The Life Sciences Report: Aethlon Medical Inc. (AEMD:NASDAQ)
has developed a novel affinity biofiltration platform that removes disease-enabling particles from the bloodstream. How effective is it, and what makes it so effective?
James Joyce: At Aethlon Medical, we have established an expansive therapeutic platform that allows us to target a wide range of disease-promoting targets from the circulatory system. Our lead product, the Aethlon Hemopurifier, provides a clinical pathway into infectious disease and cancer. In 2014, TIME magazine named the device one of the 25 best inventions of the year and also one of the 11 most remarkable advances in healthcare.
In the case of the Hemopurifer, our device integrates advanced plasma membrane technology with an affinity lectin to reduce the presence of infectious disease and oncology targets without stripping out essential components required for health. The Hemopurifier is designed for use within the existing infrastructure of dialysis and continuous renal replacement therapy machines already located in hospitals and clinics worldwide.
“The Hemopurifer integrates advanced plasma membrane technology with an affinity lectin to reduce the presence of infectious disease and oncology targets without stripping out essential components required for health.”
In human studies, we’ve treated patients with HIV and hepatitis C. We also received a lot of attention in 2014 during the Ebola outbreak for our response in treating an Ebola patient at University Hospital Frankfurt. The patient was comatose, with multiple organ failure. At the time of treatment, he had approximately 400,000 copies per milliliter of Ebola virus in his blood. After the conclusion of a single six-and-a-half-hour Hemopurifier treatment, the viral load was next measured at approximately 1,000 copies per milliliter. Five days later, the virus was undetectable. The patient made a full recovery and returned home to his wife and children. This outcome was accomplished in the absence of antiviral drug therapy.
TLSR: How does this approach compare to drug-based therapies?
JJ: Using infectious viral pathogens as an example, the primary difference between our techniques and drug techniques is that antiviral drugs are designed primarily to inhibit replication of the virus, or to fuse to the virus to inhibit it from continuing to infect healthy cells. It’s an additive therapy.
We, in contrast, are extracting viral copies from the circulatory system in real time. Blood flows through our cartridge, which has an affinity to capture viruses and shed glycoproteins that, oftentimes, are immunosuppressive. So instead of an additive therapy, you could consider our device a selective subtracted therapy. We also have the unique ability to elute the biological fluid out of the cartridge after treatment for quantification. In one hepatitis C patient who was treated overseas, we determined that during one six-hour treatment we eliminated approximately 300 billion copies of hepatitis C virus during a single six-hour treatment.
TLSR: How long is a typical treatment session?
JJ: In clinical studies to date, treatments have ranged from four to six hours. The longest treatment was the Ebola patient.
TLSR: How does your system work, and does it have any competitors?
JJ: Historically, therapeutic biofiltration devices have mostly been limited to the indiscriminate removal of disease-causing particles by molecule size, through hollow fibers or porous beads. In our case, we’re combining the capabilities of hollow fibers with an affinity lectin that binds to a unique structure co-opted from the host cell during replication. This unique structure exists across different species, families, and strains of viral pathogens. That’s what gives us broad-spectrum capability.
In terms of other therapeutic biofiltration devices, we aren’t aware of any competitors that combine a simultaneous affinity and separation mechanism.
TLSR: What are the potential applications?
JJ: In terms of infectious viral pathogens, people are often surprised to learn that more than 300 viral pathogens are known to be infectious to humans. Of those viruses, only nine are addressed with approved antiviral drug therapies. There is a tremendous need for countermeasures against Category A pathogens, which are considered bioterror or pandemic threats. In those cases, we are working to tip the balance in favor of the immune system, much like we did with the Ebola patient, to rapidly reduce viral load and allow the patient’s immune system a greater opportunity to overcome infection.
“In terms of other therapeutic biofiltration devices, we aren’t aware of any competitors that combine a simultaneous affinity and separation mechanism.”
For chronic viral conditions such as HIV or hepatitis C, we look at the ability to address mutant or drug-resistant virus strains that cause people to fail their antiviral drug therapies. Here, we can work in conjunction with drug therapies, or as a potential monotherapy for people who have become fully drug resistant.
TLSR: Where do you envision treatment occurring?
JJ: Initially, we envision that our therapies would be available in hospitals and dialysis clinics. As we expand into oncology indications, we would like to have a portable instrument that would allow our technology to be easily delivered on an outpatient basis, in physicians’ offices.
TLSR: How do you envision the Aethlon pipeline building out?
JJ: Right now, we have the ability to interchange affinity agents to create capabilities against different indications. Today, our primary focus is on advancing our technology against viral pathogens and expanding the use of the Hemopurifier into oncology.
We also have a U.S. Department of Defense contract with the Defense Advanced Research Projects Agency (DARPA), in which we’re utilizing our device platform to create new therapies for sepsis. Those are our two primary areas of focus.
Long term, we are very excited about the discovery that our Hemopurifier can capture tumor-secreted exosomes.
When we first started looking at tumor-secreted exosomes, the medical community consensus was that they were just cellular debris with no biological function. We believed that these particles were immunosuppressants. Today, it’s well understood that tumor-secreted exosomes are, in fact, immunosuppressive, and that they also play a much larger role in cancer progression. That role is related to the fact that exosomes are seeds that facilitate the creation of metastases, and they transport other particles that lead to cancer progression. Consequently, the elimination of circulating tumor-secreted exosomes would address a significant unmet medical need in cancer care.
“Our primary focus is on advancing our technology against viral pathogens and expanding the use of the Hemopurifier into oncology.”
Researchers have also reported that tumor-secreted exosomes trigger apoptosis (programmed cell death) of immune cells and contribute to drug and chemotherapy resistance. It’s also important to recognize that circulating tumor-exosome load correlates to the stage of cancer.
We believe that eliminating circulating tumor-secreted exosomes, in combination with emerging immuno-oncology drugs, should be clinically tested—especially considering the possibility that our device could combine with other therapies to improve treatment outcomes without adding drug toxicity.
TLSR: How will Aethlon make an impact in the oncology sector?
JJ: We believe the elimination of tumor-secreted exosomes could unlock the capability of emerging immuno-oncology drugs. What better way to improve the immune system’s ability to combat cancer than to have a device that targets exosome-related immune suppression working in tandem with immuno-oncology drugs designed to stimulate the ability of the immune system to combat cancer?
TLSR: Are you working with any other companies to do that?
JJ: We currently are conducting in vitro validation studies, as well as a study at the University of California, Irvine. We’re recruiting patients with nine different types of cancer to help us determine which indication we should first pursue.
TLSR: What are the regulatory hurdles? Where are you in the approval process?
JJ: We have conducted multiple studies overseas, which contributed to our obtaining approval for an investigational device exemption (IDE) by the FDA. In the U.S., we are actively moving forward to conduct a 10-patient feasibility study at DaVita Med Center Dialysis in Houston, Texas. This study provides a gateway into pivotal studies for infectious viral pathogens, where it is feasible to conduct controlled efficacy studies. The study protocol is quite similar to a protocol we successfully conducted overseas. We also hope to leverage this feasibility into future oncology indications.
TLSR: You mentioned the DARPA sepsis program. Tell me about that. How is it evolving?
JJ: We are a participant in DARPA’s Dialysis-Like Therapeutics (DLT) team program. The goal of the DLT program is to create a sepsis treatment device and then submit an IDE to the division of the Center for Devices and Radiological Health at the FDA, as a means to initiate human clinical studies. The DLT team has done tremendous work in advancing instrument designs, as well as in discovering therapeutic biofiltration mechanisms that could be beneficial in treating sepsis patients.
TLSR: Let’s talk about finances. Aethlon was listed on NASDAQ earlier this year, receiving a $6 million injection of capital. How do you plan to use these funds?
JJ: The uplisting to NASDAQ was of significant importance as it provides us with access to the broader capital markets going forward. The proceeds are primarily directed toward clinical progression.
“We believe the elimination of tumor-secreted exosomes could unlock the capability of emerging immuno-oncology drugs.”
Based on the magnitude of the underlying markets we are targeting, we believe that successful clinical progression would drive stakeholder value and allow us to access the capital markets in the future on a less dilutive basis, as compared to our options prior to listing on NASDAQ.
TLSR: Why is your management team uniquely suited to take this company forward?
JJ: We have evolved our technology from a theoretical concept into early R&D studies, then into animal studies, and then into multiple human studies, which now allows us the opportunity to work with the FDA to clinically advance our vision in the United States. As our product is a first-in-class therapy, our small team has an unrivaled understanding of our technology and the industry space.
In fact, our capabilities to selectively target disease-promoting factors from blood led to the launch of a majority-owned subsidiary, Exosome Sciences Inc. Though not our core focus, Exosome Sciences is working to expand the application of some of our affinity binding techniques into the diagnostic field.
Our methods are being tested in the Diagnosing and Evaluating Traumatic Encephalopathy Using Clinical Tests (DETECT) study, which is managed by Boston University’s Chronic Traumatic Encephalopathy (CTE) Center. CTE is a chronic neurological condition associated with sub-concussive blows to the head. It’s best known from a media standpoint for its prevalence in former NFL players.
“The uplisting to NASDAQ was of significant importance as it provides us with access to the broader capital markets going forward.”
Presently, CTE can only be diagnosed postmortem, through autopsy. There is no blood-based test to identify the disease. The Veterans Administration and our collaborators at Boston University have identified CTE in 87 of 91 brains of former NFL players that were examined post-autopsy.
The goal of the DETECT study is to discover a biomarker that could identify CTE while people are alive. We have discovered an exosome-based particle, which we call a Tausome, that we believe correlates very closely with cognitive decline. In our initial studies, we have observed that Tausome levels in former NFL players are significantly higher than that of control subjects. A manuscript that details our findings is pending publication.
TLSR: What can we expect from Aethlon near term, and five years on?
JJ: In the near-term, we need to accelerate the pace of our IDE feasibility study. We are now completing the transition of our study principal investigator, as previously disclosed. We have also been quite busy in the interim, as we have worked to improve the quality assurance, quality control, and document control functions that underlie the manufacturing of our technology. We have also been advancing methodologies through collaborations that should allow for low-cost, large-scale production of the affinity lectin that we immobilize within our Hemopurifier. We’ve been quietly building the internal engine of the company.
Now we need to move forward on the clinical side, and then leverage our outcomes into pivotal studies against chronic viral pathogens, where it is feasible to conduct controlled clinical studies. We will pursue humanitarian pathways for high-threat viral pathogens that are not treatable with antiviral drug therapies.
Parallel to our viral endeavors, we need to leverage our opportunity in the oncology space, which I believe is an untapped value driver for our company long term.
Based on our novel device mechanism and the size of underlying market opportunities, successful clinical progression might also trigger the interest of large players in the infectious disease and oncology fields.
TLSR: You just mentioned the importance of larger players. Are you looking to perhaps license the technology, develop it yourself, or partner with another company?
JJ: At this point in time, the Hemopurifier technology is developed. We have a lot of clinical experience abroad that we’re working to replicate here in the U.S.
In terms of other development opportunities, we eventually may want to partner with others to immobilize a variety of affinity agents to advance selective extracorporeal cocktail therapies to address unique yet hard-to-treat disease conditions.
As a medical device developer we don’t have the same overall clinical challenges as biologic drug developers, so we’re not forced to partner or license our technology to advance. What we really need to focus on is clinically progressing our technology and showing that it’s not just safe, but also can provide patient benefit in large disease conditions.
TLSR: Is there anything else that you’d like investors to know?
JJ: To summarize, we have an expansive therapeutic device platform. Our lead product, the Hemopurifier, provides a clinical pathway into both infectious disease and cancer. It has proven, broad-spectrum capabilities against viral pathogens, and could be an untapped value driver based on the discovery that our Hemopurifier can also capture cancer-promoting exosomes.
In terms of our DARPA DLT team, we hope to have a sepsis treatment candidate ready for an IDE submission in the coming year.
Then, on the diagnostic front, we have a manuscript pending publication related to the first blood-based biomarker candidate to identify and monitor CTE in living individuals.
TLSR: Jim, thank you very much.
James A. Joyce is the founder, chairman and CEO of Aethlon Medical. Under his leadership, Aethlon has transformed the concept of a selective therapeutic filtration device (the Aethlon Hemopurifier) into the reality of treating patients in a clinical setting, with follow-on research validating the ability of the Hemopurifier to capture a broad-spectrum of bioterror and pandemic threats as well as immunosuppressive cancer exosomes. Joyce has originated numerous collaborative relationships with government and non-government research organizations, has authored supporting publications and reports, and raised capital resources to support the mission of Aethlon Medical. He has represented the company on CNN, NBC, ABC and other media outlets, and has testified before Congress on issues related to Project BioShield legislation and the deployment of the Aethlon Hemopurifier as a countermeasure against biological weapons. In May 2011, the company introduced the Aethlon ADAPT system, a device platform that converges affinity drug agents with plasma membrane technology to create new candidate therapies against life-threatening disease conditions. From February 1993 until founding Aethlon Medical, Joyce was CEO of James Joyce & Associates. Previously, he was founder and CEO of Mission Labs Inc., was a principal at London Zurich Securities Inc., and was a member of the Denver Broncos Football Club of the National Football League. Joyce is a graduate of the University of Maryland.