A platform technology to address bioterrorism


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A report on a broad-spectrum treatment countermeasure against bioterror threats.

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A platform technology to address bioterrorism

  1. 1. A Platform Technology to Address Bioterrorism November 18, 2010 James A. Joyce Chairman & CEO, Aethlon Medical, Inc jj@aethlonmedical.com Rodney S. Kenley President, Aethlon Medical, Inc rkenley@aethlonmedical.com Richard H. Tullis, Ph.D. Chief Science Officer, Aethlon Medical, Inc rhtullis@aethlonmedical.com 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
  2. 2. 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.
  3. 3. 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
  4. 4. 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
  5. 5. 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.
  6. 6. 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,
  7. 7. 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.
  8. 8. 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.
  9. 9. 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
  10. 10. 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.