What changed in this filing

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Item 1. Business

2023-03-31 compared with 2022-03-31 · 761 added, 548 removed, 565 unchanged (70% of the section changed)

ImmunoTech Inc.

and its subsidiaries (collectively, “AIM”, “Company”, “we” or “us”) are

an immuno-pharma company headquartered in Ocala, Florida, and focused on the research and development of therapeutics to treat multiple

types of cancers, viral diseases and immune-deficiency disorders.

We have established a strong foundation of laboratory, pre-clinical

and clinical data with respect to the development of nucleic acids and natural interferon to enhance the natural antiviral defense system

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

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 CFS.

primary present business focus involves Ampligen.

Ampligen represents a dsRNA being developed for globally important cancers, viral diseases

and disorders of the immune system.

currently are proceeding primarily in four areas:

a 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.

Ampligen as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome (“ME/CFS”) and fatigue and/or Post-COVID

conditions of fatigue.

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

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 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 Standard of

Care (“SOC”), when compared to well-matched historical controls.

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.

In October 2021, we and our Contract Research Organization, 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.

In August 2022, we received Institutional Review Board

(“IRB”) approval of the trial protocol and so announced the trial’s commencement.

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.

of the differences in the scale of necessary trials, our initial primary focus when it comes to pancreatic cancer will be cases that

are locally advanced, rather than metastatic.

The number of different approaches to treating metastatic pancreatic cancer — approaches

which would be determined by treating physicians — would require a much larger, far more expensive trial than would a trial for

locally advanced pancreatic cancer.

Therefore, we are focusing on patients who have completed FOLFIRINOX and have stable disease.

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

We have also seen success

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

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 and funded by a Merck grant,

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.

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

see “ Immuno-Oncology ” below.

as an Antiviral .

have a research and pre-clinical history that indicates broad-spectrum antiviral capability of Ampligen in animals.

We hope to demonstrate

that it has the same effect in humans.

To do this, among other things, we need a population infected with a virus.

That is why we have

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 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 numerous viruses, such as Western Equine Encephalitis

Virus, Ebola, Vaccinia Virus (which is used in the manufacture of smallpox vaccine) 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.

We have also elected to explore studies (initially with healthy volunteers) outside the United States and have already conducted a study

in the Netherlands to determine the safety profile of the intranasal delivery of Ampligen.

this regard, CHDR, a foundation located in Leiden in the Netherlands, managed a Phase 1 randomized, double-blind study for us to evaluate

the safety, tolerability and biological activity of repeated administration of Ampligen intranasally.

A total of 40 healthy subjects

received either Ampligen or a placebo in the trial, with the Ampligen given at four escalating dosages across four cohorts, to a maximum

level of 1,250 micrograms.

All patients had completed study by June 2021 and the study is completed.

The Final Safety Report reported

no Serious or Severe Adverse Events at any dosage level.

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

Our quest to prove

the antiviral activities of Ampligen continues.

If Ampligen has the broad-spectrum antiviral properties that we believe that it has,

it could be a very valuable tool in treating variants of existing viral diseases, including COVID-19, or novel ones that arise in the

Unlike most developing therapeutics which attack the virus, Ampligen works differently.

We believe that it activates antiviral

immune system pathways that fight not just a particular virus or viral variant, but other similar viruses as well.

In October 2022, our IND application cleared the FDA

approval process and we are proceeding with a Phase 2 study evaluating Ampligen as a therapeutic for patients with post-COVID conditions

Additional comments were received from the FDA, which have been addressed in an amended protocol approved by

the IRB on March 30, 2023.

see “ Ampligen as a Potential Antiviral ” below.

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 myalgic encephalomyelitis/chronic fatigue

syndrome (“ME/CFS”).

In fact, in February 2013, we received a Complete Response letter (“CRL”) from the FDA for

our Ampligen NDA for ME/CFS, stating that we should conduct at least one additional clinical trial, complete various nonclinical studies

and perform a number of data analyses.

developing a comprehensive response to the FDA and a plan for a confirmatory trial for the FDA NDA, we proceeded independently in Argentina

and, in August 2016, we received approval of an NDA from ANMAT for commercial sale of Ampligen in the Argentine Republic for the treatment

of severe CFS.

In September 2019, we received clearance from the FDA to ship Ampligen to Argentina for the commercial launch and subsequent

On June 10, 2020, we received import clearance from ANMAT to import the first shipment of commercial grade vials of Ampligen into

The next steps in the commercial launch of Ampligen include ANMAT conducting a final inspection of the product and release

tests before granting final approval to begin commercial sales.

This testing and approval process is currently delayed due to ANMAT’s

internal processes and the ongoing effects of COVID-19 and.

Once final approval by ANMAT is obtained, GP Pharm will be responsible for

distributing Ampligen in Argentina.

FDA authorized an open-label treatment protocol (“AMP-511”) allowing patient access to Ampligen for treatment in a study

under which severely debilitated CFS patients have the opportunity to be on Ampligen to treat this very serious and chronic condition.

The data collected from the AMP-511 protocol through a consortium group of clinical sites provide safety information regarding the use

of Ampligen in patients with CFS.

The AMP-511 protocol is ongoing.

In October 2020, we received IRB 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 conditions.

As of December 31, 2022, there were 10 patients enrolled in

this open-label expanded access treatment protocol (including two patients with Post-COVID-19 Conditions).

As of January 31, 2023, there

have been seven such Post-COVID patients treated in the study.

AIM previously reported positive preliminary results based on data from

the first four Post-COVID Condition patients enrolled in the study.

The data show that, by week 12, compared to baseline, there was what

the investigators considered a clinically significant decrease in fatigue-related measures.

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

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.

NOTE REGARDING FORWARD-LOOKING STATEMENTS AND SUMMARY RISK FACTORS

statements in this Report contain forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E

of the Securities Exchange Act of 1934, as amended, which we refer to as the Exchange Act.

These statements are based on our management’s

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 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;

“Legal Proceedings” and Part II;

“Management’s Discussion

and Analysis of Financial Condition and Results of Operations”.

“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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“potential,” “likely,” “opportunity” and similar expressions or variations of such words are intended

to identify forward-looking statements but are not the exclusive means of identifying forward-looking statements.

to identify forward-looking statements but are not the exclusive means of identifying forward-looking statements and their absence does

not mean that a statement is not forward-looking.

Our forward-looking statements are not guarantees of performance, and actual results

could vary materially from those contained in or expressed by such statements due to risks and uncertainties.

the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are risks and

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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,

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.

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

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

and future matters related to our New Jersey facility, which by definition we cannot define at this time.

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

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approval(s), lack of study drug, or a change in priorities at the institutions sponsoring other trials.

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

We cannot assure that the clinical

studies will be successful or yield any useful data or require additional funding.

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.

Syndrome, or SARS, we have been focused on the potential role that Ampligen could play in the treatment of SARS-CoV-2 — from a

protective prophylaxis/early-onset therapeutic to a treatment for post-COVID conditions.

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.

assurance can be given that future studies will not result in findings that are different from those reported in the studies we refer

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

able to continue to operate, clearly, like all businesses, we are unable to gauge how bad this pandemic will affect our operations in

We reached out to numerous foreign governments related to COVID-19 and, if successful, may be working in these countries.

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

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

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

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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.

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 (“ANMAT”),

for commercial sale of rintatolimod (U.S.

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

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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

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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;

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

there have been no physician

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effective in the treatment of pancreatic cancer.

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.

The agreement was automatically extended for one year periods on May 20, 2021 and 2022,

and is anticipated to extend again on May 20, 2023.

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

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

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

“Research and Development;

Immuno-oncology and Pancreatic Cancer”).

No assurance can be given as to the results of these

underway trials.

No assurance 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.

and Development;

Immuno-oncology”).

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

No assurance 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.

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.

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

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

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.

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

the property for an estimated $3.9 million, with AIM’s intention to keep some space specifically for its Alferon activity.

sale was finalized on November 1, 2022, for $3.7 million net of normal closing cost.

June 2022 we entered into a lease agreement with the New Jersey Economic Development Authority for a 5,210 square-foot, state-of-the-art

R&D facility at the New Jersey Bioscience Center (“NJBC”), primarily consisting of two separate laboratory suites.

facility is AIM’s operations, research and development center.

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

The New Brunswick facility is approved

by the FDA under the Biological License Application, or BLA, for Alferon N Injection.

While we have sold the New Brunswick facility,

we maintain a certain amount of space at that facility for Alferon activities, the sale of the facility 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.

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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.

to continuing delays and other obstacles related to importing Ampligen to China, on August 10, 2022, we ended our contract with Shenzhen

Smoore Technology for the development of an Ampligen delivery device for the treatment of SARS-CoV-2.

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

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in which we operate are necessarily subject to a high degree of uncertainty and risk.

Risk Related to our Business

COVID-19 coronavirus could adversely impact our business, including our clinical trials.

We cannot predict the ultimate effects of the Covid-19 pandemic on our business

COVID-19 coronavirus could force the closure of our offices and require workers to work from

We cannot predict the ultimate effects of

the Covid-19 pandemic on our business

may require additional financing which may not be available.

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drug and related technologies are investigational and subject to regulatory approval.

we are unable to obtain regulatory approval in a timely manner, or at all, our operations

will be materially harmed and our stock adversely affected.

may be subject to product liability claims from the use of Ampligen, Alferon N Injection,

or other of our products which could negatively affect our future operations.

We have limited

product liability and clinical trial insurance.

● Uncertainty

If we are unable to obtain regulatory approval

in a timely manner, or at all, our operations will be materially harmed and our stock adversely affected.

may be subject to product liability claims from the use of Ampligen, Alferon N Injection, or other of our products which could negatively

affect our future operations.

We have limited product liability and clinical trial insurance.

of health care reimbursement for our products.

are risks of liabilities associated with handling and disposing of hazardous materials.

rely upon information technology and any failure, inadequacy, interruption or security lapse

of that technology, including any cyber security incidents, could harm our ability to operate

our business effectively.

rely upon information technology and any failure, inadequacy, interruption or security lapse of that technology, including any cyber

security incidents, could harm our ability to operate our business effectively.

loss of services of key personnel could hurt our chances for success.

financial statements are prepared in accordance with GAAP.

GAAP requires estimates, judgements and assumptions which inherently contain

uncertainties.

Associated with Our Products

side effects from the use of Ampligen or Alferon N Injection could adversely affect potential

revenues and physician/patient acceptability of our product.

side effects from the use of Ampligen or Alferon N Injection could adversely affect potential revenues and physician/patient acceptability

of our product.

Related to our activities associated with Ampligen’s potential effectiveness as a treatment for SARS-CoV-2

is not possible to predict the future of the ongoing SARS-CoV-2 global pandemic or the development

of potential treatments.

No assurance can be given that Ampligen will aid in or be applied

to the treatment of this virus.

is not possible to predict the future of the ongoing SARS-CoV-2 global pandemic or the development of potential treatments.

are available a couple of treatments for COVID-19.

No assurance can be given that Ampligen will aid in or be applied to the treatment

of this virus.

in foreign countries carries with it many risks.

Associated with Our Intellectual Property

may not be profitable unless we can protect our patents and/or receive approval for additional

pending patents.

patent position of biotechnology and pharmaceutical firms is highly uncertain and involves

complex legal and factual questions.

can be no assurance that we will be able to obtain necessary licenses if we cannot enforce

patent rights we may hold.

In addition, the failure of third parties from whom we currently

license certain proprietary information or from whom we may be required to obtain such licenses

in the future, to adequately enforce their rights to such proprietary information, could

adversely affect the value of such licenses to us.

may not be profitable unless we can protect our patents and/or receive approval for additional pending patents.

patent position of biotechnology and pharmaceutical firms is highly uncertain and involves complex legal and factual questions.

can be no assurance that we will be able to obtain necessary licenses if we cannot enforce patent rights we may hold.

the failure of third parties from whom we currently license certain proprietary information or from whom we may be required to obtain

such licenses in the future, to adequately enforce their rights to such proprietary information, could adversely affect the value

of such licenses to us.

is no guarantee that our trade secrets will not be disclosed or known by our competitors.

Associated with Our R&D

cannot predict what additional studies and/or additional testing or information may be required

Accordingly, we are unable to estimate the nature, timing, costs and necessary

efforts to complete these projects nor the anticipated completion dates.

In addition, we

have no basis for estimating when material net cash inflows may commence.

We have yet to

generate significant revenues from the sale of these developmental products.

cannot predict what additional studies and/or additional testing or information may be required by the FDA.

Accordingly, we are unable

to estimate the nature, timing, costs and necessary efforts to complete these projects nor the anticipated completion dates.

we have no basis for estimating when material net cash inflows may commence.

We have yet to generate significant revenues from the

sale of these developmental products.

Associated with Our Manufacturing

Alferon N Injection Commercial Sales were halted due to lack of finished goods inventory.

If we are unable to gain the necessary FDA approvals related to Alferon N Injection, or if

we are unable to identify a CMO or CMOs that meet our requirements, then our operations would

most likely be materially and/or adversely affected.

are no long-term agreements with suppliers of required materials and services for Ampligen

and there are a limited number of raw material suppliers.

If we are unable to obtain the

required raw materials and/or services, we may not be able to manufacture Ampligen.

are a limited number of organizations in the United States available to provide the final

manufacturing steps of formulation, fill, finish and packing sets for Alferon N Injection

and Ampligen.

is no assurance that upon successful manufacture of a drug on a limited scale basis for investigational

use will lead to a successful transition to commercial, large-scale production.

If we are unable to gain the necessary

FDA approvals related to Alferon N Injection, or if we are unable to identify a CMO or CMOs that meet our requirements, then our

operations would most likely be materially and/or adversely affected.

are no long-term agreements with suppliers of required materials and services for Ampligen and there are a limited number of raw

material suppliers.

If we are unable to obtain the required raw materials and/or services, we may not be able to manufacture Ampligen.

are a limited number of organizations in the United States available to provide the final manufacturing steps of formulation, fill,

finish and packing sets for Alferon N Injection and Ampligen.

is no assurance that upon successful manufacture of a drug on a limited scale basis for investigational use will lead to a successful

transition to commercial, large-scale production.

have limited manufacturing experience for Ampligen and Alferon N Injection.

We may not be

profitable unless we can produce Ampligen, Alferon N Injection or other products in commercial

quantities at costs acceptable to us.

We may not be profitable unless we can produce Ampligen,

Alferon N Injection or other products in commercial quantities at costs acceptable to us.

Associated with Our Licensing/Collaborations/Joint Ventures

we are unable to achieve licensing, collaboration and/or joint ventures, our marketing strategy

for Ampligen will be part of the differing health care systems around the world along with

the different marketing and distribution systems that are used to supply pharmaceutical products

to those systems.

we are unable to achieve licensing, collaboration and/or joint ventures, our marketing strategy for Ampligen will be part of the

differing health care systems around the world along with the different marketing and distribution systems that are used to supply

pharmaceutical products to those systems.

Associated with Our Marketing and Distribution

have limited marketing and sales capability.

If we are unable to obtain additional distributors

and our current and future distributors do not market our products successfully, we may not

generate significant revenues or become profitable.

If we are unable to obtain additional distributors and our current and future distributors

do not market our products successfully, we may not generate significant revenues or become profitable.

Associated with Our Competition

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market price of our stock may be adversely affected by market volatility

of a significant number of shares of our common stock in the public markets, or the perception

that such sales could occur, could depress the market price of our common stock.

of our Certificate of Incorporation and Delaware law could defer a change of our Management

which could discourage or delay offers to acquire us.

are subject to the information and periodic reporting requirements of the Exchange Act and, in accordance therewith, we file periodic

reports, proxy statements and other information with the SEC.

Such periodic reports, proxy statements and other information are available

for inspection and copying at the website of the SEC www.sec.gov .

You also may obtain a free copy of our annual reports on Form

10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, proxy statements and amendments to those reports on the day of filing

with the SEC on our website at http://www.aimimmuno.com under the Investor Relations tab for SEC Filings or by contacting the

Investor Relations Department by calling (833) 475-8247 or (352) 448-7797 or sending an e-mail message to AIM@jtcir.com.

website and the information contained on that website, or accessible from our website, is not intended to be incorporated into this Annual

Report on Form 10-K or any other filings we make with the SEC.

of a significant number of shares of our common stock in the public markets, or the perception that such sales could occur, could

depress the market price of our common stock.

of our Certificate of Incorporation and Delaware law could defer a change of our Management which could discourage or delay offers

to acquire us.

business, financial condition and operating results could be negatively affected as a result of actions by activist investors.

this regard, an activist stockholder unsuccessfully attempted to take control of us by proposing director nominees at our last annual

stockholders meeting.

file electronically with the United States Securities and Exchange Commission, or SEC, our annual reports on Form 10-K, quarterly reports

on Form 10-Q, current reports on Form 8-K, and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the

Securities Exchange Act of 1934, as amended.

We make available on our website at www.ao-inc.com free of charge, copies of these reports

as soon as reasonably practicable after filing these reports with, or furnishing them to, the SEC.We are subject to the information and

periodic reporting requirements of the Exchange Act and, in accordance therewith, we file periodic reports, proxy statements and other

information with the SEC.

Such periodic reports, proxy statements and other information are available for inspection and copying at the

website of the SEC www.sec.gov.

You also may obtain a free copy of our annual reports on Form 10-K, quarterly reports on Form

10-Q, current reports on Form 8-K, proxy statements and amendments to those reports on the day of filing with the SEC on our website

at http://www.aimimmuno.com under the Investor Relations tab for SEC Filings or by contacting the Investor Relations Department

by calling (833) 475-8247 or (352) 448-7797 or sending an e-mail message to AIM@jtcir.com.

Our Internet website and the information contained

on that website, or accessible from our website, is not intended to be incorporated into this Annual Report on Form 10-K or any other

filings we make with the SEC.

primary pharmaceutical product platform consists of Ampligen (rintatolimod), a first-in-class drug of large macromolecular double-stranded

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

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).

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.

is approved for sale in Argentina (to 2026) for severe 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 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).

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

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Access Program/Early Access Programs/clinical trials of Ampligen that have been conducted or that are ongoing include studies of the

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

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

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

cancer, breast cancer, colorectal cancer, prostate 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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AIM has supplied GP Pharm with the Ampligen required for testing and ANMAT release.

and approval process is currently delayed due to the COVID-19 pandemic and ANMAT’s internal processes.

The ongoing impact of COVID-19

in Argentina is taxing the nation’s health care system and is, understandably, the main priority of its regulators.

approval by ANMAT is obtained, GP Pharm will begin distributing Ampligen in Argentina.

We continue to pursue our Ampligen NDA, for the

treatment of CFS with the FDA.

FDA has authorized an open-label expanded access treatment protocol (“AMP-511”) allowing patient access to Ampligen in a

study under which severely debilitated CFS patients have the opportunity to be on Ampligen to treat this very serious and chronic condition.

The AMP-511 protocol started in the 1990s and is ongoing.

The data collected from the AMP-511 protocol through clinical sites provide

safety information regarding the use of Ampligen in patients with CFS.

We are establishing an enlarged database of clinical safety information

which we believe will provide further documentation regarding the absence of autoimmune disease associated with Ampligen treatment.

believe that continued efforts to understand existing data, and to advance the development of new data and information, will ultimately

support our future filings for Ampligen and/or the design of future clinical studies that the FDA requested in a CRL.

The FDA approved

an increased reimbursement level from $200 to $345 per 200 mg vial of Ampligen, due to increased production costs;

which was re-authorized

and approval process is currently delayed due to ANMAT’s internal processes and the ongoing effects of COVID-19.

Once final approval

by ANMAT is obtained, GP Pharm will be responsible for distributing Ampligen in Argentina.

We continue to pursue our Ampligen NDA, for

the treatment of CFS with the FDA.

FDA has authorized an open-label expanded access treatment protocol (fAMP-511) allowing patient access to Ampligen in a study under which

severely debilitated CFS patients have the opportunity to be on Ampligen to treat this very serious and chronic condition.

protocol started in the 1990s and is ongoing.

The data collected from the AMP-511 protocol through clinical sites provide safety information

regarding the use of Ampligen in patients with CFS.

We are establishing an enlarged database of clinical safety information which we

believe will provide further documentation regarding the absence of autoimmune disease associated with Ampligen treatment.

that continued efforts to understand existing data, and to advance the development of new data and information, will ultimately support

our future filings for Ampligen and/or the design of future clinical studies that the FDA requested in a CRL.

The FDA approved an increased

reimbursement level from $200 to $345 per 200 mg vial of Ampligen, due to increased production costs;

which was re-authorized in 2021

and again in 2022.

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

As of December 31, 2021, there

are 11 patients enrolled in this open-label expanded access treatment protocol (including 2 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;

four 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 cognitive function deficiency have reported improvements in cognitive function after Ampligen

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.

As of December 31, 2022, there were 10 patients enrolled in this open-label expanded access treatment protocol),

with seven Post-COVID patients receiving or having received treatment.

AIM previously reported positive preliminary results based on

data from the first four Post-COVID Condition patients enrolled in the study.

The data show that, by week 12, compared to baseline, there

was what the investigators considered a clinically significant decrease in fatigue-related measures.

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

an Early Access Program (“EAP”) in Europe and Turkey (the “Territory”) related to ME/CFS.

Pursuant to the agreement,

as amended, myTomorrows also is managing all Early Access Programs and Special Access Programs in Europe, Canada and Turkey to treat

pancreatic cancer and ME/CFS patients.

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.

was previously closed after the U.S.

Centers for Disease Control and Prevention (“CDC”) made a general recommendation against

the use of FluMist® at that time.

Intranasal Ampligen in combination with FluMist® was generally well-tolerated in the study.

an Early Access Program (“EAP”) in Europe and Turkey related to ME/CFS.

Pursuant to the agreement, as amended, myTomorrows

also is managing all Early Access Programs and Special Access Programs in Europe, Canada and Turkey to treat pancreatic cancer and ME/CFS

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

months on May 20, 2022.

June 2018, Ampligen was cited as outperforming two other TLR3 agonists — poly IC and natural double stranded RNA — in creating

an enhanced tumor microenvironment for checkpoint blockage therapy in the journal of Cancer Research ( http://cancerres.aacrjournals.org/content/early/2018/05/31/0008-5472.CAN-17-3985 ).

In a head-to-head study in explant culture models, Ampligen activated the TLR3 pathway and promoted an accumulation of killer T cells

but, unlike the other two TLR3 agonists, it did so without causing regulatory T cell (Treg) attraction.

These findings were considered

important because they indicate that Ampligen selectively reprograms the tumor microenvironment by inducing the beneficial aspects of

tumor inflammation (attracting killer T cells), without amplifying immune-suppressive elements such as regulatory T cells.

was conducted at the University of Pittsburgh and Roswell Park as a part of the NIH-funded P01 CA132714 and Ovarian Cancer Specialized

Program of Research Excellence (“SPORE”).

an enhanced tumor microenvironment for checkpoint blockade therapy in the journal of Cancer Research ( http://cancerres.aacrjournals.org/content/early/2018/05/31/0008-5472.CAN-17-3985 ).In

a head-to-head study in explant culture models, Ampligen activated the TLR3 pathway and promoted an accumulation of killer T cells but,

unlike the other two TLR3 agonists, it did so without causing regulatory T cell (Treg) attraction.

These findings were considered important

because they indicate that Ampligen selectively reprograms the tumor microenvironment by inducing the beneficial aspects of tumor inflammation

(attracting killer T cells), without amplifying immune-suppressive elements such as regulatory T cells.

The study was conducted at the

University of Pittsburgh and Roswell Park as a part of the NIH-funded P01 CA132714 and Ovarian Cancer Specialized Program of Research

Excellence (“SPORE”).

2018, we completed production of two commercial-size batches of more than 16,000 vials of Ampligen, following its “Fill & Finish”

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These lots passed all required testing for regulatory release for

human use and are being used for multiple programs, including the treatment of ME/CFS, the pancreatic cancer EAP in the Netherlands,

human use and are being used for multiple programs, including:

the treatment of ME/CFS;

the pancreatic cancer EAP in the Netherlands;

and will continue to be used for ongoing and future clinical studies in oncology.

3 unchanged sentences

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

Additionally, in December 2020, we added Pii as a “Fill &

Finish” provider.

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

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

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AND NON-PATENT EXCLUSIVITY RIGHTS

of December 31, 2021, we had 44 patents worldwide with 39 additional pending patent applications comprising our intellectual property.

consider patent exclusivity as a crucial component of our business.

As of December 31, 2022, we had 46 patents worldwide with 68 additional

pending patent applications comprising our intellectual property.

continually review our patents to determine if they have continuing value.

Please see “Note 4:

Patents, Trademark Rights and Other Intangibles (FASB ASC 350 General Intangibles Other than Goodwill)”

under Notes to Consolidated Financial Statements for more information on these patents.

We continually review our patents’ rights

to determine whether they have continuing value.

February 2020, we filed three provisional patent applications related to Ampligen in our efforts toward joining the global health community

in the fight against SARS-CoV-2.

These include:

1) Ampligen as a therapy and prophylaxis for COVID-19;

2) Ampligen as part of a proposed

intranasal universal coronavirus vaccine;

and 3) a high-volume manufacturing process for Ampligen.

2016, we received a new Ampligen composition of matter patent in the US (#9,315,538).

In 2015, we were granted a new composition of matter

patent (#2340307) by the European Patent Office and we received twenty-eight new patents in various EU countries.

In 2014, we were granted

a new composition of matter patent in the United States (#8722874) covering Ampligen formulations.

Ampligen U.S.

CFS treatment patent (#6130206) expired October 10, 2017 (we believe that the expiration of this patent will have minimal

impact on us;

see details on U.S.

#9315538, U.S.

#8722874 and the information from the FDA has granted “orphan drug status”

to the drug for CFS below).

Ampligen Trademark (#73617687) has been renewed through December 6, 2028.

New therapeutic use patent

applications are pending.

On May 13, 2014, the United States Patent Office issued patent U.S.

#8722874 titled “Double-Stranded

Ribonucleic Acids with Rugged Physiochemical Structure and Highly Specific Biologic Activity,” with all rights assigned to us.

The patent claims a novel form of rugged dsRNA.

Rugged dsRNA are nucleic acids with a unique composition and physical characteristic

identified with high specificity of binding to Toll-Like Receptor 3 (TLR3), thereby conveying an important range of therapeutic opportunities.

The newly discovered form of dsRNA has increased bioactivity and binding affinity to the TLR 3 receptor because of its reduced tendency

to form branched dsRNA which can inhibit receptor binding.

Pharmaceutical formulations containing the newly discovered nucleic acid as

active ingredients and methods of treatment with those formulations are also described in the issued patent.

We believe that the issuance

Patents #9315538 and #8722874 will help ensure that we retain patent protection for novel formulations of Ampligen products until

at least 2029.

September 2015, the European Patent Office granted the European version of U.S.

Patent #9315538, with all rights assigned to us.

addition to our patent rights relating to Ampligen, the FDA has granted “orphan drug status” to the drug for CFS, HIV/AIDS,

renal cell carcinoma, pancreatic cancer, and malignant melanoma.

Orphan drug status grants us protection against the potential subsequent

approval of other sponsors’ versions of the drug for these uses for a period of seven years following FDA approval of Ampligen

for each of these designated uses.

The first NDA approval for Ampligen as a new chemical entity will also qualify for four or five years

of non-patent exclusivity during which abbreviated new drug applications seeking approval to market generic versions of the drug cannot

be submitted to the FDA.

(See “Government Regulation” below.)

May 2011, a new United States Patent #7943147 was granted for the use of Ampligen as a vaccine adjuvant for use with seasonal influenza

vaccine to induce an enhanced immune response against H5N1 avian influenza.

In 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).

respect to Alferon N Injection, the composition is a complex mixture of natural interferon species that is manufactured from human leukocytes

obtained from human blood donors.

In addition, while it is the current standard by the FDA to treat biological drug products like interferon

as “Well Characterized” biologics, a process for which chemical entities can have their identity, purity, impurities, potency,

and quality controlled by chemical testing, Alferon N Injection, as a natural interferon, does not lend itself well to such testing.

Moreover, FDA continues to require that each lot of Alferon N Injection we produce be tested and released by the FDA before it can be

distributed for commercial sales.

Because of the complexity of the Alferon N Injection manufacturing process and these additional regulatory

requirements, we believe that potential manufacturers of generic, or so-called “bio-similar,” drug products are focused on

developing recombinant interferon products, rather than natural interferon products.

For these reasons, we believe that not having patent

protection should have no or little impact on us.

Additionally, at the receipt of the FDA certification for the revised Alferon N Injection

manufacturing process and techniques in New Brunswick, NJ, it is our intention to file for additional patent protection.

Patents, Trademark Rights and Other

Intangibles (FASB ASC 350 General Intangibles Other than Goodwill)” under Notes to the Consolidated Financial Statements for more

information on these patents.

are no current patent litigation proceedings involving us.

drug designation

Orphan drug designation qualifies sponsors for incentives including:

credits for qualified clinical trials

from user fees

seven years of market exclusivity after FDA approval

have received Orphan Drug Designation (ODD) from the FDA for Ampligen used in the treatment of Chronic Fatigue Syndrome, HIV, Metastatic

Melanoma, Renal Cell Carcinoma, Pancreatic Adenocarcinoma and Ebola Virus Disease.

the European Union, ODD carries ten years of market exclusivity after receiving marketing authorization.

We have received ODD from the

EU for Ampligen used in the treatment of Ebola Virus Disease and Pancreatic Adenocarcinoma and for Alferon used in the treatment of Middle

East Respiratory Syndrome.

AND DEVELOPMENT (“R&D”)

general focus during the past several fiscal years has been on the clinical development of new drug therapies based on natural immune

system enhancing technologies for the treatment of immune-based disorders including cancer and CFS.

While we have previously estimated

milestone dates when significant progress could be reported, the reality of the ongoing SARS-CoV-2 pandemic could mean the re-direction

of resources away from ongoing clinical trials and toward the research and development of potential treatments for the coronavirus.

this regard, we have widened our focus to include research and development of potential prophylactic and therapeutic applications for

the treatment of COVID-19, including the long-term effects of COVID-19.

general focus during the past several fiscal years has been on expanding the market potential of Ampligen through investigation of efficacy

(in vitro and in vivo) in different immune-based disorders including cancer and CFS.

While we have previously estimated milestone dates

when significant progress could be reported, the reality of the ongoing SARS-CoV-2 pandemic could mean the re-direction of resources

away from ongoing clinical trials and toward the research and development of potential treatments for the coronavirus.

In this regard,

we have widened our focus to include research and development of potential prophylactic and therapeutic applications for the treatment

of COVID-19, including the long-term effects of COVID-19.

Immuno-Oncology

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regimen developed by Dr.

Kalinski’s group and successfully completed the Phase 1 dose escalation in patients with resectable

colorectal cancer.

In the 1st quarter of 2017, Dr.

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

program which will continue to require a supply of Ampligen.

Kalinski’s group and successfully completed the Phase 1 dose escalation in patients with resectable colorectal

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 are:

Recurrent Ovarian Cancer - A follow-up Phase 2 study of advanced recurrent ovarian cancer

using cisplatin, pembrolizumab, plus Ampligen;

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

The underway trials include:

Cancer Trial - The Phase 2 AMP-270 clinical trial is 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.

The AMP-270 is expected to enroll

approximately 90 subjects in up to 30 centers across 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.

In March 2022, the FDA granted

clearance to proceed with the study.

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

2022, we received IRB approval of the trial protocol and so announced the trial’s commencement.

( https://clinicaltrials.gov/ct2/show/NCT05494697 ).

For the year ended December 31, 2022, we incurred expense of approximately $1,730,000.

“Immuno-Oncology;

Additional Progress and Analysis Related to Pancreatic Cancer” for more analysis.

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

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

up to 45 patients to be enrolled;

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 https://clinicaltrials.gov/ct2/show/NCT03734692

4 Metastatic Triple Negative Breast Cancer - Phase 1/2 study of metastatic triple-negative

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

patients were enrolled and treated.

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;

recruitment has

been completed;

15 patients were enrolled and treated.

enrollment has commenced, and numerous patients have commenced treatment.

We announced interim data from the study demonstrating

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

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 an Objective Response Rate (ORR) 38.5%;

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

found ORR of 8.1% and 9.9% across two cohorts.

We believe that the positive data makes this patent have heightened potential.

patents are pending in other countries.

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

therapy, including Ampligen and pembrolizumab.

Eight patients were enrolled and 6 patients were evaluable.

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

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;

p=0.019) was observed.

In contrast, Treg

marker FOXP3 or Treg attractants CCL22 or CXCL12 were not enhanced.

patients had stable disease lasting 2.4, 2.5 and 3.8 months, as of data cut off September 1, 2021.

additional patient (non-evaluable) had a partial response (breast tumor autoamputation) with massive tumor necrosis in the post-CKM

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

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

The key findings announced April 2022 included:

study’s primary endpoint was met, evidenced by increased CD8a expression post-treatment (p=0.046).

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%).

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

● Early-Stage

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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.

Investigators are currently analyzing data.

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

below Ampligen clinical trials and related activities are planned for initiation in 2022:

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 the study.

Cancer - A Phase 2 Cisplatin-Resistant Advanced Recurrent Ovarian Cancer Clinical Study

utilizing Ampligen is planned 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

Up to 24 patients to be enrolled (See:

Melanoma — Roswell Park Comprehensive Cancer Center (“Roswell Park”),

in a clinical trial fully funded by the National Cancer Institute (NCI), has commenced patient

enrollment in its Phase 2 study in subjects with primary PD-1/PD-L1 resistant melanoma.

Phase 2 study will evaluate type-1 polarized dendritic cell (αDC1) vaccine in combination

with tumor-selective chemokine modulation (“CKM”) comprised of Interferon alpha

2b, Ampligen (rintatolimod) and Celecoxib.

Up to 24 patients are 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.

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.

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

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.

positive data makes this patent have heightened potential.

Similar patents are pending in other counties.

Progress and Analysis Related to Pancreatic Cancer

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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to date that would cause the program to move forward with the approval process.

total of 42 pancreatic cancer patients received treatment with Ampligen immuno-oncology therapy under the EAP program at Erasmus MC in

the Netherlands.

total of 42 pancreatic cancer patients initially received treatment with Ampligen immuno-oncology therapy under the EAP program at Erasmus

MC in the Netherlands;

that initial program has since continued to expand and proceed with additional patients to be treated with Ampligen

Supervised by Prof.

Casper van Eijck, MD, the team at Erasmus MC in September 2020 reported data which demonstrated

a statistically significant positive survival benefit when using Ampligen in patients with locally advanced or metastatic pancreatic

cancer after systemic chemotherapy, compared with historical control patients.

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

Phase 2 clinical trials with potential sites in the Netherlands at Erasmus MC under Prof.

van Eijck, and also at major cancer research

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

van Eijck, MD.

The team at Erasmus MC in September 2020 reported data which demonstrated a statistically significant

positive survival benefit when using Ampligen in patients with locally advanced or metastatic pancreatic cancer after systemic chemotherapy,

compared with historical control patients.

We are working with our Contract Research Organization, Amarex Clinical Research LLC, to seek

FDA “fast-track.” We have applied for fast-track status;

have received denials to date;

and are currently working through

the FDA process to provide all the materials and information required to achieve fast-track status.

The IND authorization to proceed

with the Phase 2 pancreatic cancer clinical trial has been received with potential sites in the Netherlands at Erasmus MC under Prof.

van Eijck, and also at major cancer research centers in the United States such as The Buffett Cancer Center at the University

of Nebraska Medical Center (UNMC).

January 2023, we entered into an external sponsored collaborative clinical research agreement with Erasmus MC and AstraZeneca.

the agreement, Erasmus MC is planning to perform an investigator-initiated clinical study, entitled “Combining anti-PD-L1 immune

checkpoint inhibitor durvalumab with TLR-3 agonist rintatolimod in patients with metastatic pancreatic ductal adenocarcinoma for therapy

DURIPANC Study,” in which it will use both study drugs provided by AstraZeneca and AIM ImmunoTech.

Additionally:

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The study’s authors include Prof.

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

Medical Center in the Netherlands.

van Eijck, MD, PhD, the lead investigator 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

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We submitted our response to the FDA in February 2022.

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.

Amarex Clinical Research will manage the AIM-sponsored

Phase 2 study.

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 specifically to treat locally advanced pancreatic cancer

In August 2022, we received IRB approval of the trial protocol and so announced the trial’s commencement.

data was published in March 2022 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 .

In the 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 patients.

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)

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and Chronic Fatigue Syndrome (CFS), is a serious and debilitating chronic illness and a major public health problem.

is recognized by both the government and private sector as a significant unmet medical need, including the U.S.

National Institutes of

Health (“NIH”), FDA and the CDC.

The CDC states on its website at https://www.cdc.gov/me-cfs/ that “ Myalgic

encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, long-term illness that affects many body systems.

People with ME/CFS

are often not able to do their usual activities.

ME/CFS is recognized

by both the government and private sector as a significant unmet medical need, including the U.S.

National Institutes of Health (“NIH”),

FDA and the CDC.

The CDC states on its website at https://www.cdc.gov/me-cfs/ that “ Myalgic encephalomyelitis/chronic

fatigue syndrome (ME/CFS) is a serious, long-term illness that affects many body systems.

People with ME/CFS are often not able to do

their usual activities.

At times, ME/CFS may confine them to bed.

People with ME/CFS have severe fatigue and

sleep problems.

ME/CFS may get worse after people with the illness try to do as much as they want or need to do.

This symptom is known

as post-exertional malaise (PEM).

People with ME/CFS have severe fatigue and sleep problems.

get worse after people with the illness try to do as much as they want or need to do.

This symptom is called post-exertional malaise

Other symptoms can include problems with thinking and concentrating, pain, and dizziness.

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to their pre-SARS work levels,” according to Simmaron Research.

Now there is increasing evidence that patients with COVID-19

can develop a similar, ME/CFS-like illness.

Now there is increasing evidence that patients with COVID-19 can

develop a similar, ME/CFS-like illness.

These patients are commonly referred to as “Long Haulers.”

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Ampligen substantially improved physical performance in a subset of ME/CFS patients.

noted above in Overview;

Ampligen as a treatment for ME/CFS and Post-COVID Conditions , we have long been focused on seeking

the FDA’s approval for the use of Ampligen to treat ME/CFS.

In fact, in February 2013, we received a CRL from the FDA for our Ampligen

NDA for ME/CFS, stating that we should conduct at least one additional clinical trial, complete various nonclinical studies and perform

a number of data analyses.

developing a comprehensive response to the FDA and a plan for a confirmatory trial for the FDA NDA, we proceeded independently in Argentina

and, in August 2016, we received approval of an NDA from ANMAT for commercial sale of Ampligen in the Argentine Republic for the treatment

of severe CFS.

In September 2019, we received clearance from the FDA to ship Ampligen to Argentina for the commercial launch and subsequent

On June 10, 2020, we received import clearance from ANMAT to import the first shipment of commercial grade vials of Ampligen into

The next steps in the commercial launch of Ampligen include ANMAT conducting a final inspection of the product and release

tests before granting final approval to begin commercial sales.

This testing and approval process is currently delayed due to the COVID-19

pandemic and ANMAT’s internal processes.

The ongoing impact of COVID-19 in Argentina is taxing the nation’s health care system

and is, understandably, the main priority of its regulators.

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

Ampligen in Argentina.

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

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.

as a Potential Antiviral

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The MTA was extended for two years in May 2021.

There have been obstacles related to importing 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.

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.

However, progress in this area is stymied, and due to an inability to import the drug we are considering

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

regulatory support with regard to a possible clinical trial testing Ampligen’s potential as a COVID-19 prophylaxis via intranasal

Due to continuing delays and other obstacles related to importing Ampligen to China,

we ended our contract with Smoore on August 10, 2022.

August 2020, we contracted Amarex to act as our Clinical Research Organization and provide regulatory support with regard to a possible

clinical trial testing Ampligen’s potential as a COVID-19 prophylaxis via intranasal delivery.

in April 2020, we entered into confidentiality and non-disclosure agreements with numerous companies for the potential outsourcing of

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via intranasal delivery.

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.

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.

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

Phase 1 will see 12-24 patients receiving both Ampligen and interferon alpha-2b at

escalating doses.

Once that initial phase is complete, further study participants will be randomized to two arms:

one receiving the two-drug combination

and a control group who will not receive Ampligen or interferon 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 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.

We reported in September 2020 that recruitment in the trial

had begun (See clinicaltrials.gov/NCT04379518 ).

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.

one receiving the

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

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

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.

(See clinicaltrials.gov/NCT04379518) .

Due to a shortage of

qualifying subjects with COVID-19 and cancer as a result of the positive impact of vaccinations and treatments for COVID-19, Roswell

is seeking approval to expand the qualifying subject criteria to include other diseases lethal to immuno-compromised cancer

patients, such as influenza.

Accordingly, the study is temporarily suspended while seeking said approvals.

also entered into a specialized services agreement with Utah State University and have supplied Ampligen to support the University’s

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In January 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.

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

to facilitate two proposed studies/research projects:

assessment of protective potential of intranasal administration of Ampligen in SARS-CoV-2

Syrian hamster challenge model;

assessment of protective potential of intranasal Ampligen in lethal influenza mouse challenge

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

in the Leiden in the Netherlands, to manage a Phase 1 randomized, double-blind study to evaluate the safety and activity of repeated

intranasal administration of Ampligen.

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.

January 2021, we entered into a Sponsor Agreement with CHDR to manage a Phase 1 randomized, double-blind study to evaluate the safety

and activity of repeated intranasal administration of Ampligen.

AIM funded and sponsored the study.

This study was designed to assess the safety, tolerability

and biological activity of repeated administration of Ampligen intranasally.

A total of 40 healthy subjects received either Ampligen

or a placebo in the trial, with the Ampligen given at four escalating dosages across four cohorts, to a maximum level of 1,250 micrograms.

All patients had completed treatment by June 2021 and the interim results reported no Serious or Severe Adverse Events at any dosage

We believe that the trial is a critical step in our ongoing efforts to develop Ampligen as a potential prophylaxis or treatment

for COVID-19 and other respiratory viral diseases.

Amarex provided us with monitoring support during the trial.

the completion of the Phase 1 dosing, and based on its positive interim results in June 2021 (which have since been publicly supported

in a CHDR-created data visualization published in October 2021), we signed a Reservation and Start-Up Agreement with hVIVO, reserving

space in hVIVO’s quarantine facility to sponsor a Phase 2a Human Challenge Trial (“HCT”) to test Ampligen as a potential

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

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.

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

revised application was resubmitted in December 2021.

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

moving forward.

As the request would require us to first conduct an animal experiment that we believe would take approximately 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.

This study was designed to assess

the safety, tolerability and biological activity of repeated administration of Ampligen intranasally.

A total of 40 healthy subjects

received either Ampligen or a placebo in the trial, with the Ampligen given at four escalating dosages across four cohorts, to a maximum

level of 1,250 micrograms.

All patients had completed the study by June 2021 and the study is completed.

The Final Safety Report reported

no Serious or Severe Adverse Events at any dosage level.

We believe that the trial is a critical step in our ongoing efforts to develop

Ampligen as a potential prophylaxis or treatment for COVID-19 and other respiratory viral diseases.

Amarex provided us with monitoring

support during the trial.

Additionally,

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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.

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

Similarly, in ME/CFS, data supports the claim that Ampligen improves fatigue symptoms.

Then in September, we filed a patent

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and SARS-CoV-2.

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.

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.

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, the FDA responded that there was insufficient information to

support the proposed indication of post-COVID cognitive dysfunction.

We are working with Amarex to revise the study and resubmit it to

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:

● Intravenous

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

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 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.

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).

In October 2022, our IND application cleared the FDA

approval process and we are proceeding with a Phase 2 study evaluating Ampligen as a therapeutic for patients with post-COVID conditions

Additional comments were received from the FDA, which have been addressed in an amended protocol approved by

the IRB on March 30, 2023.

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

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may reemerge in the future, it appears that the spread of these disorders has diminished.

As a result, we have elected to focus our research

and development efforts on other areas at this time.

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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progression of Alzheimer’s disease.

November 2022, we received notice that the FDA had granted Orphan Drug Designation to Ampligen for the treatment of Ebola virus disease.

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

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.

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”).

According to the CDC, HPV is the most common sexually transmitted infection, with approximately 79 million Americans — most in

their late teens and early 20s — infected with HPV.

In fact, the CDC states that “HPV is so common that nearly all sexually

active men and women get the virus at some point in their lives.” Although they do not usually result in death, genital warts commonly

recur, causing significant morbidity and entail substantial health care costs.

are a group of proteins produced and secreted by cells to combat diseases.

Researchers have identified four major classes of human interferon:

alpha, beta, gamma and omega.

Alferon N Injection contains a multi-species form of alpha interferon.

The worldwide market for injectable

alpha interferon-based products has experienced rapid growth and various alpha interferon injectable products are approved for many major

medical uses worldwide.

Alpha interferons are manufactured commercially in three ways:

by genetic engineering, by cell culture, and from

human white blood cells.

All three of these types of alpha interferon are or were approved for commercial sale in the United States.

Our natural alpha interferon is produced from human white blood cells.

The potential advantages of natural alpha interferon over recombinant

(i.e., synthetic) interferon produced and marketed by other pharmaceutical firms may be based upon their respective molecular compositions.

Natural alpha interferon is composed of a family of proteins containing many molecular species of interferon.

In contrast, commercial

recombinant alpha interferon products each contain only a single species.

Researchers have reported that the various species of interferons

may have differing antiviral activity depending upon the type of virus.

Natural alpha interferon presents a broad complement of species,

which we believe may account for its higher activity in laboratory studies.

Natural alpha interferon is also glycosylated (i.e., partially

covered with sugar molecules).

Such glycosylation is not present on the currently U.S.-marketed recombinant alpha interferons.

that the absence of glycosylation may be in part responsible for the production of interferon-neutralizing antibodies seen in patients

treated with recombinant alpha interferon.

Although cell culture-derived interferon is also composed of multiple glycosylated alpha interferon

species, the types and relative quantity of these species are different from our natural alpha interferon.

N Injection [Interferon alfa-n3 (human leukocyte derived)] is a highly purified, natural-source, glycosylated, multi-species alpha interferon

There are essentially no neutralizing antibodies observed against Alferon N Injection to date and the product has a relatively

low side-effect profile.

The recombinant DNA derived alpha interferon formulations have been reported to have decreased effectiveness

after one year of treatment, probably due to neutralizing antibody formation (See “Manufacturing” and “Marketing/Distribution”

sections below for more details on the manufacture and marketing/distribution of Alferon N Injection).

The production of new Alferon

N Injection Active Pharmaceutical Ingredient, or API, is currently on hold.

We do not know when, if ever, our products will be generally

available for commercial sale for any indication.

MANUFACTURING

Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica (“ANMAT”) in Argentina approved Ampligen for commercial

distribution for the treatment of Chronic Fatigue Syndrome (“CFS”) in 2016.

Shipment of the drug product to Argentina was

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

in Argentina approved Ampligen for commercial distribution for the treatment of CFS in 2016.

Shipment of the drug product to Argentina

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

In September 2019, we received clearance

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

OI June 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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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.

(“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 existing fill and finish capacity.

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

December 2020, we added Pii as a “Fill & Finish” provider to enhance our capacity to produce Ampligen.

This addition

amplifies our manufacturing capability by providing redundancy and cost savings.

The contracts augment our existing fill and finish capacity.

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

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

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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.

Among other things, the purchaser has a 45-day right of due diligence

and has the right to terminate the agreement within that period.

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

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”)

for the manufacture of our Poly I and Poly C 12 U polynucleotides and associated test methods at Polysciences’ Warrington,

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

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.

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

pursuant to which we would sell our property for $3.9 million;

we have kept some space specifically for Alferon activity.

completed on November 1, 2022 for $3.7 million net of normal closing cost.

June 2022 we entered into a lease agreement with the New Jersey Economic Development Authority for a 5,210 square-foot, state-of-the-art

R&D facility at the New Jersey Bioscience Center (NJBC), primarily consisting of two separate laboratory suites.

The lease commenced

on July 1, 2022, and runs through August 31, 2027, but can be extended for an additional five-year period.

The facility is AIM’s

operations, research and development center.

business plan calls for the utilization of one or more CMOs 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 for the manufacture of our Poly I and Poly C 12 U polynucleotides

and associated test methods at Polysciences’ Warrington, PA location to enhance our capacity to produce the polymer precursors

to the drug Ampligen.

We are utilizing Polysciences’ 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

second product, Alferon N Injection, is approved by the FDA for commercial sales in the United States for the treatment of genital warts.

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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

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

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

In August 2021, 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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of Ampligen in the Territory.

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

January 2017, the ANMAT granted a five-year extension to a previous approval to sell and distribute Alferon N Injection (under the brand

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

12 months on May 20, 2022.

January 2017, ANMAT granted a five-year extension to a previous approval to sell and distribute Alferon N Injection (under the brand

name “Naturaferon”) in Argentina.

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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

been filed and is still under review.

In February 2013, we received ANMAT approval for the treatment of refractory patients that failed

or were intolerant to treatment with recombinant interferon, with Naturaferon in Argentina.

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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.

This agreement has expired.

We are in discussions with Asembia about the possibility

of continuing the relationship, while also exploring the possibility of working with other, similar companies.

However, we do not foresee

an immediate need for this service and so may push this search further out in our expected timeline.

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

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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.

In November 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.

major pharmaceutical competitors for Ampligen include Pfizer, GlaxoSmithKline, Merck & Co., Novartis and AstraZeneca.

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include Baxter International, Fletcher/CSI, AVANT Immunotherapeutics, AVI BioPharma and Genta.

When we recommence sales of Alferon N

Injection, it may compete with Intron® A, an injectable from Merck & Co.

by governmental authorities in the U.S.

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Five of the combined personnel

are engaged in our research, development, clinical, and manufacturing effort with 18 performing regulatory, general administration, data

processing, including bio-statistics, financial and investor relations functions.

are engaged in our research, development, clinical and manufacturing efforts, with 17 performing regulatory, general administration,

data processing, including bio-statistics, financial and investor relations functions.

We have no union employees.

we have been successful in attracting skilled and experienced scientific personnel, there can be no assurance that we will be able to

attract or retain the necessary qualified employees and/or consultants in the future.

business results depend in part on our ability to successfully manage our human capital resources, including attracting, identifying,

and retaining key talent.

Factors that may affect our ability to attract and retain qualified employees include employee morale, our

reputation, competition from other employers, and availability of qualified individuals.

We believe our commitment to our human capital

resources is an important component of our mission.

We provide all employees with the opportunity to share their opinions in open dialogues

with our human resources department and senior management.

Compensation,

Benefits and Wellness

offer fair, competitive compensation and benefits that support our employees’ overall wellness.

Further, the health and wellness

of our employees are critical to our success.

While we have been successful in attracting skilled and experienced scientific personnel,

there can be no assurance that we will be able to attract or retain the necessary qualified employees and/or consultants in the future.

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-K

Item 1. Business