a platform technology to address bioterrorism
TRANSCRIPT
A Platform Technology to Address Bioterrorism
November 18, 2010
James A. Joyce Chairman & CEO, Aethlon Medical, Inc
Rodney S. Kenley President, Aethlon Medical, Inc [email protected]
Richard H. Tullis, Ph.D.
Chief Science Officer, Aethlon Medical, Inc [email protected]
Introduction
The National Intelligence Council (NIC) has identified the threat of bioterrorism as the
most significant weapon of mass destruction (WMD) concern as the knowledge,
equipment, and pathogen components required to construct biological weapons are now
globally dispersed. There is currently no single strategy to regulate or prevent the
development of these threats. Immense spending by U.S. government agencies to
advance single-target drug and vaccine countermeasures against known bioterror threats
has produced limited results and highlights an urgent need for new defensive therapeutic
strategies. In response, the Obama administration has announced a new biodefense plan
that will fund “platform technologies” that apply to many different infectious disease
threats. The Department of Health and Human Services (HHS), which oversees all U.S.
health agencies, has decreed that broad-spectrum therapies able to combat multiple
pathogen threats will be the focal point of biodefense initiatives going forward.
Additionally, HHS has disclosed that it will discontinue policies that previously
precluded support of dual-use therapies that may have commercial applications against
disease conditions such as hepatitis-C virus (HCV) or cancer. Homeland Security
Newswire reports the FY2011 budget calls for $6.48 billion in biodefense spending,
which reconfirms the growing concern of bioterrorism and reinforces the opportunity for
organizations with novel treatment strategies that augment or overcome the limitations of
single-target drug and vaccine strategies.
Our response to these new policy initiatives has been to reestablish efforts to advance our
proprietary Hemopurifier® platform technology as a broad-spectrum treatment
countermeasure against bioterror threats. The Hemopurifier® is a first-in-class medical
device that selectively targets the removal of infectious viruses from the entire circulatory
system before the occurrence of cell and organ infection. The device also addresses a
previously unmet medical need by clearing immunosuppressive proteins that shed from
viruses to trigger apoptosis of immune cells needed to combat infection. While our
primary focus will continue to be advancing our Hemopurifier® as an adjunct therapy in
HCV care, we believe our Hemopurifier® may be the most advanced and perhaps only
true broad-spectrum countermeasure against viral threats most likely to be weaponized
against civilian and military populations. This belief is supported by human clinical
outcomes and supporting in vitro studies conducted at leading government and non-
government labs. The Drug and Vaccine Challenge
The U.S. Department of Defense (DoD) and other federal agencies, including HHS
through its Strategic National Stockpile (SNS), attempt to maintain significant quantities
of single-target medical countermeasures in preparation for public health emergencies,
including the dissemination of bioterror agents. Understanding the immense challenge of
aligning single-target drug and vaccine therapies as a predominant strategy to address an
unknown universe of bioterror threats reinforces the value of our Hemopurifier® as a
broad-spectrum platform technology. Among reasons why single-target drug and vaccine
strategies are clinically and economically problematic:
1. The benefit of drug and vaccine countermeasures stockpiled by the U.S.
government is not fully understood, as efficacy studies against agents of bioterror
are not permissible in humans. Drug and vaccine countermeasures against such
threats are solely reliant on efficacy demonstrations in animal models, which
historically are poorly predictive of treatment benefit in humans.
2. Single-target drug and vaccine countermeasures procured into the SNS expire
every few years and need to be replenished into the SNS. The resulting taxpayer
burden of purchasing and repurchasing single-target countermeasures against
pathogens that may never infect human populations is significant. The initial
purchase of a single-target countermeasure alone can exceed $1 billion.
3. Viral pathogen threats can be genetically modified to enhance the likelihood the
pathogen will be resistant to drug and vaccine countermeasures placed in the
SNS. As the expertise to accomplish genetic modification is within reach of
terrorist organizations, many experts believe the U.S. will inevitably face the
reality of this scenario.
4. Drug and vaccine strategies to defend against pathogens artificially engineered
through synthetic biology to produce a more severe or otherwise enhanced
spectrum of disease cannot be produced until after a pathogen has been released
and then identified post infection. The response time to develop, manufacture and
distribute a drug or vaccine solution to a synthetic pathogen will likely exceed the
time required to prevent massive human casualties and economic disruption.
5. Prophylactic vaccines may be useful to protect at risk medical and military
personnel against obvious known threats such as smallpox virus. However, the
expense and logistical challenge of protecting an entire civilian population with
vaccines not proven to be efficacious in humans is virtually impossible.
Furthermore, the nature of bioterrorism prohibits the ability to initiate vaccine
development until after a released pathogen has been identified. Beyond response
and manufacturing challenges, vaccine development against a highly mutable
bioterror agent may not be possible.
6. There are too many threats and limited commercial incentive for organizations to
pursue the development of drug and vaccine countermeasures against agents of
bioterrorism. A vast majority of the estimated 1400 pathogens infectious to man
are untreatable with antiviral drug and vaccine therapies. In general, until a
considerable human population becomes afflicted by a specific pathogen, there is
limited economic incentive for researchers to pursue the development of therapies
that require hundreds of millions of dollars to advance and a decade or more to
determine if the treatment candidate obtains market clearance from regulatory
agencies. The development and licensure of even one therapy requires massive
research and clinical participation. According to the California Biomedical
Research Association, it is estimated that of every 5,000 “candidate” drugs that
look promising on the lab bench, only five will enter clinical trials, and only one
achieves FDA licensure. Considering the limited number of organizations
pursuing biodefense countermeasure development, the expectation for effective
new single-target drug and vaccine strategies will very likely remain low.
The Aethlon Hemopurifier®
The Hemopurifier® provides a post-exposure treatment strategy to mitigate illness,
suffering, and death resulting from exposure to viral pathogens, including biological
weapons. The device is a highly developed broad-spectrum treatment platform as
evidenced by human clinical outcomes and in vitro studies conducted at leading
government and non-government labs. The Hemopurifier® provides rapid clearance of
viral pathogens and immunosuppressive proteins resulting in an antiviral and
immunotherapeutic mechanism to improve the benefit of stockpiled countermeasures
whose effectiveness in humans is unknown. The device also provides a countermeasure
against viral threats not addressed by drug and vaccine therapies and diminishes
challenges in addressing genetically modified or artificially engineered pathogens,
thereby filling voids in the armamentarium necessary to protect against existing,
evolving, and future threats. As our device removes and concentrates viruses from the
entire circulatory system, it also offers to assist with early pathogen diagnosis and
provides a unique strategy for treatment in advance of pathogen identification. GMP
manufacturing has already been established in the United States, and an Investigational
Device Exemption (IDE) has been submitted to the FDA to initiate clinical programs in
the United States.
Results
To date, safety of our device has been demonstrated in 68 human treatment experiences,
which also validated the ability of our device to reduce viral load in patients infected with
HCV and HIV in the absence of drug therapy benefit. In vitro studies against bioterror
and pandemic threats have verified the capture of: dengue hemorrhagic fever, ebola
hemorrhagic fever lassa hemorrhagic fever, H5N1 avian influenza (bird flu), the
reconstructed 1918 influenza virus (r1918), 2009 H1N1 influenza virus (swine flu)
hepatitis-C virus (HCV), human immunodeficiency virus (HIV), West Nile virus, and
vaccinia and monkeypox, which both serve as models for human smallpox infection.
Research Collaborators
Supportive research studies demonstrating the in vitro effectiveness of the
Hemopurifier® have been conducted with the assistance of collaborating researchers
representing the following government and non-government health organizations.
The U.S. Army Medical Research Institute of Infectious Diseases
(USAMRIID) – USAMRIID, located at Fort Detrick, Maryland, serves as the
lead laboratory for the U.S. Medical Biological Defense Research Program, and
plays a key role in national defense and in infectious disease research.
USAMRIID operates the only laboratory in the Department of Defense (DOD)
equipped to study Ebola and other highly hazardous infectious agents requiring
maximum containment at bio-safety level four (BSL-4).
The Centers for Disease Control and Prevention (CDC) – The CDC serves as
the national focus for developing and applying disease prevention and control for
the people of the United States.
The National Institute of Virology (NIV) – The NIV is a leading infectious
disease research center in India, and is designated as a collaborating laboratory of
the World Health Organization (WHO). It was established in 1952 under the
auspices of the Indian Counsel of Medical Research (ICMR) and the Rockefeller
Foundation in the United States. The ICMR was established by the Government
of India in 1911 and oversees medical research in the country.
The Battelle Biomedical Research Center (BBRC) – The BBRC is one of the
largest, private, biomedical laboratories in the country. The BBRC operates as a
subsidiary of Battelle, a global leader in science and technology, who manages
and co-manages national labs, and oversees 20,000 staff members and conducts
$3.4 billion in annual research and development.
The Southwest Foundation for Biomedical Research (SFBR) – The SFBR is
one of the world's leading independent research organizations. It is home to the
only privately owned bio-safety level-4 (BSL-4) laboratory in the United States.
This maximum containment lab allows for research on lethal pathogens for which
there are no treatments or vaccines, including bioterror and emerging pandemic
threats.
The Hemopurifier® Mechanism of Action
The Hemopurifier® is a proprietary platform technology that provides an advanced
approach to address the treatment of drug and vaccine resistant viral pathogens. The
primary component of the technology is a cartridge containing lectin-derived affinity
agents that are covalently coupled to a solid phase matrix immobilized within the spaces
between approximately 2800 capillary fibers that run the length of the cartridge. As
viruses exit infected host cells, they envelop themselves with glycoprotein structures that
are acquired from the host cell’s membrane. This host-derived envelope conveys upon
the viruses a high degree of immunity from the host defenses because they are seen as
“self”. However, the same strategy that conveys the virus’ stealth causes it to be bound
tightly to the lectin affinity agents housed in Aethlon’s Hemopurifier®. Furthermore,
these surface glycoproteins are often shed from the virus and act as immunosuppressive
agents either by binding to virus specific antibodies or by direct interaction with immune
cells that can lead to apoptosis. Immunosuppressive viral glycoproteins are also
selectively trapped by the lectin within the matrix. The avidity of the immobilized lectin
for virus is much greater than for normal serum glycoproteins, providing the
Hemopurifier® with its exquisite viral selectivity.
The technology first separates plasma containing viruses and immunosuppressive
proteins from the cellular components in blood circulation. These pathogens are then
captured and removed from the plasma as a result of selective affinity binding to
glycoprotein structures both resident on and shed from the surface of pathogenic
enveloped viruses. The plasma is then recombined with cellular components and re-
infused to the patient making sterile replacement solutions unnecessary. Once blood flow
is accessed in the patient, therapeutic filtration of the entire circulatory system can occur
through the device every 12-15 minutes.
Implementation of the Hemopurifier®
The Hemopurifier® is designed for widespread implementation as a post-exposure
treatment against viral pathogens deemed high priority category A, B, and C bioterror
and pandemic threats. To initiate treatment with the Hemopurifier®, blood circulation is
established into the filtration device via a catheter or a veno-venous stick identical to that
used in standard blood collection procedures for cell separation. Once blood flow has
been established and directed through the Hemopurifier®, infectious viruses and
immunosuppressive proteins are selectively captured from circulation prior to the
occurrence of cell and organ infection. The Hemopurifier® incorporates the use of
industry standard connectors and blood tubing, thus allowing the continuous circulation
of patient blood to be maintained with portable blood pumps or apheresis and dialysis
machines. Such flexibility allows for the Hemopurifier® to deliver therapeutic benefit in
field locations, mobile military hospitals, quarantine treatment centers, and in civilian and
military hospitals and clinics.
We have also initiated development of a second generation Hemopurifier® that allows for increased portability, expands blood access options, and enhances viral pathogen clearance. A tested prototype of this device has demonstrated a 5 to 7 fold increase in viral clearance in studies conducted by our researchers.
The Broad-Spectrum Application of the Hemopurifier®
The Hemopurifier® offers the potential to improve public health emergency preparedness
against Traditional, Enhanced, Emerging, and Advanced Agents, which represent the
entire biological and pandemic threat spectrum.
I. Traditional Agents – Traditional agents are known naturally occurring viral
pathogens classified as high-consequence threats with potential to cause mass
casualties upon dissemination. Examples include Ebola and Smallpox viruses.
The Hemopurifier® serves as an adjunct therapy to augment the benefit of
approved or available therapies for traditional agents.
The Hemopurifier® serves as first-line countermeasure against drug and
vaccine resistant traditional agents.
II. Enhanced Agents – Enhanced agents are traditional agents that have been
genetically modified to enhance their ability to harm human populations or
circumvent traditional drug and vaccine therapies.
The Hemopurifier® is a first-line countermeasure against enhanced agents
created to be drug and vaccine resistant.
The Hemopurifier® serves as a combination therapy to strengthen the benefit
of candidate therapies proven safe but unable to previously demonstrate
treatment effectiveness against unknown enhanced agents.
The Hemopurifier® assists in the initial identification of enhanced agents
through the concentration and capture of genetically modified viral pathogens
from the entire circulatory system.
III. Emerging Agents – Emerging agents are previously unrecognized pathogens that
might be naturally occurring and present a serious risk to human population, such
Severe Acute Respiratory Syndrome (SARS) or future strains of pandemic influenza.
Tools to detect and treat these threats may be limited or not exist.
The Hemopurifier® is a first-line countermeasure against emerging agents.
The Hemopurifier® serves as a combination therapy to strengthen the benefit
of candidate therapies proven safe but unable to previously demonstrate
treatment effectiveness against unknown emerging agents.
The Hemopurifier® assists in the initial identification of emerging agents
through the concentration and capture of unidentified viral pathogens from the
entire circulatory system.
IV. Advanced Agents – Advanced agents are novel pathogens that have been artificially
engineered in the laboratory to bypass traditional countermeasures or produce a more
severe or otherwise enhanced spectrum of disease.
The Hemopurifier® is a first-line countermeasure against advanced agents.
The Hemopurifier® assists in the initial identification of advanced agents
through the concentration and capture of artificially engineered pathogens from
the entire circulatory system.
In addition to broad-spectrum attributes against agents of bioterror, the Hemopurifier®
may address the needs of immunocompromised and at-risk populations, including
children, pregnant women, and senior citizens for whom the administration of single-
target drug or vaccine countermeasures may be medically contraindicated.
Conclusion
The Hemopurifier® holds promise to be an integral post-exposure treatment strategy to
mitigate illness, suffering, and death resulting from exposure to biological weapons. The
device has been demonstrated safe in initial human studies, has demonstrated robust viral
load reductions against HCV and HIV, and has proven effective in capturing many of the
worlds deadliest pathogen during in vitro studies performed at leading government and
non-government research centers. In conclusion, the unprecedented broad-spectrum
capabilities of the Hemopurifier® offer to beneficially impact the state of preparedness
for the United States and ally nations.
Certain of the statements within this report may be forward-looking and involve risks and uncertainties. Such forward-looking statements involve assumptions, known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of Aethlon Medical, Inc to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such potential risks and uncertainties include, without limitation, the Company’s ability to raise capital when needed, the Company’s ability to complete the development of its planned products, the ability of the Company to obtain FDA and other regulatory approvals permitting the sale of its products, the Company’s ability to manufacture its products and provide its services, the impact of government regulations, patent protection on the Company’s proprietary technology, product liability exposure, uncertainty of market acceptance, competition, technological change, and other risk factors. In such instances, actual results could differ materially as a result of a variety of factors, including the risks associated with the effect of changing economic conditions and other risk factors detailed in the Company’s Securities and Exchange Commission filings which can be accessed at www.SEC.gov.