Mark L. Rabe, MD, ABIHM

Transcription

1 Mark L. Rabe, MD, ABIHM

2 Safe Harbor Statement This presentation may include statements that constitute forward looking statements, which are often characterized by the terms may, believes, protects, expects or anticipates and do not reflect historical facts. Forward-looking statements involve risks, uncertainties and other factors that may cause actual results, performance or achievements of Nuvilex, Inc. and its subsidiaries to be materially different from those expressed or implied by such forward-looking statements. Forward-looking statements speak only as of the date the statement was made. Nuvilex does not undertake, and specifically declines, any obligation to update any forward-looking statements. Factors that may affect forward-looking statements and Nuvilex s business generally include, but are not limited to: (i) the risk factors, cautionary and other statements set forth in Nuvilex s periodic filings with the Securities and Exchange Commission available at and (ii) other factors that Nuvilex is currently unable to identify or quantify, but may exist in the future.

3 Cannabinoids and Cancer Medical cannabis and cannabinoids have long been accepted in the palliative treatment of cancer and the side-effects of cancer therapies: Nausea, vomiting, weight loss, lack of appetite and pain The first documented U.S. study on the anti-tumor effects of cannabis was funded by the U.S. government in 1974 at the Medical College of Virginia. The Washington Post printed an article about the study: THC slowed the growth of lung cancers, breast cancers and a virus-induced leukemia in laboratory mice, and prolonged their lives by as much as 36 percent. August 18, 1974

4 Cannabinoids and Cancer In 1997, a $2 million study conducted by the U.S. National Toxicology Program concluded: Rats and mice treated with THC over long periods of time had greater protection against malignant tumors than those left untreated. In 2006, a small pilot study with human subjects conducted by a research team in Spain showed: Possible anti-tumor activity of THC administered directly into aggressive glioblastoma multiforme brain tumors. Guzman M, et al. British Journal of Cancer. 2006; 95(2):

5 Cannabinoids and Cancer 2009: Numerous studies have found cannabinoids (THC and CBD) to have anti-cancer effects. Properties of cannabinoids include: - anti-proliferative - anti-metastatic - anti-angiogenic - pro-apoptotic In vitro and in vivo models. Cannabinoid anti-cancer effects: Lung, brain, thyroid, lymphoma, liver, skin, pancreas, uterus, breast, prostate... Reference: Alexander, et al. Mini-Review: Cannabinoids in the treatment of cancer. Cancer Letters. 2009;285(1):6-12.

6 Cannabinoids and Cancer Alexander, et al; 2009 (review of 51 studies) cannabinoids could be useful in the treatment of cancer due to their ability to regulate cellular signaling pathways critical for cell growth and survival.

7 Cell-in-a-Box Live-Cell Encapsulation

8 Cell-in-a-Box Live-Cell Encapsulation In 2013, Nuvilex acquired the exclusive, worldwide rights to use a cellulose-based live-cell encapsulation technology, known as Cell-in-a-Box, for the development of treatments for all types of cancer and for diabetes.

9 Cell-in-a-Box : A Biosustainable Factory * Molecular Precursors Prodrugs * An anti-cancer prodrug requires activation, usually by an enzyme, before it can kill cancer cells. Molecular Products Activated drug molecules

10 Cell-in-a-Box Encapsulation Process Cells are mixed with a proprietary polymer (Gel8, Polymer A) and the mixture is physically morphed into beads. The beads are allowed to fall into a polymerization bath containing polymer B. Almost immediately, a complex forms that produces the capsule membrane which grows from the outside toward the center, trapping groups of cells inside. Each capsule contains approximately 10,000 cells, but the capsules can be made larger or smaller. They can contain more or fewer cells, depending on the type and size of the cells that are encapsulated. Cells do not change properties during encapsulation.

11 Cell-in-a-Box Capsule Properties The capsules are about the size of the head of a pin. Diameter = 0.7mm Capsules serve as protective cocoons for the cells inside them. Almost any kind of live cells can be encapsulated using the Cell-in-a-Box technology;; only minor tweaking of the process is required to change from one cell type to another. The choice of cells encapsulated depends entirely upon their intended use. The number of cells per capsule depends upon the type of cells encapsulated. Since the capsules are made mainly of cellulose, they are bio-inert; no appreciable degradation of the capsules is seen after > 2 years in the human body.

12 Cell-in-a-Box Capsule Properties The capsules do not cause any inflammatory response in, or damage to, tissues near where they are placed in the body. Cells within the capsules remain alive and functioning for long periods of time (>2 years) within the body. Cells within the capsules are fully protected from attack (rejection) by the body s immune system. Encapsulated cells can be frozen and stored for long periods of time (>5 years) and then thawed successfully (>90% viability) - an important property for long-distance shipment. The encapsulation process is conducted according to cgmp standards.

13 Using Cell-in-a-Box to Treat Cancer First Capsules Containing Cancer Prodrug Activating Cells are Implanted in or near the Tumor Immune System Cells Immune System Cells Nutrients A Single Capsule Containing Cancer Prodrug-Activating Cells Waste Products

14 Using Cell-in-a-Box to Treat Cancer 1) Cancer Prodrug is Administered Then Inactive Prodrug Molecules Capsules Containing Prodrug Activating Cells Activated Drug Molecules 2) Cancer Prodrug is Activated by the Encapsulated Cells 3) Tumor Cells are Destroyed!

15 Phase 1/2 Pancreatic Cancer Trial: Results Summary Fourteen evaluable patients with advanced, inoperable pancreatic cancer were treated. Compared to historical data for Gemzar, the median survival time was increased from 23 to 44 weeks and the 1-year survival rate was increased from 18% to 36%. No treatment-related serious adverse events were seen probably because only 1/3 of the usual dose of ifosphamide was used. No inflammation of the tissues near the capsules was apparent. Some metastatic tumors in the liver were reduced in size. The encapsulated cells remained alive and functioning for >2 years after implantation. Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma. Löhr M, et al. Lancet. 2001; (357):1591. Safety, feasibility and clinical benefit of localized chemotherapy using microencapsulated cells for inoperable pancreatic cancer in a phase I/II trial. Löhr M, et al. Cancer Therapy. 2003; (1):121. Ifosphamide

16 Phase 1/2 Pancreatic Cancer Trial: Tumor Response CT Scans of Pancreatic Cancer TUMOR Before treatment 20 weeks post-treatment

17 Medical Marijuana Sciences Medical Marijuana Sciences, Inc. was established in early 2013 as a wholly-owned subsidiary of Nuvilex, Inc. The mission of Medical Marijuana Sciences, Inc. is to develop treatments for serious diseases utilizing the constituents of Cannabis. Cell-in-a-Box live-cell encapsulation technology will play a major role in the development of such treatments.

18 Targets for Cannabinoids + Cell-in-a-Box Initially, treatments for two of the deadliest and most difficult-to-treat cancers will be targeted for development, namely pancreatic and brain cancers. Pancreatic Cancer Pancreatic cancer is the fourth leading cause of cancer-related deaths in the Western world. In 2013, ~45,000 new cases and ~38,000 deaths were expected in the US alone. Difficult to treat usually not diagnosed until advanced stage of development. Only three chemotherapy treatments have been FDA-approved for advanced, inoperable pancreatic cancer: Gemzar (gemcitabine; Eli Lilly) in 1996 Gemcitabine + Tarceva (Genentech) in 2005 Gemcitabine + Abraxane (Celgene) in The effectiveness of all three treatments is limited by side effects.

19 Cannabinoids and Cancer Pancreas Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress related genes. Carracedo, et al. Cancer Research. 2006;66: Cannabinoid receptors are expressed in human pancreatic tumor cell lines and tumor biopsies at much higher levels than in normal pancreatic tissue. THC reduced the growth of tumor cells in two mouse models of pancreatic cancer. Cannabinoid treatment inhibited the spreading of pancreatic tumor cells both locally and to distant sites. CB2 receptor plays a major role in the proapoptotic effect of cannabinoids in these cells.

20 Cannabinoids and Cancer Pancreas Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. Fogli, et al. FEBS Letters. 2006;580(7): Cannabinoids produce a significant cytotoxic effect, independent of cell receptors. A CB1 antagonist interacted synergistically with the conventional chemotherapy agent 5-fluorouracil (5-FU). Conclusion: cannabinoids may exert their cytotoxic effects by crossing cell membranes and directly or indirectly disrupting the intracellular network resulting in cell death.

21 Cannabinoids and Cancer Pancreas Cannabinoids in pancreatic cancer: Correlation with survival and pain Michalski, et al. International Journal of Cancer. 2008;122(4): Correlation between low cancer cell CB1 receptor levels and survival. Inverse correlation between CB1 receptor levels and the pain status of the patients. Inverse correlation between pain symptoms and overall survival of pancreatic cancer patients. Conclusion: cannabinoid receptors may be involved in the development of pancreatic cancer pain ( warning symptom ).

22 Cannabinoids and Cancer - Brain Brain Cancer In the U.S. in 2013, more than 23,000 new cases of cancers of the brain and nervous system will be diagnosed, with more than 14,000 patient deaths. Most anticancer drugs are not effective against brain cancer because they do not cross the blood-brain barrier and so cannot attack the tumor. According to the American Cancer Society, only 11 drugs are even marginally effective against brain cancer. Cannabinoids may be good candidates against brain cancer because they readily cross the blood-brain barrier. THC CBD

23 Cannabinoids and Cancer - Brain Cannabidiol Enhances the Inhibitory Effects of Δ 9 -THC on Human Glioblastoma Cell Proliferation and Survival Marcu, et al. Molecular Cancer Therapeutics. 2010;9(1): Both THC and CBD inhibit the growth of multiple glioblastoma cell lines. CBD enhances the inhibitory effects of THC on glioblastoma cell growth. CBD + THC together may improve the overall effectiveness in the treatment of glioblastoma patients. Specifically, the combination of CBD + THC leads to modulation of specific mitogen-activated protein kinases.

24 Cannabinoids and Cancer - Brain Oct. 24, 2012: University of California San Francisco CME Course MMJ13001A: One speaker, Jeffrey Hergenrather, MD, described a particularly dramatic case seen by a San Diego colleague: a 90% reduction in the size of an infant s brain tumor achieved over the course of a year by parents applying hemp oil to the baby s pacifier before naptime and bedtime. Source: O Shaughnessy s and course attendance

25 Scientific Advisory Board Mark L. Rabe, MD, ABIHM, Chairman Centric Wellness integrative holistic medicine physician and cannabinoid medicine expert Richard M. Hyslop, PhD University of Northern Colorado biochemistry and enzymology Tom Matula, PhD University of Washington applied physics and drug/drug delivery development Brian Salmons, PhD Austrianova, President & CEO Co-inventor of Cell-in-a-Box live-cell encapsulation Garret Yount, PhD California Pacific Medical Center Research Institute molecular biology, clinical research

26 Advantages of Cannabinoids + Cell-in-a-Box The treatment uses simple radiographic techniques to implant Cell-in-a-Box capsules. The capsules are bio-inert and encapsulated cells can remain alive and functioning for long periods of time in the body. Cannabinoid molecules are plant-based and sustainable, have broad anti-cancerous and other medicinal properties, and have an excellent safety profile. Summary Objective: safe and efficacious treatments. The raw materials brought to the factory are safe and biosustainable. The factory itself is safe, bioinert, and biosustainable. Pre-clinical investigations are underway. THC CBD

27 Intellectual Property Patents associated with Nuvilex s acquisition of the worldwide, exclusive rights to use the Cellin-a-Box live-cell encapsulation technology for the development of disease treatments are: LP-AN-01-PCT / WO Encapsulated Cells Producing Retroviral Particles Granted in 37 countries 31 claims Describes the production of the capsules and their use in treating cancer US Patent # 6,776,985 LP-AN-02-PCT / WO Encapsulated Cells Producing Cytochrome P450 Granted in 37 countries 17 claims Describes the encapsulation of cells with elevated levels of the prodrug-activating cytochrome P450 enzyme and the use of the encapsulated cells in treating cancer in combination with prodrugs activated by this enzyme US Patents # 6,893,634 and # 6,540,995

28 Parting Thoughts OPINION AND RECOMMENDED RULING, FINDINGS OF FACT, CONCLUSIONS OF LAW AND DECISION OF USA DRUG ENFORCEMENT ADMINISTRATION (DEA) LAW JUDGE, DATED: SEPT Marijuana should be regulated, not scheduled. Medical marijuana should not be taxed. This is what Judge Francis Young s ruling said about cannabis: By contrast, marijuana s therapeutic ratio, like its LD-50, is impossible to quantify because it is so high. In strict medical terms marijuana is far safer than many foods we commonly consume. For example, eating ten raw potatoes can result in a toxic response. By comparison, it is physically impossible to eat enough marijuana to induce death.

29 Questions? Medical Marijuana Sciences Mark L. Rabe, MD, ABIHM Centric Wellness th Avenue San Diego, CA Office: Nuvilex Investor Relations Dillon Heins CorProminence 377 Oak Street, Concourse 2 Garden City, NY Office: dillonh@corprominence.com

30 Cell-in-a-Box