10-K
1
aethlon_10k-033121.htm
ANNUAL REPORT
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, 2021
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 92123
(Address of principal executive office) (Zip Code)
REGISTRANT’S TELEPHONE NUMBER, INCLUDING
AREA CODE: (858) 459-7800
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. ☐
Indicate by check mark whether the registrant is a shell company (as
defined in Rule 12b-2 of the Act). Yes ☐ No ☒
The aggregate market value of the common stock
held by non-affiliates of the registrant as of September 30, 2020 was approximately $16.2 million, computed by reference to the closing
sale price of the common stock of $1.35 per share on the Nasdaq Capital Market on September 30, 2020. 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 21, 2021 was 15,365,490.
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
2021 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, 2021.
TABLE OF CONTENTS
PAGE
PART I.
Item 1. Description of Business 1
Item 1A. Risk Factors 16
Item 1B. Unresolved Staff Comments 43
Item 2. Properties 43
Item 3. Legal Proceedings 43
Item 4. Mine Safety Disclosures 43
PART II.
Item 6. Selected Financial Data 44
Item 7A Quantitative and Qualitative Disclosures about Market Risk 55
Item 8. Financial Statements and Supplementary Data 55
Item 9A. Controls and Procedures 55
Item 9B. Other Information 56
PART III.
Item 10. Directors, Executive Officers and Corporate Governance 57
Item 11. Executive Compensation 57
Item 14. Principal Accounting Fees and Services 57
PART IV.
Item 15. Exhibits and Financial Statement Schedules 58
Signatures 63
Certifications
i
PART I
CAUTIONARY NOTICE REGARDING FORWARD LOOKING STATEMENTS
This Annual Report on Form
10-K, or Form 10-K, 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 Form 10-K 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 Form 10-K 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.
ITEM 1. DESCRIPTION OF BUSINESS
Unless otherwise indicated
or the context otherwise requires, references to the “Company”, “Aethlon”, “we”, “us”
and “our” refer to Aethlon Medical, Inc., combined with its majority-owned subsidiary, Exosome Sciences, Inc.
Overview and Corporate History
We are a medical technology
company focused on developing products to diagnose and treat life and organ threatening diseases. The Aethlon Hemopurifier®, or Hemopurifier,
is a clinical-stage immunotherapeutic device designed to combat cancer and life-threatening viral infections. In cancer, the Hemopurifier
is designed to deplete the presence of circulating tumor-derived exosomes that promote immune suppression, seed the spread of metastasis
and inhibit the benefit of leading cancer therapies. The U.S. Food and Drug Administration, or FDA, has designated the Hemopurifier as
a “Breakthrough Device” for two independent indications:
We believe the Hemopurifier
can be a substantial advance in the treatment of patients with advanced and metastatic cancer through the clearance of exosomes that promote
the growth and spread of tumors through multiple mechanisms. We are currently conducting a clinical trial in patients with advanced and
metastatic head and neck cancer. We are initially focused on the treatment of solid tumors, including head and neck cancer, gastrointestinal
cancers and other cancers. As we advance our clinical trials, we are in close contact with our clinical sites to navigate and assess the
impact of the COVID-19 global pandemic on our clinical trials and current timelines.
On October 4, 2019, the FDA
approved our Investigational Device Exemption, or IDE, application to initiate an Early Feasibility Study, or EFS, of the Hemopurifier
in patients with head and neck cancer in combination with standard of care pembrolizumab (Keytruda). The primary endpoint for the EFS,
which will enroll 10 to 12 subjects at a single center, will be safety, with secondary endpoints including measures of exosome clearance
and characterization, as well as response and survival rates. This study, which is being conducted at the UPMC Hillman Cancer Center in
Pittsburgh, PA, has been approved by the Institutional Review Board, or IRB, and is in the process of recruiting and treating patients.
We also believe 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 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, 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.
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 is designed to enroll up to 40 subjects
at up to 20 centers in the U.S. Subjects will have established laboratory diagnosis of COVID-19, be admitted to an intensive care unit,
or ICU, and will have acute lung injury and/or severe or life threatening disease, among other criteria. Endpoints for this study, in
addition to safety, will include reduction in circulating virus as well as clinical outcomes (NCT # 04595903). The initial sites for this
trial, Hoag Memorial Hospital Presbyterian in Newport Beach, CA and Hoag Hospital – Irvine in Irvine, CA and Loma Linda Hospital
in Loma Linda, CA, have completed clinical trial agreements, and have received IRB approval in the case of the Hoag hospitals, and are
preparing to open for patient enrollment. Under Single Patient Emergency Use regulations, the Company has also treated two patients with
COVID-19 with the Hemopurifier.
We are also the majority owner
of Exosome Sciences, Inc., or ESI, a company focused on the discovery of exosomal biomarkers to diagnose and monitor life-threatening
diseases. Included among ESI’s activities is the advancement of a TauSomeTM biomarker candidate to diagnose chronic traumatic
encephalopathy, or CTE, in the living. ESI previously documented TauSome levels in former NFL players to be nine times higher than same
age-group control subjects. Through ESI, we are also developing exosome based biomarkers in patients with, or at risk for, a number of
cancers. We consolidate ESI’s activities in our consolidated financial statements.
Successful outcomes of human
trials will also be required by the regulatory agencies of certain foreign countries where we plan to 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 more recently will help protect the proprietary nature of the Hemopurifier treatment technology.
In addition to the foregoing,
we are monitoring closely the impact of the COVID-19 global pandemic on our business and have taken steps designed to protect the health
and safety of our employees while continuing our operations. Given the level of uncertainty regarding the duration and impact of the COVID-19
pandemic on capital markets and the U.S. economy, we are unable to assess the impact of the worldwide spread of SARS-CoV-2 and the resulting
COVID-19 pandemic on our timelines and future access to capital. We are continuing to monitor the spread of COVID-19 and its potential
impact on our operations. The full extent to which the COVID-19 pandemic will impact our business, results of operations, financial condition,
clinical trials, and preclinical research will depend on future developments that are highly uncertain, including actions taken to contain
or treat COVID-19 and their effectiveness, as well as the economic impact on national and international markets.
We were formed on March 10,
1999. Our executive offices are located at 9635 Granite Ridge Drive, Suite 100, San Diego, California 92123. Our telephone number is (858)
459-7800. Our website address is www.aethlonmedical.com.
The Mechanism of the Hemopurifier
The Hemopurifier is an affinity
hemofiltration device designed for the single-use removal of 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 application, 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 binds to
a glycosylated, or sugar substituted, membrane, which exosomes and most infectious viruses share.
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 multiple other outside labs including the Centers for Disease Control, or CDC, the United States Army Medical
Research Institute of Infectious Diseases, or USAMRIID, Battelle Memorial Research Institute and others, we have demonstrated that the
mini-Hemopurifier can bind and clear multiple different glycosylated, or containing sugar molecules on their membranes, viruses. These
viruses include HIV, hepatitis C, or HCV, Dengue, West Nile, multiple strains of influenza, Ebola, Chikungunya, 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 Early Feasibility Study conducted in the U.S.
under an FDA approved Investigational Device Exemption, or IDE.
On March 13, 2017, we concluded
an FDA-approved early feasibility study 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 biologic 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 is designed to enroll up to 40 subjects
at up to 20 centers in the U.S. Subjects will have established laboratory diagnosis of COVID-19, be admitted to an intensive care unit,
or ICU, and will have acute lung injury and/or severe or life threatening disease, among other criteria. Endpoints for this study, in
addition to safety, will include reduction in circulating virus as well as clinical outcomes (NCT # 04595903). The initial sites for this
trial, Hoag Memorial Hospital Presbyterian in Newport Beach, CA and Hoag Hospital – Irvine in Irvine, CA and Loma Linda Hospital
in Loma Linda, CA, have completed clinical trial agreements, and have received IRB approval in the case of the Hoag hospitals, and are
preparing to open for patient enrollment.
Under
Single Patient Emergency Use regulations, the Company has also treated two patients with COVID-19 with the Hemopurifier. The Company recently
published a manuscript reviewing case studies covering those 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 (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
(CRRT). The patient ultimately expired three hours after being placed on CRRT because of the advanced stage of the patient’s disease.
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 U.S. 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,
we applied for and were granted a Breakthrough Designation by the FDA “... 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, twelve 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 twelve treated patients.
Of these twelve 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.
The Hemopurifier in Cancer
While hepatitis C is no longer
a major commercial opportunity in developed markets due to the wide availability of curative, oral direct acting anti-viral agents, we
continue to investigate potential viral targets for the Hemopurifier. Recently, however, our primary focus has been on the evaluation
of the Hemopurifier in cancer, where we have shown in non-clinical studies that it is capable of clearing exosomes, which are subcellular
particles that are secreted by both normal and malignant cells. Tumor derived exosomes, have been shown in multiple laboratories to be
critical components in the progression of cancers. They can mediate resistance to chemotherapy, resistance to targeted agents such as
trastuzumab (Herceptin), metastasis and resistance to the newer immuno-oncology agents, such as pembrolizumab (Keytruda). Based on these
observations and data, in November 2019 the FDA granted us a second Breakthrough Designation “...for the treatment of individuals
with advanced or metastatic cancer who are either unresponsive to or intolerant of standard of care therapy, and with cancer types in
which exosomes have been shown to participate in the development or severity of the disease.”
On October 4, 2019, the FDA
approved our IDE application to initiate an EFS of the Hemopurifier in patients with head and neck cancer in combination with standard
of care pembrolizumab (Keytruda). The primary endpoint for the EFS, which will enroll 10 to 12 subjects at a single center, will be safety,
with secondary endpoints including measures of exosome clearance and characterization, as well as response and survival rates. This study,
which is being conducted at the UPMC Hillman Cancer Center in Pittsburgh, PA, has been approved by the IRB and is in the process of recruiting
and treating patients.
Exosome Sciences, Inc. – Majority Owned Biomarker Discovery
Company
We are the majority owner
of Exosome Sciences, Inc., or ESI, a company focused on the discovery of exosomal biomarkers to diagnose and monitor life-threatening
disease conditions that may be current or future therapeutic targets for Aethlon Medical. At present, the priority of ESI is directed
toward exosomal biomarkers to diagnose and monitor cancer and neurological disorders.
Since it began operations
in 2013, ESI researchers disclosed the discovery of an exosomal biomarker that may be associated with neurodegenerative diseases that
involve the abnormal accumulation of tau protein in the brain. These diseases, known as tauopathies, are a family of 21 different neurological
disorders that include Alzheimer’s disease and Chronic Traumatic Encephalopathy, or CTE. Related to CTE, the ESI team was invited
to participate in a National Institutes of Health, or NIH, funded research study with The Boston University CTE Center. In the study,
ESI researchers investigated an exosomal tau biomarker, or TauSome, as a candidate to diagnose and monitor CTE in living individuals.
At the present time, CTE can only be diagnosed through post-mortem brain autopsy.
The results of the study indicated
that TauSome levels in the blood of former professional American football players, a high CTE risk group, were significantly higher as
compared to same-age group control subjects who did not participate in activities that involved repetitive head trauma. Additionally,
high TauSome levels also correlated with poor performance in cognitive decline testing. These results were published in an article entitled
“Preliminary Study of Plasma Exosomal Tau as a Potential Biomarker for Chronic Traumatic Encephalopathy” in the Journal
of Alzheimer’s Disease on April 12, 2016.
To further validate these
observations, ESI has initiated a follow-on study to evaluate TauSome levels in up to 200 former professional football players and control
subjects. If fully enrolled, the study would be the largest study to date related to the advancement of a candidate biomarker to diagnose
and monitor CTE in the living. Enrollment of study participants began in March 2018 at the Translational Genomics Research Institute,
or TGEN, in Phoenix, AZ. Kendall Van Keuren-Jensen, Ph.D., Co-Director of TGEN’s Center for Noninvasive Diagnostics is the principal
investigator at this site location. Dr. Van Keuren-Jensen is neurodegenerative disease thought leader whose research includes discovery
and detection of biomarkers for central nervous system disorders. Additional site locations are anticipated.
In September 2019, we announced
that ESI had entered into a collaboration with the Hoag Hospital Presbyterian in Newport Beach, California to identify and characterize
potential early disease markers for cancer diagnostics, cancer progression and treatment resistance. The Principal Investigator on this
study is Michael Demeure, M.D., program director of Precision Medicine at Hoag. Samples from patients at Hoag will be analyzed by ESI
scientists to identify and characterize exosomal “liquid biopsy” markers of cancer incidence and progression. We believe that
our recently announced NCI-SBIR Phase II contract to develop a benchtop instrument to isolate and characterize exosomes could substantially
expand the capabilities of the ESI programs.
U.S. GOVERNMENT CONTRACTS
We have recognized revenue
under the following three government contracts/grants over the past two years:
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 an 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 is $1,860,561 and runs for the period from September 16, 2019 through September 15, 2021.
The work to be performed pursuant
to this Award Contract focuses on melanoma exosomes. This work follows from our completion of a phase I contract for the Topic 359 solicitation
that ran from September 2017 through June 2018. Following on the phase I work, the deliverables in the phase II program involve the design
and testing of a pre-commercial prototype of a more advanced version of the exosome isolation platform.
During the fiscal year ended
March 31, 2021, we completed the milestones relevant to the first nine months of the fiscal year. As a result, we recorded $436,427 of
government contract revenue on the Phase 2 Melanoma Cancer Contract in the fiscal year ended March 31, 2021. During the three
month period ended March 31, 2021, we did not complete all of the milestones relevant to that time period, as a result, we recorded $114,849
as deferred revenue related to the Phase 2 Melanoma Cancer Contract.
Breast Cancer Grant
In the fiscal year ended March
31, 2021, we completed and submitted the final reports applicable to this NCI grant (number 1R43CA232977-01). The title of this Small
Business Innovation Research, or SBIR, Phase I grant is “The Hemopurifier Device for Targeted Removal of Breast Cancer Exosomes
from the Blood Circulation,” or the Breast Cancer Grant.
This NCI Phase I grant period
originally ran from September 14, 2018 through August 31, 2019. In August 2019, we applied for and received a no cost, twelve month extension
on this grant; through August 31, 2020. The total amount of the firm grant was $298,444. The grant called for two subcontractors to work
with us. Those subcontractors were University of Pittsburgh and Massachusetts General Hospital.
During the fiscal year ended
March 31, 2021, we recorded the remaining $188,444 of revenue related to the Breast Cancer Grant, as we achieved two of the three milestones
related to the Breast Cancer Grant. We concluded in our final report to the SBIR that our pre-clinical results demonstrated that our work
under the grant provided support that the Hemopurifier has the capacity to clear exosomes from breast cancer patients. That amount previously
was recorded as deferred revenue.
As of March 31, 2021, we received
all of the funds allocated to the Breast Cancer Grant and have submitted the final reports applicable to this grant.
Subaward with University of Pittsburgh
In 2020, we entered into a cost reimbursable subaward
arrangement with the University of Pittsburgh in connection with an NIH contract entitled “Depleting Exosomes to Improve Responses
to Immune Therapy in HNNCC.” Our share of the award is $256,750. We recorded $34,233 of revenue related to this subaward in the
fiscal year ended March 31, 2021.
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 $2,072,000 and $927,000 in the fiscal years ended March 31, 2021 and 2020, 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 50
issued patents and pending applications worldwide. We currently have five issued U.S. patents and 35 issued patents in countries outside
of the United States. In addition, we have 11 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 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:
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
16/415,713 Affinity capture of circulating biomarkers 5/17/19 Owned
16/459,220 Methods and compositions for quantifying exosomes 7/01/19 Owned
Foreign Patents
PATENT # PATENT NAME ISSUANCE DATE OWNED OR LICENSED EXPIRATION DATE
Foreign Patent Applications
APPLICATION # APPLICATION NAME FILING DATE OWNED OR LICENSED
International Patent Applications
APPLICATION # APPLICATION NAME FILING DATE OWNED OR LICENSED
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 U.S. as of October 2012. The agreement provided
for an upfront payment of 53 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 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. We believe that our Hemopurifier is
a first-in-class therapeutic candidate and we are not aware of any affinity hemofiltration device being market cleared in any country
for the single-use removal of circulating viruses or tumor-derived exosomes.
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 FDA’s Center for Devices
and Radiological Health, or 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 (beginning January 1, 2022) 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 penalties, including, without limitation, damages, fines, imprisonment, exclusion from participation in government healthcare
programs, additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to
resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations, any of which could adversely
affect our ability to operate our business and our results of operations.
From time to time, legislation
is drafted and introduced in Congress that could significantly change the statutory provisions governing the regulatory approval, manufacture
and marketing of regulated products or the reimbursement thereof. For example, in the U.S., the Patient Protection and Affordable Care
Act, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively, PPACA, among other things, reduced and/or
limited Medicare reimbursement to certain providers and imposed an annual excise tax of 2.3% on any entity that manufactures or imports
medical devices offered for sale in the United States, with limited exceptions. However, the 2020 federal spending package permanently
eliminated, effective January 1, 2020, this PPACA-mandated medical device tax. On December 14, 2018, a Texas U.S. District Court Judge
ruled that the PPACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress as part
of the legislation enacted in 2017, informally titled the Tax Cuts and Jobs Act of 2017. Additionally, on December 18, 2019, the U.S.