PharmaCyte Biotech’s recently appointed CEO Kenneth L. Waggoner, is solely focused on hitting major milestones and marks 2015 as a banner year for PharmaCyte Biotech, Inc. (OTCQB:PMCB), a Silver Spring, MD-based clinical stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box®.
The Company recently announced that the world class team of scientists, physicians and academics that make up its international Diabetes Consortium is now complete with the addition of the final two members, Dr. Thomas Stratmann of the University of Barcelona in Spain and Dr. Axel Kornerup Hansen of the University of Copenhagen in Denmark.
The Company recently reported that a member of PharmaCyte Biotech’s international Diabetes Consortium, Prof. Ann Simpson, and her colleagues at the University of Technology Sydney and the University of Sydney in Australia published major research describing the “reversal of diabetes in diabetic mice following transplantation of an insulin-secreting human liver cell line: Melligen cells” in the journal Molecular Therapy – Methods & Clinical Development.
In March, the Company announced that the genetically modified cells that are required for its three planned clinical trials in pancreatic cancer patients have been fully tested and are in the process of being propagated to produce all of the cells necessary for the clinical trials. We recently sat down with Mr. Waggoner to discuss how he is repositioning PharmaCyte Biotech into one of biotech’s key companies.
Q. What makes your platform technology, Cell-in-the-Box, a value proposition?
Cell-in-a-Box® is a remarkably versatile platform technology that can be used to develop treatments for all kinds of serious diseases, such as cancer and insulin-dependent diabetes. Cell-in-a-Box® is a type of technology where genetically modified living cells are encapsulated in small, pin-head-sized, spherical protective cocoons. These cocoons, or capsules, have pores in their outer shell that allow nutrients to enter the capsules to nourish the cells inside and to allow waste products from those cells to leave the capsules. The capsules are protective of the cells inside them because their pores are too small to allow the encapsulated cells to escape, where they would be destroyed by the patient’s immune system, and the pores are too small to allow the cells from the patient’s immune system to enter the capsules and destroy the cells inside.
Cell encapsulation has been around for many years. A number of materials have been used, the most common being alginate which is derived from seaweed. PharmaCyte Biotech is using cellulose sulphate for its cell encapsulation. Cellulose sulphate offers a number of advantages over other encapsulation materials because it is derived from a naturally occurring plant derived-polymer that is relatively easy to obtain at reproducible quality and is free from impurities. In addition, it has excellent biocompatibility. Cells in the capsules survive well and even grow within the capsules. Further, once the capsules are implanted into a body, they are not rejected by the body’s immune system and there is no immune or inflammatory response against the capsule material or the cells within the capsules. Cellulose sulphate encapsulated cells have already been tested in two human clinical trials and have been shown to be safe. In these trials, the cells in the capsules allowed lower, non-toxic doses of a chemotherapy drug to have equal or greater anti-tumor effects than standard, toxic doses of the same drug.
The Cell-in-a-Box® capsules are extremely robust and do not break down even after two years in a human body. The strength of our capsules allows them to be implanted using a needle or a catheter without damage to the patient. In addition, capsules containing living cells can be frozen and stored for more than 5 years, and when thawed, the frozen cells come back to life with more than 95% viability. These properties are important for long-term storage and for shipment over long distances as would be required for the commercialization of our encapsulated products. To our knowledge, no other form of live-cell encapsulation produces capsules that possess these unique properties. Without the ability to freeze the encapsulated cells, the capsules would need to be used almost immediately after production. This unique advantage alone sets PharmaCyte Biotech apart from any other cell encapsulation company in the world.
Q: Can you describe some of the major milestones you’ve been able to accomplish since coming on board?
KENNETH: First and foremost, PharmaCyte Biotech has been completely transformed from a nutraceutical company into a pure biotechnology company. We are no longer in the nutraceutical business. Some of the other major milestones include the following:
The financial position of PharmaCyte Biotech has become the strongest in the Company’s history. We are virtually debt-free and have access to all of the necessary capital required to meet both our short-term and long-term financial commitments.
We are well underway in completing the necessary steps to commence three clinical trials using our Cell-in-a-Box® technology. The first will be a Phase 2b clinical trial of our pancreatic cancer treatment. Our pancreatic cancer treatment will be compared “head-to-head” with the current best available treatment for the disease. This treatment is the combination of gemcitabine with Celgene’s drug Abraxane®. We expect to begin this clinical trial in the third quarter of 2015.
We are also underway in completing preparations for two other clinical trials related to the “quality of life” of patients with advanced pancreatic cancer and other abdominal tumors. These clinical trials deal with treatments for the: (i) intractable and virtually untreatable pain about 20-25% of patients with advanced pancreatic cancer suffer from; and (ii) accumulation of fluid (knows as ascites) in the abdomen that is extremely uncomfortable for patients with pancreatic cancer and other abdominal tumors. Because ascites fluid can contain cancer cells and these cells can seed and form new tumors, oncologists must frequently remove ascites fluid from patients. This is costly and painful. There is no treatment on the market to slow down the accumulation of ascites fluid. We believe our treatment will. We expect to start both clinical trials late in the third quarter of 2015.
We commenced and concluded our first preclinical study (4 groups of tumor bearing mice) that was conducted by Translational Drug Development (TD2) in the U.S. to determine the ability of our treatment of Cell-in-a-Box® plus ifosfamide to delay the accumulation of malignant ascites fluid. An expanded study (12 groups of mice) is currently being conducted by TD2. This study is designed to further define the parameters that will be needed for our future clinical trial in this area.
Our treatment for advanced, inoperable pancreatic cancer was granted the Orphan Drug designation by the U.S. Food and Drug Administration (FDA) in December 2014. Granting of this designation means that PharmaCyte Biotech will receive 7 years of marketing exclusivity in the U.S. for its pancreatic cancer treatment and reduced taxes and assistance from the FDA in the further development of our treatment.
We obtained the worldwide rights to use a genetically modified cell that produces insulin on demand in direct proportion to the amount of glucose (sugar) in their surroundings. These rights were obtained from the University of Technology Sydney (UTS) where Prof. Ann Simpson, along with her colleagues at UTS, have spent years developing this unique cell line called “Melligen.”
We have completed a study at the University of Veterinary Medicine Vienna (UVM) to determine if the Melligen cells have the propensity to form tumors in the body. The Melligen cells were found to be as “safe” as the genetically modified cells used in the previous clinical trials in pancreatic cancer in terms of potential tumor formation in the body over time. We have also begun studies to establish the parameters by which the Melligen cells can produce and store insulin in response to glucose levels in their surroundings.
Through a Collaborative Research Agreement with the Vorarlberg Institute for Vascular Investigation and Treatment in Austria, Dr. Eva-Maria Brandtner has been appointed our Director of Diabetes Program Development. Dr. Brandtner was responsible for studies with the Melligen cells during her previous tenure with our partner, Austrianova, as its Chief Scientist.
An international Diabetes Consortium has been established by PharmaCyte Biotech. The Diabetes Consortium brings together a global coalition of world class experts from various universities and institutions in several countries around the world. All 16 members of the Consortium are committed to developing a treatment for insulin-dependent diabetes using PharmaCyte Biotech’s Cell-in-a-Box® live-cell encapsulation technology combined with human non-pancreatic, insulin-producing cells.
Several contracts and Collaborative Research Agreements have been entered into with leading research universities, scientists, academics and institutions around the globe that will facilitate PharmaCyte Biotech’s development of its cancer and diabetes treatments.
We obtained the exclusive worldwide license from Austrianova to use the Cell-in-a-Box® live cell encapsulation technology in combination with compounds obtained or developed from constituents of Cannabis, known as cannabinoids, for the treatment of diseases and their related symptoms.
- Progress is underway at the University of Northern Colorado in an attempt to identify a cell line that can be encapsulated using the Cell-in-a-Box® technology, which, in turn, can be used together with cannabinoid or cannabinoid-like prodrugs as treatment for deadly and difficult to treat cancers, such as brain cancer.
- The company changed its name from Nuvilex, Inc. to PharmaCyte Biotech, Inc. to emphasize that it has fully transitioned from a nutraceutical company to a purely biotechnology company.
- Significant changes have been made at the Board of Directors level, including a new member with major pharmaceutical experience being named as our first replacement Board member. Others members are in the final interview process, all of whom will be widely experienced in the life sciences.
Q: What has been some of the challenges in this repositioning of PharmaCyte Biotech?
KENNETH: There have been several challenges.
We had to fully transition from a nutraceutical company to a biotechnology company. That required us to plan our path forward to advance our technology and to attract and retain outstanding scientists, physicians and academics that would enable us to develop our treatments for cancer and diabetes.
We had to put our financial house in order. First we had to pay off significant debt. Then we had to find funding to insure our overall development plan could be implemented. We initially obtained an institutional investor who committed $27 million to us. Then we sought additional funding with improved terms that would enable us to complete all that we had planned.
We had to undertake a world-wide search to select the most appropriate Contract Research Organizations (CROs) to design and conduct our clinical trials.
We needed to identify and obtain the rights to a non-pancreatic sourced cell line that would produce insulin on demand when encapsulated using our Cell-in-a-Box® technology. That required an extensive search and then in-depth negotiations with UTS that led to our exclusive world-wide license to use Melligen cells to treat insulin-dependent diabetes.
We had to find a way to accelerate the preclinical development of our treatment for insulin-dependent diabetes. To do so, we formed a coalition of world-class experts from various universities and institutions in several countries around the world to tackle what is clearly a world-wide epidemic – insulin dependent diabetes. We now have a 16-member international Diabetes Consortium. Each member brings to the Consortium unique and complimentary capabilities that, together, will serve to accelerate our overall development timeline.
We had to completely restructure senior management and the Board of Directors to fully align the Company commensurate with becoming a pure biotech play.
Q: You’ve had several major peer-reviewed papers? What is the significance of these studies? Can you explain why these are key to PharmaCyte’s medical story?
KENNETH: There are three papers that have a direct effect on what we are doing at PharmaCyte Biotech. The first two have to do with our pancreatic cancer treatment and the third concerns our work with diabetes.
The first paper reports on the results of the Phase 1/2 clinical trial of our treatment in patients with advanced, inoperable pancreatic cancer. In this trial, 14 elderly and very sick patients were treated at a single study site in Germany with the combination of Cell-in-a-Box® plus low dose ifosfamide. All patients were treated with a single implantation of 300 Cell-in-a-Box® capsules with each capsule containing about 10,000 cells that are capable of converting the ifosfamide into its cancer-killing form. The capsules were implanted, using interventional radiography, with a catheter that was threaded through an artery in the leg to the pancreas where they were deposited as close to the cancerous tumor as possible. Then ifosfamide was administered intravenously at one-third of its “normal” dose. Only two treatments of ifosfamide were given about three weeks apart. This was a single-arm study; no comparator arm was used, but the results were compared to historical data for gemcitabine – the only drug approved at that time for the treatment of advanced, inoperable pancreatic cancer.
The results from this clinical trial showed that the Cell-in-a-Box® plus low dose ifosfamide combination increased the average lifespan of patients from about 5.7 months for gemcitabine to about 11 months with the combination and doubled the percentage of one-year survivors from 18% to 36%. Importantly, while the use of gemcitabine was associated with serious side effects, virtually no side effects were seen with the Cell-in-a-Box® plus ifosfamide treatment. The “quality of life” of the patients was vastly improved because of treatment. In addition, some beneficial effect was seen on metastatic lesions (from the pancreatic cancer) in the liver as a result of treatment with the Cell-in-a-Box® plus low dose ifosfamide combination. Thus, the major conclusion from this trial was that the combination of Cell-in-a-Box® plus low dose ifosfamide was a safe and effective treatment for patients with advanced, inoperable pancreatic cancer.
The second paper reports the results of a single-arm Phase 2 clinical trial in which 13 patients with advanced, inoperable pancreatic cancer were treated at 4 study sites in Europe. The only difference between this Phase 2 clinical trial and the Phase 1/2 clinical trial was that the dose of ifosfamide used was doubled to two-thirds of the normally used dose of this drug. This was done in an attempt to increase the anticancer effectiveness of the ifosfamide. The main conclusion taken from this trial was that the combination of Cell-in-a-Box® plus one-third the normal dose of ifosfamide was the appropriate treatment to use in all future clinical trials for a safe and effective antitumor treatment of advanced, inoperable pancreatic cancer.
The third peer reviewed paper titled, “Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells” was published in the journal Molecular Therapy – Methods & Clinical Development. The article describes the development and preclinical testing of the Melligen cells developed by Prof. Simpson and her colleagues at UTS. Most importantly, however, the authors note that, for the Melligen cells to be effective in treating Type 1 diabetes in humans where the insulin-producing β cells of the pancreas have been destroyed, it will be necessary to protect those cells from rejection by the body’s immune system after they have been introduced into the body. The article points out that one way to protect the Melligen cells would be to encapsulate the cells in protective “cocoons” prior to being placed into a diabetic patient. If this is done, the authors believe that encapsulated Melligen cells may offer a cure for Type 1 diabetes.
PharmaCyte Biotech’s live cell encapsulation technology, Cell-in-a-Box®, appears to be the ideal encapsulation technology for this purpose. In fact, Melligen cells have already been successfully encapsulated using the Cell-in-a-Box® process and experiments are already underway to ensure that encapsulation does not detract from the beneficial properties of the Melligen cells in any way.
Q: Can you explain your clinical trial programs?
One of PharmaCyte Biotech’s clinical trials consists of a Phase 2b clinical trial where our pancreatic cancer treatment will be compared “head-to-head” with the best available chemotherapy (Abraxane® plus gemcitabine) for advanced pancreatic cancer. The Phase 2b clinical trial will be conducted in Australia by Clinical Network Services (CNS). PharmaCyte Biotech’s pancreatic cancer treatment consists of encapsulating genetically modified cells that are capable of converting the inactive cancer drug ifosfamide into its cancer killing form, using the Cell-in-a-Box® live cell encapsulation technology. The encapsulated cells are placed as close to the cancerous tumor as possible to enable the delivery of the highest levels of the cancer-killing drug at the source of the cancer. The patient is then given the inactive cancer drug ifosfamide intravenously at one-third the normal dose. When the blood carrying the ifosfamide comes in contact with the encapsulated live cells, the ifosfamide is converted into its cancer-killing form which then enters the tumor and kills its cancer cells. There is one major difference between our Phase 2b clinical trial and the earlier clinical trials. In the two clinical trials previously completed, only two courses of the low-dose ifosfamide were given to the patients. We will give our patients courses of low-dose ifosfamide until they are no longer showing benefits from doing so, as is usually the case in cancer chemotherapy. This will be done to maximize the antitumor effectiveness of our treatment.
Two additional clinical trials will be conducted in the U.S. by Translational Drug Development (TD2). The Chief Development Officer of TD2, renowned pancreatic cancer specialist Dr. Daniel D. Von Hoff, will play a significant role in these trials. The trials will determine the effectiveness of PharmaCyte Biotech’s treatment for advanced pancreatic cancer in: (i) reducing the severe and untreatable pain that occurs in 20-25% of patients with advanced pancreatic cancer; and (ii) slowing the accumulation of malignant fluid (ascites) that accompanies the development of pancreatic and other solid cancerous tumors in the abdomen. This ascites fluid can be very problematic for patients because it can cause distention of the abdomen, severe pain, and even breathing problems. Accordingly, it must be removed on a regular basis – a painful and very costly procedure. There is currently no treatment available that will slow the accumulation of malignant ascites fluid.
Q: What other milestones do you hope to accomplish in 2015?
The major milestones for the remainder of 2015 are:
1. Complete the population of our Board of Directors with individuals who have extensive experience in life sciences and who have associated business expertise.
- Fully populate our Scientific Advisory Board with world-class physicians and scientists experienced in the fields of cancer and diabetes.
- Initiation of the Phase 2b clinical trial in Australia in patients with advanced pancreatic cancer. This is expected to begin in late 3Q2015.
2. Initiation of the Phase 1/2 clinical trial on the effectiveness of PharmaCyte’s pancreatic cancer treatment dealing with pain associated with advanced pancreatic cancer. This trial, to be conducted in the U.S., is expected to begin in late 3Q2015.
3. Initiation of the Phase 1/2 clinical trial on the effectiveness of PharmaCyte’s pancreatic cancer treatment in slowing the accumulation of malignant ascites fluid. This trial, to also be conducted in the U.S., is expected to occur in late 3Q2015 or early 4Q2015.
4. The initiation of these three clinical trials is dependent on the approval for use of the Cell-in-a-Box® live cell encapsulation facility that has been constructed in Bangkok, Thailand, by our partner, Austrianova. This facility must be approved as being compliant with current Good Manufacturing Practices (cGMP) standards by Thailand’s and Australia’s drug regulatory authorities as well as by the U.S. FDA.
5. Completion of our laboratory and small animal studies with the Melligen cells that are necessary to develop our treatment for insulin-dependent diabetes. These studies are designed to obtain data that will be required by regulatory authorities before any human clinical trials can occur.