Aethlon Medical, Inc. Form 10-K
Table of Contents
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 10-K
(MARK ONE)
☒ ANNUAL
REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended March 31, 2024
OR
☐ TRANSITION
REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from ________ to __________
COMMISSION FILE NUMBER 001-37487
Aethlon Medical, Inc.
(Exact name of registrant as specified in its charter)
(State or other jurisdiction of (I.R.S. Employer
incorporation or organization) Identification No.)
San Diego, California 92121
(Address of principal executive office) (Zip Code)
REGISTRANT’S TELEPHONE NUMBER, INCLUDING AREA
CODE: (619) 941-0360
SECURITIES REGISTERED PURSUANT TO SECTION 12(b) OF
THE EXCHANGE ACT:
SECURITIES REGISTERED UNDER SECTION 12(g) OF THE EXCHANGE
ACT:
NONE
(TITLE OF CLASS)
Indicate by check mark if the registrant is a well-known seasoned issuer,
as defined in Rule 405 of the Securities Act. Yes ☐No☒
Indicate by check mark if the registrant is not required to file reports
pursuant to Section 13 or 15(d) of the Act. Yes ☐No☒
Indicate by check mark whether the registrant (1)
has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months
(or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements
for the past 90 days. Yes☒ No ☐
Indicate by check mark whether the registrant has
submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of
this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes☒ No ☐
Indicate by check mark whether the registrant is a
large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See
the definitions of “large accelerated filer,” “accelerated filer”, “smaller reporting company”, and
“emerging growth company” in Rule 12b-2 of the Exchange Act. (Check one)
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ☒ Smaller reporting company ☒
Emerging growth company ☐
If an emerging growth company, indicate by check mark
if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards
provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant has
filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting
under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its
audit report. ☐
If securities are registered pursuant to Section 12(b) of the Act, indicate
by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously
issued financial statements. ☐
Indicate by check mark whether any of those error corrections are restatements
that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during
the relevant recovery period pursuant to § 240.10D-1(b). ☐
Indicate by check mark whether the registrant is a shell company (as defined
in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒
The aggregate market value of the common stock held
by non-affiliates of the registrant as of September 29, 2023 (the last trading day of the registrant’s most recently completed second
quarter) was approximately $5.5 million, computed by reference to the closing sale price of the common stock of $2.258 per share on the
Nasdaq Capital Market on September 29, 2023. Shares of common stock held by each executive officer and director and by each person who
owns 10% or more of the outstanding common stock have been excluded in that such persons may be deemed to be affiliates. The determination
of affiliate status is not necessarily a conclusive determination for other purposes.
The number of shares of the common stock of the registrant outstanding
as of June 25, 2024 was 13,899,725.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the registrant’s proxy statement
to be filed with the Securities and Exchange Commission, or SEC, pursuant to Regulation 14A in connection with the registrant’s
2024 Annual Meeting of Stockholders, which will be filed subsequent to the date hereof, are incorporated by reference into Part III of
this Annual Report on Form 10-K. Such proxy statement will be filed with the SEC not later than 120 days following the end of the registrant’s
fiscal year ended March 31, 2024.
TABLE OF CONTENTS
PAGE
PART I.
Item 1. Business 1
Item 1A. Risk Factors 15
Item 1B. Unresolved Staff Comments 45
Item 1C. Cybersecurity 45
Item 2. Properties 46
Item 3. Legal Proceedings 47
Item 4. Mine Safety Disclosures 47
PART II.
Item 6. [Reserved] 48
Item 7A. Quantitative and Qualitative Disclosures about Market Risk 57
Item 8. Financial Statements and Supplementary Data 57
Item 9A. Controls and Procedures 57
Item 9B. Other Information 59
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 59
PART III.
Item 10. Directors, Executive Officers and Corporate Governance 60
Item 11. Executive Compensation 60
Item 14. Principal Accountant Fees and Services 60
PART IV.
Item 15. Exhibits and Financial Statement Schedules 61
Signatures 65
i
CAUTIONARY NOTICE REGARDING FORWARD LOOKING STATEMENTS
This Annual Report on Form 10-K,
or Annual Report, contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933,
as amended, or Securities Act, and Section 21E of the Securities Exchange Act of 1934, as amended, or the Exchange Act, which are
subject to the safe harbor created by those sections.
We may, in some cases, use words
such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,”
“may,” “plan,” “potential,” “predict,” “project,” “should,” “will,”
“would” or the negative of these terms, and similar expressions that convey uncertainty of future events or outcomes to identify
these forward-looking statements. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking
statements and are based upon our current expectations, beliefs, estimates and projections, and various assumptions, many of which, by
their nature, are inherently uncertain and beyond our control. Such statements, include, but are not limited to, statements contained
in this Annual Report relating to our business, business strategy, products and services we may offer in the future, the timing and results
of future regulatory filings, the timing and results of future clinical trials, and capital outlook. Forward-looking statements are based
on our current expectations and assumptions regarding our business, the economy and other future conditions. Because forward looking statements
relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. Our
actual results may differ materially from those contemplated by the forward-looking statements. They are neither statement of historical
fact nor guarantees of assurance of future performance. We caution you therefore against relying on any of these forward-looking statements.
Important factors that could cause actual results to differ materially from those in the forward looking statements include, but are not
limited to, a decline in general economic conditions nationally and internationally; the ability to protect our intellectual property
rights; competition from other providers and products; risks in product development; inability to raise capital to fund continuing operations;
changes in government regulation; the ability to complete capital raising transactions, and other factors (including the risks contained
in Item 1A of this Annual Report under the heading “Risk Factors”) relating to our industry, our operations and results of
operations and any businesses that may be acquired by us. Should one or more of these risks or uncertainties materialize, or should the
underlying assumptions prove incorrect, actual results may differ significantly from those anticipated, believed, estimated, expected,
intended or planned.
Factors or events that could cause
our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them, nor can we assess the
impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ
materially from those contained in any forward-looking statements we may make. Given these uncertainties, you should not place undue reliance
on these forward-looking statements. We cannot guarantee future results, levels of activity, performance or achievements. Except as required
by applicable law, we undertake no obligation to and do not intend to update any of the forward-looking statements to conform these statements
to actual results.
ii
SUMMARY RISK FACTORS
Below is a summary of the principal factors that make
an investment in our securities speculative or risky. This summary does not address all of the risks that we face. Additional discussion
of the risks summarized in this risk factor summary, and other risks that we face, can be found below under the heading “Risk Factors”
in Part I of this Annual Report and should be carefully considered, together with other information in this Annual Report and our other
filings with the SEC before making investment decisions regarding our securities.
· Our Hemopurifier technology may become obsolete.
· Our success is dependent in part on our executive officers.
ii
PART I
ITEM 1. BUSINESS
Unless otherwise indicated or
the context otherwise requires, references to the “Company”, “Aethlon”, “we”, “us” and
“our” refer to Aethlon Medical, Inc.
Overview and Corporate History
Overview
We are a medical therapeutic company focused on developing
the Hemopurifier, a clinical-stage immunotherapeutic device designed to combat cancer and life-threatening viral infections and for use
in organ transplantation. In human studies, 164 sessions with 38 patients, the Hemopurifier was safely utilized and demonstrated the potential
to remove life-threatening viruses. In pre-clinical studies, the Hemopurifier has demonstrated the potential to remove harmful exosomes
and exosomal particles from biological fluids, utilizing its proprietary lectin-based technology. This action has potential applications
in cancer, where exosomes and exosomal particles may promote immune suppression and metastasis, and in life-threatening infectious diseases.
The U.S. Food and Drug Administration, or FDA, has designated the Hemopurifier as a “Breakthrough Device” for two independent
indications:
Oncology
We believe the Hemopurifier may be a substantial advancement
in the treatment of patients with advanced and metastatic cancer through its design to bind to and remove harmful exosomes and exosomal
particles that promote the growth and spread of tumors. In October 2022, we formed a wholly-owned subsidiary in Australia to initially
conduct oncology-related clinical research, then seek regulatory approval and commercialize our Hemopurifier in Australia. We are currently
working with our contract research organization, or CRO, on preparations to conduct a clinical trial in Australia in patients with solid
tumors, including head and neck cancer, and gastrointestinal cancers.
In January 2023, we entered into an agreement with
North American Science Associates, LLC, or NAMSA, a world leading medical technology CRO offering global end-to-end development services,
to oversee our planned clinical trials investigating the Hemopurifier for oncology indications. Pursuant to the agreement, NAMSA agreed
to manage our planned clinical trials of the Hemopurifier for patients in the United States and Australia with various types of cancer
tumors.
We recently completed
an in vitro binding study of relevant oncology targets, to provide pre-clinical evidence to support our trial design and translational
endpoints. Our study indicated positive results from this study, providing evidence that our Hemopurifier removes extracellular vesicles,
or EVs, from plasma. This translational study provides pre-clinical evidence to support our planned phase 1 safety, feasibility and dose-finding
clinical trials of our Hemopurifier in patients with solid tumors who have stable or progressive disease during anti-PD-1 monotherapy
treatment, such as Keytruda® or Opdivo®. In addition to an interested initial trial site in India, we had three interested sites
in Australia that were awaiting our completion of this in vitro binding study. We added the data from this study to our Clinical
Investigator Brochure and submitted that brochure to the Ethics Committee of Royal Adelaide Hospital in Australia and in June 2024, we
received approval for our proposed phase 1 oncology trial from the Ethics Committee from Royal Adelaide Hospital. We are currently in
the process of applying to the Ethics Committees of the two additional interested clinical trial sites in Australia and the site in India.
Life-Threatening Viral Infections
We also believe that the Hemopurifier can be part of
the broad-spectrum treatment of life-threatening highly glycosylated, or carbohydrate coated, viruses that are not addressed with an already
approved treatment. In small-scale or early feasibility human studies, the Hemopurifier has been used in the past to treat individuals
infected with human immunodeficiency virus, or HIV, hepatitis-C and Ebola.
Additionally, in vitro, the Hemopurifier
has been demonstrated to capture Zika virus, Lassa virus, MERS-CoV, cytomegalovirus, Epstein-Barr virus, Herpes simplex virus, Chikungunya
virus, Dengue virus, West Nile virus, smallpox-related viruses, H1N1 swine flu virus, H5N1 bird flu virus, Monkeypox virus and the reconstructed
Spanish flu virus of 1918. In several cases, these studies were conducted in collaboration with leading government or non-government research
institutes.
We believe the Hemopurifier can be part of the treatment
of severe SARS-CoV-2 viremia/COVID-19, or COVID-19, cases. COVID viremia is detected in approximately 34% of patients and is associated
with severity, requirement for intensive care unit, or ICU, stay, development of multi-organ failure and poor outcomes. EVs and exosomal
miRNAs may play a role in the spread of infection as well as ongoing inflammation, development of coagulopathy and lung injury. Our proprietary
Galanthus nivalis agglutinin, or GNA, affinity resin has been shown to bind multiple clinically relevant SARS-CoV-2 variants. Furthermore,
studies have demonstrated in vitro removal of seven SARS-CoV2 variants (104 PFU/mL) in phosphate buffered saline passed over a
column of GNA affinity resin (1g) three times, with capture efficiencies between 53% and 89%.
On June 17, 2020, the FDA approved a supplement to
our open Investigational Device Exemption, or IDE, for the Hemopurifier in viral disease to allow for the testing of the Hemopurifier
in patients with SARS-CoV-2/COVID-19, or COVID-19, in a new feasibility study. That study was designed to enroll up to 40 subjects
at up to 20 centers in the United States. Subjects were to have established laboratory diagnosis of COVID-19, be admitted to an ICU and
have acute lung injury and/or severe or life-threatening disease, among other criteria. Endpoints for this study, in addition to safety,
included reduction in circulating virus, as well as clinical outcomes (NCT # 04595903). In January 2021, the Hemopurifier was used to
treat a viremic patient, under our emergency use approval, with a predicted risk of mortality of 80% and the Hemopurifier was able to
reduce the patient’s SARS-CoV-2 plasma viral load by 58.4%. In June 2022, the first patient in this study was enrolled and
completed the Hemopurifier treatment phase of the protocol. Due to the lack of COVID-19 patients in the ICUs of our trial sites, we terminated
this study in 2022. However, our IDE for this indication remains open, as we have an active COVID-19 trial in India and wish to preserve
the option of enrolling patients if the situation with COVID-19 changes.
Under Single Patient Emergency Use regulations, Aethlon
has treated two patients with COVID-19 with the Hemopurifier, in addition to the COVID-19 patient treated with our Hemopurifier in our
COVID-19 clinical trial discussed above.
We previously reported a disruption in our Hemopurifier
supply, as our then existing supply of Hemopurifiers expired on September 30, 2022 and, also as previously disclosed, we are dependent
on FDA approval of qualified suppliers to manufacture our Hemopurifier. We recently completed final testing in order to begin manufacturing
Hemopurifiers at our new manufacturing facility in San Diego, California for use in planned U.S. clinical trials, using GNA from our current
supplier. In April 2024, we received a notice of approval from the FDA for our IDE supplement to add our San Diego manufacturing facility
and we now are able to manufacture Hemopurifiers at this site. We also have sufficient Hemopurifiers on hand for use in our planned Australia
and India oncology trials. Our intended transition to a new supplier for GNA, a component of our Hemopurifier, continues to be delayed
as we work with the FDA for approval of our supplement to our IDE, which is required to make this manufacturing supplier change. We are
working with the FDA to qualify this second supplier of our GNA.
We also obtained ethics review board, or ERB, approval
from and entered into a clinical trial agreement with Medanta Medicity Hospital, a multi-specialty hospital in Delhi NCR, India, for a
COVID-19 clinical trial at that location.
In May 2023, we received ERB approval from the MAMC,
for a second site for our clinical trial in India to treat severe COVID-19. MAMC was established in 1958 and is located in New Delhi,
India. MAMC is affiliated with the University of Delhi and is operated by the Delhi government.
We now have two sites in India for this trial with
the Medanta Medicity Hospital and Maulana Azad Medical College, or MAMC. One patient has been treated to date; however, we have been informed
by our CRO that a new COVID-19 subvariant was detected in India recently. Our COVID-19 trial in India remains open in the event that there
are COVID-19 admissions to the ICUs at our sites in India.
Organ Transplantation
Additionally, based on preclinical
data with acellular kidney perfusates, we believe that the Hemopurifier has potential applications in organ transplantation. We are investigating
whether the Hemopurifier, when incorporated into a machine perfusion organ preservation circuit, can remove harmful viruses, exosomes,
RNA molecules, cytokines, chemokines and other inflammatory molecules from recovered organs. We initially are focused on recovered kidneys
from deceased donors. We have previously demonstrated the removal of multiple viruses and exosomes and exosomal particles from buffer
solutions, in vitro, utilizing a scaled-down version of our Hemopurifier and believe this process could reduce transplantation
complications by improving graft function, reducing graft rejection, maintaining or improving organ viability prior to transplantation,
and potentially reducing the number of kidneys rejected for transplant.
Successful outcomes of human
trials will also be required by the regulatory agencies of certain foreign countries where we plan to market and sell the Hemopurifier.
Some of our patents may expire before FDA approval or approval in a foreign country, if any, is obtained. However, we believe that certain
patent applications and/or other patents issued to us more recently will help protect the proprietary nature of our Hemopurifier treatment
technology.
In addition to the foregoing, we are monitoring closely
the impact of inflation, recent bank failures and the war between Russia and Ukraine and the military conflicts in Israel and the surrounding
areas, as well as related political and economic responses and counter-responses by various global factors on our business. Given the
level of uncertainty regarding the duration and impact of these events on capital markets and the U.S. economy, we are unable to assess
the impact on our timelines and future access to capital. The full extent to which inflation, recent bank failures and the ongoing military
conflicts will impact our business, results of operations, financial condition, clinical trials and preclinical research will depend on
future developments, as well as the economic impact on national and international markets that are highly uncertain.
On March 10, 1999, Aethlon, Inc., a California corporation,
Hemex, Inc., a Delaware corporation and the accounting predecessor to Aethlon, Inc., and Bishop Equities, Inc., a publicly traded Nevada
corporation, completed an Agreement and Plan of Reorganization structured to result in Bishop Equities, Inc.'s acquisition of all of the
outstanding common stock of Aethlon, Inc. and Hemex, Inc. Under the plan's terms, Bishop Equities, Inc. issued shares of its common stock
to the stockholders of Aethlon, Inc. and Hemex, Inc. such that Bishop Equities, Inc. then owned 100% of each company. Upon completion
of the transaction, Bishop Equities, Inc. was renamed Aethlon Medical, Inc. Our executive offices are located at 11555 Sorrento Valley
Road, Suite 203, San Diego, California 92121. Our telephone number is (619) 941-0360. Our website address is www.aethlonmedical.com. The
information contained on, or that can be accessed through, our website is not part of, and is not incorporated into, this Annual Report.
The Mechanism of the Hemopurifier
The Hemopurifier is an affinity
hemofiltration device designed for the single-use removal of harmful exosomes and life-threatening viruses from the human circulatory
system. In the United States, the Hemopurifier is classified as a combination product whose regulatory jurisdiction is the Center for
Devices and Radiological Health, or CDRH, the branch of FDA responsible for the premarket approval of all medical devices.
In our current applications, our
Hemopurifier can be used on the established infrastructure of continuous renal replacement therapy, or CRRT, and dialysis instruments
located in hospitals and clinics worldwide. It could also potentially be developed as part of a proprietary closed system with its own
pump and tubing set, negating the requirement for dialysis infrastructure. Incorporated within the Hemopurifier is a protein called a
lectin, that aids in binding exosomes and viruses.
The Hemopurifier - Clinical Trials In Viral Infections
The initial development of the
Hemopurifier was focused on viral infections. In non-clinical bench experiments using a laboratory version of the Hemopurifier, performed
in Company labs as well as in multiple other outside labs, including the Centers for Disease Control and Prevention, or CDC, the United
States Army Medical Research Institute of Infectious Diseases, or USAMRIID, Battelle Memorial Research Institute and others, we have demonstrated
that a miniature version of the Hemopurifier can bind and clear multiple different glycosylated viruses. These viruses include HIV, HCV,
Dengue, West Nile, multiple strains of influenza, Ebola, Chikungunya, smallpox, monkeypox, multiple herpes viruses, a MERS-CoV related
pseudovirus and others.
Initial clinical trials on the
Hemopurifier were conducted overseas on dialysis patients with HCV, with a subsequent EFS conducted in the United States under an FDA
approved IDE.
On March 13, 2017, we concluded
an FDA-approved EFS under an IDE in end stage renal disease patients on dialysis who were infected with HCV. The study was conducted at
DaVita MedCenter Dialysis in Houston, Texas. We reported that there were no device-related adverse events in enrolled subjects who met
the study inclusion-exclusion criteria. We also reported that an average capture of 154 million copies of HCV (in International Units,
I.U.) within the Hemopurifier during four-hour treatments. Prior to this approval, we collected supporting Hemopurifier data through investigational
human studies conducted overseas.
SARS-CoV-2/COVID-19
SARS-COV-2, the causative agent
of COVID-19 is a member of the coronavirus family, which includes the original SARS virus, SARS-CoV, and the MERS virus. SARS-CoV-2, like
all coronaviruses, is glycosylated. This suggests that the Hemopurifier could potentially clear it from biological fluids, including blood.
On June 17, 2020, the FDA approved
a supplement to our open IDE for the Hemopurifier in viral disease to allow for the testing of the Hemopurifier in patients with SARS-CoV-2/COVID-19
in a New Feasibility Study. That study was designed to enroll up to 40 subjects at up to 20 centers
in the United States. Subjects had to have an established laboratory diagnosis of COVID-19, be admitted to an ICU, and have acute lung
injury and/or severe or life-threatening disease, among other criteria. Endpoints for this study, in addition to safety, include reduction
in circulating virus, as well as clinical outcomes (NCT # 04595903). In June 2022, the Company completed the treatment protocol for its
first patient in this study.
In
September 2021, we entered into an agreement with a leading global CRO to oversee our U.S. clinical studies investigating the Hemopurifier
for critically ill COVID-19 patients. Due to lack of COVID-19 patients in the ICUs of our trial sites, we terminated this study
in 2022.
Under
Single Patient Emergency Use regulations, we have also treated two patients with COVID-19 with the Hemopurifier, in addition to
the COVID-19 patient treated with our Hemopurifier in our COVID-19 clinical trial discussed above. We
published a manuscript reviewing case studies covering those two Single Patient Emergency Use treatments entitled “Removal of COVID-19
Spike Protein, Whole Virus, Exosomes and Exosomal microRNAs by the Hemopurifier® Lectin-Affinity Cartridge in Critically Ill Patients
with COVID-19 Infection.”
The
manuscript described the use of the Hemopurifier for a total of nine sessions in two critically ill COVID-19 patients. The first case
study demonstrated the improvement in the patient who was a SARS-COV-2 positive COVID-19 present at entry to the hospital, with associated
coagulopathy, or CAC, lung injury, inflammation, and tissue injury despite the absence of demonstrable COVID-19 viremia at the start of
treatment at Day 22 and having demonstrated strong viremia earlier in the patient’s disease cycle, suggesting that the significant
removal of exosomes contributed to the patient’s recovery. This patient received eight Hemopurifier treatments without complications
and eventually was weaned from a ventilator and was discharged from the hospital.
The
second patient case study demonstrated in vivo removal of SARS-CoV-2 virus from the blood stream of an infected patient. This patient
completed a six-hour Hemopurifier treatment without complications and subsequently was placed on continuous renal replacement therapy,
or CRRT. The patient ultimately expired three hours after being placed on CRRT because of the advanced stage of the patient’s disease.
In
May 2022, we announced the publication of a pre-print manuscript featuring data that demonstrated our proprietary GNA affinity resin was
able to bind seven clinically relevant SARS-CoV-2 variants in vitro, including the Delta and Omicron variants. Viral capture efficiency
with the GNA affinity resin ranged from 53% to 89% for all variants tested. The GNA affinity resin is a key component of the Hemopurifier.
The manuscript is titled "Removal of Clinically Relevant SARS-CoV-2 Variants by An Affinity Resin Containing Galanthus nivalis Agglutinin"
and was published in bioRxiv.
We
previously commissioned Battelle Memorial Institute in 2008 to run a monkeypox virus, or MPV, in vitro study using a mini-Hemopurifier.
This study demonstrated that high concentrations of MPV (approximately 35 thousand cpu/ml) were rapidly depleted from cell culture fluids
when circulated through the Hemopurifier. The study data indicated that the Hemopurifier removed 44 percent of infectious MPV in the first
hour of testing, 82 percent after six hours, and 98 percent after 20 hours. The studies were conducted in triplicate and data verification
was provided by real-time polymerase chain reaction.
The Hemopurifier – Clinical Trials Conducted Overseas in Viral
Infections
EBOLA Virus
In December of 2014, Time Magazine
named the Hemopurifier a “Top 25 Invention” as the result of treating an Ebola-infected physician at Frankfurt University
Hospital in Germany. The physician was comatose with multiple organ failure at the time of treatment with the Hemopurifier. At the American
Society of Nephrology Annual Meeting, Dr. Helmut Geiger, Chief of Nephrology at Frankfurt University Hospital reported that the patient
received a single 6.5 hour Hemopurifier treatment. Prior to treatment, viral load was measured at 400,000 copies/ml. Post-treatment viral
load reported to be at 1,000 copies/ml. Dr. Geiger also reported that 242 million copies of Ebola virus were captured within the Hemopurifier
during treatment. The patient ultimately made a full recovery. Based on this experience, the Company filed an Expanded Access protocol
with the FDA to treat Ebola virus infected patients in up to ten centers in the United States and a corresponding protocol was approved
by HealthCanada. These protocols remain open allowing Hemopurifier treatment to be offered to patients presenting for care in both countries.
In 2018, the FDA designated the Hemopurifier as a Breakthrough Device “... for the treatment of life-threatening viruses that
are not addressed with approved therapies.”
Hepatitis C Virus (HCV)
Prior to FDA approval of the IDE
feasibility study, we conducted investigational HCV treatment studies at the Apollo Hospital, Fortis Hospital and the Medanta Medicity
Institute in India. In the Medanta Medicity Institute study, 12 HCV-infected individuals were enrolled to receive three six-hour Hemopurifier
treatments during the first three days of a 48-week peginterferon+ribavirin treatment regimen. The study was conducted under the leadership
of Dr. Vijay Kher. Dr. Kher’s staff reported that Hemopurifier therapy was well tolerated and without device-related adverse events
in the 12 treated patients.
Of these 12 patients, ten completed
the Hemopurifier-peginterferon+ribavirin treatment protocol, including eight genotype-1 patients and two genotype-3 patients. Eight of
the ten patients achieved a sustained virologic response, which is the clinical definition of treatment cure and is defined as undetectable
HCV in the blood 24 weeks after the completion of the 48-week peginterferon+ribavirin drug regimen. Both genotype-3 patients achieved
a sustained virologic response, while six of the eight genotype-1 patients achieved a sustained virologic response, which defines a cure
of the infection.
Hemopurifier - Human Immunodeficiency Virus (HIV)
In addition to treating Ebola
and HCV-infected individuals, we also conducted a single proof-of-principle treatment study at the Sigma New Life Hospital in an AIDS
patient who was not being administered HIV antiviral drugs. In the study, viral load was reduced by 93% as the result of 12 Hemopurifier
treatments (each four hours in duration) that were administered over the course of one month.
U.S. GOVERNMENT CONTRACTS
We did not recognize revenue from
government contracts in the fiscal year ended March 31, 2024. We have recognized revenue under the following government contract/grant
in the fiscal year ended March 31, 2023:
Phase 2 Melanoma Cancer Contract
On September 12, 2019, the National
Cancer Institute, or NCI, part of the National Institutes of Health, or NIH, awarded to us a SBIR Phase II Award Contract, for NIH/NCI
Topic 359, entitled “A Device Prototype for Isolation of Melanoma Exosomes for Diagnostics and Treatment Monitoring”, or the
Award Contract. The Award Contract amount was $1,860,561 and, as amended, ran for the period from September 16, 2019 through September
15, 2022.
The work performed pursuant to
this Award Contract was focused on melanoma exosomes. This work followed from our completion of a Phase I contract for the Topic 359 solicitation
that ran from September 2017 through June 2018, as described below. Following on the Phase I work, the deliverables in the Phase II program
involved the design and testing of a pre-commercial prototype of a more advanced version of the exosome isolation platform.
The Award Contract ended on September
15, 2022 and we presented the required final report to the NCI. As the NCI completed its close out review of the contract, we recognized
as revenue $574,245 on our statement of operations for the fiscal year ended March 31, 2023.
Research and Development Costs
A substantial portion of our
operating budget is used for research and development activities. The cost of research and development, all of which has been charged
to operations, amounted to approximately $2,520,000 and $2,745,000 in the fiscal years ended March 31, 2024 and 2023, respectively.
Intellectual Property
We currently own or have license
rights to a number of U.S. and foreign patents and patent applications and endeavor to continually improve our intellectual property position.
We consider the protection of our technology, whether owned or licensed, to the exclusion of use by others, to be vital to our business.
While we intend to focus primarily on patented or patentable technology, we also rely on trade secrets, unpatented property, know-how,
regulatory exclusivity, patent extensions and continuing technological innovation to develop our competitive position. We also own certain
trademarks.
Our success depends in large part
on our ability to protect our proprietary technology, including the Hemopurifier product platform, and to operate without infringing the
proprietary rights of third parties. We rely on a combination of patent, trade secret, copyright and trademark laws, as well as confidentiality
agreements, licensing agreements and other agreements, to establish and protect our proprietary rights. Our success also depends, in part,
on our ability to avoid infringing patents issued to others. If we were judicially determined to be infringing on any third-party patent,
we could be required to pay damages, alter our products or processes, obtain licenses or cease sales of products or certain activities.
To protect our proprietary medical
technologies, including the Hemopurifier product platform and other scientific discoveries, we have a portfolio of over 46 issued patents
and pending applications worldwide. We currently have five issued U.S. patents and 24 issued patents in countries outside of the United
States. In addition, we have 17 patent applications pending worldwide related to our Hemopurifier product platform and other technologies.
We are seeking additional patents on our scientific discoveries.
It is possible that our pending
patent applications may not result in issued patents, that we will not develop additional proprietary products that are patentable, that
any patents issued to us may not provide us with competitive advantages or will be challenged by third parties and that the patents of
others may prevent the commercialization of products incorporating our technology. Furthermore, others may independently develop similar
products, duplicate our products or design around our patents. U.S. patent applications are not immediately made public, so it is possible
that a third party may obtain a patent on a technology we are actively using.
There is a risk that any patent
applications that we file and any patents that we hold or later obtain could be challenged by third parties and declared invalid or unenforceable.
For many of our pending applications, patent interference proceedings may be instituted with the U.S. Patent and Trademark Office, or
the USPTO, when more than one person files a patent application covering the same technology, or if someone wishes to challenge the validity
of an issued patent. At the completion of the interference proceeding, the USPTO will determine which competing applicant is entitled
to the patent, or whether an issued patent is valid. Patent interference proceedings are complex, highly contested legal proceedings,
and the USPTO’s decision is subject to appeal. This means that if an interference proceeding arises with respect to any of our patent
applications, we may experience significant expenses and delays in obtaining a patent, and if the outcome of the proceeding is unfavorable
to us, the patent could be issued to a competitor rather than to us. Third parties can file post-grant proceedings in the USPTO,
seeking to have issued patent invalidated, within nine months of issuance. This means that patents undergoing post-grant proceedings may
be lost, or some or all claims may require amendment or cancellation, if the outcome of the proceedings is unfavorable to us. Post-grant
proceedings are complex and could result in a reduction or loss of patent rights. The institution of post-grant proceedings against our
patents could also result in significant expenses.
Patent law outside the United
States is uncertain and in many countries, is currently undergoing review and revisions. The laws of some countries may not protect our
proprietary rights to the same extent as the laws of the United States. Third parties may attempt to oppose the issuance of patents to
us in foreign countries by initiating opposition proceedings. Opposition proceedings against any of our patent filings in a foreign country
could have an adverse effect on our corresponding patents that are issued or pending in the United States. It may be necessary or useful
for us to participate in proceedings to determine the validity of our patents or our competitors’ patents that have been issued
in countries other than the United States. This could result in substantial costs, divert our efforts and attention from other aspects
of our business, and could have a material adverse effect on our results of operations and financial condition. Outside of the United
States, we currently have pending patent applications or issued patents in Europe, India, Russia, Canada, Japan, Singapore and Hong Kong.
In addition to patent protection,
we rely on unpatented trade secrets and proprietary technological expertise. It is possible that others could independently develop or
otherwise acquire substantially equivalent technology, somehow gain access to our trade secrets and proprietary technological expertise
or disclose such trade secrets, or that we may not successfully ultimately protect our rights to such unpatented trade secrets and proprietary
technological expertise. We rely, in part, on confidentiality agreements with our marketing partners, employees, advisors, vendors and
consultants to protect our trade secrets and proprietary technological expertise. We cannot assure you that these agreements will not
be breached, that we will have adequate remedies for any breach or that our unpatented trade secrets and proprietary technological expertise
will not otherwise become known or be independently discovered by competitors.
Patents
The following table lists our issued patents and patent
applications, including their ownership status, including relevant patent term adjustments (PTA), which is a process of extending the
term of a U.S. patent:
Patents Issued in the United States
PATENT # PATENT NAME ISSUANCE DATE OWNED OR LICENSED EXPIRATION DATE
Patent Applications Pending in the United States
APPLICATION # APPLICATION NAME FILING DATE OWNED OR LICENSED
Foreign Patents
PATENT # PATENT NAME ISSUANCE DATE OWNED OR LICENSED EXPIRATION DATE
Pending Foreign Patent Applications
APPLICATION # APPLICATION NAME FILING DATE OWNED OR LICENSED
Pending International Patent Applications
APPLICATION # APPLICATION NAME FILING DATE OWNED OR LICENSED
Trademarks
APPLICATION NAME FILING DATE OWNED OR LICENSED
Trademarks
In addition to the Tausome, Sansagitta
and Hemosagitta trademarks noted in the above table, we also have trademark registrations in the United States for Hemopurifier and Aethlon
Medical, Inc., and obtained a trademark registration in India for Hemopurifier. We also have common law trademark rights in Aethlon ADAPTTM
and ELLSATM.
Licensing and Assignment Agreements
On November 7, 2006, we executed
an assignment agreement with the London Health Science Center Research, Inc. under which an invention and related patent rights for a
method to treat cancer were assigned to us. The invention provides for the "Extracorporeal removal of microvesicular particles"
for which the U.S. Patent and Trademark Office granted a patent (Patent No.8,288,172) in the United States as of October 2012. The agreement
provided for an upfront payment of six shares of unregistered common stock and a 2% royalty on any future net sales of all products or
services, the sale of which would infringe in the absence of the assignment granted under this agreement. We are also responsible for
paying certain patent application and filing costs. Under the assignment agreement, we own the patents until their respective expirations.
Under certain circumstances, ownership of the patents may revert to the London Health Science Center Research, Inc. if there is an uncured
substantial breach of the assignment agreement.
Industry & Competition
The industry for treating infectious
disease and cancer is extremely competitive, and companies developing new treatment procedures face significant capital and regulatory
challenges. As our Hemopurifier is a clinical-stage device, we have the additional challenge of establishing medical industry support,
which will be driven by treatment data resulting from human clinical studies. Should our device become market cleared by the FDA or the
regulatory body of another country, we may face significant competition from well-funded pharmaceutical organizations. Additionally, we
would likely need to establish large-scale production of our device in order to be competitive. Our competitors include blood filters
produced by Exthera Medical Corporation.
Government Regulation
The Hemopurifier is subject to
regulation by numerous regulatory bodies, primarily the FDA, and comparable international regulatory agencies. These agencies require
manufacturers of medical devices to comply with applicable laws and regulations governing the development, testing, manufacturing, labeling,
marketing, storage, distribution, advertising and promotion, and post-marketing surveillance reporting of medical devices. As the primary
mode of action of the Hemopurifier is attributable to the device component of this combination product, the CDRH has primary jurisdiction
over its premarket development, review and approval. Failure to comply with applicable requirements may subject a device and/or its manufacturer
to a variety of administrative sanctions, such as issuance of warning letters, import detentions, civil monetary penalties and/or judicial
sanctions, such as product seizures, injunctions and criminal prosecution.
FDA’s Pre-market Clearance and Approval
Requirements
Each medical device we seek to
commercially distribute in the United States will require either a prior 510(k) clearance, unless it is exempt, or a pre-market approval
from the FDA. Generally, if a new device has a predicate that is already on the market under a 510(k) clearance, the FDA will allow that
new device to be marketed under a 510(k) clearance; otherwise, a premarket approval, or PMA, is required. Medical devices are classified
into one of three classes—Class I, Class II or Class III—depending on the degree of risk associated with each
medical device and the extent of control needed to provide reasonable assurance of safety and effectiveness. Class I devices are
deemed to be low risk and are subject to the general controls of the Federal Food, Drug and Cosmetic Act, such as provisions that relate
to: adulteration; misbranding; registration and listing; notification, including repair, replacement, or refund; records and reports;
and good manufacturing practices. Most Class I devices are classified as exempt from pre-market notification under section 510(k)
of the FD&C Act, and therefore may be commercially distributed without obtaining 510(k) clearance from the FDA. Class II devices
are subject to both general controls and special controls to provide reasonable assurance of safety and effectiveness. Special controls
include performance standards, post market surveillance, patient registries and guidance documents. A manufacturer may be required to
submit to the FDA a pre-market notification requesting permission to commercially distribute some Class II devices. Devices deemed
by the FDA to pose the greatest risk, such as life-sustaining, life-supporting or implantable devices, or devices deemed not substantially
equivalent to a previously cleared 510(k) device, are placed in Class III. A Class III device cannot be marketed in the United
States unless the FDA approves the device after submission of a PMA. However, there are some Class III devices for which FDA has
not yet called for a PMA. For these devices, the manufacturer must submit a pre-market notification and obtain 510(k) clearance in orders
to commercially distribute these devices. The FDA can also impose sales, marketing or other restrictions on devices in order to assure
that they are used in a safe and effective manner. We believe that the Hemopurifier will be classified as a Class III device and as such
will be subject to PMA submission and approval.
Pre-market Approval Pathway
A pre-market approval application
must be submitted to the FDA for Class III devices for which the FDA has required a PMA. The pre-market approval application process
is much more demanding than the 510(k) pre-market notification process. A pre-market approval application must be supported by extensive
data, including but not limited to technical, preclinical, clinical trials, manufacturing and labeling to demonstrate to the FDA’s
satisfaction reasonable evidence of safety and effectiveness of the device.
After a pre-market approval application
is submitted, the FDA has 45 days to determine whether the application is sufficiently complete to permit a substantive review and thus
whether the FDA will file the application for review. The FDA has 180 days to review a filed pre-market approval application, although
the review of an application generally occurs over a significantly longer period of time and can take up to several years. During this
review period, the FDA may request additional information or clarification of the information already provided. Also, an advisory panel
of experts from outside the FDA may be convened to review and evaluate the application and provide recommendations to the FDA as to the
approvability of the device.
Although the FDA is not bound
by the advisory panel decision, the panel’s recommendations are important to the FDA’s overall decision making process. In
addition, the FDA may conduct a preapproval inspection of the manufacturing facility to ensure compliance with the Quality System Regulation,
or QSR. The agency also may inspect one or more clinical sites to assure compliance with FDA’s regulations.
Upon completion of the PMA review,
the FDA may: (i) approve the PMA which authorizes commercial marketing with specific prescribing information for one or more indications,
which can be more limited than those originally sought; (ii) issue an approvable letter which indicates the FDA’s belief that
the PMA is approvable and states what additional information the FDA requires, or the post-approval commitments that must be agreed to
prior to approval; (iii) issue a not approvable letter which outlines steps required for approval, but which are typically more onerous
than those in an approvable letter, and may require additional clinical trials that are often expensive and time consuming and can delay
approval for months or even years; or (iv) deny the application. If the FDA issues an approvable or not approvable letter, the applicant
has 180 days to respond, after which the FDA’s review clock is reset.
Emergency Use Authorizations,
or EUAs, are granted by FDA in public health emergencies but allow use of the authorized device only during the period of the respective
public health emergency, and do not change the requirement to ultimately seek PMA approval after the authorization period has ended.
Clinical Trials
Clinical trials are almost always
required to support pre-market approval and are sometimes required for 510(k) clearance. In the United States, for significant risk devices,
these trials require submission of an application for an IDE to the FDA. The IDE application must be supported by appropriate data, such
as animal and laboratory testing results, showing it is safe to test the device in humans and that the testing protocol is scientifically
sound. The IDE must be approved in advance by the FDA for a specific number of patients at specified study sites. During the trial, the
sponsor must comply with the FDA’s IDE requirements for investigator selection, trial monitoring, reporting and recordkeeping. The
investigators must obtain patient informed consent, rigorously follow the investigational plan and study protocol, control the disposition
of investigational devices and comply with all reporting and recordkeeping requirements. Clinical trials for significant risk devices
may not begin until the IDE application is approved by the FDA and the appropriate institutional review boards, or IRBs, at the clinical
trial sites. An IRB is an appropriately constituted group that has been formally designated to review and monitor medical research involving
subjects and which has the authority to approve, require modifications in, or disapprove research to protect the rights, safety and welfare
of human research subjects. The FDA or the IRB at each site at which a clinical trial is being performed may withdraw approval of a clinical
trial at any time for various reasons, including a belief that the risks to study subjects outweigh the benefits or a failure to comply
with FDA or IRB requirements. Even if a trial is completed, the results of clinical testing may not demonstrate the safety and effectiveness
of the device, may be equivocal or may otherwise not be sufficient to obtain approval or clearance of the product.
Ongoing Regulation by the FDA
Even after a device receives clearance or approval
and is placed on the market, numerous regulatory requirements apply. These include:
· establishment registration and device listing;
Some changes to an approved PMA
device, including changes in indications, labeling or manufacturing processes or facilities, require submission and FDA approval of a
new PMA or PMA supplement, as appropriate, before the change can be implemented. Supplements to a PMA often require the submission of
the same type of information required for an original PMA, except that the supplement is generally limited to that information needed
to support the proposed change from the device covered by the original PMA. The FDA uses the same procedures and actions in reviewing
PMA supplements as it does in reviewing original PMAs.
Failure by us or by our suppliers
to comply with applicable regulatory requirements can result in enforcement action by the FDA or state authorities, which may include
any of the following sanctions:
· operating restrictions, partial suspension or total shutdown of production;
· withdrawing approvals that have already been granted; and
· criminal prosecution.
The Medical Device Reporting laws
and regulations require us to provide information to the FDA when we receive or otherwise become aware of information that reasonably
suggests our device may have caused or contributed to a death or serious injury as well as a device malfunction that likely would cause
or contribute to death or serious injury if the malfunction were to recur. In addition, the FDA prohibits an approved device from being
marketed for off-label use. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label
uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability, including substantial
monetary penalties and criminal prosecution.
Newly discovered or developed
safety or effectiveness data may require changes to a product’s labeling, including the addition of new warnings and contraindications,
and also may require the implementation of other risk management measures. Also, new government requirements, including those resulting
from new legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory clearance or
approval of our products under development.
Healthcare Regulation
In addition to the FDA’s
restrictions on marketing of pharmaceutical products, the U.S. healthcare laws and regulations that may affect our ability to operate
include: the federal fraud and abuse laws, including the federal anti-kickback and false claims laws; federal data privacy and security
laws; and federal transparency laws related to payments and/or other transfers of value made to physicians (defined to include doctors,
dentists, optometrists, podiatrists and chiropractors) and other healthcare professionals (such as physicians assistants and nurse practitioners)
and teaching hospitals. Many states have similar laws and regulations that may differ from each other and federal law in significant ways,
thus complicating compliance efforts. For example, states have anti-kickback and false claims laws that may be broader in scope than analogous
federal laws and may apply regardless of payor. In addition, state data privacy laws that protect the security of health information may
differ from each other and may not be preempted by federal law. Moreover, several states have enacted legislation requiring pharmaceutical
manufacturers to, among other things, establish marketing compliance programs, file periodic reports with the state, make periodic public
disclosures on sales and marketing activities, report information related to drug pricing, require the registration of sales representatives,
and prohibit certain other sales and marketing practices. These laws may adversely affect our sales, marketing and other activities with
respect to any product candidate for which we receive approval to market in the United States by imposing administrative and compliance
burdens on us.
Because of the breadth of these
laws and the narrowness of available statutory exceptions and regulatory safe harbors, it is possible that some of our business activities,
particularly any sales and marketing activities after a product candidate has been approved for marketing in the United States, could
be subject to legal challenge and enforcement actions. If our operations are found to be in violation of any of the federal and state
laws described above or any other governmental regulations that apply to us, we may be subject to significant civil, criminal, and administrative