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Phytotherapy Agents
After
decades of diligent research, medical oncology is only now beginning to
see increased patient survival times. Even still, the rate of failure
of the best drugs is humbling to researchers. Throughout the world,
thousands of companies are endeavoring to develop better therapies for
proliferative cell diseases. Many of these companies orient their focus
into single areas of research, such as gene therapy, cytotoxins, or
targeted delivery systems that carry existing therapy agents
preferentially to a cancer cell.
ShimodaAtlantic™ has several novel drug projects underway, each
of which is remarkably different from the other, yet, each of which is
complementary to the other in one or more aspects.
SAOB-0401
Our lead phytotherapy investigative agent is SAOB-0401
(Xenavex™). This drug is derived through a chemical/mechanical
means from parts of the evergreen shrub nerium oleander L. The drug is
already marketable as a cardiology medication, but, we are
investigating it for its potential as a NF-kB and AP-1 locker. In
commercial form, the drug is known as Xenavex™ and is available
as a federally controlled prescription drug item. The NDC number for
Xenavex is 14213-001-01/02/03.
In the mid 1990's, oleander, as a potential therapy, rose to attention
when a Turkish physician, Huseyin Ozel made contact with a group of
interested American investors, who financed a drug development project
based on Dr. Ozel's patent for a hot-water extraction from the oleander
shrub.
Our drug differs markedly from Dr. Ozel's drug, which he calls
"Anvirzel™."
Researchers publishing in peer review journals have reported that the
chief cytotoxic agent in any oleander extract is a substance called
oleandrin. Oleandrin is not water soluble. It is however, highly
soluble in ethanol, which is what we use to make SAOB-0401.
In the year 2000, Dr. Ozel's drug went through a Phase I test at the
Cleveland Clinic. Physicians later reported that although their tests,
which were not intended to achieve any therapeutic effect, did result
in disease stabilization in 3 of the 15 patients that they were able to
report on.
Anvirzel™ requires a patient to undergo a daily intramuscular
injection. Our drug is administered under the tongue. Our tests suggest
that SAOB-0401 (Xenavex™) has a significantly higher oleandrin
content, and on that basis, we are now preparing to engage in a Phase
I/II clinical study of the drug in non-small cell lung cancer patients.
Xenavex™ is a prescription pharmaceutical, available in 3ml, 10ml
and 30ml vials in liquid form. In February, 2005, we filed a Form 2657
with the FDA to list the drug iin the NDC database in those package
forms. The only indications for any oleander derived drug are related
to its cardioglycoside qualities. There is presently no credible
scientific evidence to warrant any claim that it is a cancer drug. The
purpose of the clinical studies, however, is to see if there is a
scientific basis to pursue investigation of the drug as a cancer
therapeutic.
Xenavex™ has several unique properties that we propose to further
investigate, including its reported ability to mimic gene therapy in
cystic fibrosis cases. M.D. Anderson researchers reported in one paper
published in 2000, that oleandrin has potential as an antiviral agent,
and mentioned HIV as a specific virus that might be suceptible to its
cytotoxic properties.
Xenavex™ bypasses the multidrug resistance pump in treatment
refractory cancer cells since it is a member of the glucose family.
Status of
Xenavex™/SAOB-0401
Xenavex™ is available as a prescription item. For the purposes of
our clinical studies, we have renamed Xenavex as "SAOB-0401" in order
to demark it as an investigational new drug, insofar as any uses other
than its labeled indications are concerned.
Compassionate Use
Program
For patients who meet the FDA's criteria for a single patient
investigational new drug treatment program, ShimodaAtlantic™ will
cooperate with qualified physicians in cases where the drug is
considered as a treatment of last resort. We strongly discourage any
physician from writing off-label prescriptions for Xenavex™. The
Food and Drug Administration has an office in their CDER oncology
division that reviews single patient IND's quickly. Our position is
that the extra safety margin afforded by FDA case review is a better
practice than off-label prescribing.
For patients who qualify for a single patient IND, there is no charge
for SAOB-0401/Xenavex™. We have developed an Investigator's
Brochure, as well as sample protocols, including informed consent
forms, to assist physicians who desire pursuit of the single patient
IND program.
Clinical Trials -
SAOB-0401
SAOB-0401/Xenavex is planned for a mid-2005 launch in clinical trial
NCT00101322, entitled, "Study of SAOB-0401 (Xenavex™) in
advanced non-small cell lung cancer." This study is designed as a Phase
I/II study since our goal is to explore the maximum tolerated dosage
(MTD) in each individual patient. This requires us to place each
patient in dose escalation until MTD is reached. Xenavex™
(NDC 14213-001-02) is similar to digoxin in its pharmacokinetics and
pharmacodynamics.
Like digoxin, each patient has an optimal dosage level. In a cancer
patient, our study will seek to determine the highest tolerable dosage
in each patient, in order to assess strategies of maximizing
bioavailability of the drug in the patient's system.
SAOB-0405
This is an early development stage substance. It is a member of
the alcohol family, and is a potential therapeutic agent for
mesothelioma and lung cancer. Preclinical studies of the substance, in
a nebulized form, indicates a high order of selective cytotoxicity for
A549 non-small cell lung cancer cell. This phytochemical is derived
from citrus, and exhibits a potential for selective cytoxicity withl
minimal side effects. We have two more in vitro studies planned before
progressing to animal testing.
Our development plan is to expand the study to mice, to assess the
pharmacokinetics and pharmacodynamics of the substance. If no serious
safety or toxicity issues emerge, we will expand the study from there.
Our plan is to finish preclinical assessments in 2005, and determine
the future of the project at that point.
Targeted Nanotherapy
SAOB-0500
This project is a targeted nanotherapy agent coupled with an external
energy field module. In its current phase, the project relies on
intratumoral injection of a either a gold nanoparticle labeled with
glucose and excited by a ultra low frequency alternating magnetc field
(AMF), or, a PEG/glucose labeled magnetite particle that is excited by
a higher-frequency AMF. The current treatment protocol plan is based on
novel research from Nagoya University (Japan) researchers who were able
to cause tumor destruction by heating rat tumors in serial treatment
cycles. In their model, an induced immune response was also observed
which led to the test animal's native immune system recognizing and
eventually destroying tunor tissue in the test animal that had not been
treated.
The energy fields
intended for use are known to be otherwise safe to humans and do not
cause damage to non-targeted tissues.
The working plan for
initial human applications of the system will likely require that a
patient undergo a procedure to place a shunt (for drug delivery) into
the largest tumor mass. Additionally, four .5mm fiber-optic temperature
probes will be placed in (2 probes) and adjacent to (2 more probes) the
tumor mass. The temperature probes are then connected to a computer
interface that will control the energy output in such a manner as to
heat the tumor to a target temperature, plus/minus 1 degree centigrade.
The other probes are to assure patient safety by monitoring normal
tissue temperature during the treatment procedures.
Xenavex™
Our Xenavex™
Phase II FDA clinical trial program will initially explore the
effectiveness of a nerium oleander L. derivative, oleandrin, as
a potential monotherapy for mesothelioma and non-small cell lung
cancer. In the near term, additional Phase II studies are planned for
the purpose of exploring efficacy of Xenavex™ in treating cancer
of the breast, the prostate, BRO melanoma and pediatric
medulloblastoma.
Xenavex™ is an
ethanolic botanical extract compound of various cardioglycosides
derived from oleander, a toxic plant that has been investigated and
used as a "traditional medicine" for over 1,000 years. Modern oleander
based drugs have previously been made in both China and Russia, where
they are used as cardiology drugs. Our experience thus far is that the
ethanolic extraction process results in higher ratios of the active
moieties than extractions made from other processes.
Pediatric cancers,
such as primitive neuroectodermal tumor (PNET) (medulloblastomas) are
very difficult to treat. Even successful cases result in devastating
side effects to the patient. Xenavex™ crosses the blood/brain
barrier, thereby suggesting its possible use in treating pediatric
brain cancers. We anticipate a separate Phase II program to investigate
the potential of Xenavex™ as a pediatric cancer monotherapy.
Xenavex™ is a
prescription item for its labeled indications related to cardiovascular
disease. It is not approved for any other indication such as a
proliferative cell disorder. In October, 2004, after extensive
consideration, ShimodaAtlantic changed its pollicy regarding
availability of Xenavex™ to patients seeking access to the drug
under single patient investigational new drug applications (FDA Form
1571). Since then, we have provided access to the drug to qualified
physicians for investigational or "off-label" usage.
Vaccine &
Immune Response Stimulation
Our early-stage
vaccine project is investigating whether the human immune system can be
stimulated to react to, and, destroy tumor cells, based on their unique
protein structure. The goal o the project is to develop an autologous
vaccine derived from the patient's own tumor.
European investigators
have reported some success in triggering the body's natural immune
response to cancer cells, by introducing protein fragments similar to
those created by cancer cells, but in much larger quantities than a
tumor normally produces.
Our current research
focuses on heat-shock proteins, cytokeratin-19 fragments and its
CYFRA-21 subunits as being
potential immune system stimulators.
The investigation will
seek to determine if by introducing a large amount of the protein
fragments, the immune response is enhanced, thereby triggering the
body’s natural defense against cell disorders.
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