Item 1. Business
ITEM
1.
Business
GENERAL
AIM
ImmunoTech Inc. and its subsidiaries (collectively, “AIM”, “Company”, “we” or “us”)
are an immuno-pharma company headquartered in Ocala, Florida and focused on the research and development of therapeutics to treat
multiple types of cancers, various viruses and immune-deficiency disorders. We have established a strong foundation of laboratory,
pre-clinical and clinical data with respect to the development of nucleic acids and natural interferon to enhance the natural
antiviral defense system of the human body and to aid the development of therapeutic products for the treatment of certain cancers
and chronic diseases.
AIM’s
flagship products include Ampligen® (rintatolimod), a first-in-class drug of large macromolecular RNA (ribonucleic acid) molecules,
and Alferon N Injection® (Interferon Alfa-N3). A first-in-class drug is also known as a new molecular entity that contains
an active moiety. Ampligen has not been approved by the FDA or marketed in the US.
Since
the outbreak of SARS-CoV-2, the novel virus that causes COVID-19, we have been actively engaged in determining whether Ampligen
could be an effective treatment for this virus or could be part of a vaccine. We believe that Ampligen has the potential to be
both an early-onset treatment for and prophylaxis against SARS-CoV-2. Ampligen also has potential as a COVID-19 vaccine strategy
that combines Ampligen as an immune enhancer seeking to boost the efficacy of intranasal and other vaccines and, as to intranasal,
also convey cross-reactivity and cross-protection against future mutations. We believe that prior studies of Ampligen in SARS-CoV-1
animal experimentation may predict similar protective effects against the new virus.
Beginning
in April 2020, we entered into confidentiality and non-disclosure agreements with numerous companies for the potential outsourcing
of the production of polymer, enzyme, placebo as well as Ampligen and one Contract Research Organization which may also assist
with the planning, presentation and filing of documents with the FDA. These confidentiality and non-disclosure agreements are
only the initial step in forging relationships with these entities to obtain contract manufacturers and research partners. No
assurance can be given as to how many of these, initial explorations, if any, will result in definitive arrangements or, with
regard to potential research partners, what research arrangements will develop and thereafter prove fruitful.
Ampligen
represents a dsRNA being developed for globally important cancers, viral diseases and disorders of the immune system. Ampligen
has in the clinic demonstrated the potential for standalone efficacy in a number of solid tumors. We have also seen success in
increasing survival rates and efficacy in the treatment of animal tumors when Ampligen is used in combination with checkpoint
blockade therapies. This success in the field of immuno-oncology has guided our focus toward the potential use of Ampligen as
a combinational therapy for the treatment of a variety of solid tumor types. There are currently multiple Ampligen clinical trials
testing Ampligen in humans — both underway and planned — at major cancer research centers. Ampligen was used as a
monotherapy to treat pancreatic cancer patients in an Early Access Program (EAP) approved by the Inspectorate of Healthcare in
the Netherlands at Erasmus Medical Center. In September, we reported receipt of statistically significantly results of positive
survival benefit when using Ampligen in patients with locally advanced/metastatic pancreatic cancer after systemic chemotherapy.
We will work with our Contract Research Organization, Amarex Clinical Research LLC, to seek FDA “fast-track” and possibly
even FDA “breakthrough” designations and to obtain authorization to conduct a follow-up pancreatic cancer Phase 2/3
clinical trial with sites in the Netherlands at Erasmus MC under Prof. van Eijck, and also at major cancer research centers in
the United States.
Ampligen
is also being evaluated for the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We are currently sponsoring
an expanded access program for ME/CFS patients in the U.S. In August 2016, we received approval of our New Drug Application (NDA)
from Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica (ANMAT) for commercial sale of Ampligen in the Argentine
Republic for the treatment of severe CFS. With regulatory approval in Argentina, Ampligen is the world’s only approved therapeutic
for ME/CFS. On June 10, 2020, we received import clearance from ANMAT to import the first shipment of commercial grade vials of
Ampligen to Argentina. The next steps in the commercial launch of Ampligen include ANMAT conducting a final inspection of the
product and release tests before granting final approval to begin commercial sales. We have supplied GP Pharm with the Ampligen
required for testing and ANMAT release. This testing and approval process is currently delayed due to the COVID-19 pandemic and
ANMAT’s internal processes. Once final approval by ANMAT is obtained, GP Pharm will begin distributing Ampligen in Argentina.
We continue to pursue our Ampligen NDA, for the treatment of CFS with the FDA.
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Alferon
N Injection is approved for a category of sexually transmitted diseases infection and patients that are intolerant to recombinant
interferon in Argentina. Alferon is the only natural-source, multi-species alpha interferon currently approved for sale in the
U.S. for the intralesional treatment of refractory (resistant to other treatment) or recurring external condylomata acuminata/genital
warts (GW) in patients 18 years of age or older. Certain types of human papilloma viruses cause GW. We also have approval from
ANMAT for the treatment of refractory patients that failed or were intolerant to treatment with recombinant interferon in Argentina.
We
operate a 30,000 sq. ft. facility in New Brunswick, NJ, where we conduct testing and have produced limited quantities of active
pharmaceutical ingredients (“API”) for our products. We have reviewed our operations at the facility and believe that
some of the equipment most likely should be upgraded to realize greater efficiencies, when and if we require more API than is
currently in storage. We are also exploring engaging a Contract Manufacturing Organization (“CMO”) to produce API.
While we believe we have sufficient API to meet our current needs, we are also continually exploring new efficiencies so as to
maximize our ability to fulfill future obligations.
AVAILABLE
INFORMATION
We
are subject to the information and periodic reporting requirements of the Exchange Act and, in accordance therewith, we file periodic
reports, proxy statements and other information with the SEC. Such periodic reports, proxy statements and other information are
available for inspection and copying at the website of the SEC www.sec.com. You also may obtain a free copy of our annual reports
on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, proxy statements and amendments to those reports on
the day of filing with the SEC on our website at http://www.aimimmuno.com under the Investor Relations tab for SEC Filings or
by contacting the Investor Relations Department by calling 888-557-6480 or (352) 448-7797 or sending an e-mail message to ir@aimimmuno.com .
Our Internet website and the information contained on that website, or accessible from our website, is not intended to be incorporated
into this Annual Report on Form 10-K or any other filings we make with the SEC.
OUR
PRODUCTS
Our
primary pharmaceutical product platform consists of Ampligen®, a first-in-class drug of large macromolecular double-stranded
(ds) RNA (ribonucleic acid) molecules, and our FDA-approved natural alpha-interferon product, Alferon N Injection®.
Ampligen®
Ampligen
is approved for sale in Argentina for severe Chronic Fatigue Syndrome (CFS) and is an experimental drug in the United States
currently undergoing clinical development for the treatment of certain cancers and ME/CFS. Over its developmental history,
Ampligen has received various designations, including Orphan Drug Product Designation (FDA and European Medicines Agency
(“EMA”)), Treatment protocol (e.g., “Expanded Access” or “Compassionate” use
authorization) with Cost Recovery Authorization (FDA) and “promising” clinical outcome recognition based on the
evaluation of certain summary clinical reports (“AHRQ” or Agency for Healthcare Research and Quality). Ampligen
represents the first drug in the class of large (macromolecular) dsRNA molecules to apply for NDA review. Based on the
results of published, peer reviewed pre-clinical studies and clinical trials, we believe that Ampligen may have
broad-spectrum anti-viral and anti-cancer properties. We believe that nucleic acid compounds represent a potential new class
of pharmaceutical products designed to act at the molecular level for treatment of many human diseases. There are two forms
of nucleic acids, deoxyribonucleic acid (“DNA”) and ribonucleic acid (“RNA”). DNA is a group of
naturally occurring molecules found in chromosomes, the cell’s genetic machinery. RNA is a group of naturally occurring
informational molecules which orchestrate a cell’s behavior which, in turn, regulates the action of groups of cells,
including the cells which compromise the body’s immune system. RNA directs the production of proteins and regulates
certain cell activities including the activation of an otherwise dormant cellular defense against viruses and tumors. Our
drug technology utilizes specifically-configured RNA and is a selective Toll-like Receptor 3 (TLR3) agonist that is
administered intravenously. Ampligen has been assigned the generic name rintatolimod by the United States Adopted Names
Council (USANC) and has the chemical designation poly(I):poly(C 12 U).
EAP/clinical
trials of Ampligen that have been conducted or that are ongoing include studies of the potential treatment of patients with renal
cell carcinoma, malignant melanoma, non-small cell lung, ovarian, breast, colorectal, prostate and pancreatic cancer, ME/CFS,
Hepatitis B and HIV.
We
have received approval of our NDA from ANMAT for commercial sale of rintatolimod (U.S. tradename: Ampligen) in the Argentine Republic
for the treatment of severe CFS. The product will be marketed by GP Pharm, our commercial partner in Latin America. On September
19, 2019, we received clearance from the FDA to ship Ampligen to Argentina for the commercial launch and subsequent sales. We
are currently working with GP Pharm on the commercial launch of Ampligen in Argentina. Commercialization in Argentina will require,
among other things, GP Pharm to establish disease awareness, medical education, creation of an appropriate reimbursement level,
design of marketing strategies and completion of manufacturing preparations for launch and ANMAT conducting a final inspection
of the product and release tests before granting final approval to begin commercial sales. This testing and approval process is
currently delayed due to the COVID-19 pandemic and ANMAT’s internal processes. Once final approval by ANMAT is obtained,
GP Pharm will begin distributing Ampligen in Argentina. We continue to pursue our Ampligen NDA, for the treatment of CFS with
the FDA.
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The
FDA has authorized an open-label expanded access treatment protocol, (“AMP-511”), allowing patient access to Ampligen
in an open-label safety study under which severely debilitated CFS patients have the opportunity to be on Ampligen to treat this
very serious and chronic condition. The data collected from the AMP-511 protocol through clinical sites provide safety information
regarding the use of Ampligen in patients with CFS. We are establishing an enlarged data base of clinical safety information which
we believe will provide further documentation regarding the absence of autoimmune disease associated with Ampligen treatment.
We believe that continued efforts to understand existing data, and to advance the development of new data and information, will
ultimately support our future filings for Ampligen and/or the design of future clinical studies that the FDA requested in a complete
response letter. The FDA approved the increase reimbursement level from $200 to $345 per 200 mg vial of Ampligen, due to increased
production costs; which was re-authorized in 2020. At this time, we do not plan on passing this adjustment along to the patients
in this program. As of December 31, 2020, there are 10 patients enrolled in this open-label expanded access treatment protocol.
In October 2020, we received Institutional Review Board (IRB) approval for the expansion of the AMP-511 Expanded Access Program
(EAP) clinical trial for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) to include patients previously diagnosed
with SARS-CoV-2 following clearance of the virus, but who still demonstrate chronic fatigue-like symptoms.
In
May 2016, we entered into a five-year agreement with myTomorrows, a Netherlands based company, for the commencement and management
of an Early Access Program (“EAP”) in Europe and Turkey (the “Territory”) related to ME/CFS. Pursuant
to the agreement, as amended, myTomorrows also will manage all Early Access Programs and Special Access Programs in Europe, Canada
and Turkey to treat pancreatic cancer and ME/CFS patients.
In
April 2018, we completed data analysis of an intranasal human safety study of Ampligen plus FluMist® known as AMP-600. The
study was previously closed after the US Centers for Disease Control and Prevention (“CDC”) recommended against the
use of FluMist®. Intranasal Ampligen in combination with FluMist® was generally well-tolerated in the study.
In
June 2018, Ampligen was cited as outperforming two other TLR3 agonists, poly IC and natural double stranded RNA, in creating an
enhanced tumor microenvironment for checkpoint blockage therapy in the journal of Cancer Research ( http://cancerres.aacrjournals.org/content/early/2018/05/31/0008-5472.CAN-17-3985 ).
In a head-to-head study in explant culture models, Ampligen activated the TLR3 pathway and promoted an accumulation of killer
T cells but, unlike the other two TLR3 agonists, it did so without causing regulatory T cell (Treg) attraction. These findings
were considered important because they indicate that Ampligen selectively reprograms the tumor microenvironment by inducing the
beneficial aspects of tumor inflammation (attracting killer T cells), without amplifying immune suppressive elements such as regulatory
T cells. The study was conducted at the University of Pittsburgh and Roswell Park as a part of the NIH-funded P01 CA132714 and
Ovarian Cancer Specialized Program of Research Excellence (SPORE). Based upon these findings we and Roswell Park expanded our
existing scientific collaboration to advance the clinical development of Ampligen which has shown promise in preclinical studies
when combined with checkpoint inhibitors (CPIs). The parties executed a Memorandum of Understanding (“MOU”) designed
to further assess the clinical potential of Ampligen in treating certain cancers. This phase I/II study will evaluate the potential
of Ampligen to enhance the immune mediated effects of CPIs in patients with advanced solid tumors including bladder, melanoma
and renal cell carcinoma. At the moment, this study is on hold as we await updates and next steps from Roswell Park.
In
2018, we completed production of two commercial-size batches of more than 16,000 vials of Ampligen, following its “Fill
& Finish” at Jubilant HollisterStier, the Contract Manufacturing Organization. These lots passed all required testing
for regulatory release for human use and are being used for multiple programs including the treatment of ME/CFS, the pancreatic
cancer EAP in the Netherlands, and will continue to be used for ongoing and future clinical studies in oncology. Additionally,
two lots of Ampligen were manufactured in December 2019 and January 2020 at Jubilant. The current manufactured lots of Ampligen
have been fully tested and released for commercial product launch in Argentina and for clinical trials. Additionally, in December
2020, we added Pharmaceutics International Inc. (“Pii”) as a “Fill & Finish” provider to enhance our
capacity to produce Ampligen. This addition amplifies our manufacturing capability by providing redundancy and cost savings. The
contracts augment our existing fill and finish capacity.
Alferon
N Injection®
Alferon
N Injection is the registered trademark for our injectable formulation of natural alpha interferon. Alferon is the only natural-source,
multi-species alpha interferon currently approved for sale in the U.S. and Argentina for the intralesional (within lesions) treatment
of refractory (resistant to other treatment) or recurring external genital warts in patients 18 years of age or older. Alferon
is also approved in Argentina for the treatment of refractory patients that failed or were intolerant to treatment with recombinant
interferons. Certain types of human papilloma viruses (“HPV”) cause genital warts, a sexually transmitted disease
(“STD”). According to the CDC, HPV is the most common sexually transmitted infection, with approximately 79 million
Americans — most in their late teens and early 20s — infected with HPV. In fact, the CDC states that “HPV is
so common that nearly all sexually active men and women get the virus at some point in their lives.” Although they do not
usually result in death, genital warts commonly recur, causing significant morbidity and entail substantial health care costs.
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Interferons
are a group of proteins produced and secreted by cells to combat diseases. Researchers have identified four major classes of human
interferon: alpha, beta, gamma and omega. Alferon N Injection contains a multi-species form of alpha interferon. The world-wide
market for injectable alpha interferon-based products has experienced rapid growth and various alpha interferon injectable products
are approved for many major medical uses worldwide. Alpha interferons are manufactured commercially in three ways: by genetic
engineering, by cell culture, and from human white blood cells. All three of these types of alpha interferon are or were approved
for commercial sale in the U.S. Our natural alpha interferon is produced from human white blood cells.
The
potential advantages of natural alpha interferon over recombinant (synthetic) interferon produced and marketed by other pharmaceutical
firms may be based upon their respective molecular compositions. Natural alpha interferon is composed of a family of proteins
containing many molecular species of interferon. In contrast, commercial recombinant alpha interferon products each contain only
a single species. Researchers have reported that the various species of interferons may have differing antiviral activity depending
upon the type of virus. Natural alpha interferon presents a broad complement of species, which we believe may account for its
higher activity in laboratory studies. Natural alpha interferon is also glycosylated (partially covered with sugar molecules).
Such glycosylation is not present on the currently U.S. marketed recombinant alpha interferons. We believe that the absence of
glycosylation may be, in part, responsible for the production of interferon-neutralizing antibodies seen in patients treated with
recombinant alpha interferon. Although cell culture-derived interferon is also composed of multiple glycosylated alpha interferon
species, the types and relative quantity of these species are different from our natural alpha interferon.
Alferon
N Injection [Interferon alfa-n3 (human leukocyte derived)] is a highly purified, natural-source, glycosylated, multi-species alpha
interferon product. There are essentially no neutralizing antibodies observed against Alferon N Injection to date and the product
has a relatively low side-effect profile. The recombinant DNA derived alpha interferon formulations have been reported to have
decreased effectiveness after one year of treatment, probably due to neutralizing antibody formation.
See
“Manufacturing” and “Marketing/Distribution” sections below for more details on the manufacture and marketing/distribution
of Alferon N Injection.
PATENTS
AND NON-PATENT EXCLUSIVITY RIGHTS
As
of December 31, 2020, we had 43 patents worldwide with 10 additional pending patent applications comprising our intellectual property.
Please see “Note 5: Patents, Trademark Rights and Other Intangibles (FASB ASC 350 General Intangibles Other than Goodwill)”
under Notes to Consolidated Financial Statements for more information on these patents. We continually review our patents’
rights to determine whether they have continuing value.
In
February 2020, we filed three provisional patent applications related to Ampligen in our efforts toward joining the global health
community in the fight against SARS-CoV-2. These include: 1) Ampligen as a therapy and prophylaxis for COVID-19; 2) Ampligen
as part of a proposed intranasal universal coronavirus vaccine; and 3) a high-volume manufacturing process for Ampligen.
In
2016, we received a new Ampligen composition of matter patent in the US (#9,315,538). In 2015, we were granted a new composition
of matter patent (#2340307) by the European Patent Office and we received twenty-eight new patents in various EU countries. In
2014, we were granted a new composition of matter patent in the United States (#8722874) covering Ampligen formulations.
The
Ampligen U.S. CFS treatment patent (#6130206) expired October 10, 2017 (we believe that the expiration of this patent will have
minimal impact on us; see details on U.S. #9315538, U.S. #8722874 and the information from the FDA has granted “orphan drug
status” to the drug for CFS below). Our U.S. Ampligen Trademark (#73617687) has been renewed through December 6, 2028. New
therapeutic use patent applications are pending. On May 13, 2014, the United States Patent Office issued patent U.S. #8722874
titled “Double-Stranded Ribonucleic Acids with Rugged Physiochemical Structure and Highly Specific Biologic Activity,”
with all rights assigned to us. The patent claims a novel form of rugged dsRNA. Rugged dsRNA are nucleic acids with a unique composition
and physical characteristic identified with high specificity of binding to Toll-Like Receptor 3 (TLR3), thereby conveying an important
range of therapeutic opportunities. The newly discovered form of dsRNA has increased bioactivity and binding affinity to the TLR
3 receptor because of its reduced tendency to form branched dsRNA which can inhibit receptor binding. Pharmaceutical formulations
containing the newly discovered nucleic acid as active ingredients and methods of treatment with those formulations are also described
in the issued patent. We believe that the issuance of U.S. Patents #9315538 and #8722874 will help ensure that we retain patent
protection for novel formulations of Ampligen products until at least 2029.
6
In
September 2015, the European Patent Office granted the European version of U.S. Patent #9315538, with all rights assigned to us.
In
addition to our patent rights relating to Ampligen, the FDA has granted “orphan drug status” to the drug for CFS,
HIV/AIDS, renal cell carcinoma, pancreatic cancer, and malignant melanoma. Orphan drug status grants us protection against the
potential subsequent approval of other sponsors’ versions of the drug for these uses for a period of seven years following
FDA approval of Ampligen for each of these designated uses. The first NDA approval for Ampligen as a new chemical entity will
also qualify for four or five years of non-patent exclusivity during which abbreviated new drug applications seeking approval
to market generic versions of the drug cannot be submitted to the FDA. (See “Government Regulation” below.)
In
May 2011, a new United States Patent #7943147 was granted for the use of Ampligen as a vaccine adjuvant for use with seasonal
influenza vaccine to induce an enhanced immune response against H5N1 avian influenza.
With
respect to Alferon, the composition is a complex mixture of natural interferon species that is manufactured from human leukocytes
obtained from human blood donors. In addition, while it is the current standard by the FDA to treat biological drug products like
interferon as “Well Characterized” biologics, a process for which chemical entities can have their identity, purity,
impurities, potency, and quality controlled by chemical testing, Alferon, as a natural interferon, does not lend itself well to
such testing. Moreover, FDA continues to require that each lot of Alferon we produce be tested and released by the FDA before
it can be distributed for commercial sales. Because of the complexity of the Alferon manufacturing process and these additional
regulatory requirements, we believe that potential manufacturers of generic, or so-called “bio-similar,” drug products
are focused on developing recombinant interferon products, rather than natural interferon products. For these reasons, we believe
that not having patent protection should have no or little impact on us. Additionally, at the receipt of the FDA certification
for the revised Alferon manufacturing process and techniques in New Brunswick, NJ, it is our intention to file for additional
patent protection.
RESEARCH
AND DEVELOPMENT (“R&D”)
Our
general focus during the past several fiscal years has been on the clinical development of new drug therapies based on natural
immune system enhancing technologies for the treatment of immune-based disorders including cancer and CFS. While we have previously
estimated milestone dates when significant progress could be reported, the reality of the ongoing SARS-CoV-2 pandemic could mean
the re-direction of resources away from ongoing clinical trials and toward the research and development of potential treatments
for the coronavirus. In this regard, we have widened our focus to include research and development of potential therapeutic
applications for the treatment of COVID-19, including the long-term effects of COVID-19.
Cancer
We
have been working with the University of Pittsburgh’s chemokine modulation research initiative which includes the use of
Ampligen as a potential adjuvant to modify the tumor microenvironment (TME) with the goal of increasing anti-tumor responses to
check point inhibitors (CPI). As part of this collaboration, we haves supplied Ampligen (rintatolimod) to the University. The
study, under the leadership of Robert P. Edwards, MD, chair of gynecologic services at Magee-Women’s Hospital of the University
of Pittsburgh School of Medicine, and Professor of Surgery Pawel Kalinski, M.D., Ph.D., at Roswell Park, Buffalo, N.Y., involved
the chemokine modulatory regimen developed by Dr. Kalinski’s group and successfully completed the Phase 1 dose escalation
in patients with resectable colorectal cancer. In the 1st quarter of 2017, Dr. Kalinski relocated to Roswell Park in Buffalo,
NY and has established a cancer program which will continue to require a supply of Ampligen.
In
October 2018, we signed a clinical trial agreement with Roswell Park to evaluate Ampligen in combination with checkpoint inhibitors
(CPIs). The Phase IIa clinical trial will evaluate the immune-mediated effects of cytokine modulation in combination with CPIs
in patients with primary resistance to CPI therapy. The protocol will seek to evaluate the combination of Ampligen and CPIs in
patients with advanced urothelial carcinoma, renal cell carcinoma and melanoma. Ampligen is our investigational immune-enhancing
TLR3 agonist that has demonstrated a robust anti-cancer effect in preclinical models when combined with CPIs. This new agreement
expands the extensive prior clinical and preclinical work into the clinical checkpoint blockade arena and offers the opportunity
to begin evaluation of this combination therapy in patients with a variety of solid tumors where large numbers of patients do
not respond or progress following treatment with standard CPI-based therapy. At the moment, this study is on hold as we
await updates and next steps from Roswell Park.
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Currently,
six Ampligen clinical trials are underway at university cancer centers testing whether tumor microenvironments can be reprogrammed
to increase the effectiveness of cancer immunotherapy, including checkpoint inhibitors:
●
Advanced
Recurrent Ovarian Cancer - Phase 1 / 2 study of intraperitoneal chemo-immunotherapy in advanced recurrent ovarian cancer;
Phase 1 portion establishes intraperitoneal safety. Awaiting publication of Phase I results. https://clinicaltrials.gov/ct2/show/NCT02432378
●
Advanced
Recurrent Ovarian Cancer - A follow-up Phase 2 study of advanced recurrent ovarian cancer using cisplatin, pembrolizumab,
plus Ampligen; up to 45 patients to be enrolled; enrollment has commenced, and numerous patients have commenced treatment.
https://clinicaltrials.gov/ct2/show/NCT03734692
●
Stage
4 Metastatic Triple Negative Breast Cancer - Phase 2 study of metastatic triple-negative breast cancer using chemokine
modulation therapy, including Ampligen and pembrolizumab. All patients have been treated or are in treatment. https://www.clinicaltrials.gov/ct2/show/NCT03599453
●
Stage
4 Colorectal Cancer Metastatic to the Liver - Phase 2a study of Ampligen as component of chemokine modulatory regimen
on colorectal cancer metastatic to liver; the majority of the 12 planned patients enrolled and treated. https://clinicaltrials.gov/ct2/show/NCT03403634
●
Early-Stage
Prostate Cancer - Phase 2 study investigating the effectiveness and safety of aspirin and Ampligen with or without interferon-alpha
2b (Intron A) compared to no drug treatments in a randomized three-arm study of patients with prostate cancer before undergoing
radical prostatectomy. Patient enrollment has been initiated in this study designed for up to 45 patients. https://clinicaltrials.gov/ct2/show/NCT03899987
●
Early-Stage
Triple Negative Breast Cancer - Phase 1 study of chemokine modulation plus neoadjuvant chemotherapy in patients with early-stage
triple negative breast cancer has received FDA authorization; the objective of this study is to evaluate the safety and tolerability
of a combination of Ampligen, celecoxib with or without Intron A, when given along with chemotherapy; the goal of this approach
is to increase survival. This study is recruiting patients designed for up to 24 patients. https://clinicaltrials.gov/ct2/show/NCT04081389
Six
Ampligen clinical trials are planned for initiation in 2021:
●
Brain-Metastatic
Breast Cancer — Phase 2 study to assess the effectiveness of a three-pronged strategy combining distinct immunotherapy
approaches, including Ampligen. Roswell Park and Moffitt Cancer Center have both received “Breakthrough Awards”
from the U.S. Department of Defense (DOD). Together, these separate but parallel proposed clinical trials are receiving approximately
$15 million in DOD funding to study Ampligen. Roswell Park is currently working on its draft of the IND, which its study and
Moffitt’s study require before next steps can be taken.
●
Stage
4 Refractory Metastatic Colorectal Carcinoma — Phase 2 study that will evaluate Ampligen in combination with pembrolizumab
in refractory metastatic colorectal carcinoma at Roswell Park. Up to 25 patients to be enrolled. This is expected to be funded
by grants, testing Ampligen and pembrolizumab. See: https://www.clinicaltrials.gov/show/NCT04119830
●
Refractory
Melanoma — Phase 2 study that will evaluate polarized dendritic cell vaccine, interferon alpha-2, Ampligen and celecoxib
for the treatment of HLA-A2+ refractory melanoma at Roswell Park. Up to 24 patients to be enrolled. See: https://www.clinicaltrials.gov/show/NCT04093323
●
Stage
4 Urothelial, Melanoma and Renal Cell Carcinoma — Phase 2 study of advanced urothelial (bladder), melanoma and renal
cell carcinoma, resistant to checkpoint blockade, that will evaluate Ampligen in combination with a checkpoint blockade therapy
at Roswell Park. Protocol design and funding currently being finalized.
●
Non-Small
Cell Lung Cancer — First-line therapy for non-small cell lung cancer with SOC chemotherapy that will evaluate Ampligen
in combination with pembrolizumab at University of Nebraska Medical Center. Dr. V. Ernani, PI. Study design and budget being
developed. However, we now anticipate an extended delay, as other studies with funding have moved ahead of the Ampligen project.
Roswell Park is exploring a pilot study to establish proof of concept.
●
Advanced
Pancreatic Cancer — Phase 2 study in advanced pancreatic cancer using checkpoint blockade plus Ampligen at University
of Nebraska Medical Center and Erasmus University. Protocol and budget being developed. This proposed study may be based on
data from our Dutch EAP (see below) and UNMC animal experiment showing synergy between Ampligen and checkpoint therapy. A
second confirmatory animal trial has been completed; while it did not replicate the previous survival results, it did demonstrate
a significant anti-tumor effect.
8
In
addition, the National Cancer Institute awarded $14.5 million to Roswell Park to study Ampligen as part of five Roswell Park-led
chemokine modulation clinical trials in melanoma, colorectal and ovarian cancers.
In
January 2017, the EAP through our agreement with myTomorrows designed to enable access of Ampligen to ME/CFS patients was extended
to pancreatic cancer patients beginning in the Netherlands. myTomorrows is our exclusive service provider in Europe and Turkey
and will manage all EAP activities relating to the pancreatic cancer extension of the program. In February 2018, the agreement
with myTomorrows was extended to cover Canada to treat pancreatic cancer patients, pending government approval. There have been
no physician requests to date that would cause the program to move forward with the approval process.
As
of the date of this Report, 42 pancreatic cancer patients have received treatment with Ampligen immuno-oncology therapy under
the EAP program at Erasmus MC in the Netherlands. Supervised by Prof. Casper van Eijck, MD, the team at Erasmus MC found a statistically
significantly positive survival benefit when using Ampligen in patients with locally advanced/metastatic pancreatic cancer after
systemic chemotherapy. We will work with our Contract Research Organization, Amarex Clinical Research LLC, to seek FDA “fast-track”
and possibly even FDA “breakthrough” designations and to obtain IND authorizations to conduct a follow-up pancreatic
cancer Phase 2/3 clinical trial with sites in the Netherlands at Erasmus MC under Prof. van Eijck, and also at major cancer research
centers in the United States. Additionally:
●
In
December 2020, the FDA granted Ampligen Orphan Drug Designation status for the treatment of pancreatic cancer. The Orphan
Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the treatment,
prevention or diagnosis of a rare disease or condition, which is one that affects less than 200,000 persons in the United
States or meets cost recovery provisions of the act. The status helps incentivize the treatment of therapies to treat unmet
medical needs by providing a company with seven years of exclusivity rights once a drug reaches market.
●
In
February 2021, our subsidiary, NV Hemispherx Biopharma Europe, received formal notification from the European Commission (EC)
approving the Orphan Medicinal Product Application for Ampligen as a treatment for pancreatic cancer. Orphan products, once
commercially approved in the European Union (EU), receive benefits including up to ten years of protection from market competition
from similar medicines with similar active component and indication for use that are not shown to be clinically superior.
In
September, we reported receipt of statistically significant results of positive survival benefit when using Ampligen in patients
with locally advanced/metastatic pancreatic cancer after systemic chemotherapy versus matched historical controls.
Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome (“ME/CFS”)
Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome (“ME/CFS”), also known as Chronic Fatigue Immune Dysfunction Syndrome (“CFIDS”)
and Chronic Fatigue Syndrome (“CFS”), is a serious and debilitating chronic illness and a major public health problem.
ME/CFS is recognized by both the government and private sector as a significant unmet medical need, including the U.S. National
Institutes of Health (“NIH”), FDA and the CDC. The CDC states on its website at https://www.cdc.gov/me-cfs/
that “ Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, long-term illness that affects many body
systems. People with ME/CFS are often not able to do their usual activities. At times, ME/CFS may confine them to bed. People
with ME/CFS have severe fatigue and sleep problems. ME/CFS may get worse after people with the illness try to do as much as they
want or need to do. This symptom is known as post-exertional malaise (PEM). Other symptoms can include problems with thinking
and concentrating, pain, and dizziness. ”
Many
severe ME/CFS patients become completely disabled or totally bedridden and are afflicted with severe pain and mental confusion
even at rest. ME/CFS is characterized by incapacitating fatigue with profound exhaustion and extremely poor stamina, sleep difficulties
and problems with concentration and short-term memory. It is also accompanied by flu-like symptoms, pain in the joints and muscles,
tender lymph nodes, sore throat and new headaches. A distinctive characteristic of the illness is a worsening of symptoms following
physical or mental exertion, which do not subside with rest.
In
October 2016, an analysis of a subset of CFS patients from the AMP-516 Phase 3 study was performed and presented at the IACFS/ME
annual meeting in Fort Lauderdale, FL. The ITT Population (n=208) was separated into two subsets based primarily on baseline CFS
symptom duration (2-8 years (n=75) and <2 years plus >8 years (n=133)). Responder analyses of the ITT Population and both
subsets were performed. Responder analyses of Ampligen vs. placebo patients improving ET duration from baseline by ≥25% shows
over twice the percentage of patients with clinical enhancement in ET effect in the Ampligen cohort compared to placebo for the
2-8-year subset vs. the ITT population. This subset may assist in the design of future clinical studies of Ampligen in the treatment
for ME/CFS patients.
The
high number of younger people being hospitalized for COVID-19 suggests considerable numbers of people in the prime of their lives
may have a COVID-induced ME/CFS-like illness in their future. Individuals with CFS lost an estimated $20,000 in 2002, implying
a total societal loss of $9.1 billion. Twenty-five percent ($2.3 billion) resulted from lost household productivity, and the remaining
75% ($6.8 billion) from lost labor force productivity.
9
In
June of 2020, we filed a provisional patent application for, among other discoveries, the use of Ampligen as a potential early-onset
therapy for the treatment of COVID-19 induced chronic fatigue.
Many
survivors of the first SARS-CoV-1 epidemic in 2003 continued to report chronic fatigue, difficulty sleeping and shortness of breath
months after recovering from the acute illness. “After one year, 17% of patients had not returned to work and 9% more had
not returned to their pre-SARS work levels” ( Simmaron Research ). Now there is increasing evidence that patients with
COVID-19 can develop a similar, ME/CFS-like illness. These patients are commonly referred to as “Long Haulers.” http://simmaronresearch.com/2020/04/will-covid-19-leave-an-explosion-of-me-cfs-cases-in-its-wake/
In
October 2020, we received Institutional Review Board (IRB) approval for the expansion of the AMP-511 Expanded Access Program (EAP)
clinical trial for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) to include patients previously diagnosed with SARS-CoV-2
following clearance of the virus, but who still demonstrate chronic fatigue-like symptoms.
On
November 2, 2020, we announced the publication of statistically significant data detailing how Ampligen could have a considerable
positive impact on people living with ME/CFS when administered in the early stages of the disease. The data were published in
PLOS ONE , a peer-reviewed open access scientific journal published by the Public Library of Science. AIM researchers found
that the TLR3 agonist Ampligen substantially improved physical performance in a subset of ME/CFS patients.
COVID-19
Following
the SARS-CoV-1 outbreak in 2002-03, Ampligen exhibited excellent antiviral properties and protective survival effect in NIH-contracted
studies of SARS-infected mice, which is very similar to SARS-CoV-2, the novel virus that causes COVID-19.
●
The
Barnard 2006 study ( https://journals.sagepub.com/doi/abs/10.1177/095632020601700505 ) found that Ampligen reduced virus
lung levels to below detectable limits.
●
The
Day 2009 study ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787736/ ) found that, instead of 100% mortality, there
was 100% protective survival.
We
compared key transcription regulatory sequences of SARS-CoV-1 to SARS-CoV-2 and found significant similarities, suggesting highly
probable extension of the antiviral effects of Ampligen in the earlier NIH-contracted SARS experiments to COVID-19.
The
SARS-CoV-2 virus – which causes COVID-19 – shares important genomic and pathogenic similarities with SARS-CoV-1 (hence
its name). Since Ampligen has shown antiviral activity against more distantly related coronaviruses, there was a reasonable probability
that the antiviral effects of Ampligen against SARS-CoV-1 will likely extend to SARS-CoV-2, as discussed below, recently, Ampligen
has demonstrated in vitro antiviral activity against SARS-CoV-2. We believe that this creates a compelling case for clinical trials
to evaluate Ampligen as a potential tool in the fight against COVID-19.
Since
the late 2019 outbreak of SARS-CoV-2, we have been actively engaged in determining whether Ampligen could be an effective treatment
for this virus or could be part of a vaccine. We believe that Ampligen has the potential to be both an early-onset treatment for
and prophylaxis against SARS-Cov-2. We believe that prior studies of Ampligen in SARS-CoV-1 animal experimentation may predict similar protective
effects against the new virus.
In
February 2020, we filed three provisional patent applications related to Ampligen in our efforts toward joining the global health
community in the fight against the deadly coronavirus (See: https://aimimmuno.com/press-release/aim-immunotech-files-provisional-patent-application-for-the-use-of-ampligenr-as-a-potential-therapy-for-covid-19-induced-chronic-
fatigue/). Our three provisional patent applications include: 1) Ampligen as a therapy for the coronavirus; 2) Ampligen as part
of a proposed intranasal universal coronavirus vaccine that combines Ampligen with inactivated coronavirus, conveying immunity
and cross-protection and; 3) a high-volume manufacturing process for Ampligen. Under the Patent Cooperation Treaty of 1970, which
provides international protections for patents, these three provisional patent applications were converted in to two international
patent applications based on the date of their filings.
10
In
early April 2020, we entered into a Material Transfer Agreement (MTA) with Shenzhen Smoore Technologies located in Shenzhen China,
the world’s largest manufacturer of inhalation devices. Pursuant to this agreement, Smoore has agreed to run preliminary
tests in China to the efficacy of Smoore’s inhalation delivery device using Ampligen. Initial testing will include evaluation
of Ampligen with regards to safety and characterization of the inhaler vapor properties. Additional testing will study the particle
size of various Ampligen concentrations in aqueous solutions obtainable using Smoore’s technology. The goal of these studies
is to establish a reproducible method to obtain an Ampligen-containing atomized mist that can deliver biologically active Ampligen
deep into the lung airways of humans. There have been delays related to importing Ampligen to China. We are working with Smoore
to alleviate these issues and to identify a mutually beneficial course of action that would allow us to move forward with the
proposed testing of Ampligen. We will announce when the shipment for testing purposes has been completed. The MTA with Smoore
expires on April 1, 2021, with the possibility of continued cooperation between us and Smoore under ongoing consideration.
On
August 6, 2020, we contracted Amarex Clinical Research LLC (“Amarex”) to act as our Clinical Research Organization
and provide regulatory support with regard to a clinical trial testing Ampligen’s potential as a COVID-19 prophylaxis via
intranasal delivery. We anticipate conducting the Phase I study using the Centre for Human Drug Research (CHDR) in The Netherlands.
Amarex is expected to help provide monitoring support. For the subsequent Phase II/III studies we expected to incur clinical
trial costs of up to $4-5 million. We expect that Phase I will consist of 40 test subjects and cost about $1 million.
In March 2020, the
Japanese National Institute of Infectious Diseases (“NIID”) initiated preliminary laboratory testing of Ampligen as
a potential treatment for COVID-19. On July 1, 2020, we entered into a trilateral material transfer and research agreement with
the NIID and Shionogi & Co., Ltd. (“Shionogi”), one of Japan’s premier pharma companies, to test the Company’s
drug Ampligen as a potential vaccine adjuvant for COVID-19. Per this agreement, the details of all preclinical and clinical results
will remain confidential until released by NIID and Shionogi. The Company was notified by Shionogi on November 17, 2020 that Shionogi
intends to utilize a TLR agonist other than AIM’s Ampligen as Shionogi’s designated adjuvant in its ongoing efforts
to develop a potential Shionogi vaccine for COVID-19.
Beginning
in April 2020, we entered into confidentiality and non-disclosure agreements with numerous companies for the potential outsourcing
of the production of polymer, enzyme, placebo as well as Ampligen, and one Contract Research Organization, Amarex, which will
provide regulatory support related to a clinical trial testing Ampligen’s potential as a COVID-19 prophylaxis via intranasal
delivery.
In
addition, we joined with ChinaGoAbroad (CGA) to facilitate the entry of Ampligen into the People’s Republic of China (PRC)
for use as a prophylactic/early-onset therapeutic against COVID-19. CGA is a member-based online information platform and offline
advisory firm serving to facilitate two-way international transactions relating to the PRC in collaboration with the China Overseas
Development Association (CODA). The relationship with ChinaGoAbroad is ongoing.
On
May 11, 2020, the FDA authorized an IND for Roswell Park to conduct a Phase 1/2a study of a regimen of Ampligen and interferon
alpha in cancer patients with mild or moderate COVID-19 infections. This new clinical trial, sponsored by the Roswell Park in
collaboration with us, will test the safety of this combination regimen in patients with cancer and mild to moderate COVID-19,
and the extent to which this therapy will promote clearance of the SARS-CoV-2 virus from the upper airway. It is planned that
the phase 1/2a study will enroll up to 44 patients in two stages. Phase 1 will see 12-24 patients receiving both Ampligen and
interferon alfa-2b at escalating doses. Once that initial phase is complete, further study participants will be randomized to
two arms: one receiving the two-drug combination and a control group who will not receive Ampligen or interferon alfa but will
receive best available care. We intend to be a financial sponsor of the study and will provide Ampligen at no charge for this
study.
On
July 6, 2020, we entered into a clinical trial agreement with Roswell Park pursuant to which Roswell Park will conduct a Phase
1/2a trial of Ampligen (rintatolimod) in combination with interferon alfa, in cancer patients with COVID-19, the disease caused
by the SARS-CoV-2 coronavirus. We and the National Cancer Institute are supporting this trial. We reported in September 2020 that
recruitment in the trial had begun. See: clinicaltrials.gov/NCT04379518. On November 25, 2020, the first patient in the study
had been enrolled and treated.
We
also entered into a material transfer agreement with the University of Rochester for a series of in vitro experiments to test
the direct antiviral activity of Ampligen on SARS-CoV-2, as well as the mechanism of action. They are currently engaged in experiments
with multiple cell lines as they work to establish the study model system. We also entered into a specialized services agreement
with Utah State University and have supplied Ampligen to support the University’s Institute for Viral Research in its research
into SARS-CoV-2. The Utah State results show that Ampligen was able to decrease SARS-CoV-2 infectious viral yields by 90% at clinically
achievable intranasal Ampligen dosage levels.
On
October 6, 2020, we received Institutional Review Board (IRB) approval for the expansion of the AMP-511 Expanded Access Program
(EAP) clinical trial for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) to include patients previously diagnosed
with SARS-CoV-2, but who still demonstrate chronic fatigue-like symptoms. Patients in the trial are treated with our flagship
pipeline drug Ampligen. On January 6, 2021, we commenced with the treatment of the first previously diagnosed COVID-19
patient with long-COVID symptoms in the AMP-511 study.
11
On
November 29, 2020, we entered into a Material Transfer and Research Agreement with Leyden Laboratories, B.V., (“Leyden Lab”)
to facilitate two proposed studies/research projects:
●
An
assessment of protective potential of intranasal administration of Ampligen in SARS-CoV-2 Syrian hamster challenge model;
and
●
An
assessment of protective potential of intranasal Ampligen in lethal influenza mouse challenge model.
On
January 11, 2021, we entered into a Sponsor Agreement with the Centre for Human Drug Research (CHDR), a foundation located in
the Leiden in the Netherlands, to manage a proposed Phase 1 randomized, double-blind study to evaluate the safety and activity
of repeated intranasal administration of Ampligen. In February 2021, the Ethics Committee in the Netherlands issued its approval
for commencement of the study. The current study plans call for the enrollment of eight healthy subjects in each of four Ampligen
treatment groups and eight placebo subjects, for a total of 40 healthy subjects. This will assess the safety, tolerability and
biological activity of repeated administration of Ampligen intranasally. The subjects will receive intranasal dosing every other
day for 13 days, for a total of seven doses each. We are funding the clinical study. We consider such a study to be an important
part of our ongoing efforts to develop an intranasal COVID-19 treatment.
Other
Diseases
In
Europe, the EMA has approved the Orphan Medicinal Products Designation for rintatolimod (Ampligen) as a potential treatment of
Ebola virus disease and for Alferon N Injection, also known as interferon alfa-n3, as a potential treatment of MERS.
We
concluded our series of collaborations designed to determine the potential effectiveness of Ampligen and Alferon N as potential
preventative and/or therapeutic treatments for Ebola related disorders. Although we believe that the threat of both MERS and Ebola
globally may reemerge in the future, it appears that the spread of these disorders has somewhat diminished. As a result, we have
elected to focus our research and development efforts on other areas at this time.
MANUFACTURING
The
Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica (ANMAT) in Argentina approved Ampligen for commercial distribution
for the treatment of Chronic Fatigue Syndrome (CFS) in 2016. Shipment of the drug product to Argentina was initiated in 2018 to
complete the release testing by ANMAT needed for commercial distribution. On September 19, 2019, we received clearance from the
FDA to ship Ampligen to Argentina for the commercial launch and subsequent sales. We are currently working with GP Pharma on the
commercial launch of Ampligen in Argentina See “Our Products; Ampligen” above.
Jubilant
HollisterStier (Jubilant) is our authorized CMO for Ampligen for our approval in Argentina. Since the 2017 engagement of Jubilant
to manufacture Ampligen, two lots of Ampligen consisting of more than 16,000 units have been manufactured and released in year
2018. The first lot was designated for human use in the US in the cost recovery CFS program and for expanded oncology clinical
trials. The second lot has been designated for these programs in addition to commercial distribution in Argentina for the treatment
of CFS. The production of additional polymer (Ampligen intermediates) took place in 2019 at our New Brunswick facility. Additionally,
two lots of Ampligen were manufactured in December 2019 and January 2020 at Jubilant. The current manufactured lots of Ampligen
have been fully tested and released for commercial product launch in Argentina and for clinical trials.
In
December 2020, we added Pharmaceutics International Inc. (“Pii”) as a “Fill & Finish” provider to
enhance our capacity to produce the drug Ampligen. This addition amplifies our manufacturing capability by providing redundancy
and cost savings. The contracts augment our existing fill and finish capacity.
Alferon
is approved by the FDA for commercial sales in the US for the treatment of genital warts. It is also approved by ANMAT in Argentina
for commercial sales for the treatment of genital warts and in patients who are refractory to treatment with recombinant interferons.
Commercial
sales of Alferon in the United States will not resume until new batches of commercial filled and finished product are produced
and released by the FDA. While our facility is approved by the FDA under the Biologics License Application (“BLA”)
for Alferon, this status will need to be reaffirmed by an FDA pre-approval inspection. We will also need the FDA’s approval
to release commercial product once we have submitted satisfactory stability and quality release data. Currently, the manufacturing
process is on hold and there is no definitive timetable to have the facility back online.
We
have reviewed our operations at the facility and believe that some of the equipment most likely should be upgraded to realize
greater efficiencies, when and if we require more API than is currently in storage. We are also exploring engaging a Contract
Manufacturing Organization (“CMO”) to produce API. While we believe we have sufficient API to meet our current needs,
we are also continually exploring new efficiencies so as to maximize our ability to fulfill future obligations.
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Licensing/Collaborations/Joint
Ventures
To
maximize the availability of Ampligen to patients on a worldwide basis, we have embarked on a strategy to license the product
and/or to collaborate and/or create a joint venture with companies that have the demonstrated capabilities and commitment to successfully
gain approval and commercialize Ampligen in their respective territories of the world. Ideal partners would have the following
characteristics: well established global and regional experience and coverage, robust commercial infrastructure, strong track
record of successful development and registration of in-licensed products, as well as a therapeutic area fit (ME/CFS, immuno-oncology,
etc.).
MARKETING/DISTRIBUTION
In
May 2016, we entered into a five-year exclusive Renewed Sales, Marketing, Distribution and Supply Agreement (the “Agreement”)
with GP Pharm. Under this Agreement, GP Pharm was responsible for gaining regulatory approval in Argentina for Ampligen to treat
severe CFS in Argentina and for commercializing Ampligen for this indication in Argentina. We granted GP Pharm the right to expand
rights to sell this experimental therapeutic into other Latin America countries based upon GP Pharm achieving certain performance
milestones. We also granted GP Pharm an option to market Alferon N Injection in Argentina and other Latin America countries. See
“Our Products; Ampligen” above.
In
January 2017, the ANMAT granted a five-year extension to a previous approval to sell and distribute Alferon N Injection (under
the brand name “Naturaferon”) in Argentina. This extends the approval until 2022. In February 2013, we received the
ANMAT approval for the treatment of refractory patients that failed or were intolerant to treatment with recombinant interferon,
with Naturaferon in Argentina.
In
May 2016, we entered into a five-year agreement (the “Impatients Agreement”) with Impatients, N.V. (“myTomorrows”),
a Netherlands based company, for the commencement and management of an EAP in Europe and Turkey (the “Territory”)
related to ME/CFS. Pursuant to the agreement, myTomorrows, as our exclusive service provider and distributor in the Territory,
is performing EAP activities. These activities will be directed to (a) the education of physicians and patients regarding the
possibility of early access to innovative medical treatments not yet the subject of a Marketing Authorization (regulatory approval)
through named-patient use, compassionate use, expanded access and hospital exemption, (b) patient and physician outreach related
to a patient-physician platform, (c) the securing of Early Access Approvals (exemptions and/or waivers required by regulatory
authorities for medical treatments prior to Marketing Authorization) for the use of such treatments, (d) the distribution and
sale of such treatments pursuant to such Early Access Approvals, (e) pharmacovigilance (drug safety) activities and/or (f) the
collection of data such as patient-reported outcomes, doctor-reported experiences and registry data. We are supporting these efforts
and supplying Ampligen to myTomorrows at a predetermined transfer price. In the event that we receive Marketing Authorization
in any country in the Territory, we will pay myTomorrows a royalty on products sold. Pursuant to the Impatients Agreement, the
royalty would be a percentage of Net Sales (as defined in the Impatients Agreement) of Ampligen sold in the Territory where Marketing
Authorization was obtained, and the maximum royalty would be a percentage of Net Sales. The formula to determine the percentage
of Net Sales will be based on the number of patients that are entered into the EAP. We believe that disclosure of the exact maximum
royalty rate and royalty termination date could cause competitive harm. However, to assist the public in gauging these terms,
the actual maximum royalty rate is somewhere between 2% and 10% and the royalty termination date is somewhere between five and
fifteen years from the First Commercial Sale of a product within a specific country. The parties established a Joint Steering
Committee comprised of representatives of both parties to oversee the EAP. No assurance can be given that activities under the
EAP will result in Marketing Authorization or the sale of substantial amounts of Ampligen in the Territory.
In
January 2017, the EAP through our agreement with myTomorrows designed to enable access of Ampligen to ME/CFS patients has been
extended to pancreatic cancer patients beginning in the Netherlands. myTomorrows is our exclusive service provider in the Territory
and will manage all EAP activities relating to the pancreatic cancer extension of the program.
In
February 2018, we signed an amendment to the EAP with myTomorrows. This amendment extended the territory to cover Canada to treat
pancreatic cancer patients, pending government approval.
In
March 2018, we signed an amendment to the EAP with myTomorrows, pursuant to which myTomorrows will be our exclusive service provider
for special access activities in Canada for the supply of Ampligen for the treatment of ME/CFS.
In
December 2020, we entered into a signed Letter of Agreement with myTomorrows for the delivery of Ampligen for the treatment of
up to 16 pancreatic cancer patients.
In
August 2017, we extended our agreement with Asembia LLC, formerly Armada Healthcare, LLC, to undertake the marketing, education
and sales of Alferon N Injection throughout the United States. We are currently exploring an expansion of this relationship.
13
COMPETITION
The
major pharmaceutical competitors for Ampligen include Pfizer, GlaxoSmithKline, Merck & Co., Novartis and AstraZeneca. Biotech
competitors include Baxter International, Fletcher/CSI, AVANT Immunotherapeutics, AVI BioPharma and Genta. When we recommence
sales of Alferon N Injection, it will compete with Intron® A, an injectable from Merck & Co.
GOVERNMENT
REGULATION
Regulation
by governmental authorities in the U.S. and foreign countries is and will be a significant factor in the manufacture and marketing
of Alferon products and our ongoing research and product development activities. Ampligen and other products developed from the
ongoing research and product development activities will require regulatory clearances prior to commercialization. In particular,
new drug products for humans are subject to rigorous pre-clinical and clinical testing as a condition for clearance by the FDA
and by similar authorities in foreign countries. The process of seeking these approvals, and the ongoing process of compliance
with applicable statutes and regulations, has and will continue to require the expenditure of substantial resources. Any failure
by us or our collaborators or licensees to obtain, or any delay in obtaining, regulatory approvals could materially adversely
affect the marketing of any products developed by us and our ability to receive product or royalty revenue. We have received Orphan
Drug designation for certain therapeutic indications, which we believe might under certain conditions help to accelerate the process
of drug development and commercialization. Alferon N Injection is only approved for use in intralesional treatment of refractory
or recurring external genital warts in patients 18 years of age or older. Use of Alferon N Injection for other applications requires
regulatory approval.
We
are subject to various federal, state and local laws, regulations and recommendations relating to such matters as safe working
conditions, laboratory and manufacturing practices, the experimental use of animals and the use of and disposal of hazardous or
potentially hazardous substances, including infectious disease agents, used in connection with our research work.
For
more information about the current status of Alferon N Injection and Ampligen, please see “Our Products” above.
HUMAN
CAPITAL
As
of December 31, 2020, we had personnel consisting of twenty-one (21) full-time employees and two (2) part-time employees. Five
(5) of the combined personnel are engaged in our research, development, clinical, and manufacturing effort with eighteen (18)
performing regulatory, general administration, data processing, including bio-statistics, financial and investor relations functions.
We have no union employees.
While
we have been successful in attracting skilled and experienced scientific personnel, there can be no assurance that we will be
able to attract or retain the necessary qualified employees and/or consultants in the future.