Research

BREONICS, Inc. is a biomedical research and development company applying its novel bioengineering technologies to create innovative medical products for the clinical organ transplantion and tissue replacement markets. BREONICS' Exsanguinous Metabolic Support (EMS) enables continued oxidative metabolism and function in organs while isolated from the rest of the human body providing a number of unique opportunities for medical application.

EMS for Clinical Transplantation

Transplantation is the therapy of choice for people with end-stage organ failure. For end-stage heart, liver and lung disease, transplantation is the only life-saving remedy. In the case of end-stage renal disease (ESRD), transplantation is generally preferred to dialysis because, if the graft is tolerated, it is the only therapy that allows the patient to lead a normal life. However, the use of transplantation as a life saving modality is severely limited by the shortage of organs. In the U.S. there are approximately 400,000 patients with ESRD for whom the number of cadaveric kidneys available for transplantation rarely gets beyond 12,000 in any given year. The reason for this disparity is a combination of technical and ethical factors that limit the donor selection criteria.

Present-day hypothermic organ preservation technology is dependent upon excising and chilling the organ to temperatures between 4-8°C in order to suspend metabolism and limit the effects of warm ischemia (WI), the lack of oxygen normally supplied by the blood. Without the cold to suspend metabolism and without blood flow to provide oxygen the organ rapidly loses its ability to function. Complicating the procurement process is the ethical need to attain consent for donation before recovering the organ. Consequently the patients who meet the criteria for organ donation are primarily heart-beating cadaveric donors (HBD). These are patients who have suffered trauma and are maintained on life support in an Intensive Care Unit (ICU) prior to declaring death by brain criteria. This accounts for approximately 5% of the trauma fatalities population. Unfortunately the greatest potential for procuring more organs is in the 95% of the trauma patient population where circulatory arrest has existed for greater than 30 minutes postmortem without any intervention. These are considered the uncontrolled Deceased by Cardiac Death (DCD) Patients where WI damage would preclude organ donation by current criteria.

The EMS concept is based upon BREONICS’ ability to intervene during the period of WI and reverse the injury cascade by reestablishing cellular equilibrium. EMS restores metabolic function by providing the necessary substrates and nutrients to sustain the organ at near physiologic temperature. Data from BREONICS' pre-clinical animal studies demonstrated that EMS could successfully resuscitate kidneys following as much as 2 hours of WI insult. When the resuscitated kidneys were implanted, they confirmed recovery of normal renal function.

EMS Development

By addressing the dynamic and technical barriers associated with overcoming warm ischemic injury, EMS will be the first technology that can be used to intervene after ischemic damage has occurred to resuscitate and repair damaged kidneys. This unique ability of EMS is transformational because it changes today’s limitation of recovering cadaveric kidneys from within minutes of death to within a window of several hours postmortem. EMS’ potential to redefine the existing donor criteria is what makes the technology distinct and why it should not be confused with traditional organ preservation techniques.

Preclinical Studies

The EMS perfusion solution and breadboard delivery system have been developed, tested and optimized over a 10-year period in a large animal model that included approximately 300 canine transplants. The discoveries and results have been published in numerous peer reviewed scientific journals.

These preclinical trials have demonstrated the ability of EMS to resuscitate and repair warm ischemic damage providing a rationale for our planned clinical approach to expand organ donor criteria to include patients deceased by cardiac death.

Clinical Development

BREONICS has adopted an integrated clinical development plan that merged a highly qualified multidisciplinary team that includes the resources and staff from three leading national transplantation programs. The clinical and surgical physicians, researchers, engineers and business professionals dedicated to the project have a broad spectrum of expertise in clinical transplantation, biomedical engineering, regulatory approval, organ procurement procedures and reimbursement.

Immunocloaking

Systemic administration of immunosuppressive drugs to prevent graft rejection has remained the foundation of clinical transplantation. However, chronic immunosuppression therapy poses risks for significant drug-induced side-effects and higher rates of both malignancies and opportunistic infections. The side-effects of immunosuppressive drugs can be attributed to the fact that it is currently not possible to block rejection of allografts without simultaneously suppressing other immune functions as well. Most importantly, our dependence upon systemic immunosuppression contributes to the chronic organ shortage by limiting our ability to significantly expand donor criteria using warm is chemically damaged organs from donors after cardiac death (DCD).

To address this problem we have developed an innovative technology that provides a non- systemic treatment that can be applied pre-transplantation in an organ-specific manner. The technology- NB-LVF4 consists of a bioengineered barrier membrane comprised of type IV collagen, vitrogen, fibronectin and laminin,. The components are polymerized into a tri-dimensional transparent membrane. The interaction between the vascular endothelial cells and the recognition domains within the barrier membrane is receptor specific via the laminin and fibronectin portions of the membrane. The membrane is applied to 'immunocloak" the luminal surfaces within the vascular space by covering the point of contact between vascular endothelium and the host immune system. The result is a bioengineered apical surface that is non-thrombogenic and non-immunogenic. We believe the technology functions as a barrier to cellular migration while simultaneously allowing the free diffusion of nutrients and oxygen.

Other EMS Applications

• Pre-transplant treatment of a graft to prevent rejection.
• Targeted delivery system for gene therapy.
• Targeted high-dose chemotherapy delivery to an isolated organ, or regionalized tissue.
• Adjunct to thrombolytic therapy to resuscitate ischemically damaged tissue secondary to occlusive disease such as heart attack and stroke.
• As a technology platform for tissue engineering of biohybrids such as biosynthetic blood vessels and organs.