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 www.sec.gov; and (ii) other factors that
Nuvilex is currently unable to identify or quantify, but may exist in the future.
Corporate Profile
Exchange: OTC.QB
Stock Symbol: : NVLX
Recent Close: $0.45
Fiscal Year End: April 30
Shares Outstanding: 638M
Market Cap: $250M
52-Wk Range: $0.62 - $0.04
a/o (03/04/14)
Introduction
In 2013, Nuvilex acquired the exclusive, worldwide rights to use a
cellulose-based live-cell encapsulation technology, known as Cell-ina-Box™, for the development of treatments for all types of cancer
and for diabetes.
Nuvilex Pipeline
Pipeline
Live-Cell Encapsulation plus
Ifosfamide (IFEX®) for Pancreatic
Cancer
Pre-Clinical
Phase 1
Phase 2
Phase 3
Live-Cell Encapsulation plus
Cyclophosphamide (CYTOXAN®)
for Breast Cancer
Pre-Clinical
Phase 1
Phase 2
Phase 3
Live-Cell Encapsulation plus
Insulin-Producing Cells for
Diabetes
Pre-Clinical
Phase 1
Phase 2
Phase 3
Live-Cell Encapsulation plus
Cannabinoids for Brain and
Pancreatic Cancers
Pre-Clinical
Phase 1
Phase 2
Phase 3
Cell-in-a-Box™ Live-Cell Encapsulation
The 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 and 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.
Cell-in-a-Box Capsules… Microscopy
0.7 mm
View of a Single Capsule
Capsule Cross Section Showing Cells
Cell-in-a-Box Encapsulation… Properties
 The capsules are about the size of the head of a pin.
 The 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.
Cell-in-a-Box Encapsulation… 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 has been conducted according to cGMP standards.
Cell-in-a-Box Encapsulation… Advantages
 Other types of live-cell encapsulation use
biological materials such as alginate (from
seaweed) and chitosan; such materials must be
extensively purified to remove contaminating
substances, e.g. endotoxins, before they are
used - this is not necessary with Cell-in-a-Box.
 As capsules made of biological material
degrade, they can also elicit inflammatory
responses in, and cause damage to, nearby
tissues - this does not occur with Cell-in-aBox.
 Capsules made from such biological materials
are less “robust” than Cell-in-a-Box capsules and
degrade over time (a few months) in the body;
Cell-in-a-Box capsules remain intact for >2 years.
 Long-term freezing and then thawing of
capsules made from biological materials is
problematic and, as a consequence,
successful long distance shipping can be
affected - this is not a problem with Cell-in-aBox.
 As a consequence of capsule degradation, the
cells inside the capsules can escape and be
attacked by the hosts’ immune systems - this
does not occur with Cell-in-a-Box.
 Unlike Cell-in-a-Box encapsulation, some
other forms of live-cell encapsulation have
not been carried out according to cGMP
standards.
Cell-in-a-Box … Cancer Use
First…
Capsules Containing Cancer Prodrug–Activating Cells
are Implanted in or near the Tumor…
Immune
System
Cells
Immune
System
Cells
Nutrients
Waste Products
A Single Capsule Containing
Cancer Prodrug-Activating Cells
Cell-in-a-Box … Cancer Use
Then –
1) Cancer Prodrug is Administered…
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!
Pancreatic Cancer… Statistics and Characteristics
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.
Pancreatic cancer is difficult-to-treat because it is usually not diagnosed until it is at an
advanced stage of development.
The only single-drug treatment for advanced pancreatic cancer is Gemzar® (gemcitabine),
approved by the FDA in 1996.
Since 2000, more than 30 Phase 3 clinical trials have been conducted to try to improve upon
Gemzar®. Less than 5 have been successful.
Pancreatic Cancer… Combination Chemotherapies
In 2005, gemcitabine + Tarceva® was approved as first-line therapy.
This combination was approved, in part, because, compared to gemcitabine plus placebo,
it increased the median survival from 6.0 to 6.4 months and the 1-year survival rate from
19% to 24%.
In September, 2013, the combination of gemcitabine plus Abraxane® was approved by the FDA
and replaced gemcitabine + Tarceva® as the “gold standard” for the disease.
As compared to gemcitabine alone, the gemcitabine + Abraxane® combination increased
the median survival from 6.7 to 8.5 months and the 1-year survival rate by about 59%.
The use of both combinations is associated with serious side effects.
Phase ½ Pancreatic Cancer Trial… Procedures
Live cells containing the drug-activating enzyme CYP2B1 were encapsulated using the
Cell-in-a-Box technology.
Using radiography, a single implantation of 300 capsules (about 10,000 cells/capsule) was
made in the blood supply near the pancreas, and therefore the tumor.
Patients received two courses of chemotherapy with the anti-cancer prodrug* ifosfamide
(Ifex®), administered intravenously at 1/3 of the “normal” dose usually employed in treating
other types of cancer.
-------------* An anti-cancer prodrug requires “activation,” usually by some enzyme, before it can “kill”
cancer cells.
Phase ½ Pancreatic Cancer Trial… Procedures
Fourteen evaluable patients with advanced, inoperable pancreatic cancer were treated.
Quality-of-life data were collected from all 14 patients.
Radiography
Placement of the
Catheter
Capsule
Implantation
Post-Capsule
Implantation Vessel recovery
Phase ½ Pancreatic Cancer Trial… Tumor Response
CT Scans of Pancreatic Cancer
TUMOR
Before Treatment
20 Weeks after Treatment
Phase ½ Pancreatic Cancer Trial… Results Summary
As 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 form 18% to 36%
Side effects normally associated with ifosfamide were reduced in severity – no
treatment-related serious adverse events were seen – probably because only 1/3 of the
“usual” dose of drug was used.
No side effects were seen that could be attributed to the presence of the capsules. 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.
Phase 1/2 Pancreatic Cancer Trial… Publications
Relevant literature citations:
Löhr M., Hoffmeyer A., Kröger J-C., Freund M., Hain J., Holle A., Karle P., Knöfel W.T., Liebe S.,
Müller P., Nizze H., Renner M., Saller R.M., Wagner T., Hauenstein K., Günzburg W.H., and
Salmons B. Microencapsulated cell-mediated treatment of inoperable pancreatic
carcinoma. The Lancet, Vol. 357, p. 1591 (2001).
Löhr M., Kröger J-C., Hoffmeyer A., Freund M., Hain J., Holle A., Knöfel W.T., Liebe S., Nizze H., Renner M.,
Saller R., Müller P., Wagner T., Hauenstein K., Salmons B., and Günzburg W.H. Safety, feasibility and
clinical benefit of localized chemotherapy using microencapsulated cells for inoperable pancreatic
cancer in a phase I/II trial. Cancer Therapy, Vol. 1, p. 121 (2003).
Pancreatic Cancer Treatments - a Comparison
TREATMENT
Gemzar®
(gemcitabine)
CONTROL
TRIAL
PHASE
MEDIAN SURVIVAL (months)
ONE-YEAR SURVIVAL RATE
TREATMENT
CONTROL
TREATMENT
CONTROL
5-Fluorouracil
3
5.7*
4.2*
18%*
2%*
Gemcitabine +
Tarceva® 2
Gemcitabine +
Placebo
3
6.4**
6.0**
24%**
19%**
Gemcitabine +
Abraxane® 3
Gemcitabine +
Placebo
3
8.5***
6.7***
35%***
22%***
Cell Encapsulation +
Ifosfamide
Historical Data
for Gemzar®
2
11.0
5.7*
36%
18%*
1,2,3
1
Approved (see year of approval below) as first-line therapy for advanced, unresectable, or metastatic pancreatic cancer.
1 Approved
by FDA in 1996.
2 Approved
by FDA in 2005.
3 Approved
by FDA in 2013.
* From Full Prescribing Information (Package Insert) for Gemzar®.
** From Full Prescribing Information (Package Insert) for Tarceva®
*** From Full Prescribing Information (Package Insert) for Abraxane®
----------------------------------------------------------NOTE: All three gemcitabine –containing treatments are associated with serious side effects.
Nuvilex’s treatment has no serious effects associated with it.
Preparations for Future Pancreatic Cancer Trials
 Contracts have been signed with Fisher BioServices and Inno Biologics.
 Fisher BioServices will store the drug-activating cells on a long-term basis.
 Inno Biologics is conducting the initial cloning of the drug-activating cells.
 Initial contacts have been made with CROs who will assist in all aspects of the
conduct of future trials.
 cGMP-compliant manufacturing facilities for the Cell-in-a-Box encapsulation are
being established in Thailand.
Breast Cancer
Cell-in-a-Box and Breast Cancer… Treatment
A two-arm Phase 1/2 veterinary trial in dogs with spontaneously-occurring mammary
tumors has been carried out.
Arm 1 –encapsulated drug-activating cells were implanted in the tumors and then the
dogs were treated with cyclophosphamide.
Arm 2 – the dogs were treated with cyclophosphamide alone.
The anti-cancer prodrug cyclophosphamide was used instead of ifosfamide because
cyclophosphamide is currently used in breast cancer treatment regimens.
The cells that were encapsulated were the same as those used in pancreatic cancer trials
because ifosfamide and cyclophosphamide are converted to their cancer-killing forms in
the same way.
Cell-in-a-Box and Breast Cancer… Results
The capsules were well tolerated; there were no serious “safety” issues.
Significantly greater tumor shrinkage seen in the dogs in “Arm 1” than in those in
“Arm 2.”
One dog had two tumors; one tumor was treated with encapsulated cells +
cyclophosphamide whereas the other tumor was treated with cyclophosphamide
alone.
The tumor treated with encapsulated cells + cyclophosphamide shrank by 70%
as compared to the14% shrinkage seen in the tumor treated with drug alone.
Other Cancers and Treatments
Cell-in-a-Box: What Else for Cancer?
Other cancers:
Breast
Liver
Head and neck
Prostate
Other “solid” tumors that are accessible
Cells that activate more than one anticancer drug could be encapsulated; by
doing so, combination chemotherapies may be accomplished.
Cells that produce anti-angiogenic factors could be encapsulated. These may be
useful in combination with surgical resection/debulking.
Diabetes
Diabetes… Statistics, Market Size, and Characteristics
About 370 million people have been diagnosed with the disease worldwide and
approximately185 million remain undiagnosed.
The market for diabetes drugs and devices has been projected to exceed $114
Billion by 2018.
The serious, debilitating and even deadly complications from diabetes have
become a serious “drain” on medical resources.
Complications from diabetes include heart disease, vision loss, kidney disease
and nerve damage.
Diabetes is characterized by sustained high levels of glucose (a source of
energy for cells) in the blood. Blood glucose levels are regulated by insulin
produced by the “islet cells” of the pancreas.
Diabetes… The Problem and a Possible solution
Type 1 (juvenile-onset) diabetes – the pancreas cannot produce enough insulin and
daily insulin administration is required.
Type 2 (adult-onset) diabetes - the pancreas may produce insulin, but the insulin
produced is not able to “do its job” (insulin resistance).
Type 2 diabetes can be controlled by modifications in diet, exercise and diabetes
medications. Over time, type 2 diabetics may need daily insulin administration.
To avoid the necessity for daily injections of insulin, pancreatic islet cell (insulinproducing) transplantations have been studied.
Transplantation of Encapsulated Xenographic Islet Cells
To preclude the necessity for lifelong administration of immunosuppressive drugs if
“naked” xenographic islet cells are transplanted, these cells have been
encapsulated using alginate.
However, the limited lifespan (in the body) of alginate-based capsules and the
deleterious consequences that can result from their breakdown may be
problematic in terms of developing a long-lived treatment for diabetes.
Encapsulation of insulin-producing cells, rather than xenographic
pancreatic islet cells, using the Cell-in-a-Box technology may circumvent
most, if not all, of the above problems.
Studies with Cell-in-a-Box and Insulin-producing Cells
Conclusions from these studies include:
Through the use of the Cell-in-a-Box encapsulation technology, a
type of “artificial pancreas” was created.
The fact that the implanted insulin-producing cells were not attacked
by rats’ immune systems testified to long-term protective capability
of Cell-in-a-Box’s cellulose-based capsules.
Two of the major problems associated with pancreatic islet cell
transplantations are avoided by using Cell-in-a-Box because:
(a) an adequate supply of insulin-producing cells is available;
(b) no potent immunosuppressive drugs are required.
The Company
Medical Marijuana Sciences, Inc. was established in early 2013 as a wholly-owned
subsidiary of Nuvilex, Inc.
The initial mission of Medical Marijuana Sciences, Inc., is to develop treatments for
two of the deadliest forms of cancer, namely pancreatic cancer and brain cancer, by
using constituents of Cannabis (cannabinoids).
The cellulose-based live-cell encapsulation technology licensed (worldwide,
exclusive) by Nuvilex and known as Cell-in-a-Box™ will play a major role in the
development of such treatments.
Background
Since the early 1970s, cannabinoids have been known to alleviate the pain and/or nausea
and vomiting associated with serious diseases such as cancer.
Several drugs have been approved by the FDA and drug regulatory authorities in other
countries for pain and/or nausea and vomiting.
The best known cannabinoids are tetrahydrocannabinol, or THC, and cannabidiol, or CBD.
CBD does not have psychotropic effects associated with it. Accordingly, plants rich in CBD
and low in THC have been proposed as being most useful for medicinal purposes.
In 2003, the US Government, through its Department of Health and Human Services was
granted a major patent (US Patent #6330507) titled “Cannabinoids as Antioxidants and
Neuroprotectants” that deals with the use of cannabinoids in treating neurological damage
from strokes, trauma, or from neurological diseases (Alzheimer’s, Parkinson’s, etc.)
Initial Targets for Cannabinoids + Cell-in-a-Box
Initially, treatments for two of the deadliest and most difficult-to-treat cancers, those of the
pancreas and brain, will be targeted for development.
Pancreatic Cancer - To date, only three chemotherapy treatments have been approved by
the FDA for the treatment of advanced, inoperable pancreatic cancer:
– Gemzar® (gemcitabine; Eli Lilly) in 1996
– gemcitabine + Tarceva (Genentech) in 2005
– gemcitabine + Abraxane in 2013
The effectiveness of all three treatments is limited by side effects.
Cannabinoids such as CBD and THC have been shown to be effective against pancreatic
cancer in preclinical studies.
A Pancreatic Cancer Treatment
1.
Cell-in-a-Box™ capsules containing
cells that have an enzyme that
activates the inactive prodrugs THCA
and/or CBDA are implanted in or
near the tumor
3.
4.
2.
The inactive prodrugs THCA and/or
CBDA may be delivered by a series of
IV infusions or PO via raw plant
extracts
Cancer-killing
THC and/or CBD
are produced
Tumor cells
are killed
Initial Targets for Cannabinoids + Cell-in-a-Box
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 and more than 14,000 people will die from them.
Most anticancer drugs are not effective against brain cancer because they do not cross the
“blood-brain barrier” and so cannot attack the tumor.
Cannabinoids may be good candidates against brain cancer, particularly glioblastoma
multiforme, because they readily cross the “blood-brain” barrier.
According to the American Cancer Society, only 11 drugs are even marginally effective
against brain cancer.
Development of a Possible Cancer Treatment
The process for developing a treatment would include:
First – Develop a cell line with high activity of a decarboxylase enzyme capable of converting
CBDA and THCA into CBD and THC, respectively.
Second – Encapsulate these cells using the Cell-in-a-Box™ technology.
Third – Implant the Cell-in-a-Box™ capsules in, or near, the tumor.
Fourth – Administer the prodrugs CBDA and/or THCA orally or intravenously, possibly at low
dosage to minimize deleterious side effects (e.g.,the psychoactive effects associated with THC).
Advantages of Cannabinoids + Cell-in-a-Box
For Patients:
The treatment uses simple radiographic implantation of Cell-in-a-Box™ capsules.
The capsules are bio-inert and the encapsulated cells can remain alive and functioning for
long periods of time in the body.
THCA and CBDA are non-toxic and non-psychoactive.
There is potential for home-based THCA and CBDA prodrug delivery via juiced marijuana
plant extracts as an alternative to (or in addition to) clinic-based infusion.
Safety and efficacy.
Advantages of Cannabinoids + Cell-in-a-Box
For Investors:
Nuvilex’s treatment would employ the proprietary live-cell encapsulation technology
with the encapsulated cells having the capability to activate cannabinoids via a
decarboxylase enzyme.
The product would contain no Schedule I compounds thus avoiding legal issues.
The potential exists for home-based cannabinoid prodrug delivery via juiced marijuana
plant extracts as an alternative to (or in addition to) clinic-based IV infusion.
Cannabinoid-based treatments may prove useful against a variety of solid tumors.
Intellectual Property
Patents associated with our acquisition of the worldwide, exclusive rights to use the Cell-ina-Box live-cell encapsulation technology for the development of disease treatments are:
LP-AN-01-PCT / WO9701357
“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 / WO9735994
“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
The Nuvilex Management Team
Kenneth L. Waggoner, - Chief Executive Officer and President
Patricia Gruden, - Chairman of the Board and Chief Financial Officer
Dr. Robert F. Ryan - Chief Scientific Officer
Dr. Gerald W. Crabtree - Chief Operating Officer
Questions?
Investor Relations
Dillon Heins
CorProminence
377 Oak Street
Concourse 2
Garden City, NY 11530
Office: 218-839-9051
Email: dillonh@corprominence.com