What changed in this filing

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Item 2. Management’s Discussion and Analysis

2022-05-13 compared with 2021-11-15 · 721 added, 566 removed, 509 unchanged (72% of the section changed)

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current beliefs, expectations and assumptions about future events, conditions and results and on information currently available to us.

Discussions containing these forward-looking statements may be found, among other places, in this “Management’s Discussion

and Analysis of Financial Condition and Results of Operations” section;

Part II, Item 1 “Legal Proceedings”;

II, Item 1A “Risk Factors”.

Discussions containing these forward-looking statements may be found, among other places, in this Report in Part I, Item 7.

“Management’s

Discussion and Analysis of Financial Condition and Results of Operations”;

Part II, Item 1.

“Legal Proceedings”;

Part II, Item 1A.

“Risk Factors”, as well as the following sections of our Annual Report on Form 10-K for the year ended

December 31, 2021:

“Business”, Part I;

“Risk Factors”, Part I;

“Legal Proceedings”,

Part I and Part II;

“Management’s Discussion and Analysis of Financial Condition and Results of Operations”.

statements, other than statements of historical fact, included or incorporated herein regarding our strategy, future operations, financial

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uncertainties inherent in our business including, without limitation:

the potential therapeutic effect of our products, the possibility

of obtaining regulatory approval, our ability to find senior co-development partners with the capital and expertise needed to commercialize

our products and to enter into arrangements with them on commercially reasonable terms, our ability to manufacture and sell any products,

our ability to enter into arrangements with third-party vendors, market acceptance of our products, our ability to earn a profit from

sales or licenses of any drugs, our ability to raise additional capital should we encounter unexpected expenses or deplete our current

reserves, our ability to discover new drugs in the future, changing market conditions, changes in laws and regulations affecting our

industry, and issues related to our New Brunswick, New Jersey facility.

are in various stages of seeking to determine whether Ampligen will be effective in the treatment of multiple types of cancers, immune-deficiency

disorders and viral diseases.

We discuss in this Report our current and anticipated future activities, all of which are subject to change

for a number of reasons.

Significant additional testing and trials will be required to determine whether Ampligen will be effective in

our ability to adequately fund our projects as we will need additional

funding to proceed with our objectives, the potential therapeutic effect of our products, the possibility of obtaining regulatory approval,

our ability to find senior co-development partners with the capital and expertise needed to commercialize our products and to enter into

arrangements with them on commercially reasonable terms, our ability to manufacture and sell any products, our ability to enter into

arrangements with third party vendors, market acceptance of our products, our ability to earn a profit from sales or licenses of any

drugs, our ability to discover new drugs in the future, changing market conditions, changes in laws and regulations affecting our industry,

and issues related to our New Brunswick, New Jersey facility.

are in various stages of seeking to determine whether Ampligen will be effective in the treatment of multiple types of viral diseases,

cancers, and immune-deficiency disorders.

We discuss in this Report our current and anticipated future activities, all of which are subject

to change for a number of reasons.

Significant testing and trials will be required to determine whether Ampligen will be effective in

the treatment of these conditions.

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In addition, initiation of planned

clinical trials may not occur due to many factors including lack of regulatory approval(s) or lack of study drug.

Even if these clinical

trials are initiated, we cannot assure that the clinical studies will be successful or yield any useful data or require additional funding.

We recognize that all cancer centers, like all medical facilities, must make the COVID-19 pandemic their priority.

Therefore, there is

the potential for delays in clinical trial enrollment and reporting in ongoing studies.

No assurance can be given that future studies

will not result in findings that are different from those reported in the studies we refer to.

Additionally,

the pandemic is disrupting world health and world economies and most likely will continue to do so for a long time.

Many countries are

dealing with COVID-19 and have made that their primary health focus.

While we are able to continue to operate, like all businesses we

are unable to gauge how bad this pandemic will affect our operations in the future (e.g.

in Argentina, where we believe COVID-19 is affecting

our commercialization efforts).

Operating in foreign countries carries with it a number of risks, including potential difficulties in

enforcing intellectual property rights.

We cannot assure that our potential operations in foreign countries will not be adversely affected

by these risks.

We have filed a number of provisional patent applications.

No assurance can be given that our current or future patent

applications ultimately will be granted.

clinical trials may not occur secondary to many factors including lack of regulatory approval(s) or lack of study drug.

Even if these

clinical trials are initiated, we cannot assure that the clinical studies will be successful or yield any useful data or require additional

the outbreak of the COVID-19 coronavirus and our prior research into Ampligen’s antiviral activity against Severe Acute Respiratory

Syndrome, or SARS, we now are focusing on the potential of Ampligen to serve as a protective prophylaxis and an early-onset therapeutic

for severe respiratory viruses, including SARS-CoV-2.

Our beliefs rely on a number of studies.

No assurance can be given that future

studies will not result in findings that are different from those reported in the studies we refer to.

The pandemic is disrupting world

health and world economies and most likely will continue to do so for a long time.

While we are able to continue to operate, clearly,

like all businesses, we are unable to gauge how bad this pandemic will affect our operations in the future.

We reached out to numerous

foreign governments related to COVID-19 and, if successful, will be working in these countries.

Operating in foreign countries carries

with it a number of risks, including potential difficulties in enforcing intellectual property rights.

We cannot assure that our potential

operations in foreign countries will not be adversely affected by these risks.

We have filed provisional patent applications related

to the COVID-19 coronavirus.

However, these filings do not assure that patents will ultimately be granted.

February 2013, we received a Complete Response Letter (CRL) from the Food and Drug Administration, or FDA, for our Ampligen New Drug

Application, or NDA, for the treatment of CFS.

The FDA communicated that we should conduct at least one additional clinical trial, complete

various nonclinical studies and perform a number of data analyses.

Accordingly, the remaining steps to potentially gain FDA approval

of the Ampligen NDA, the final results of these and other ongoing activities could vary materially from our expectations and could adversely

affect the chances for approval of the Ampligen NDA.

These activities and the ultimate outcomes are subject to a variety of risks and

uncertainties, including but not limited to risks that (i) the FDA may ask for additional data, information or studies to be completed

and (ii) the FDA may require additional work related to the commercial manufacturing process to be completed or may, in

the course of the inspection of manufacturing facilities, identify issues to be resolved.

A proposed confirmatory trial and responses

to the CRL are being worked on now by our R&D team and consultants.

August 2016, we received approval of our NDA from Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica, or ANMAT, for

commercial sale of rintatolimod (U.S.

Ampligen®) in the Argentine Republic for the treatment of severe CFS.

will be marketed by GP Pharm, our commercial partner in Latin America.

We believe, but cannot assure, that this approval provides a platform

for potential sales in certain countries within the European Union under regulations that support cross-border pharmaceutical sales of

licensed drugs.

In Europe, approval in a country with a stringent regulatory process in place, such as Argentina, should add further

validation for the product as the Early Access Program, or EAP, as discussed below and underway in Europe in pancreatic cancer.

approval is only an initial, but important, step in the overall successful commercialization of our product.

There are a number of actions

that must occur before we could be able to commence commercial sales in Argentina.

In September 2019, we received clearance from the

FDA to ship Ampligen to Argentina for the commercial launch and subsequent sales.

In June 2020, we received import clearance from ANMAT

to import the first shipment of commercial grade vials of Ampligen into Argentina.

We are currently working with GP Pharma on the commercial

launch of Ampligen in Argentina.

Commercialization in Argentina will require, among other things, an appropriate reimbursement level,

appropriate marketing strategies, 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.

Approval of rintatolimod for severe CFS in the Argentine Republic

does not in any way suggest that the Ampligen NDA in the United States or any comparable application filed in the European Union or elsewhere

will obtain commercial approval.

May 2016, we entered into a five-year agreement with myTomorrows, a Netherlands based company, for the commencement and management of

an EAP in Europe and Turkey related to CFS.

Pursuant to the agreement, myTomorrows, as our exclusive service provider and distributor

in this territory, is performing EAP activities.

In January 2017, the EAP was extended to pancreatic cancer patients beginning in the

In February 2018, we signed an amendment to extend the territory to cover Canada to treat pancreatic cancer patients, pending

government approval.

In March 2018, we signed an amendment to which myTomorrows will be our exclusive service provider for special access

activities in Canada for the supply of Ampligen for the treatment of CFS.

MyTomorrows provides services related to the supply and distribution

of Ampligen to patients in Early Access Programs (EAP) which is initiated through a physician’s request;

there have been no physician

requests that have led to government approval, therefore no patients have been treated under an EAP for either pancreatic cancer or CFS

No assurance can be given that we can sufficiently supply product should we experience an unexpected demand for Ampligen in

our clinical studies, the commercial launch in Argentina or pursuant to the EAPs.

No assurance can be given that Ampligen will prove

effective in the treatment of pancreatic cancer.

The agreement was automatically extended for a period of 12 months on May 20, 2021,

and will automatically extend for an additional period of 12 months on May 20, 2022.

Ampligen clinical trials are underway, in various phases of development and activity, with a number of subjects enrolled at university

cancer centers testing whether tumor microenvironments can be reprogrammed to increase the effectiveness of cancer immunotherapy, including

checkpoint blockade.

One site of clinical trials is Roswell Park and the other is the University of Pittsburgh Medical Center.

“Research and Development;

Immuno-oncology”).

No assurance can be given as to the results of these underway trials.

can be given as to whether some or all of the planned additional oncology clinical trials will occur and they are subject to many factors,

including lack of regulatory approval(s), lack of study drug, or a change in priorities at the sponsoring universities or cancer centers.

Even if these additional clinical trials are initiated, as we are not the sponsor, we cannot assure that these clinical studies or the

studies underway will be successful or yield any useful data.

In addition, initiation of planned clinical trials may not occur secondary

to many factors including lack of regulatory approval(s) or lack of study drug.

Even if these clinical trials are initiated, we cannot

assure that the clinical studies will be successful or yield any useful data or require additional funding.

overall objectives include plans to continue seeking approval for commercialization of Ampligen in the United States and abroad as well

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We do not know when, if ever, our products will be generally available for commercial sale for any indication.

conduct testing and have produced limited quantities of active pharmaceutical ingredients (“API”) for our products at our

We are in the planning stages of updating the manufacturing and laboratory suites with state-of-the-art, mobile-ready

equipment that can be used either there or in future alternate space.

While we believe we have sufficient API to meet our current needs,

we also are continually exploring new efficiencies so as to maximize our ability to fulfill future obligations.

In lieu of modernizing

the facility or in addition thereto, our current and active production plan is to shift to the utilization of Contract Manufacturing

Organizations (“CMO”), while maintaining on-site teams for QC, QA, R&D, bench and small-batch manufacturing.

production of new Alferon API inventory at the facility cannot begin until the validation phase is complete.

While the facility has already

been approved by the FDA under the Biological License Application (“BLA”) for Alferon, this status will need to be reaffirmed

through revalidation of our revised process and systems, submission of a supplemental application and, potentially, a successful Pre-Approval

Inspection by the FDA prior to commercial sale of newly produced inventory product.

If we determine that we need expanded capacity,

and/or we determine not to move forward with re-validating the facility, we will need to move forward with other possibilities to produce

If we are unable to gain the necessary FDA approvals related to the manufacturing process and/or final product of new Alferon

inventory, our operations most likely will be materially and/or adversely affected.

In light of these contingencies, there can be no

assurances that the approved Alferon N Injection product will be returned to production on a timely basis, if at all, or that if and

when it is again made commercially available, it will return to prior sales levels.

strived to maximize the outsourcing of certain components of our manufacturing, quality control, marketing and distribution while maintaining

control over the entire process through our quality assurance and regulatory groups.

We cannot provide any guarantee that the facility

or our contract manufacturers will pass an FDA pre-approval inspection for Alferon N Injection manufacturing.

production of new Alferon N Injection Active Pharmaceutical Ingredient, or API, is currently on hold.

While the New Brunswick facility

is approved by the FDA under the Biological License Application, or BLA, for Alferon N Injection, and we intend to maintain a certain

amount of space at the to-be-sold facility, the sale of the facility — announced in March 2022 — will move up the timeline

for contracting with a CMO, or CMOs, capable of producing Alferon, and receiving FDA approval to do so, prior to commercial sale of newly

produced inventory product.

If and when we obtain a reaffirmation of FDA BLA status and have begun production of new Alferon N Injection

API, it will need FDA approval as to the quality and stability of the final product before commercial sales can resume.

We may need additional

funds to finance the validation process.

If we are unable to gain the necessary FDA approvals related to the manufacturing process and/or

final product of new Alferon N Injection inventory, our operations most likely will be materially and/or adversely affected.

of these contingencies, there can be no assurances that the approved Alferon N Injection product will be returned to production on a

timely basis, if at all, or that if and when it is again made commercially available, it will return to prior sales levels.

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.

contracts augment our active and in-process fill and finish capacity.

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.

AIM and Smoore signed a two-year extension of their MTA in May 2021.

We are exploring avenues

to further test Ampligen as an inhalation therapy in the United States and Europe, while Smoore continues to work toward receiving authorization

to import Ampligen to China.

believe, and are investigating, Ampligen’s potential role in enhancing the activity of influenza vaccines.

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of the human body, and to aid the development of therapeutic products for the treatment of certain cancers and chronic diseases.

flagship products are Ampligen (rintatolimod), a first-in-class drug of large macromolecular RNA (ribonucleic acid) molecules, and Alferon

N Injection (Interferon Alfa-N3).

flagship products are Ampligen® (rintatolimod), a first-in-class drug of large macromolecular RNA (ribonucleic acid) molecules, and

Alferon N Injection® (Interferon alfa-n3).

Ampligen has not been approved by the FDA or marketed in the United States.

Ampligen is approved

for commercial sale in the Argentine Republic for the treatment of severe Chronic Fatigue Syndrome (“CFS”).

is approved for commercial sale in the Argentine Republic for the treatment of severe Chronic Fatigue Syndrome (“CFS”).

primary present business focus involves Ampligen.

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and disorders of the immune system.

currently are proceeding primarily in three areas:

plus Standard of Care (“SOC”) to treat pancreatic cancer patients, and in other cancers, as a potential therapeutic that

modifies the tumor microenvironment with the goal of increasing anti-tumor responses to check point inhibitors and with SOC.

Ampligen’s antiviral activities and potential use as a prophylactic or treatment for existing viruses, mutations thereof or

as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome (“ME/CFS”) and what we refer to as Post-COVID-19

Cognitive Dysfunction (“PCCD”).

currently are proceeding primarily in four areas:

randomized controlled study to evaluate efficacy and safety of Ampligen compared to a control group to treat locally advanced pancreatic

cancer patients.

Ampligen in other cancers, as a potential therapy that modifies the tumor microenvironment with the goal of increasing anti-tumor

responses to check point inhibitors.

Ampligen’s antiviral activities and potential use as a prophylactic or treatment for existing viruses, new viruses and mutated

viruses thereof.

as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome (“ME/CFS”) and fatigue and/or difficulty thinking/concentrating

as the predominate Post-COVID conditions (as referenced on CDC website Sept.

are prioritizing our activities in an order related to the stage of development, with those clinical activities such as pancreatic cancer,

ME/CFS and PCCD having priority over antiviral experimentation.

We intend that priority clinical work be conducted in FDA- or EMA-authorized

trials which could support a potential future New Drug Application (“NDA”).

However, our antiviral experimentation is designed

to accumulate additional preliminary data supporting our hypothesis that Ampligen is a powerful, broad-spectrum prophylaxis and early-onset

therapeutic that may confer enhanced immunity and cross-protection.

Accordingly, we will conduct our antiviral programs in those venues

most readily available and able to generate valid proof-of-concept data, including foreign venues.

Cancer and Immuno-Oncology .

ME/CFS and Post-COVID conditions having priority over antiviral experimentation.

We intend that priority clinical work be conducted in

FDA- or EMA-authorized trials which could support a potential future New Drug Application (“NDA”).

However, our antiviral

experimentation is designed to accumulate additional preliminary data supporting our hypothesis that Ampligen is a powerful, broad-spectrum

prophylaxis and early-onset therapeutic that may confer enhanced immunity and cross-protection.

Accordingly, we will conduct our antiviral

programs in those venues most readily available and able to generate valid proof-of-concept data, including foreign venues.

Immuno-Oncology .

are focused on pancreatic cancer because testing results, to date, primarily conducted in the Netherlands, have been very promising.

The Netherlands study generated statistically significant data indicating that Ampligen extended survival well beyond the SOC.

data support the proposition that Ampligen, when administered in patients with locally advanced or metastatic pancreatic cancer after

systemic chemotherapy showed a statistically significant increase in survival rate.

In October 2021, we and our Contract Research Organization,

Amarex Clinical Research LLC (“Amarex”), submitted an Investigational New Drug (“IND”) application and an accompanying

application for Fast Track status to the U.S.

Food and Drug Administration (“FDA”) for a planned Phase 2 study of Ampligen

as a therapy for locally advanced or metastatic late-stage pancreatic cancer.

We believe that the potential benefits for patients with

late-stage pancreatic cancer, a terminal disease, well outweighs any risks involved in administering Ampligen.

Assuming this trial and

subsequent planned clinical trials confirm the existing data, our goal is to then submit an NDA for use of Ampligen in pancreatic cancer

The Netherlands study generated statistically significant data indicating that Ampligen extended survival well beyond the Standard of

Care (“SOC”).

These data support the proposition that Ampligen, when administered to either patients with locally

advanced or metastatic pancreatic cancer after systemic chemotherapy showed a statistically significant increase in survival rate.

October 2021, we and our Contract Research Organization, Amarex Clinical Research LLC (“Amarex”), submitted an Investigational

New Drug (“IND”) application to the U.S.

Food and Drug Administration (“FDA”) for a planned Phase 2 study of

Ampligen as a therapy for locally advanced or metastatic late-stage pancreatic cancer.

The FDA placed the study on Clinical Hold in November

2021 and provided valuable feedback on the study design.

We submitted our response to the Clinical Hold in February 2022.

In March 2022,

we received notification from the FDA that the Clinical Hold was released and cleared, meaning that we are now able to proceed with the

Assuming this trial and subsequent planned clinical trials confirm the existing data, our goal is to then submit an NDA for use

of Ampligen in pancreatic cancer patients.

has also demonstrated in the clinic the potential for standalone efficacy in a number of solid tumors.

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survival rates and efficacy in the treatment of animal tumors when Ampligen is used in combination with checkpoint blockade therapies.

These successes in the field of immuno-oncology have guided our efforts toward the potential use of Ampligen as a combinational therapy

for the treatment of a variety of solid tumor types.

The first of our patent applications in this space was granted by the Netherlands

on March 15, 2021.

see “Immuno-Oncology and Pancreatic Cancer” below.

In fact, in March 2022 we announced interim data from an investigator-initiated, Phase 2, single-arm, efficacy/safety trial to evaluate

the effectiveness of combining intensive locoregional intraperitoneal (IP) chemoimmunotherapy of cisplatin with IP Ampligen (TLR-3 agonist)

and IV infusion of the checkpoint inhibitor pembrolizumab for patients with recurrent platinum-sensitive ovarian cancer.

We believe that

data from the study, which is being conducted by the University of Pittsburgh Medical Center, demonstrated that when combining three

drugs – Ampligen and pembrolizumab, which are both immune therapies, with cisplatin, a chemotherapy – evidence of increased

biomarkers associated with T cell chemotaxis and cytolytic function has been seen.

Importantly, increases of these biomarkers in the

tumor microenvironment have been correlated with favorable tumor responses.

These successes in the field of immuno-oncology have guided

our efforts toward the potential use of Ampligen as a combinational therapy for the treatment of a variety of solid tumor types.

first of our patent applications in this space was granted by the Netherlands on March 15, 2021.

see “Immuno-Oncology” below.

as an Antiviral .

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spent significant resources on COVID-19 (the disease caused by SARS-CoV-2) which is active and still infecting many subjects.

would need to be done to get Ampligen to market as a broad-spectrum antiviral, we believe that it is important to focus our efforts on

first and thoroughly proving the concept, especially while there is still a large COVID-19-infected population.

Previously, we conducted

animal studies that yielded positive results utilizing Ampligen to treat Western Equine Encephalitis Virus, Ebola and SARS-CoV-1.

have conducted experiments in SARS-CoV-2 showing Ampligen has a powerful impact on viral replication.

We believe that prior studies of

Ampligen in SARS-CoV-1 animal experimentation may predict similar protective effects against SARS-CoV-2.

have conducted and designed studies both in the United States and abroad and sought guidance from the FDA.

In our communications with

the FDA, the FDA has requested that we provide additional data to assist the agency in evaluating the potential risks and benefits of

administering Ampligen to asymptomatic and mild COVID-19 individuals.

However, as discussed in more detail below, where the threat to

the patient from COVID-19 is high, the FDA has already authorized Ampligen in a clinical trial of patients with COVID-19 who have

a pre-existing cancer.

would need to be done to get Ampligen to market as a broad-spectrum antiviral, we believe that it is important to focus our efforts first

and foremost on thoroughly proving the concept, especially while there is still a large COVID-19-infected population.

Previously, animal

studies were conducted that yielded positive results utilizing Ampligen to treat Western Equine Encephalitis Virus, Ebola and SARS-CoV-1.

We have conducted experiments in SARS-CoV-2 showing Ampligen has a powerful impact on viral replication.

The prior studies of Ampligen

in SARS-CoV-1 animal experimentation may predict similar protective effects against SARS-CoV-2.

FDA has requested that we provide additional data to assist the agency in evaluating the potential risks and benefits of administering

Ampligen to asymptomatic and mild COVID-19 individuals.

However, as discussed in more detail below, where the threat to the patient from

COVID-19 is high, the FDA has already authorized Ampligen in a clinical trial of patients with COVID-19 who have a pre-existing cancer.

That Phase 1/2a study utilizing Ampligen is underway.

We have also elected to conduct studies (initially

with healthy volunteers) outside the United States, primarily in the Netherlands and the United Kingdom.

We have also elected to explore studies (initially with healthy volunteers) outside

the United States, and have already conducted an intranasal safety study in the Netherlands.

this regard, the Centre for Human Drug Research (“CHDR”), a foundation located in Leiden in the Netherlands, managed a Phase

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Safety Report reported no Serious or Severe Adverse Events at any dosage level.

the completion of the Phase 1 dosing in the CHDR managed study, and based on its positive interim results, we engaged hVIVO to conduct

a Human Challenge Trial (“HCT”) at their quarantine facility in the U.K.

to test Ampligen as a potential intranasal antiviral

therapy using a human Rhinovirus hRV (common cold virus) and Influenza.

In an HCT, subjects are intentionally exposed to particular diseases

to test how the diseases will respond to potential therapeutics.

We believe that an HCT will allow us to expedite the development process

for Ampligen by ensuring full exposure of both the control group and the Ampligen group, so as to assess whether Ampligen has a prophylactic

We have submitted a study protocol to the Oxford Research Ethics Committee (“REC”)/Medicines and Healthcare

Regulatory Agency (“MHRA”) on September 10, 2021.

The REC approved the protocol, but the MHRA provided a response outlining

areas of the submission where it requires additional information.

We intend to re-submit its proposed protocol as soon as possible.

some two years after COVID-19 first appeared, the world has a number of vaccines and some promising therapeutics.

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see “Ampligen as a Potential Antiviral” below.

as a treatment for ME/CFS and PCCD

as a treatment for ME/CFS and Post-COVID Conditions

have long been focused on seeking the FDA’s approval for the use of Ampligen to treat ME/CFS.

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approval for the expansion of the AMP-511 protocol to include patients previously diagnosed with SARS-CoV-2 following clearance of the

virus, but who still demonstrate chronic fatigue-like symptoms that we refer to as Post-COVID-19 chronic fatigue.

As of September 30,

2021, there are 14 patients enrolled in this open-label expanded access treatment protocol (including 3 post-COVID-19 patients with cognitive

dysfunction).Early data from the ongoing AMP-511 Expanded Access Program has indicated that patients with cognitive function deficiency

have reported improvements in cognitive function after Ampligen treatment.

virus, but who still demonstrate chronic fatigue-like symptoms that we refer to as Post-COVID conditions.

As of March 31, 2022, there

are 11 patients enrolled in this open-label expanded access treatment protocol (including 2 post-COVID-19 patients).

Early data from

the ongoing AMP-511 Expanded Access Program has indicated that patients with Post-COVID conditions (such as fatigue and cognitive function

deficiency) have reported improvements after receiving Ampligen.

plan on a comprehensive follow through with the FDA regarding the use of Ampligen as a treatment for ME/CFS.

have learned a great deal since the FDA’s CRL and plan to adjust our approach to concentrate on specific ME/CFS symptoms.

to the CRL and a proposed confirmatory trial are being worked on now by our R&D team and consultants.

We have learned a great

deal since the FDA’s CRL and plan to adjust our approach to concentrate on specific ME/CFS symptoms.

Responses to the CRL and a

proposed confirmatory trial are being worked on now by our R&D team and consultants.

see “Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (“ME/CFS”)” below.

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(ds) RNA (ribonucleic acid) molecules, and our FDA-approved natural alpha-interferon product, Alferon N Injection.

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”

is approved for sale in Argentina (to 2026) 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 antiviral and anti-cancer properties.

Based on the results of published, peer-reviewed pre-clinical studies and clinical trials,

we believe that Ampligen may have broad-spectrum antiviral and anti-cancer properties.

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.

Ampligen represents the first drug in the class of large (macromolecular) dsRNA molecules to apply

for NDA review.

There are two forms of nucleic acids:

deoxyribonucleic acid (“DNA”) and ribonucleic

acid (“RNA”).

deoxyribonucleic acid (“DNA”) and ribonucleic acid (“RNA”).

DNA is a group of naturally occurring molecules found in chromosomes, the cell’s genetic machinery.

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 comprise 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 can be administered intravenously,

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 comprise 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 can be administered intravenously,

intranasally and intraperitoneally.

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potential treatment of patients with renal cell carcinoma, malignant melanoma, non-small cell lung cancer, ovarian cancer, breast cancer,

colorectal cancer, prostate cancer, pancreatic cancer, ME/CFS, Hepatitis B, HIV, COVID-19, Long COVID and Post-COVID-19 Cognitive Dysfunction.

colorectal cancer, prostate cancer, pancreatic cancer, ME/CFS, Hepatitis B, HIV, COVID-19 and Post-COVID conditions.

have received approval of our NDA from ANMAT for the commercial sale of Ampligen in the Argentine Republic for the treatment of severe

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initiated in 2018 to complete the release testing by ANMAT needed for commercial distribution.

On September 19, 2019, we received clearance

In September 2019, we received clearance

from the FDA to ship Ampligen to Argentina for the commercial launch and subsequent sales.

On June 10, 2020, we received import clearance

In June 2020, we received import clearance

from ANMAT to import the first shipment of commercial grade vials of Ampligen into Argentina.

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At this time, we do not plan on passing this adjustment along to the patients in this program.

As of September 30, 2021, there

are 14 patients enrolled in this open-label expanded access treatment protocol (including 3 post-COVID-19 patients with cognitive dysfunction).

In October 2020, we received IRB approval for the expansion of the AMP-511 Expanded Access Program clinical trial for ME/CFS to include

patients previously diagnosed with SARS-CoV-2 following clearance of the virus, but who still demonstrate chronic fatigue-like symptoms;

three of the 13 patients enrolled have post-COVID chronic-fatigue-like symptoms.

Early data from the ongoing AMP-511 Expanded Access

Program has indicated that patients with cognitive function deficiency have reported improvements in cognitive function after Ampligen

As of March 31, 2022, there are

11 patients enrolled in this open-label expanded access treatment protocol (including 2 Post-COVID-19 patients).

In October 2020, we

received IRB approval for the expansion of the AMP-511 Expanded Access Program clinical trial for ME/CFS to include patients previously

diagnosed with SARS-CoV-2 following clearance of the virus, but who still demonstrate chronic fatigue-like symptoms that we refer to

as Post-COVID conditions;

two of the 11 patients enrolled have post-COVID chronic-fatigue-like symptoms.

Early data from the ongoing

AMP-511 Expanded Access Program has indicated that patients with Post-COVID conditions (such as fatigue and cognitive function deficiency)

have reported improvement after receiving Ampligen.

May 2016, we entered into a five-year agreement with myTomorrows, a Netherlands based company, for the commencement and management of

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pancreatic cancer and ME/CFS patients.

The agreement was automatically extended for a period of 12 months on May 20, 2021.

The agreement was automatically extended for a period of 12 months on May 20, 2021 and will automatically

extend for an additional period of 12 months on May 20, 2022.

April 2018, we completed data analysis of an intranasal human safety study of Ampligen-plus-FluMist®, known as AMP-600.

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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.

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.

in December 2019 and January 2020 at Jubilant HollisterStier.

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

(“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 active and in-process fill and finish

N Injection is the registered trademark for our injectable formulation of natural alpha interferon.

Alferon is the only natural-source,

Alferon N Injection is the only natural-source,

multi-species alpha interferon currently approved for sale in the United States 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.

is also approved in Argentina for the treatment of refractory patients that failed or were intolerant to treatment with recombinant interferons.

N Injection is also approved in Argentina for the treatment of refractory patients that failed or were intolerant to treatment with recombinant

Certain types of human papilloma viruses (“HPV”) cause genital warts, a sexually transmitted disease (“STD”).

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Immuno-Oncology

and Pancreatic Cancer

potential of Ampligen as an immuno-oncology therapeutic has been a major focus of AIM since the company’s current leadership took

over in 2016.

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”).

potential of Ampligen as an immuno-oncology therapeutic has been a major focus of AIM since our current leadership took over in 2016.

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 have supplied Ampligen 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.

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

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.

Additionally,

in October 2018 we signed a clinical trial agreement with Roswell Park to evaluate Ampligen in combination with checkpoint inhibitors.

However, after several years of successful studies and trials, we are now strategically narrowing our focus to trials and activities

that have the shortest potential path to FDA and EMA drug approval – in other words, to put our energy into the tasks where clinical

results suggest an opportunity for expedited success.

These potential trials would be AIM-sponsored and AIM-funded.

Ampligen clinical trials are underway at major university cancer centers testing whether tumor microenvironments can be reprogrammed

to increase the effectiveness of cancer immunotherapy, including checkpoint inhibitors, The underway trials are:

Recurrent Ovarian Cancer - A follow-up Phase 2 study of advanced recurrent ovarian cancer using cisplatin, pembrolizumab, plus

up to 45 patients to be enrolled;

enrollment has commenced, and numerous patients have commenced treatment.

Kalinski relocated to Roswell Park in Buffalo, NY and has established a cancer program which

will continue to require a supply of Ampligen.

Ampligen clinical trials are underway or recently completed at major university cancer centers testing whether tumor microenvironments

can be reprogrammed to increase the effectiveness of cancer immunotherapy, including checkpoint inhibitors.

The underway trials include:

Recurrent Ovarian Cancer

of the Phase 1 portion of a Phase 1/2 study of intraperitoneal chemo-immunotherapy in advanced recurrent ovarian cancer were published

in the American Association for Cancer Research publication, Clinical Cancer Research (Clin Cancer Res January 19 2022 DOI:

10.1158/1078-0432.CCR-21-3659).

The study results represent an important extension of prior studies using human tumor explants that showed Ampligen’s potentially

important role as a TLR3 agonist acting synergistically with high-dose IFNα and celecoxib to selectively enhance Teff cell-attractants

while suppressing Treg-attractants in the tumor microenvironment with a concomitant increase in the Teff/Treg ratio.

The importance

of boosting the Teff/Treg ratio in the tumor microenvironment is that it is associated with the conversion of ‘cold’

tumors into ‘hot’ tumors, which have an increased sensitivity to chemo-immunotherapy and an improved chance of showing

tumor regression.

The Phase 1 portion was designed to establish intraperitoneal safety.

The Phase 2 portion of the study is planned

to be conducted in the future.

https://clinicaltrials.gov/ct2/show/NCT02432378

4 Metastatic Triple Negative Breast Cancer - Phase 1/2 study of metastatic triple-negative breast cancer using chemokine modulation

therapy, including Ampligen and pembrolizumab.

Eight patients were enrolled and treated.

follow-up Phase 2 study of advanced recurrent ovarian cancer using cisplatin, pembrolizumab, plus Ampligen;

up to 45 patients to

enrollment has commenced, and numerous patients have commenced treatment.

We recently announced interim data from

the study , which demonstrated that evidence of increased biomarkers associated with T cell chemotaxis and cytolytic function

was seen when combining Ampligen, pembrolizumab and cisplatin.

Increases of these biomarkers in the tumor microenvironment have been

correlated with favorable tumor responses.

Interim results announced March 2022 detailed an observed clinical response rate of 61%

includes two complete and three partial tumor responses, plus three patients with stable disease among the 13 evaluable patients.

An important priority will be to confirm these findings through continuing to enroll patients onto this study https://clinicaltrials.gov/ct2/show/NCT03734692

March 2021, we were granted a patent by the Netherlands Patent Office with granted patent claims that include, but are not limited to,

the use of Ampligen as a combination cancer therapy with checkpoint blockade inhibitors (e.g.

pembrolizumab, nivolumab).

from an investigator-initiated, Phase 2, single-arm, efficacy/safety trial demonstrated that evidence of increased biomarkers associated

with T cell chemotaxis and cytolytic function was seen when combining Ampligen, pembrolizumab and cisplatin.

It is critical to note that

increases of these biomarkers in the tumor microenvironment have been correlated with favorable tumor responses.

All told, the study

has seen a Clinical Benefit Rate of 61.6%;

a study of pembrolizumab alone in the treatment of advanced recurrent ovarian cancer

found Objective Response Rates of 7.4% and 9.9% across two cohorts.

The positive data makes this patent have heightened potential.

patents are pending in other counties.

4 Metastatic Triple Negative Breast Cancer - Phase 1 study of metastatic triple-negative

breast cancer using chemokine modulation therapy, including Ampligen and pembrolizumab.

patients were enrolled and 6 patients were evaluable.

https://www.clinicaltrials.gov/ct2/show/NCT03599453.

4 Colorectal Cancer Metastatic to the Liver - Phase 2a study of Ampligen as a component of chemokine modulatory regimen on colorectal

cancer metastatic to liver;

15 patients were enrolled and treated.

The key findings announced April 2022 included:

pre-determined primary endpoint of efficacy was met (increase in CD8 in TME).

increase of immune markers upon treatment was observed:

CD8 mRNA (6.1-fold;

p-0.034), GZMB

mRNA (3.5-fold;

p=0.058), ratios of CD8 /FOXP3 and GZMB/FOXP3 (5.7-fold;

p=0.036, and 7.6-fold;

p=0.024 respectively), thus successfully meeting the pre-determined primary endpoint in the

study (increase in CD8 in TME).

addition, an increase in CTL attractants CXCL10 (2.6-fold;

p=0.104) and CCL5 (3.3-fold;

was observed.

In contrast, Treg marker FOXP3 or Treg attractants CCL22 or CXCL12 were not

patients had stable disease lasting 2.4, 2.5 and 3.8 months, as of data cut off September

additional patient (non-evaluable) had a partial response (breast tumor autoamputation) with

massive tumor necrosis in the post-CKM biopsy.

4 Colorectal Cancer Metastatic to the Liver - Phase 2a study of Ampligen as a component

of chemokine modulatory regimen on colorectal cancer metastatic to liver;

recruitment has

been completed;

19 patients were enrolled and 12 patients were evaluable for the primary

https://clinicaltrials.gov/ct2/show/NCT03403634.

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

The key findings announced

April 2022 included:

study’s primary endpoint was met, evidenced by increased CD8a expression post-treatment

increase in the CD8a/CD4 (p=0.03), CD8a/FOXP3 (p<0.01) and GZMB/FOXP3 (p<0.01) ratios.

expression of CTL-attracting chemokines CCL5 (p=0.08), CXCL9 (p=0.05), and CXCL10 (p=0.06)

were increased, while expression of the Treg/MDSC attractant CXCL12 (p=0.07) was decreased

post-treatment.

OS was 10.5 (90% CI 2.2-15.2) months, and the median PFS was 1.5 (90% CI 1.4, 1.8) months.

tumor responses were seen.

The treatment was well tolerated.

Of all enrolled patients (N=19),

adverse events were noted in 74% of patients, with the most common being fatigue (58%).

3 or higher adverse events were rare (5%).

● 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

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.

Patient enrollment has been initiated in this study designed for up to 45

https://clinicaltrials.gov/ct2/show/NCT03899987

Additionally,

we are awaiting publication of the results of a Phase 1/2 study of intraperitoneal chemo- immunotherapy in advanced recurrent ovarian

The Phase 1 portion was designed to establish intraperitoneal safety.

● 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, Interim results announced in March 2022 detailed data gathered from

evaluating paclitaxel’s impact on chemokine production in the human breast tumor microenvironment

(TME) and the ability of a chemokine modulatory regimen (CKM) of Ampligen and Interferon-α

to mitigate potentially undesirable aspects of taxane chemotherapy.

Based on the results,

we believe that the combination chemokine modulatory regimen including Ampligen has the potential

to mitigate undesirable aspects of taxane chemotherapy.

https://clinicaltrials.gov/ct2/show/NCT04081389

below Ampligen clinical trials and related activities are planned for initiation in 2021-22:

2 Pancreatic Cancer Trial / FDA Fast Track Designation - In October 2021, AIM and Amarex, submitted an IND application and an

accompanying application for Fast Track status with the FDA for a planned Phase 2 study of Ampligen as a therapy for locally advanced

or metastatic late-stage pancreatic cancer.

Cancer - We plan to develop a Phase 2 Cisplatin Resistant Advanced Recurrent Ovarian Cancer Clinical Study utilizing Ampligen

at the University of Pittsburgh.

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.

below Ampligen clinical trials are in the planning stages:

2 Pancreatic Cancer Trial - In October 2021, AIM and Amarex submitted an IND application

with the FDA for a planned Phase 2 study of Ampligen as a therapy for locally advanced or

metastatic late-stage pancreatic cancer.

The FDA placed the study on Clinical Hold in November

2021 and provided valuable feedback on the study design.

We submitted our response to the

Clinical Hold in February 2022.

In March 2022, we received notification from the FDA that

the Clinical Hold was released and cleared, meaning that we are now able to proceed with

In April 2022, we executed a work order with Amarex to manage the clinical trial.

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

Up to 24 patients to be enrolled (See:

https://www.clinicaltrials.gov/show/NCT04093323).

part of this business and scientific strategy, and after lengthy discussions with Roswell Park Comprehensive Cancer Center, we have determined

that it is not in our stockholders’ best interests to relinquish “Third-Party Beneficiary” rights to any of our pre-existing

intellectual property without appropriate compensation and licensing terms.

This business decision has created an impasse which means

we will not be moving forward with certain planned trials at Roswell Park.

These trials are:

colorectal carcinoma trial;

proposed brain metastatic triple-negative breast cancer trial;

proposed non-small cell lung cancer trial;

urothelial, melanoma and renal cell carcinoma trial.

unlike pancreatic cancer and advanced recurrent ovarian cancer, these previous planned studies are not on our near-term critical path

for future NDAs.

Therefore, these will only become a priority after we accomplish our near-term goals related to pancreatic cancer and

advanced recurrent ovarian cancer where data supports priority status.

January 2017, the EAP established under our agreement with myTomorrows to enable access of Ampligen to ME/CFS patients was extended to

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cancer after systemic chemotherapy, compared with historical control patients.

We will work with our Contract Research Organization,

We are working with our Contract Research Organization,

Amarex Clinical Research LLC, to seek FDA “fast-track” and to obtain IND authorizations to conduct follow-up pancreatic cancer

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van Eijck, and also at major cancer research

centers in the United States.

centers in the United States such as The Buffett Cancer Center at the University of Nebraska Medical Center (UNMC).

Additionally:

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

The status helps incentivize the treatment of therapies to treat unmet medical needs by providing a company with seven

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.

February 2021, our subsidiary, NV Hemispherx Biopharma Europe, received formal notification from the European Commission (“EC”)

granting Orphan Medicinal Product Designation 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.

February 2021, our subsidiary, NV Hemispherx Biopharma Europe, received formal notification

from the European Commission (“EC”) granting Orphan Medicinal Product Designation

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.

June 2021, Ampligen was featured in a publication containing state-of-the-art methodologies in the peer-reviewed medical journal Cancers

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cancer cells”, including:

● Stimulation

of interferon regulatory factors and activation of the interferon signaling pathway,

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“ Rintatolimod Induces Antiviral Activities in Human Pancreatic Cancer Cells:

Opening for an Anti-COVID-19

Opportunity in Cancer Patients?” Cancers is a peer-reviewed, open access journal of oncology published semimonthly online

Opening for an

Anti-COVID-19 Opportunity in Cancer Patients?” Cancers is a peer-reviewed, open access journal of oncology published

semimonthly online by MDPI.

The study’s authors include Prof.

van Eijck, MD, PhD, the lead investigator for an EAP at Erasmus Medical Center

in the Netherlands.

March 2021, we were granted a patent by the Netherlands Patent Office.

The granted patent claims include, but are not limited to, the

use of Ampligen as a combination cancer therapy with checkpoint blockade inhibitors (e.g.

pembrolizumab, nivolumab).

October 2021, we and Amarex submitted an IND application and an accompanying application for Fast Track status with the FDA for a planned

Phase 2 study of Ampligen as a therapy for locally advanced or metastatic late-stage pancreatic cancer.

The Buffett Cancer Center at

UNMC and Erasmus MC in the Netherlands are expected to be the primary study sites, although additional sites are anticipated.

AMP-270 clinical trial of approximately 250 subjects will be a Phase 2, randomized, open-label, controlled, parallel-arm study with the

primary objective of comparing the efficacy of Ampligen when added to SOC versus SOC alone for subjects with advanced pancreatic carcinoma

recently treated with FOLFIRINOX chemotherapy regimen (secondary objectives include comparing safety and tolerability).

Encephalomyelitis/Chronic Fatigue Syndrome

van Eijck, MD, PhD, the lead investigator for an EAP at Erasmus

Medical Center in the Netherlands.

October 2021, we and Amarex submitted an IND application with the FDA for a planned Phase 2 study of Ampligen as a therapy for locally

advanced or metastatic late-stage pancreatic cancer.

In December 2021, the FDA responded with a Clinical Hold on the proposed study.

We submitted our response to the FDA in February 2022.

In March 2022, we received notification from the FDA that the Clinical Hold was

released and cleared, meaning that we are now able to proceed with the study.

The AMP-270 clinical trial is planned to be a randomized,

open-label, controlled, parallel-arm study with the primary objective of comparing the efficacy of Ampligen versus a no treatment control

group following FOLFIRINOX for subjects with locally advanced pancreatic adenocarcinoma.

Secondary objectives include comparing safety

and tolerability.

We plan to enroll approximately 90 subjects across up to 30 centers in the U.S.

The Buffett Cancer Center

at the University of Nebraska Medical Center (UNMC) and Erasmus MC in The Netherlands are expected to be the primary study sites.

April 2022, we executed a work order with Amarex to manage the Phase 2 clinical trial.

In March 2022, we announced the publication of

positive data in a manuscript titled, “ Rintatolimod (Ampligen®) enhances numbers of peripheral B cells and is associated

with longer survival in patients with locally advanced and metastasized pancreatic cancer pre-treated with FOLFIRINOX:

a single-center

named patient program, ” in Cancers Special Issue:

Combination and Innovative Therapies for Pancreatic Cancer .

single-center, named-patient program, patients with locally advanced pancreatic cancer (LAPC) or metastatic disease were treated with

Ampligen for 6 weeks, at 2 doses per week with 400 mg per infusion.

The study found that Ampligen improved the median survival of these

The study’s primary endpoints were the Systemic Immune-Inflammation Index (SIII), the Neutrophils to Lymphocyte Ratio

(NLR), and absolute counts of 18 different populations of circulating immune cells as measured by flow cytometry.

Secondary endpoints

were progression-free survival (PFS) and overall survival (OS).

The median overall survival in the Ampligen group was 19 months, compared

to a historical control group and subgroup (7.5 and 12.5, respectively) that did not receive Ampligen.

in March 2022, we announced that study data evaluating the direct effects of Ampligen on human pancreatic ductal adenocarcinoma (PDAC)

cells was accepted for presentation at the 15th Annual International Hepato-Pancreato-Biliary Association World Congress in New York,

For the study, three PDAC cell lines (CFPAC-1, MIAPaCa-2, and PANC-1) were treated with various concentrations of Ampligen and their

corresponding vehicle control.

The proliferation and migration effects were examined using in-vitro assays and the molecular effect was

examined by targeted gene expression profiling.

Additionally human PDAC samples were used to validate the expression of toll-like receptor

3 (TLR3) by immunohistochemistry.

Results from the study demonstrated Ampligen decreased the proliferation and migration ability of CFPAC-1

In addition, it decreased the proliferation of MIAPaCa-2 cells and the migration of PANC-1 cells.

However, it did not have a dual

effect in MIAPaCa-2 and PANC-1 cells.

Interestingly, TLR3 was highly expressed in CFPAC-1 cells, low expressed in MIAPaCa-2 and not expressed

Gene expression analysis revealed the upregulation of interferon-related genes, chemokines, interleukins and cell cycle regulatory

The heterogeneity of TLR3 expression was confirmed in human PDAC samples.

Based on these results, treating pancreatic cancer with

Ampligen may have a direct anti-tumor effect in pancreatic cancer cells expressing TLR-3.

Encephalomyelitis/Chronic Fatigue Syndrome (“ME/CFS”)

Encephalomyelitis/Chronic Fatigue Syndrome (“ME/CFS”), also known as Chronic Fatigue Immune Dysfunction Syndrome (“CFIDS”)

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studies of SARS-CoV-1-infected mice, which is very similar to SARS-CoV-2, the novel virus that causes COVID-19.

Barnard 2006 study ( https://journals.sagepub.com/doi/abs/10.1177/095632020601700505 ) found that Ampligen reduced virus lung

levels to below detectable limits.

Day 2009 study ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787736/ ) found that, instead of 100% mortality, there was 100%

protective survival using Ampligen.

Barnard 2006 study ( https://journals.sagepub.com/doi/abs/10.1177/095632020601700505 )

found that Ampligen reduced virus lung levels to below detectable limits.

Day 2009 study ( https://www.sciencedirect.com/science/article/pii/S0042682209005832

found that, instead of 100% mortality, there was 100% protective survival using Ampligen.

compared key transcription regulatory sequences of SARS-CoV-1 to SARS-CoV-2 and found significant similarities, suggesting highly probable

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of their filings.

April 1, 2020, we entered into a Material Transfer and Research Agreement (“MTA”) with Shenzhen Smoore Technology to study

the utilization of an innovative Smoore inhalation delivery device and Ampligen as a potential treatment approach for the SARS-CoV-2

April 2020, we entered into a Material Transfer and Research Agreement (“MTA”) with Shenzhen Smoore Technology to study the

utilization of an innovative Smoore inhalation delivery device and Ampligen as a potential treatment approach for the SARS-CoV-2 pandemic.

The MTA was extended for two years in May 2021.

There have been obstacles related to importing Ampligen to China.

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 outside of China.

On parallel paths, over the past year, Smoore focused on the development of a

personal inhalation device designed to administer Ampligen, given temperature parameters of dsRNA.

Contemporaneously, we have studied

the safety and efficacy of Ampligen using an ex vivo 3D model in primary human respiratory epithelial cells at Utah State University,

which showed that Ampligen was able to decrease SARS-CoV-2 infectious viral yields by 90% at clinically achievable intranasal Ampligen

dosage levels, and conducted intranasal safety testing.

AIM and Smoore signed a two-year extension of the MTA in May 2021.

We are exploring

avenues to further test Ampligen as an inhalation therapy in the United States and Europe, while Smoore continues to work toward receiving

authorization to import Ampligen to China.

We have been 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 outside of China.

On parallel paths, over the past year, Smoore focused on the development of a personal

inhalation device designed to administer Ampligen, given temperature parameters of dsRNA.

Contemporaneously, we have studied the safety

and efficacy of Ampligen using an ex vivo 3D model in primary human respiratory epithelial cells at Utah State University, which showed

that Ampligen was able to decrease SARS-CoV-2 infectious viral yields by 90% at clinically achievable intranasal Ampligen dosage levels,

and conducted intranasal safety testing.

We are exploring avenues to further test Ampligen as an inhalation therapy in the United States

and Europe, while Smoore continues to work toward receiving authorization to import Ampligen to China.

However, progress in this area

is stymied, and due to difficulty importing experimental drugs (such as Ampligen) we are considering our options.

August 2020, we contracted Amarex Clinical Research LLC (“Amarex”) to act as our Clinical Research Organization and provide

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via intranasal delivery.

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.

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 COVID-19 infections.

This clinical trial, sponsored by Roswell Park in collaboration with us, will test the safety

of this combination regimen in patients with cancer and COVID-19, and the extent to which this therapy will promote clearance of the

SARS-CoV-2 virus from the upper airway.

addition, in February 2020 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”).

While this relationship is currently inactive, we remain open to

utilizing ChinaGoAbroad if and when an opportunity arises.

May 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 COVID-19 infections.

This clinical trial, sponsored by Roswell Park in collaboration with us, will test the safety of this

combination regimen in patients with cancer and COVID-19, and the extent to which this therapy will promote clearance of the SARS-CoV-2

virus from the upper airway.

Several subjects have been treated and recruitment continues.

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.

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 alpha-2b at escalating

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 are a financial

sponsor of the study and will provide Ampligen at no charge for this study.

one receiving the two-drug combination

and a control group who will not receive Ampligen or interferon alpha but will receive best available care.

We are a financial sponsor

of the study and will provide Ampligen at no charge for this study.

July 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

of Ampligen (rintatolimod) in combination with interferon alpha, in cancer patients with COVID-19, the disease caused by the SARS-CoV-2

We and the National Cancer Institute are supporting this trial.

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had begun (See clinicaltrials.gov/NCT04379518 ).

On November 25, 2020, the first patient in the study had been enrolled and treated.

In November 2020, the first patient in the study had been enrolled and treated.

This study was amended to add 20 patients, with 10 randomized to receive a single dose of Ampligen and 10 patients to receive current

best therapies.

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.

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.

October 2020, we received IRB approval for the expansion of the AMP-511 Expanded Access Program clinical trial for ME/CFS to include

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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 (i.e., Long Hauler) in the AMP-511 study.

Enrollment of Long Hauler patients continues in the study.

In January 2021, we commenced with the treatment of the first previously diagnosed COVID-19

patient with long-COVID symptoms (i.e., Long Hauler) also known as Post-COVID Conditions in the AMP-511 study.

Enrollment of post-COVID

patients continues in the study.

November 2020, we entered into a Material Transfer and Research Agreement with Leyden Laboratories, B.V., (“Leyden Lab”)

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intranasal antiviral therapy using a human Rhinovirus hRV (common cold virus) and Influenza.

This antiviral study will be conducted by

hVIVO, a subsidiary of Open Orphan plc, a rapidly growing specialist pharmaceutical services clinical research organization and world

leader in vaccine and antiviral testing using human challenge clinical trials.

We have submitted its study protocol to the Oxford

Research Ethics Committee (“REC”)/Medicines and Healthcare Regulatory Agency (“MHRA”) on September 10, 2021.

The REC approved the protocol, but the MHRA provided a response outlining areas of the submission where it requires additional information.

We intend to re-submit our proposed protocol as soon as possible.

an HCT, subjects are intentionally exposed to particular diseases to test how the diseases will respond to potential therapeutics.

HCT will allow us to expedite the development process for Ampligen by ensuring full exposure of both the control group and the Ampligen

group, so as to assess whether there is a prophylactic effect.

A successful Phase 2a study could also establish Ampligen as a potential

prophylaxis against future viral variants and future novel respiratory viruses for which there are no current therapies, as well as known

viruses such as SARS-CoV-2, which causes COVID-19.

reached two important milestones in the HCT in September 2021.

One, we submitted the study protocol to the MHRA.

Two, we and hVIVO

executed the Clinical Trial Agreement.

This antiviral study was to be conducted

by hVIVO, a subsidiary of Open Orphan plc.

We submitted a study protocol to the Oxford Research Ethics Committee (“REC”)/Medicines

and Healthcare Regulatory Agency (“MHRA”) in September 2021.

The REC approved the protocol, but the MHRA provided a response

outlining areas of the submission where it requires additional information.

A response was submitted to MHRA in October 2021.

provided a “favorable opinion” to proceed, but the MHRA issued a Non-Acceptance response in November 2021.

A full revised

application was resubmitted in December 2021.

The MHRA issued Grounds for Non-Acceptance and requested additional data before moving

As the request would require us to first conduct an animal experiment that we believe would take at least six months to complete,

we determined that continuing with the HCT application process would not be a prudent use of our resources, so we terminated our agreement

with hVIVO and officially notified the MHRA of our decision to withdraw our application.

As the MHRA’s Grounds for Non-Acceptance

had already been issued, our withdrawal was technically recognized as a rejection of the proposed study.

Additionally,

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In August, we filed an application for Ampligen

as both an intranasal and an intravenous therapy for what we describe as Post-COVID-19 Cognitive Dysfunction (“PCCD”).

people suffering from PCCD, including some young adults, can be afflicted with severe difficulties in concentrating;

as both an intranasal and an intravenous therapy for what we describe as Post-COVID conditions.

The people suffering from Post-COVID

conditions, including some young adults, can be afflicted with severe difficulties in concentrating;

serious memory problems;

and the inability to live an active lifestyle, to work and even to perform everyday tasks.

Early data has demonstrated that patients

with symptoms of PCCD being treated with Ampligen in the ongoing AMP-511 Expanded Access Program have reported improvements in cognitive

inability to live an active lifestyle, to work and even to perform everyday tasks.

Early data has demonstrated that patients with symptoms

of Post-COVID conditions being treated with Ampligen in the ongoing AMP-511 Expanded Access Program have reported improvements in cognitive

Similarly, in ME/CFS, data supports the claim that Ampligen improves cognitive function.

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and SARS-CoV-2.

believe that these two provisional patent applications were important steps that allowed us to move forward with proposed studies in

We followed both with Pre-Investigational New Drug Applications in September.

One pre-IND was for a Phase 2, two-arm, randomized,

double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of Ampligen in patients experiencing PCCD.

subjects will be randomized 1:1 to receive twice weekly infusions of Ampligen or placebo for a period of 12 weeks.

Amarex Clinical Research,

an NSF International company, is managing the FDA submission and will manage the clinical trial.

The pre-IND meeting request was transferred

to the FDA’s Division of Neurology by the FDA’s Covid Scientific Technical Triage Team.

September 24, 2021, we submitted another pre-IND meeting request for two separate Phase 2 clinical studies to study the potential of

Ampligen as both an infusion and an intranasal therapy for early-onset COVID-19.

The two clinical trials would be Phase 2, randomized,

double-blind, placebo-controlled studies to evaluate the efficacy and safety of Ampligen as an:

addition to securing these two provisional patent applications, we also moved forward with proposed studies in these areas and with Pre-Investigational

New Drug Applications in September 2021.

One pre-IND was for a Phase 2, two-arm, randomized, double-blind, placebo-controlled, multicenter

study to evaluate the efficacy and safety of Ampligen in patients experiencing Post-COVID conditions (originally referred to as Post-COVID

Cognitive Dysfunction (PCCD) and being revised to Post-COVID conditions).

Eighty subjects will be randomized 1:1 to receive twice

weekly infusions of Ampligen or placebo for a period of 12 weeks.

Amarex Clinical Research, an NSF International company, is managing

the FDA submission and will manage the clinical trial.

The pre-IND meeting request was transferred to the FDA’s Division of Neurology

by the FDA’s Covid Scientific Technical Triage Team.

In November 2021, the FDA responded that there was insufficient information

to support the proposed indication of Post-COVID Cognitive Dysfunction (PCCD).

We are working with Amarex to revise the study

and resubmit it to the FDA as Post-COVID conditions.

September 2021, we submitted another pre-IND meeting request for two separate Phase 2 clinical studies to study the potential of Ampligen

as both an infusion and an intranasal therapy for early-onset COVID-19.

The two clinical trials would be Phase 2, randomized, double-blind,

placebo-controlled studies to evaluate the efficacy and safety of Ampligen as an:

therapy – 200 mg of Ampligen or placebo, with five doses over a treatment period of 17 days;

therapy – 1,250 μg spray (625 μg per nostril), with seven doses over a treatment period of 15 days.

FDA responded that it was premature and denied our meeting request, noting the primary reason that we first needed to address

its comments on two prior similar pre-IND submissions related to the potential risks of administering Ampligen to patients with asymptomatic

or mildly symptomatic COVID-19 were justified by potential benefits .

We plan on responding to the FDA regarding the early onset

COVID-19 submission.

The FDA has already authorized Ampligen for a clinical trial in cancer patients, and subjects have been and will

be treated in the investigator-sponsored Phase 2 trial at the Roswell Park Comprehensive Cancer Center.

Our plans to study Ampligen in

asymptomatic and mild COVID-19 cases await further consideration of the different risks and benefits associated with those trials.

FDA responded that it was premature and denied our meeting request, noting the primary reason that we first needed to address its comments

on two prior similar pre-IND submissions related to the potential risks of administering Ampligen to patients with asymptomatic or mildly

symptomatic COVID-19 were justified by potential benefits.

We plan to respond to the FDA regarding the early onset COVID-19 submission.

The FDA has already authorized Ampligen for a clinical trial in cancer patients, and subjects have been and will be treated in the investigator-sponsored

Phase 2 trial at the Roswell Park Comprehensive Cancer Center.

Our plans to study Ampligen in asymptomatic and mild COVID-19 cases await

further consideration of the different risks and benefits associated with those trials.

Europe, the EMA has approved the Orphan Medicinal Products Designation for Ampligen as a potential treatment of Ebola virus disease and

for Alferon N Injection as a potential treatment of MERS.

concluded our series of collaborations designed to determine the potential effectiveness of Ampligen and Alferon N as potential preventive

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.

concluded our series of collaborations designed to determine the potential effectiveness of Ampligen and Alferon N Injection as potential

preventive 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 diminished.

April 2021, we entered into an MTA with the University of Cagliari Dipartimento di Scienze della Vita e dell’Ambiente (“UNICA”),

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reverse VP35 inhibition of interferon production in biological systems.

The research is active and ongoing.

May 2021, we filed a U.S.

Provisional Patent Application for Ampligen as a potential therapeutic to possibly slow, halt, or reverse

the progression of Alzheimer’s disease.

Provisional Patent Application for Ampligen as a potential therapeutic to possibly slow, halt, or reverse the

progression of Alzheimer’s disease.

MANUFACTURING

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initiated in 2018 to complete the release testing by ANMAT needed for commercial distribution.

On September 19, 2019, we received clearance

In September 2019, we received clearance

from the FDA to ship Ampligen to Argentina for the commercial launch and subsequent sales.

On June 10, 2020, we received import clearance

In June 2020, we received import clearance

from ANMAT to import the first shipment of commercial grade vials of Ampligen into Argentina.

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Ampligen” above).

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 were manufactured and released in 2018.

lots have been designated for human use in the United States in the cost recovery CFS program and for expanded oncology clinical trials.

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 addition, we have supplied GP Pharm with the

Ampligen required for testing and ANMAT release.

Once final approval by ANMAT is obtained, we anticipate that GP Pharm will begin distributing

Ampligen in Argentina.

our approval in Argentina, in 2017 we engaged Jubilant HollisterStier (“Jubilant”) to be our authorized CMO for Ampligen.

Two lots of Ampligen consisting of more than 16,000 units were manufactured and released in 2018;

these lots have been designated for

human use in the United States in the cost recovery CFS program and for expanded oncology clinical trials.

The production of additional

polymer (Ampligen intermediates) took place in 2019 at our New Brunswick facility.

Additionally, Jubilant manufactured two more lots

of Ampligen in December 2019 and January 2020.

The current manufactured lots of Ampligen have been fully tested and released for commercial

product launch in Argentina and for clinical trials.

In addition, we have supplied GP Pharm with the Ampligen required for testing and

ANMAT release.

Once final approval by ANMAT is obtained, we anticipate that GP Pharm will begin distributing Ampligen in Argentina.

December 2020, we added Pharmaceutics International Inc.

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contracts augment our existing fill and finish capacity.

is approved by the FDA for commercial sales in the United States 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.

sales of Alferon in the United States will not resume until new batches of commercial filled and finished product are produced and released

While our facility is approved by the FDA under the Biologics License Application (“BLA”) for Alferon, we will

need the FDA’s approval to release commercial product once we have submitted satisfactory stability and quality release data, FDA

has conducted an inspection, if required, and FDA has approved our new manufacturing process.

Currently, we are not manufacturing Alferon

and there is no definitive timetable to resume production at the facility.

have reviewed our operations at the New Brunswick facility and determined that some of the equipment should be upgraded to realize greater

efficiencies.

This may include ensuring a state-of-the-art facility capable of meeting potential increased demand for Ampligen.

determine that we need expanded capacity, and/or we determine not to move forward with upgrading the facility, we will need to move forward

with other possibilities to produce API.

We are exploring engaging a Contract Manufacturing Organization (“CMO”) to produce

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.

In this regard, on April 5, 2021, we approved a proposal from Polysciences Inc.

We are prepared to initiate the production of additional Ampligen when and if

May 2021, we exercised our option to re-purchase the New Brunswick manufacturing facility, pursuant to the terms of the March 2018 sale

and lease-back agreement.

We thereafter sold certain equipment and machinery that we determined to be obsolete and no longer needed for

current or future manufacturing.

Then, on March 3, 2022, we entered into an Agreement of Sale and Purchase with Acellories, Inc.

pursuant to which we will sell our property for $3.9 million.

The buyer has a mortgage contingency, with the clause expiring on June

Assuming that condition is met, we would anticipate closing on or before July 1, 2022.

forward, we will require one or more Contract Manufacturing Organizations (“CMO”) to produce Ampligen API.

While we believe

we have sufficient Ampligen API to meet our current needs, we are also continually exploring new efficiencies so as to maximize our ability

to fulfill future obligations.

In this regard, in April 2021, we approved a proposal from Polysciences Inc.

(“Polysciences”)

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PA location to enhance our capacity to produce the polymer precursors to the drug Ampligen.

We are working with Polysciences to finalize

a Service Agreement and a Quality Agreement.

We continue to search for additional CMOs so as to create redundancy and, additionally,

to meet the potential need for larger quantities of API.

May 13, 2021, we exercised our option to re-purchase the New Brunswick manufacturing facility, pursuant to the terms of the March 16,

2018 sale and lease-back agreement.

We thereafter sold certain equipment and machinery that we determined to be obsolete and no longer

needed for current or future manufacturing.

We are utilizing Polysciences’s expertise

to refine our approach to polymer production.

Additionally, we continue to be open to the possibility of agreements with other CMOs,

so as to create redundancy and to meet the potential need for larger quantities of API.

second product, Alferon N Injection, is approved by the FDA for commercial sales in the United States 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 N Injection 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 New Brunswick facility has FDA approval under

the Biologics License Application (“BLA”) for Alferon N Injection, and we intend to maintain a certain amount of space at

the to-be-sold facility, we will need the FDA’s approval to release commercial product once we have identified our new manufacturing

approach and submitted satisfactory stability and quality release data;

the FDA has conducted any required inspections;

and the FDA has

approved our new manufacturing process.

Currently, we are not manufacturing Alferon N Injection and there is no definitive timetable

to resume production.

Licensing/Collaborations/Joint

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The GP Pharm contract was extended in May 2021, and will now end on May 24, 2024.

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

In August 2021, the ANMAT granted

a five-year extension to a previous approval to sell and distribute Ampligen to treat severe CFS in Argentina.

This extends the approval

May 2016, we entered into a five-year agreement (the “Impatients Agreement”) with Impatients, N.V.

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The agreement was automatically extended for a period of 12 months on May 20, 2021.

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.

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.

A request to extend the approval beyond 2022 has

been filed and is under review.

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.

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 the Territory and will manage

all EAP activities relating to the pancreatic cancer extension of the program.

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.

This agreement has expired and we are currently in discussions with Asembia exploring

the continuation and expansion of this relationship.

February 2018, we signed an amendment to the EAP with myTomorrows.

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16 pancreatic cancer patients.

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.

This agreement has expired and we are currently in discussions with Asembia exploring

the continuation and expansion of this relationship.

In November 2021, we entered into a signed Letter of Agreement with myTomorrows for the delivery of Ampligen

for the treatment of up to an additional 5 pancreatic cancer patients.

In March 2022, we entered into a signed Letter of Agreement with

myTomorrows for the delivery of Ampligen for the treatment of up to an additional 10 pancreatic cancer patients.

have a defined contribution plan, entitled the AIM ImmunoTech Employees 401(k) Plan and Trust Agreement (the “401(k) Plan”).

Our full time employees are eligible to participate in the 401(k) Plan following one year of employment.

Subject to certain limitations

imposed by federal tax laws, participants are eligible to contribute up to 15% of their salary (including bonuses and/or commissions)

Participants’ contributions to the 401(k) Plan may be matched by us at a rate determined annually by the Board of Directors.

participant immediately vests in his or her deferred salary contributions, while our contributions will vest over one year.

Our 6% matching

contribution was reinstated effective January 1, 2021.

For the nine months ended September 30, 2021, our contributions towards the 401(k)

Plan were approximately $106,000.

A 6% matching

contribution by us was reinstated effective January 1, 2021.

For the period ending March 31, 2022 we made $37,000 in contributions and

for the period ending December 31, 2021 $139,000 contributions were made.

Accounting Pronouncements

Recent Accounting Pronouncements”.

About Off-Balance Sheet Arrangements

Accounting Policies

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OF OPERATIONS

months ended September 30, 2021, versus three months ended September 30, 2020

net loss was approximately $3,826,000 and $3,306,000 for the three months ended September 30, 2021, and 2020, respectively, representing

months ended March 31, 2022 versus three months ended March 31, 2021

net loss was approximately $3,820,000 and $3,579,000 for the three months ended March 31, 2022, and 2021, respectively, representing

an increase in loss of approximately $241,000 or 7%.

This increase in loss was primarily due to the following:

increase in research and development cost of $904,000;

increase in a gain from sale of income tax operating tax operating losses of $72,000;

increase of $20,000 from the 2020 quarterly reevaluation of certain redeemable warrants;

increase in loss on investments, net of $934,000;

increase in gain from sale of Income tax operating of $9,000;

increase of the quarterly revaluation of certain redeemable warrants of $68,000;

decrease in interest and other income of $27,000;

decrease in interest expense and finance cost of $50,000;

decrease in research and development expenses of $388,000;

decrease in general and administrative expenses of $40,000;

decrease in production costs of $160,000.

decrease in selling general and administrative cost of $286,000;

decrease in interest expense and other finance cost of $51,000;

decrease in interest income of $89,000.

loss per share was $(0.08) and $(0.08) for the three months ended September 30, 2021, and 2020, respectively.

The weighted average number

of shares of our common stock outstanding as of September 30, 2021, was 47,846,074 as compared to 38,907,546 as of September 30, 2020.

from our Ampligen Cost Recovery Program were $33,000 and $36,000 for the quarters ended September 30, 2021 and 2020, respectively.

was a decrease in revenues of $3,000.

The revenue was generated from the Expanded Access Program and our FDA-approved, open-label treatment

protocol (“AMP-511”) that allows patient access to Ampligen for treatment in an open-label safety study.

costs were approximately $157,000 and $204,000, respectively, for the three months ended September 30, 2021, and 2020, representing a

decrease of $47,000 in production costs in the current period.

These costs primarily represent reduced utility cost for decreased production

levels in the three months ending September 30, 2021.

and Development Costs

and Development (“R&D”) costs for the three months ended September 30, 2021, were approximately $2,006,000 as compared

to $1,102,000 for the quarter ended September 30, 2020, reflecting an increase of approximately $904,000 or 82%.

The reason for the increase

in research and development costs was due to increases in clinical research of $807,000 and clinical expenses of $130,000 offset by decreases

in Ampligen compliance and stability of $35,000.

and Administrative Expenses

and Administrative (“G&A”) expenses for the three months ended September 30, 2021, and 2020 were approximately

$1,799,000 and $2,085,000, respectively, reflecting a decrease of approximately $286,000 or 14%.

The decrease in G&A expenses

during the current period was mainly due to professional fees of $305,000, and offset by an increase in salaries,

benefits, and other compensation of $78,000.

income decreased $89,000 in the three months ended September 30, 2021, compared to the three months ended September 30, 2020, the decrease

is primarily related to the reclassification out of other comprehensive income of debt securities sold at a loss during the period.

Expense and Other Finance Costs

and other finance costs in the three months ending September 31, 2021 was zero due to no outstanding

debt compared to $51,000 in the period ending September 30, 2020.

quarterly revaluation of certain redeemable warrants resulted in a non-cash adjustment to the redeemable warrants liability for the three

months ended September 30, 2021, which amounted to a gain of approximately $51,000 compared to a gain of $31,000 for September 30, 2020

(See Note 12:

Fair Value - for the various factors considered in the valuation of redeemable warrants).

Tax Operating Losses

quarterly income tax benefit for the three months ended September 30, 2021, amounted to a gain of approximately $72,000 due primarily

to the provision of the 2020 New Jersey NOL.

months ended September 30, 2021 versus nine months ended September 30, 2020

net loss was approximately $13,281,000 and $10,466,000 for the nine months ended September 30, 2021, and 2020, respectively, representing

an increase in loss of approximately $2,815,000 or 27%.

This increase in loss was primarily due to the following:

increase in extinguishment of financing obligation and note payable of $2,843,000;

increase in research and development expenses of $1,304,000;

increase in production costs of $66,000;

increase in income tax operating tax of $542,000;

decrease in selling, general and administrative cost of $15,000;

a decrease in interest income of $31,000;

decrease in revenue of $36,000;

decrease of $142,000 from the 2020 quarterly reevaluation of certain redeemable warrants;

gain on sale of assets of $216,000;

decrease in interest expense and other finance cost of $550,000.

loss per share was $(0.28) and $(0.36) for the nine months ended September 30, 2021, and 2020, respectively.

The weighted average number

of shares of our common stock outstanding as of September 30, 2021, was 47,156,158 as compared to 28,826,283 as of September 30, 2020.

from our Ampligen Cost Recovery Program were $85,000 and $121,000 for the nine months ended September 30, 2021, and 2020, respectively.

There was a decrease in revenues of $36,000.

The change in revenue is related to timing of orders and shipments in the nine months ended

September 30, 2020.

The revenue was generated from the Expanded Access Program and our FDA approved open-label treatment protocol, (“AMP-511”),

that allows patient access to Ampligen for treatment in an open-label safety study.

costs were approximately $674,000 and $608,000, respectively, for the nine months ended September 30, 2021, and 2020, representing an

increase of $66,000 in production costs in the current period.

These costs primarily represent production expenses related to increased

maintenance costs, offset by reduced utility costs in the nine months ended September 30, 2021.

loss per share was $ (0.08) and $(0.08) for the years ended March 31, 2022, and 2021, respectively.

The weighted average number of shares

of our common stock outstanding as of March 31, 2022, was 47,994,672 as compared to 45,726,855 as of March 31, 2021.

from our Ampligen® Cost Recovery Program were $33,000 and $28,000 for the quarters ended March 31, 2022 and 2021, respectively.

change was due primarily to the increase in drug utilization for the AMP-511 study for the two sites that are open and treating patients.

costs were approximately $77,000 and $237,000, respectively, for the three months ended March 31, 2022, and 2021, representing a decrease

of $160,000 in production costs in the current period.

The decrease was due primarily to a reduction in depreciation for the building

that is held for sale.

and Development Costs

and Development (“R&D”) costs for the nine months ended September 30, 2021, were approximately $4,749,000 as compared

to $3,445,000 for the quarter ended September 30, 2020, reflecting an increase of approximately $1,304,000 or 38%.

The reason for the

increase in research and development costs was due to increases in clinical expenses of $1,345,000, offset by decreases in Ampligen compliance

and stability test costs of $41,000.

Research and Development (“R&D”) costs for the three months ended March 31, 2022, were approximately $1,036,000 as compared

to $1,424,000 for the same period a year ago, reflecting a decrease of approximately $388,000.

The primary reason for the decrease in

research and development costs was largely due to a decrease in clinical trials that ended in the prior year and not starting new trials

in the current period, of $686,000 offset by an increase of $121,000 for outside contractors due to outsourcing testing

and Administrative Expenses

and Administrative (“G&A”) expenses for the quarters ended September 30, 2021, and 2020 were approximately $6,055,000

and Administrative (“G&A”) expenses for the three months ended March 31, 2022, and 2021, were approximately $2,072,000

and $2,112,000, respectively, reflecting a decrease of approximately $40,000.

The decrease in G&A expenses during the current period

was mainly due to an increase in salaries, benefits and other compensation of $842,000, offset by decreases in stock compensation of

$723,000, public relations of $43,000 and professional fees of $91,000.

income decreased $31,000 in the nine months ended September 30, 2021, compared to the nine months ended September 30, 2020, driven

by a decrease primarily the reclassification out of other comprehensive income of debt securities sold of $126,000, offset by

the increase in interest income from investments.

Expense and Other Finance Costs

and other finance costs decreased $550,000 in the nine months ended September 30, 2021, mostly due to the costs associated with the long-term

debt which were in effect in the nine months ended September 30, 2020.

The long-term debt was extinguished in the second quarter of 2020.

quarterly revaluation of certain redeemable warrants resulted in a non-cash adjustment to the redeemable warrants liability for the nine

months ended September 30, 2021, which amounted to a gain of approximately $22,000 compared to a loss of $120,000 for September 30, 2020

(See Note 12:

The decrease in G&A expenses during the

current period was mainly due to a decrease in stock compensation of $284,000, offset by an increase in accounting, professional

and legal fees of $213,000, insurance expense of $120,000, salaries and payroll expenses of $24,000, travel of $16,000.

on Investments, net

on investments for the three months ended March 31, 2022, and 2021 represents a loss of approximately $934,000, driven primarily from

the unrealized loss on securities of $915,000.

and Other Income

and other income for the three months ended March 31, 2022 and 2021 represents a net decrease of approximately $27,000 due to the financing

obligation of the sale leaseback in the period ending March 31, 2021 and not in the period ending March 31, 2022.

quarterly revaluation of certain redeemable warrants resulted in a non-cash adjustment to the redeemable warrants liability amounted

to a gain of $31,000 for the three months ended March 31, 2022, compared to a loss of approximately $37,000 in March 31, 2021 (see “Financial

Fair Value” for the various factors considered in the valuation of redeemable warrants).

Extinguishment

of Financing Obligation and Note Payable

the nine months ended September 30, 2020, there was a gain of $142,000 related to the prepayment of the note payable.

the nine months ended September 30, 2021, there was a loss on the extinguishment of debt of $2,701,000 related to the repurchase of the

manufacturing facility (See note 13 Financing Obligating Arising from Sales Leaseback Transaction).

Tax Operating Losses

quarterly income tax benefit for the nine months ended September 30, 2021, amounted to a gain of approximately $542,000 due primarily

to the provision of the 2020 New Jersey NOL.

from sale of income tax operating losses

quarterly income tax benefit for the three months ended March 31, 2022 amounted to a gain of approximately $190,000 compared to a gain

of $181,000 for the three months ended March 31, 2021 due primarily to a deferred tax asset recorded in 2021 for the New Jersey NOL to

be sold in 2022.

and Capital Resources

of September 30, 2021, we had approximately $53,659,000 in cash, cash equivalents and marketable securities.

As of December 31, 2020,

we had approximately $54,378,000 in cash, cash equivalents and marketable securities.

Cash used in operating activities for the nine

months ended September 30, 2021, was $8,220,000 compared to $7,514,000 for the nine months ended September 30, 2020.

The change of $706,000

was a decrease in prepaid and other current assets of $700,000, a decrease in accrued interest of $230,000, tax benefit from the gain

on the sale of New Jersey NOL of $542,000, offset the increase in stock compensation of $724,000.

used in investing activities for the nine months ended September 30, 2021, was approximately $995,000 compared to cash used in investing

activities of approximately $8,982,000 for the same period in 2020, representing a change of $7,987,000.

The primary reason for the change

during the current period is the purchase and sale of marketable securities of $762,000 compared to the $8,672,000 for the same period

in 2020, and by the proceeds from the sale of property and equipment of $245,000.

provided by financing activities for the nine months ended September 30, 2021, was approximately $8,063,000 compared to approximately

$53,522,000 for the same period in 2020, a decrease of $45,459,000.

The primary reason for the decrease in the nine months ended September

30, 2021, is our receipt of net proceeds of approximately $12,917,000 from the sale common stock pursuant to our 2019 EDA with

Maxim Group compared to $58,066,000 for the same period in 2020.

July 2021, we executed a Reservation and Start-Up Agreement (the “Agreement”) with hVIVO Services Limited (“hVIVO”),

and subsequently signed a clinical trial agreement (“CTA”) in September.

We have paid hVIVO approximately $672,000,

representing half of the booking fee for use of its quarantine facility.

The balance of the agreement is approximately $3,398,000.

“COVID19” above).

January 2021, we entered into a Sponsor Agreement with the Centre for Human Drug Research (“CHDR”) for a Phase 1

clinical study to assess the safety, tolerability and biological activity of Ampligen as a potential intranasal therapy.

paid CHDR approximately $1,010,000.

The balance of the agreement is approximately $70,000.

used in operating activities for the period ended March 31, 2022, was approximately $2,758,000 compared to approximately $3,045,000 for

the same period in 2021, representing a change of $287,000.

The primary reasons for this change in cash used in operations in 2022 was

related to non-cash charges which primarily consisted of $242,000 in stock compensation, $915,000 of loss on investments, net, and $227,000

of gain from sale of income tax operating losses.

The main changes in working capital were an increase in accounts payable and a decrease

in accrued expenses.

used in/provided by investing activities for the period ended March 31, 2022, was approximately $346,000 used in compared to $523,000

provided by for the same period in 2021, representing a change of $869,000.

The primary reason for the change during the current period

is the purchase of marketable securities for the years ended March 31, 2022 and March 31,2021 of $720,000 and $1,151,000, respectively

offset by the sale of marketable securities of $407,000 and $2,039,000, respectively.

provided by financing activities for the period ended March 31, 2022, was approximately $0 compared to approximately $12,794,000 for

the same period in 2021, a decrease of $12,794,000.

The primary reason for this decrease was our receipt of $12,887,000 in net proceeds

from the sale of shares in the first three months of 2021.

of March 31, 2022, AIM had approximately $44,543,000 in cash, cash equivalents and marketable securities, inclusive of approximately

$15,554,000 in Marketable Securities, representing a decrease of approximately $3,725,000 from December 31, 2021.

are committed to a focused business plan oriented toward finding senior co-development partners with the capital and expertise needed

to commercialize the many potential therapeutic aspects of our experimental drugs and our FDA approved drug Alferon.

to commercialize the many potential therapeutic aspects of our experimental drugs and our FDA approved drug Alferon N Injection.

development of our products requires the commitment of substantial resources to conduct the time-consuming research, preclinical development,

2 unchanged sentences

that we have adequate funds to meet our anticipated operational cash needs and fund current clinical trials over approximately the next

twenty-four months from the issuance of the financial statements.

At present we do not generate any material revenues from operations,

and we do not anticipate doing so in the near future.

We may need to obtain additional funding in the future for new studies and/or if

current studies do not yield positive results, require unanticipated changes and/or additional studies.

If we are unable to commercialize

and sell Ampligen and/or recommence material sales of Alferon N Injection, our operations, financial position and liquidity may be adversely

impacted, and additional financing may be required.

There can be no assurances that, if needed, we will be able to raise adequate funds

or enter into licensing, partnering or other arrangements to advance our business goals.

We may seek to access the public equity market

whenever conditions are favorable, even if we do not have an immediate need for additional capital at that time.

We are unable to estimate

the amount, timing or nature of future sales of outstanding common stock or instruments convertible into or exercisable for our common

Any additional funding may result in significant dilution and could involve the issuance of securities with rights, which are

senior to those of existing stockholders.

proceeds from our financings have been used to fund infrastructure growth including manufacturing, regulatory compliance and market development

along with our efforts regarding the Ampligen manufacturing and the Ampligen NDA.

twenty-four months.

In addition, in February 2022, the SEC declared our new S-3 shelf Registration Statement effective which will allow

us to raise additional capital in the future.

At present we do not generate any material revenues from operations, and we do not anticipate

doing so in the near future.

We may need to obtain additional funding in the future for new studies and/or if current studies do not

yield positive results, require unanticipated changes and/or additional studies.

If we are unable to commercialize and sell Ampligen

and/or recommence material sales of Alferon N Injection, our operations, financial position and liquidity may be adversely impacted,

and additional financing may be required.

There can be no assurances that, if needed, we will be able to raise adequate funds or enter

into licensing, partnering or other arrangements to advance our business goals.

We may seek to access the public equity market whenever

conditions are favorable, even if we do not have an immediate need for additional capital at that time.

We are unable to estimate the

amount, timing or nature of future sales of outstanding common stock or instruments convertible into or exercisable for our common stock.

Any additional funding may result in significant dilution and could involve the issuance of securities with rights, which are senior

to those of existing stockholders.

See Part I, Item 1A - “Risk Factors;

We may require additional financing which may not be

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 2. Management’s Discussion and Analysis