ITEM 1. DESCRIPTION OF BUSINESS
GENERAL OVERVIEW
The Aethlon Medical mission is to create innovative medical devices that address unmet medical needs in cancer, infectious disease, and other life-threatening conditions. Our Aethlon ADAPT™ System is a technology platform that delivers therapeutic mechanisms that previously did not exist in the marketplace.
The Aethlon ADAPT™ product pipeline includes the Aethlon Hemopurifier® to address infectious disease and cancer, and HER2osome™ to target HER2+ breast cancer. We are also developing a medical device and delivery instrument to reduce the incidence of sepsis in combat-injured soldiers and civilians through a contract award from the Defense Advanced Research Projects Agency (DARPA). The Aethlon ADAPT™ (Adaptive Dialysis-Like Affinity Platform Technology) system converges affinity drug agents and plasma membrane technology to create selective therapeutic filtration devices that target the removal of disease-promoting factors from the entire circulatory system.
The Aethlon Hemopurifier®
Our lead product candidate, the Aethlon Hemopurifier® represents the genesis of the Aethlon ADAPT™ system. In pre-clinical studies, the Hemopurifier® has demonstrated broad-spectrum capabilities against viral pathogens, immunosuppressive glycoproteins, and exosomes that promote the spread of cancer and other life-threatening disease conditions. In human studies, safety of the device has been demonstrated in approximately 100 treatment experiences conducted at research hospitals, including the Apollo, Fortis, and Medanta Medicity Institute in India. Hemopurifier® therapy has been demonstrated to be well tolerated and capable of reducing viral load in HIV and hepatitis C virus (HCV) infected individuals without the administration of antiviral drugs. We are now advancing our Hemopurifier® as an adjunct strategy to improve the benefit of infectious disease and cancer treatment regimens. We have recently disclosed very promising results from Hemopurifier® therapy being administered to HCV-infected individuals in combination with interferon-ribavirin drug therapy. This study is being conducted at the Medanta Medicity Institute.
Based on studies conducted by both government and non-government research organizations, the Hemopurifier® has also demonstrated the ability to capture a broad-spectrum of viral bioterror and pandemic threats. The Hemopurifier® is a single-use disposable cartridge designed for implementation within the established infrastructure of dialysis machines and other blood pump systems already located in hospitals and clinics worldwide. To initiate Hemopurifier® therapy, blood circulation is accessed via a catheter or other blood access device. In design, the Hemopurifier® contains lectin affinity agents that bind to high-mannose structures unique to glycoproteins that coat viruses and immunosuppressive exosomes that are secreted by cancerous tumors. The lectin affinity agent is immobilized to surround approximately 2,800 porous hollow fibers that run the interior length of our device. During Hemopurifier® therapy, viral and exosomal targets are separated from circulation through the fiber walls and away from blood cells and other essential blood components. Once separated, viruses, immunosuppressive glycoproteins, and exosomes are then selectively bound from circulation by the immobilized lectin prior to the occurrence of cell and organ infection or apoptosis of immune cells.
In 2010, we established "good manufacturing practice" (GMP) for the manufacture of the Hemopurifier® in an FDA-approved facility in San Diego, California. We believe the HCV treatment study that we are currently conducting in India will lead to potential commercialization in India, and we are advancing strategies to initiate clinical programs in the United States and the European Union. We believe our Hemopurifier® is positioned to address four significant market opportunities:
1.) Cancer:
The Hemopurifier® addresses a major unmet medical need in cancer, the ability to inhibit the spread of tumor-secreted exosomes or microvesicles. Exosomes have recently emerged to become a vital therapeutic target as they play an instrumental role in promoting tumor progression by inducing programmed cell death of anti-cancer immune cells. As a result of inhibiting the immune response, exosomes increase the proliferation and spread of many forms of cancer. The particles also seed the spread of tumor metastasis, promote angiogenesis (essential for tumor survival and growth), increase tumor aggressiveness, and contribute to anti-cancer drug resistance. Exosomes have also been discovered to have immunosuppressive roles in infectious disease and may accelerate the pathogenesis of other disease conditions as they have been reported to induce or amplify inflammatory and pathological conditions including, cardiovascular disease, hypertension, neurodegenerative disorders, diabetes, and rheumatic diseases.
In vitro studies have documented that the Hemopurifier® captures ovarian, breast, lymphoma, melanoma, and colorectal cancer exosomes. Additionally, the capture of exosomes underlying HIV infection and tuberculosis has also been validated.
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2.) Hepatitis-C Virus (HCV):
We are currently conducting an HCV clinical treatment program at the Medanta Medicity (Medicity), which is one of India’s largest multi-super specialty institutes. The goal of our study is to demonstrate the utility of our Hemopurifier(R) as an adjunct therapy to accelerate viral load reduction when administered at the outset of standard of care drug therapy. We recently reported that the presence of HCV was undetectable in all infected patients that have been treated with the Aethlon Hemopurifier® in combination with peginterferon+ribavirin (PR) drug therapy and monitored for at least ninety days. In the Medicity study, HCV-infected individuals were enrolled to receive up to three, six-hour Hemopurifier® treatments during the first three days of PR drug therapy. To date, Hemopurifier® therapy has been well tolerated in the Medicity study and without device-related adverse events in nine treated patients. Of these nine patients, six patients were infected with HCV genotype-1; two patients were infected with HCV genotype-3; and one patient was infected with HCV genotype-5. Of the nine reported patients, seven had been monitored for more than ninety days. All seven currently maintain undetectable viral load, including three patients who have been monitored for more than 48-weeks. Two patients initiated Hemopurifier® therapy on April 18th and April 30th and have not yet been monitored for extended viral load suppression.
In addition to demonstrating safety and early efficacy against multiple HCV genotypes, a clinical objective of the Medicity study is to evaluate whether the Hemopurifier® can accelerate HCV eradication to levels associated with treated patients who achieve the highest rate of viral cure, including individuals that previously failed or relapsed PR drug regimens. In the study, we observed that viral load depletion during the Hemopurifier® + PR drug therapy phase was greatest in hard-to-treat genotype-1 patients with high viral load. In one treated patient, baseline HCV RNA dropped from 5,800,000 IU/ml to 1,840 IU/ml when measured after the third day of Hemopurifier® + PR therapy, representing a 3.49 log or 99.96% reduction of viral load. In another patient, baseline HCV RNA dropped from 8,760,000 IU/ml to 4,665 IU/ml when measured on day-3, representing a 3.27 log or 99.96% reduction. By contrast, a moderate viral load Hemopurifier® patient with baseline HCV RNA of 1,340,000 IU/ml dropped to 54,900 IU/ml when measured on day-3, representing a 1.38 log or 95.9% reduction.
As the result of July 2011 discussions with reviewers at the Center for Devices and Radiological Health (the FDA branch responsible for approving medical devices in the US), we expanded our Medicity protocol to establish a data point that would quantify the amount of HCV captured within the Hemopurifier® during a single treatment. In one analyzed cartridge, we reported that researchers recovered and measured that approximately 300 billion (300,000,000,000) copies of HCV had been captured within the Hemopurifier® during a single six-hour treatment at the Medicity. Beyond the impact of inhibiting progeny virus replication, we feel the viral capture data point defines the contribution Hemopurifier® therapy can provide to current and future antiviral drug treatment regimens. We believe such a data point is unprecedented as the previous ability to measure the benefit of HCV therapies has primarily been limited to measuring changes in the amount of virus that can be detected in circulation. We are now preparing to resubmit an investigational device exemption (IDE) to the FDA that will request permission to initiate human clinical studies in the United States.
3) Human Immunodeficiency Virus (HIV):
Antiviral drug regimens provide HIV infected patients with an effective tool to inhibit disease progression. However, many patients inevitably become resistant to their drug therapies and are left with limited treatment options. We believe our Hemopurifier(R) provides a device-based antiviral and immunotherapeutic mechanism to inhibit the spread of all HIV strains, thus providing fully drug resistant patients with a treatment strategy to inhibit disease progression. In a proof of principal treatment study, our Hemopurifier® reduced viral load by 93% in an HIV-AIDS infected individual without the administration of antiviral drug therapy. The study protocol provided for 12 Hemopurifier® treatments, each four hours in duration, that were administered over the course of one month. We have since discovered that the Hemopurifier® is able to capture exosomes that transport NEF protein, which is known to suppress the immune response in HIV-infected individuals.
4.) Bioterror and Pandemic Threats:
Based on established human safety data and pre-clinical studies conducted by government and non-government research institutes, we believe our Hemopurifier® is an advanced broad-spectrum treatment countermeasure against bioterror and pandemic threats, and the sole therapeutic strategy against viral threats that are not treatable with drug or vaccine therapies. Pre-clinical in vitro studies have demonstrated the ability of our Hemopurifier® to capture Ebola Virus, Dengue Virus, Lassa Virus, West Nile Virus, Monkeypox Virus, H5N1 Avian Influenza Virus, the 2009 H1N1 Swine Flu Virus, and the reconstructed H1N1 Spanish Flu of 1918 virus.
EXOSOME SCIENCES, INC.
We established Exosome Sciences (ESI) in October of 2009 as a wholly owned subsidiary to advance diagnostic tools created by our researchers to identify the presence of exosomes in blood and other fluids. The research diagnostic tool resulting from the efforts of our researchers is ELLSA™, an Enzyme Linked Lectin Specific Assay that has been validated to identify the presence of exosomes underlying the human immunodeficiency virus (HIV), tuberculosis (TB), and various forms of cancer, including ovarian, melanoma, breast, lymphoma, and colorectal. While we have received product orders, our focus is directed toward therapeutic opportunities. As such, we plan to license or sell ELLSA™ and other related research diagnostic tools.
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TRANSITION TO REVENUE STAGE ORGANIZATION
In May of 2011, we introduced and began marketing the Aethlon ADAPT™ system. On September 30th, 2011, we entered into a $6.8 million multi-year contract with the Defense Advanced Research Projects Agency (DARPA) resulting from our response to a program entitled “Dialysis-Like Therapeutics.” Under this contract, our tasks include the development of a dialysis-like device to prevent sepsis, a fatal bloodstream infection that is often the cause of death in combat-injured soldiers. As a result of achieving five contract milestones between October 1, 2011 and March 31, 2012, we reported $1,358,189 in contract revenue at our March 31 fiscal year end.