About the Okyanos Heart Institute

The Okyanos Heart Institute was founded to provide a new and more advanced treatment option for patients with chronic coronary artery disease, cardiac stem cell therapy. We are using a European Union approved cell processing device to offer cell therapy treatment in a center of excellence in Freeport, Bahamas by a medical team led by prominent U.S. cardiologist, Dr. Howard Walpole. Okyanos Heart Institute is the first healthcare service provider to offer cardiac cell therapy based on the PRECISE trial. This technology has been used in multiple clinical trials to safely and effectively to treat approximately 4,000 people across the globe.

Dr. Howard Walpole, MD, serves as the interventional cardiologist and chief medical officer at Okyanos Heart Institute. Dr. Walpole is a U.S.-educated cardiologist. In his 25 years of practice, Dr. Walpole has done approximately 5,000 catheter-based interventions and 12,000 diagnostic catheterizations as well as myocardial biopsies.
Dr. Walpole received his bachelor of science degree from the University of Georgia, his M.D. from the Medical College of Georgia and his M.B.A. from the Goizueta School of Business, Emory University.
Previously, as the chief of cardiac sciences at Saint Thomas Hospital in Nashville, Tennessee, Dr. Walpole led the strategy and operations of Saint Thomas Cardiac Sciences division of Saint Thomas Hospital, a medical center with 3,300 employees and a service population of approximately two million across three states. This division included 37 cardiologists, five cardiac surgeons and nine cardiac anesthesiologists.

Phone: 1-855-OKYANOS (659-2667)
Web: www.okyanos.com

Questions & Answers

Q: The statement from Cytori on the PRECISE trial said the procedure was safe and "Exercise capacity as reflected by maximum oxygen consumption (MVO2) during treadmill testing a reflection of cardiac functional capacity, was sustained in the ADRC treated group but declined in the placebo group at 6 and 18 months." Is there more detail now available on the outcome? Is there any other facility that is treating patients with the Cytori method for Coronary Artery Disease (CAD), or is it still research only?
A: The PRECISE 36-month was included in the recently published peer-reviewed paper: "The difference in the change in MVO2 from baseline to 6 and 18 months was significantly better in ADRC-treated patients compared with controls. The ADRC-treated patients showed significant improvements in total left ventricular mass by magnetic resonance imaging and wall motion score index. Single-photon emission computed tomography results suggested a reduction in inducible ischemia in ADRC-treated patients up to 18 months.
We understand that several facilities internationally are planning to treat patients outside of trials but this would be for the providers or Cytori to discuss.

Q: What is the life span of injected stem cells?
A: The cells stay in the myocardium for several days. Their primary mechanism is signaling the resident cells. ADRCs have been shown to grow new myocardial cells but it is not the primary mechanism. The primary mechanisms are angiogenesis (growth of new blood vessels), ant-inflammation, preventing further cell death and modulating the immune system.

Q:Is there a difference between mesenchymal and placenta cell life?
A: The placental cells that have been used in clinical trials are MSCs but we do not know whether they would have a longer cell life than ADRCs.

Q: Is activation of these cells necessary and if so, how is this best accomplished?
A: The cells respond to an inflammatory signal which is resident in the damaged tissue into which they are introduced so there should be not be a requirement to activate the cells.

Q: Should "blood vessel-forming cells" be used with injections?
A: Angiogenesis is a primary mechanism of ADRCs so it is not necessary to supplement or complement them with other biologics.

Q: What kind of counts are needed for MSC's and placenta stem cells to make a treatment viable?
A: In reviewing the literature more is not necessarily better. The trials we have studied including PRECISE seem to show the best efficacy with around 40 million cells. Trials which used 100 million cells reported less efficacy than groups that were within the 40 million range cited above. There is no reason to believe placental cell counts should be higher or lower but research would be required to establish that.

Q: What evidence has given you the confidence to move ahead with treating CAD patients with adipose derived stem cells?
A: PRECISE plus the vast number of patients who have been treated for ischemic conditions with ADRCs or mesenchymal cells either in cardiac trials or others. There have been over 60 clinical trials. The meta-analysis published in Circulation, June 2012 had very compelling evidence that cardiac cell therapy is both safe and efficacious.

Q: Will Okyanos add cell culturing facilities if it turns out expanded stem cells are more beneficial for CAD?
A: We will if it is proven that cultured cells are more potent but the literature to date indicates that with each doubling the cells lose potency. ADRCs do not require culturing as they have up to 2500x more stem cells than bone marrow and per Buying New Soul by Dr. Perin and Dr. Willerson they maintain potency later in life.

Q: Your website said patients who use supplemental oxygen do not qualify for treatment. Why is that?
A: The point is that patients who are too sick to travel may be too high risk for the procedure. In the future, will you be able to accommodate patients who have cardiac disease and COPD for instance? We hope to be able to assuming they are not high risk for the procedure and we have regulatory approval. Many patients have a combination of the two and many do use supplemental oxygen. We understand that and will focus on ensuring they can be treated safely and efficaciously. That is the most important standard.

Q: If Okyanos is doing same day stem cell therapy, why did you decide to go offshore when this procedure is not restricted in the U.S.?

A: Stem cell clinics operating in the U.S. have interpreted FDA regulations and discussions differently than Okyanos has. We believe being in a regulated jurisdiction such as the Bahamas but being convenient for U.S. citizens is more prudent for patients.

Q: What conditions in the U.S. would allow you to operate here?
A: FDA approval.

Q: Is it strictly business related that you have chosen to treat patients in the Bahamas?
A: As we are using internationally-approved technology in a regulated jurisdiction we feel that is in the best interest of patients.

Q: I have been researching and found a very interesting mode of treatment that permits and enhances homing of stem cells to a target area. An extensive body of research has demonstrated that increasing transient SDF-1 expression post-tissue injury promotes tissue repair after acute organ injury by preventing cell death and recruiting stem cells to the damaged region. Recent articles from several laboratories have demonstrated SDF-1 therapeutic potential for treatment of stroke, wound management, diabetes, peripheral artery disease, critical limb ischemia, ischemic kidney disease, and spinal cord repair. The tissue-preserving and reparative effects of SDF-1 led Juventas Therapeutics(a private clinical-stage company developing novel therapies for ischemic cardiovascular disease), to develop potential therapies utilizing SDF-1 to treat ischemic cardiovascular disease, peripheral artery disease and hard-to-heal wounds. Juventas has demonstrated that therapeutic interventions which prolong or re-establish the ability of SDF-1 to stimulate the stem cell homing process and activate tissue protective mechanisms may be beneficial for patients that have suffered tissue damage, such as after a heart attack. Your thoughts?
A: SDF-1 is not the active component but stimulates stem cells to be angiogenic (grow new blood vessels). SDF-1 is found in the ADRC population so that benefit, to a greater or lesser degree, is inherent in the Okyanos treatment.

Q: The Okyanos website indicates you won't be treating patients until summer 2014. This is summer, 2014. Are you now treating patients. If not, when do you expect to treat your first patients?
A:
We will be treating patients in Sept. How are doctors responding in the U.S. to their patients who want to go to Okyanos? We have generally had a positive response from U.S. Cardiologists and have received referrals from some as well. Not all cardiologists or doctors are at the same place on the learning curve as others so responses do vary.

Q: What about research? Will you be publishing any outcome studies or case reports?
A: We will keep a robust registry and publish the results. We are contracting with a third-party clinical research organization (CRO) to ensure that the data is objectively analyzed.

Q: Would patients who have suffered a heart attack recover more fully or faster if treatment was done soon after?
A: The optimal time is sooner rather than later post-heart attack but the window has not been clearly defined as cell type as well as timing and delivery method play a factor.

Q: Does the age of a patient matter as to how many stem cells can be harvested as well as the quality of those cells?
A: In bone marrow the cell counts go down with age and post 62 years old, with other diseases, smoking history etc seem to lose potentcy. ADRCs appear to maintain cell counts and viability as fat could not stay alive without blood flow and the cells live within niches of the blood vessel lining in the adipose tissue.

Q: Also, what type of delivery do you believe is the most effective? Direct injection, IV or what?
A: We believe direct injection makes the most sense and has shown the best results in clinical trials.

Q: Do you also advocate and counsel lifestyle changes post treatment such as diet, supplements, exercise program?
A: Yes, absolutely. We plan to have a robust after-care program but this does require the cooperation of the patient.