Clinical Results | RegenoCELL Therapeutics, Inc. - Adult Stem Cell Therapy for Congestive Heart Failure

Clinical Results

The mission of RegenoCELL Therapeutics, Inc. is to bring stem cell therapy treatments to the market as quickly as possible. The Company’s therapy utilizes a process to identify and process adult stem cells found in a patient’s blood. These adult stem cells are grown into large numbers in vitro (outside the body) and then encouraged to differentiate into angiogenic precursor cells or blood vessel forming cells for the treatment of congestive heart failure. These adult stem cells can also be used for the treatment of other conditions such as peripheral artery disease. Currently congestive heart failure patients cleared for treatment have one-half liter of blood drawn which is sent to the Company’s cell processing facility in Israel. After the adult stem cells in the patient’s blood have been extracted and grown into large numbers of angiogenic precursor cells, they are sent to Bangkok, Thailand, the Dominican Republic or other locations where importation of the stem cell therapy is permitted for infusion into the patient in a minimally invasive procedure. The stem cell therapy is either delivered through a catheter similar to angioplasty or injected directly into the myocardium. All patients are private pay. RCLL’s primary asset is Regenocell Laboratories, Ltd., a wholly owned Israeli corporation, which is manufacturing the stem cell therapy product used to treat congestive heart failure and peripheral artery disease. Marketing of the stem cell therapy product either directly or through distributors is done by Regenocell, Ltd., a wholly owned Antigua and Barbuda corporation. RCLL’s plan to further build its business is to submit an IND to the Food and Drug Administration and its equivalent to the European Medicines Agency to initiate clinical trials in order to apply and obtain approval for the treatment of peripheral artery disease in the United States and Europe. There are over ten million people suffering from the lack of sufficient blood flow to the extremities in the United States and an equal number in Europe. This disease is most often experienced by diabetics in their toes and lower legs. Pilot studies have demonstrated that there is new blood vessel formation which saves the patient from what would progress to amputation.

Background
Heart failure is one of the most detrimental of diseases. Over 65 million people suffer from coronary artery disease which leads to heart attacks. Heart attacks lead to congestive heart failure. Over 5 million people in the United States suffer from congestive heart failure with 500,000 dying from it each year. The mean life expectancy of someone with end stage heart failure is 6 months.

There are therapies to treat congestive heart failure. But there comes a treatment point when the only option may be a heart transplant. Over 25,000 people are on the transplant lists but fewer than 2,500 receive one. The mean life expectancy of a heart transplant recipient is 8 years. A new therapeutic approach to treat this disease is needed.

Stem cell transplantation is an emerging therapeutic approach to treat various diseases. For congestive heart failure, the aim of transplantation is to replace damaged cells and establish new blood vessels to restore contractility and blood supply to the heart. Early efforts showed promise but also demonstrated the difficulty in achieving consistent results.

Stem cells are cells which have the ability to produce other cells identical to themselves or to differentiate into specific cell lineages. With these properties, stem cells play important roles in normal development and in the regeneration and repair of damaged tissue through the ability to differentiate into the type of cell needed for growth or repair.

The adult stem cells and other mature cells extracted from the circulating blood have been selected because of their ability to differentiate into angiogenic precursor cells, or blood vessel forming cells. They are grown in sufficient numbers to have a clinical effect on a patient. When these angiogenic precursor cells are administered to the patient, they are primed to form new blood vessels.

Umbilical cord blood stem cells are also capable of significant differentiation. While not being subject to ethical controversy as embryonic stem cells, they still possess a genome which is different than the patient’s genome. Many different choices may get a similarity in genomes but it will never be an identical match to the one person whose umbilical cord blood is being used to create the stem cells.

Adult stem cells are different. They are autologous, meaning that they are derived from the patient for use in that patient. Typical sources of adult stem cells include bone marrow or blood. Any tissue of the patient may be used. Adult stem cells are capable of differentiating into a variety of cell types without a risk of immunological rejection. Adult stem cells do not have the safety concerns associated with embryonic and umbilical cord blood stem cells.

A New Approach
The focus of RCLL is on adult stem cells derived from the patient’s blood. In circulating blood, the numbers of adult stem cells present are less than 1% of 1% of all the cells found in the blood. At its manufacturing operations in Israel, sufficient adult stem cells are segregated from a half liter of blood drawn from the patient and then rapidly grown from tens of thousands into many millions over a five day period. This occurs in a standard class 10,000 clean room with the handling of the cells under a class 100 hood.

Being able to use circulating blood as the starting source for the adult stem cells has eliminated many of the problems previously encountered. These have included side effects associated with immune system stimulants designed to increase the number of circulating stem cells to requiring larger quantities of blood than the standard half liter blood draw used by this new approach.

Once the adult stem cells have been grown in sufficient numbers to have a clinical effect on the patient, the growing conditions are managed to encourage the adult stem cells to differentiate into angiogenic precursor cells, or blood vessel forming cells. In other words when these angiogenic precursor cells are administered to the patient, they are primed to form new blood vessels.

This stem cell therapy is autologous, meaning that it is derived from the patient, grown outside of the patient into angiogenic precursor cells, and then administered to the same patient. For congestive heart failure, the most often used route of administration is intracoronary, or use of a catheter from the femoral artery in the leg to the heart to release the RCLL adult stem cell therapy. This procedure is done in a catherization laboratory on an out patient basis. Patient recovery time is similar to patients undergoing angiograms or angioplasty.

Clinical Results
The results to date have been impressive. After an animal trial in nude rats demonstrated safety and efficacy after myocardial infarction, a clinical trial was conducted with 24 patients. Statistically significant improvements between baseline and the three month and six month follow-up were achieved for:

• Improvement in the six minutes walking test
• Increase in metabolic equivalent units (METs) during the stress test
• Decrease in the perfusion defect at region of the target artery, meaning it has improved
• Decrease in the Canadian Cardiovascular Society (CCS) Grading Scale, meaning the patient
has improved

Clinical trials results summary: parameter results at baseline, 3 and 6 months follow-up, presented as mean±S/E. P value is calculated using a paired t-test. A. Six minute walking distance. B. Canadian Cardiovascular Society Grading Scale (CCS) for Angina Pectoris. C. Metabolic Equivalent Units (METs) assessed at stress test. D. Perfusion defect percentage of the target artery measured by 99mTc on Sestamibi scan (SPECT).

Subsequent to this clinical trial, compassionate use treatment of no option congestive heart failure patients began. In total over five hundred (500) patients have been treated with this stem cell therapy. The compassionate use results are very similar to the initial clinical trial reported. Many of these compassionate use patients are from the United States and are still living many years after they had been told they would not survive more than three to six months.

Cardiac Results
Heart scans from one patient reveal that this treatment not only resulted in the formation of new blood vessels but also in the repair of damaged heart tissue with healthy tissue.

Before Treatment After Treatment

Peripheral Artery Disease
The same RCLL adult stem cell treatment can be used to treat peripheral artery disease. In the United Sates, there are over 10 million people suffering from the lack of sufficient blood flow to the extremities with an equal number in Europe. This disease is most often experienced by diabetics in their toes and lower legs. The RCLL adult stem cell treatment derived from the patient’s blood will be used to treat this disease. Pilot studies have demonstrated that there is new blood vessel formation which saves the patient from what would progress to an amputation. Administration is through multiple injections in the lower part of the limb with peripheral artery disease.

Before Treatment After Treatment

The image to the right shows circulation that has been established by treatment. The top arrow is pointing to the area that the adult stem cell therapy was injected into the leg and where the new blood vessels formed. The bottom arrow shows the new blood flow to the lower leg and foot.

RCLL will take this indication through the Food and Drug Administration and European Medicines Agency regulatory process in order to obtain approval to market this treatment in the United States and Europe. The market potential for this product is enormous given the market size, the lack of effective alternatives once vascular surgery no longer provides relief, and the consequence of no alternatives which is amputation.