WHAT IS THE TRANSMEDICS ORGAN CARE SYSTEM?

TransMedics has developed the world's first commercial, portable, warm blood perfusion system that allows a new type of organ transplant, called a living organ transplant. This new technology, called an Organ Care System, is designed to maintain organs in a warm, functioning state outside of the body to optimize their health and allow continuous clinical evaluation. Hearts beat, lungs breathe, kidneys produce urine, livers produce bile. Through the use of proprietary technology, the Organ Care System is designed to:

Increase the amount of time that an organ can be maintained outside the body in a condition suitable for transplantation by reducing time dependent ischemic injury Provide surgeons the opportunity to assess the function of the organ outside the body Enable resuscitation of the organ and potentially improve function after removal from donor

TransMedics has developed the Organ Care System based on the company's warm blood perfusion technology. The product contains novel technologies that simulate the conditions of the human body and allow the organ to function as it normally does. The system integrates a compact wireless monitor, an organ specific perfusion module, and proprietary solutions for organ maintenance. Donor blood is used, and the system provides for blood oxygenation and flow from an internal gas supply and pulsatile pumping system. TransMedics' proprietary solution is infused to replenish depleted nutrients and other necessary substrates in the blood. The system warms the organ as necessary, maintains humidity, and protects the organ from contamination. The system enables full functional, biochemical and metabolic assessment of the organ. In addition, the system may enable the utilization of organs that are currently not used due to the limitation of the existing preservation method, by allowing the transplant surgeon the time to potentially resuscitate the organ ex vivo to build up its energy stores, optimize its function and perform full viability assessment prior to transplantation. We believe that the OCS potentially offers substantial benefits to patients, physicians and third party payors, including:

Improved patient outcomes; Increased utilization of available organs; Expanded supply of organs; and Reduced total cost of care.

ORGAN CARE SYSTEM KEY SYSTEM FUNCTIONS

Physiological Monitoring Blood Oxygenation Warming Pulsatile Flow

ENABLING THE FUNCTIONAL ASSESSMENT OF ORGANS FOR THE FIRST TIME OUTSIDE OF THE BODY HOW DOES THE TRANSMEDICS ORGAN CARE SYSTEM WORK?
The Organ Care System is comprised of two principal components, a portable platform and an organ specific perfusion set, operating together as an integrated technology.

The portable console houses all elements of the system, including oxygen supply and a pump that is used to maintain pulsatile flow of warm, nutrient-rich blood to the organ. Operator exchangeable batteries provide full system power during transport. A wireless monitor controls and displays the system functions. The monitor also provides important information to allow assessment of the organ by the physician. In the case of the heart, parameters such as aortic pressure, coronary flow, blood temperature, and heart rate are monitored.

At the core of the Organ Care System is the Perfusion Module, a transparent, sterile chamber designed to protect the organ and maintain the appropriate, warm temperature and humidity. In the case of heart transplant surgery, the organ is placed in the module and revived to a beating state. The perfusion module is designed to enable sterile ultrasound assessment of the organ as well as blood sampling for off-line analysis.

Organs that are maintained in a functioning state outside the body continue to utilize nutrients as they would in vivo. The TransMedics Solution set is designed specifically to deliver the nutrients and substrates required to keep the transplant organ healthy during transport.

WHAT ARE THE BENEFITS OF THE TRANSMEDICS ORGAN CARE SYSTEM?

Since the advent of transplantation, the cornerstone of organ preservation has been cold ischemic storage. Although this method was intended to help reduce the extent of organ damage during transport, significant damage still occurs. The more time that passes, the more damage occurs. Living organ transplant performed with the TransMedics Organ Care System could resolve many of the limitations associated with cold ischemic storage. By pumping warm, oxygenated, nutrient-rich blood through the organ from the time of removal until it is implanted, the organ may withstand longer periods of time outside of the body and be less vulnerable to damage during transportation to the recipient. More extensive testing for function and tissue matching may also be possible with a functioning organ. We have designed the Organ Care System to offer the following potential advantages over cold ischemic preservation:

Less time dependent ischemic inujury to donor organs Ability to evaluate the functional status of donor organs outside the body Ability to resuscitate organs after removal from the donor

In addition, by increasing the number of transplantable organs and decreasing the risk of post-transplant complications, this technology could potentially provide significant cost benefits to the healthcare system, including:

Improved patient outcomes

Increased utilization of available organs Expansion of the pool of potential donors Reduced total cost of care

HOW ARE DONOR ORGANS CURRENTLY PRESERVED?

Since the advent of transplantation, the cornerstone of organ preservation has been cold ischemic storage. This has remained virtually unchanged for more than 25 years. Ischemia refers to an organ with no blood circulation. Organs without blood circulation are not able to function during storage. At normal temperatures, rapid cell death would occur in a donor organ in an ischemic state. Preserving the organ at sub-normal temperatures reduces metabolic demands and slows the rate of organ cell death. The organ is usually immersed in solutions in an effort to further reduce damage to cells. The cooled organ is transported in an ordinary beverage cooler from the donor site to the facility where the transplantation will be taking place.

WHAT ARE THE LIMITATIONS OF THIS PRESERVATION METHOD?

The three most critical limitations associated with cold ischemic storage include:

The narrow window of time allowed for safe transport. Although cold ischemic storage helps reduce the extent of organ damage during transport, damage does occur. The more time that passes, the more damage occurs; if too much time elapses, the organ will become unusable. For example, we estimate that the majority of hearts are transplanted within four hours of retrieval from the donor. This greatly restricts the geographic distance allowed between donor and recipient. In fact, healthy donor organs sometimes go unused simply because there are no matched recipients within a close enough range to receive the organ in time. The potential for damage, even within "safe" time limits. Even when an organ can be transplanted within the narrow time frame allotted for safe storage, the organ invariably suffers some degree of damage, which can contribute to sub-optimal outcomes. Anticipated organ damage during ischemic storage has an impact on decisions about the usability of donor organs. Many organs are not used because of the potential for further damage during cold ischemic storage. Inability to test the organ for function. Because transplant organs are preserved in a "non-functioning" state during cold ischemic storage, during which they are extremely susceptible to damage, they cannot be further evaluated to determine the functional status. Thus, there is a risk of transplanting an organ with underlying disease that could not be detected during surgical removal.

WHAT CAN BE DONE TO IMPROVE ORGAN STATUS DURING PRESERVATION?

Many approaches to improving outcomes with cold ischemic storage have been explored, including different types of preservative solutions and mechanical perfusion; but none have demonstrated consistent clinical benefits over traditional cold storage. The fact remains, during the period of ischemia during preservation, the organ is at risk of being damaged. The ability to maintain donor organs in a warm, "living" state outside the body could resolve many of limitations associated with cold ischemic storage. By pumping warm, oxygenated, nutrient-rich blood through the organ from the time of removal until it is implanted, the organ could potentially withstand longer periods of time outside of the body and be less vulnerable to damage during transportation to the recipient. More extensive testing for function and tissue matching might also be possible with a functioning organ.

TransMedics Organ Care System Michael Giuliano Biomedical Engineering University of Rhode Island TransMedics has developed the world's first commercial, portable, warm blood perfusion system that allows a new type of organ transplant, called a living organ transplant. This new technology, called an Organ Care System, is designed to maintain

organs in a warm, functioning state outside of the body to optimize their health and allow continuous clinical evaluation. Through the use of proprietary technology, the Organ Care System is designed to increase the amount of time that an organ can be maintained outside the body in a condition suitable for transplantation by reducing time dependent ischemic injury, provide surgeons the opportunity to assess the function of the organ outside the body, and enable resuscitation of the organ and potentially improve function after removal from donor. The system integrates a compact wireless monitor, an organ specific perfusion module, and proprietary solutions for organ maintenance. The OCS optimizes the organs health and allows for continuous clinical evaluation. Physicians can perform visual, functional and metabolic

assessment of the organ to reduce the risk of organ rejection and increase the number of organs accepted for transplant. Current cold ischemic preservation and transportation methods which essentially consist of transporting the organ in an ordinary beverage cooler create severe time limitations, as well as potential injury to the organ, resulting in significant underutilization of the current pool of consented, donated organs. The number of people requiring a life-saving transplant continues to rise faster than the number of available donors. Of the 96,000 people in the U.S. currently waiting for a donor organ, only a third will receive a transplant, while nearly 7,000 will die each year while waiting for an organ. This means approximately 19 transplant candidates die each day while waiting to receive a donor organ. The PROTECT trial is the PROspective multi-center European Trial to Evaluate the safety and performance of the Organ Care System for Heart Transplants. In this non-randomized, multi-center European study, 20 consented patients received donated hearts that were maintained by the OCS in a perfused and physiologic beating state for a mean time of 3.7 hours. The study met the primary endpoints, and achieved 30-day patient and graft

survival of 100 percent. Additionally, the OCS resulted in rapid time to recovery for patients as evidenced by the median length of time patients spent on a ventilator and in the ICU, which were 10.7 hours and 24.3 hours, respectively. The trial sites participating in the PROTECT I study included the Clinic for Thoracic & Cardiovascular Medicine, Bad Oeynhausen, the German Heart Institute in Berlin, Germany, Papworth Hospital in Cambridge, UK and Harefield Hospitals, NHS Trusts in Middlesex, UK. These data show the Organ Care System is safe in maintaining human hearts for transplant in near physiologic conditions, reducing ischemic injury, to improve patient outcomes," said Dr. Gero Tenderich from the Thoracic and Cardiovascular Surgery, Heart Center North Rhine-Westphalia, Bad Oeynhausen, Germany. The OCS represents a significant advancement in organ transplant surgery over current standards of care. [1]"Journal of Heart & Lung Transplantation." Journal of Heart & Lung Transplantation 25 (1997): 1510-595. [2] "Organ Care System: , Inc." TransMedics. 20 Feb. 2009 <http://www.transmedics.com/wt/page/organ _care>.