunteers. The main findings from these in vitro assays show that in normal blood:
1. Oxycyte does not result in direct platelet activation as measured by changes in platelet surface activated glycoprotein (“GP”) IIb-IIIa, platelet surface P-selectin, monocyte-platelet aggregates, neutrophil-platelet aggregates, platelet-derived procoagulant particles, or whole blood platelet aggregation;
2. Oxycyte at high concentrations (3 to 6 times the clinically expected maximum blood levels) does result in changes to platelet response to activation indicated by a decrease in thrombin receptor activating peptide (TRAP)-stimulated platelet aggregation, a decreased TRAP-stimulated platelet surface P-selectin expression, and a decrease in TRAP-stimulated neutrophil-platelet aggregates.
3. Oxycyte does not affect nitric oxide inhibition of platelet activation; and finally,
4. Oxycyte does not result in changes in platelet response to activation as measured by shear-dependent platelet adhesion to Von Willebrand Factor, a blood glycoprotein involved in hemostasis.
Over the past year, OBI has collaborated with an immunology consultant to develop a thorough preclinical immunocompetency plan to determine if Oxycyte adversely affects bacterial opsonization and immune competence to an infectious challenge. Following FDA's approval of the study design and protocols, we have four studies underway to assess the impact of Oxycyte on the overall health of the immune system, bacterial opsonization and phagocytic activity, innate immunity, and its effect on the primary immune response cells of the liver and spleen. The models included in the studies are an influenza host resistance model, a Streptococcal host resistance model, and a Listeria host resistance model.
Two other preclinical tasks that are part of this U.S. Army-funded program will assess the effects of Oxycyte on platelet distribution, thrombosis and hemostasis in a primate model of acute systemic inflammation and assess the effects of Oxycyte on the efficacy of platelet transfusion in the treatment of thrombocytopenia in a rat model of intracranial hemorrhage (ICH). The development of the ICH model is nearing completion with the definitive study expected to begin in early 2013. Data will be collected in the primate study using imaging techniques (gamma scintigraphy and MRI). The protocol is currently being reviewed by the Animal Care and Use Review Office (ACURO). ACURO oversees and implements the Army's animal use and care policies. The first phase of this work is scheduled to begin in November.
“Overseeing this very important research program for the last year has been very rewarding as this work is going to expand significantly the body of knowledge regarding the safety of Oxycyte, as well as PFCs as a therapeutic class,” said Stephanie Anderson, Director of Preclinical Research and Development at OBI. “With a clearer understanding of the actual significance of the biological effects of Oxycyte, this product could become an important option for medical professionals caring for traumatic brain injury patients or other patients who suffer acute ischemic events that deprive their tissues of oxygen.”
Currently in its sixth quarter, the two year program is scheduled to be completed by mid-2013. It is funded by a $2.1 million U.S. Army reimbursement grant.
Oxycyte is an odorless, milky white emulsion consisting of a perfluorocarbon, disodium, water, egg yolk phospholipids and a few other ingredients in very small amounts. It is a sterile, non-pyrogenic emulsion consisting of submicron particles (medium diameter 200-250 nanometers) of perfluoro(t-butylcyclohexane), in an aqueous medium that is slightly hypertonic and mildly buffered to a neutral pH range. It must be formulated in an aqueous emulsion for intravenous administration. Research has shown that PFCs can dissolve and release large amounts of gases, including the blood gases oxygen and carbon dioxide without binding at high concentrations of inspired oxygen.
About Oxygen Biotherapeutics, Inc.
Oxygen Biotherapeutics, Inc. is developing medical products that efficiently deliver oxygen to tissues in the body. The company has developed a proprietary perfluorocarbon (PFC) therapeutic oxygen carrier called Oxycyte® that is currently in clinical and preclinical studies for intravenous delivery for indications such as traumatic brain injury, decompression sickness and stroke. The company is also developing PFC-based creams and gels for topical delivery to the skin for dermatologic conditions and potentially wound care. In addition, the Company has commercialized its Dermacyte® line of skin care cosmetics for the anti-aging market.
Caution Regarding Forward-Looking Statements
This news release contains certain forward-looking statements by the company that involve risks and uncertainties and reflect the company's judgment as of the date of this release. The forward-looking statements are subject to a number of risks and uncertainties including matters beyond the company's control that could lead to delays in new product introductions and customer acceptance of these new products, and other risks and uncertainties as described in our filings with the Securities and Exchange Commission, including in the current Form 10-Q filed on September 19, 2012, and our annual report on Form 10-K filed on July 24, 2012, as well as other filings with the SEC. The company disclaims any intent or obligation to update these forward-looking statements beyond the date of this release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
Oxygen Biotherapeutics, Inc.
Ellen Corliss, 919-855-2112
SVP, Investor Relations &