AIM ImmunoTech Inc. (AIM) 2024年年度報告「NYSE」.pdf

《AIM ImmunoTech Inc. (AIM) 2024年年度報告「NYSE」.pdf》由會員分享，可在線閱讀，更多相關《AIM ImmunoTech Inc. (AIM) 2024年年度報告「NYSE」.pdf（72頁珍藏版）》請在三個皮匠報告上搜索。

1、 UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington,D.C.20549 FORM 10-K X ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d)OF THESECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31,2024 OR TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d)OF THESECURITIES EXCHANGE ACT OF 1934 For

2、 the transition period from _ to _ Commission File No.001-27072 AIM IMMUNOTECH INC.(Exact name of registrant as specified in its charter)Delaware 52-0845822(State or other jurisdiction of(I.R.S.Employer Identificationincorporation or organization)Number)2117 SW Highway 484,Ocala FL 34473(Address of

3、principal executive offices)(Zip Code)Registrants telephone number,including area code:(352)448-7797(Former name,former address and former fiscal year,if changed since last report)Securities registered pursuant to Section 12(b)of the Act:Title of each class Trading Symbol Name of each exchange on wh

4、ich registeredCommon Stock,par value$0.001 per share AIM NYSE American Securities registered pursuant to Section 12(g)of the Act:(Title of Each Class)NONE Indicate by check mark if the registrant is a well-known seasoned issuer,as defined in Rule 405 of the Securities Act.Yes X No Indicate by check

5、mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d)of the Act.Yes No X Indicate by check mark whether the registrant(1)has filed all reports required to be filed by Section 13 or 15(d)of the Securities Exchange Act of 1934 during the preceding 12months(or f

6、or such shorter period that the registrant was required to file such reports),and(2)has been subject to such filing requirements for the past 90 days.YesX No Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Ru

7、le 405 of Regulation S-T(232.405 ofthis chapter)during the preceding 12 months(or for such shorter period that the registrant was required to submit such files).YesX No Indicate by check mark whether the registrant is a large accelerated filer,an accelerated filer,a non-accelerated filer,a smaller r

8、eporting company or an emerging growth company.See definitions of large accelerated filer,”accelerated filer”,smaller reporting company”and emerging growth company”in Rule 12b-2 of the Exchange Act:Large accelerated filerAccelerated filerXNon-accelerated filerXSmaller reporting company Emerging grow

9、th company If an emerging growth company,indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financialaccounting standards pursuant to Section 13(a)of the Exchange Act.Indicate by checkmark whether the registrant has fi

10、led a report on and attestation to its managements assessment of the effectiveness of its internal control over financialreporting under Section 404(b)of the Sarbanes-Oxley Act(15 U.S.C.7262(b)by the registered public accounting firm that prepared or issued its audit report.If securities are registe

11、red pursuant to Section 12(b)of the Act,indicate by check mark whether the financial statements of the registrant included in the filing reflect the correctionof an error to previously issued financial statements.Indicate by check mark whether any of those error corrections are restatements that req

12、uired a recovery analysis of incentive-based compensation received by any of theregistrants executive officers during the relevant recovery period pursuant to 240.10D-1(b).Indicate by check mark whether the registrant is a shell company(as defined in Rule 12b-2 of the Exchange Act).Yes No X The aggr

13、egate market value of the voting and non-voting common equity held by non-affiliates at June 30,2024,the last business day of the registrants most recently completedsecond fiscal quarter was$20,793,354.The number of shares of the registrants Common Stock outstanding as of March 24,2025 was 72,290,03

14、0.DOCUMENTS INCORPORATED BY REFERENCE:None.TABLE OF CONTENTS PagePART I ITEM 1.Business.3 ITEM 1A.Risk Factors.22 ITEM 1B.Unresolved Staff Comments.36 ITEM 1C.Cybersecurity36 ITEM 2.Properties.36 ITEM 3.Legal Proceedings.37 ITEM 4.Mine Safety Disclosures.37 PART II ITEM 5.Market for the Registrants

15、Common Equity,Related Stockholder Matters and Issuer Purchases of Equity Securities.38 ITEM 6.Reserved38 ITEM 7.Managements Discussion and Analysis of Financial Condition and Results of Operations.38 ITEM 7A.Quantitative and Qualitative Disclosures About Market Risk.43 ITEM 8.Financial Statements an

16、d Supplementary Data.43 ITEM 9.Changes in and Disagreements with Accountants on Accounting and Financial Disclosure.43 ITEM 9A.Controls and Procedures.43 ITEM 9B.Other Information.44 ITEM 9C.Disclosure Regarding Foreign Jurisdictions that Prevent Inspections.44 PART III ITEM 10.Directors,Executive O

17、fficers and Corporate Governance.45 ITEM 11.Executive Compensation.52 ITEM 12.Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters.61 ITEM 13.Certain Relationships and Related Transactions and Director Independence.63 ITEM 14.Principal Accountant Fees and Se

18、rvices.63 PART IV ITEM 15.Exhibits and Financial Statement Schedules.64 ITEM 16.Form 10-K Summary.70 2 PART I ITEM 1.Business GENERAL AIM ImmunoTech Inc.and its subsidiaries(collectively,AIM”,Company”,we”or us”)are an immuno-pharma company headquartered in Ocala,Florida,and focusedon the research an

19、d development of therapeutics to treat multiple types of cancers,viral diseases and immune-deficiency disorders and to treat cancers for which there arecurrently inadequate or unmet therapies.We have established a strong foundation of laboratory,pre-clinical and clinical data with respect to the dev

20、elopment of nucleic acids andnatural 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 andchronic diseases.AIMs flagship products are Ampligen(rintatolimod)and Alferon N Injection(Inter

21、feron alfa).Ampligen is a double-stranded RNA(dsRNA”)molecule being developedfor globally important cancers,viral diseases and disorders of the immune system.Ampligen has not been approved by the FDA or marketed in the United States but is approvedfor commercial sale in the Argentine Republic for th

22、e treatment of severe Chronic Fatigue Syndrome(CFS”).The Company is currently proceeding primarily in four areas:Conducting clinical trials to evaluate the efficacy and safety of Ampligen for the treatment of pancreatic cancer.Evaluating Ampligen across multiple cancers as a potential therapy that m

23、odifies the tumor microenvironment with the goal of increasing anti-tumor responses tocheckpoint inhibitors.Exploring Ampligens antiviral activities and potential use as a prophylactic or treatment for existing viruses,new viruses and mutated viruses thereof.Evaluating Ampligen as a treatment for my

24、algic encephalomyelitis/chronic fatigue syndrome(ME/CFS”)and fatigue and/or the Post-COVID condition offatigue.Evaluating Ampligen as a vaccine adjuvant in the combination of Ampligen and AstraZenecas FluMist as an intranasal vaccine for influenza,including avianinfluenza.The Company is prioritizing

25、 activities in an order related to the stage of development,with those clinical activities such as pancreatic cancer,ME/CFS and Post-COVIDconditions having priority over antiviral experimentation.The Company intends that priority clinical work be conducted in trials authorized by the FDA or European

26、 MedicinesAgency(EMA”),which trials support a potential future NDA.However,AIMs antiviral experimentation is designed to accumulate additional preliminary data supporting theirhypothesis that Ampligen is a powerful,broad-spectrum prophylaxis and early-onset therapeutic that may confer enhanced immun

27、ity and cross-protection.Accordingly,AIM willconduct antiviral programs in those venues most readily available and able to generate valid proof-of-concept data,including foreign venues.We have recently announced that we have engaged Amarex Clinical Research(Amarex”),our Clinical Research Organizatio

28、n,with the application and eventualmanagement of a follow-up Investigational New Drug(IND”)application for the study of a potential avian influenza combination therapy of our Ampligen and AstraZenecasFluMist,a nasal spray vaccine that helps prevent seasonal influenza.We are seeking collaborative gra

29、nts from government and industry to defray the cost of the study.Inaddition,we recently announced that the Erasmus Medical Center Safety Committee grants approval to proceed with a Phase 2 Study of Ampligen and Imfinzi as a potentialcombination therapy for late-stage pancreatic cancer.Immuno-Oncolog

30、y We are focused on pancreatic cancer because testing results to date primarily conducted in the Netherlands have been very promising.The Netherlands studygenerated statistically significant data indicating that Ampligen extended survival well beyond the Standard of Care(SOC”),when compared to well-

31、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 Researc

32、h Organization,Amarex,submitted an Investigational New Drug(IND”)application to the FDA for a planned Phase 2 study of Ampligen as a therapy for locally advanced or metastatic late-stage pancreatic cancer.Ampligen appears in clinic testing to have potential for standalone efficacy in a number of oth

33、er solid tumors.We have also seen success in increasing survival rates andefficacy in the treatment of animal tumors when Ampligen is used in combination with checkpoint blockade therapies.In fact,in March 2022 we announced interim data from aninvestigator-initiated,Phase 2,single-arm,efficacy/safet

34、y trial to evaluate the effectiveness of combining intensive locoregional intraperitoneal(IP)chemoimmunotherapy ofcisplatin with IP Ampligen(TLR-3 agonist)and IV infusion of the checkpoint inhibitor pembrolizumab for patients with recurrent platinum-sensitive ovarian cancer.We believe thatdata from

35、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

36、chemotaxis and cytolyticfunction has been seen.Importantly,increases of these biomarkers in the tumor microenvironment have been correlated with favorable tumor responses.These successes in thefield of immuno-oncology have guided our efforts toward the potential use of Ampligen as a combinational th

37、erapy for the treatment of a variety of solid tumor types.The first ofour patent applications in this space was granted by the Netherlands on March 15,2021.3 Please see Immuno-Oncology”below.Ampligen as a Potential Antiviral We have a research and pre-clinical history that indicates broad-spectrum a

38、ntiviral capability of Ampligen in animals.We hope to demonstrate that it has the same effectin 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 bySARS-CoV-2)which is active and still infect

39、ing many subjects.While much would need to be done to get Ampligen to market as a broad-spectrum antiviral,we believe that it isimportant 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 s

40、tudieswere conducted that yielded positive results utilizing Ampligen to treat numerous viruses,such as Western Equine Encephalitis Virus,Ebola,Vaccinia Virus(which is used in themanufacture of smallpox vaccine)and SARS-CoV-1.We have conducted experiments in SARS-CoV-2 showing Ampligen has a powerfu

41、l impact on viral replication.The priorstudies of Ampligen in SARS-CoV-1 animal experimentation may predict similar protective effects against SARS-CoV-2.We announced in February 2025 our intention to pursue a study of a potential avian influenza combination therapy of Ampligen and AstraZenecas FluM

42、ist,a nasalspray vaccine that helps prevent seasonal influenza.The new proposed clinical trial would expand upon previous Company-sponsored clinical research at the University ofAlabama-Birmingham(UAB”),which indicated that intranasal delivery of Ampligen after the intranasal delivery of the FluMist

43、 seasonal influenza vaccine increased the immuneresponse to seasonal variants in the vaccine by greater than four-fold and induced cross-reactive secretory Immunoglobulin A against highly pathogenic avian influenza virusstrains H5N1,H7N9 and H7N3.We are seeking collaborative grants from government a

44、nd industry to defray the cost of the study.We believe that this pre-clinical and clinicalwork to date combined with the ever-growing threat of Avian influenza strongly supports our decision to move forward with this second Ampligen and FluMist study inhumans.In this regard,CHDR,a foundation located

45、 in Leiden in the Netherlands,managed a Phase 1 randomized,double-blind study for us to evaluate the safety,tolerability,andbiological 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 give

46、n atfour escalating dosages across four cohorts,to a maximum level of 1,250 micrograms.The study was completed,and the Final Safety Report reported no Serious or Severe AdverseEvents at any dosage level.While there are approved therapies for COVID-19,we believe that,if Ampligen has the broad-spectru

47、m antiviral properties that we believe that it has,it could be a veryvaluable tool as a therapeutic or treatment for variants of existing viral diseases,including COVID-19,or novel ones that arise in the future.Unlike most developing therapeuticswhich attack the virus,Ampligen works differently.We b

48、elieve that it activates antiviral immune system pathways that fight not just a particular virus or viral variant,but othersimilar viruses as well.Please see Ampligen as a Potential Antiviral”below.Ampligen as a Treatment for ME/CFS and Post-Covid ConditionsWe have long been focused on seeking the F

49、DAs approval for the use of Ampligen to treat ME/CFS.In fact,in February 2013,we received a CRL from the FDA for ourAmpligen NDA for ME/CFS.We believe the Phase 3 results provided in the NDA were positive.The CRL indicated that we should conduct at least one additional clinical trial,complete variou

50、s nonclinical studies and perform a number of data analyses.4 While 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 August2016,we received approval of an NDA from ANMAT for commercial sale of Ampligen i

51、n the Argentine Republic for the treatment of severe CFS.In September 2019,we receivedclearance from the FDA to ship Ampligen to Argentina for the commercial launch and subsequent sales.On June 10,2020,we received import clearance from ANMAT to importthe first shipment of commercial grade vials of A

52、mpligen into Argentina.The next steps in the commercial launch of Ampligen include ANMAT conducting a final inspection of theproduct and release tests before granting final approval to begin commercial sales.This testing and approval process is ongoing due to ANMATs internal processes.Once finalappr

53、oval by ANMAT is obtained,GP Pharm will be responsible for distributing Ampligen in Argentina.The FDA authorized an open-label treatment protocol,AMP-511,allowing patient access to Ampligen for treatment in a study under which severely debilitated CFSpatients have the opportunity to be on Ampligen t

54、o treat this very serious and chronic condition.The data collected from the AMP-511 protocol through a consortium group ofclinical 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 theexpan

55、sion 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-likesymptoms that we refer to as Post-COVID conditions.As of December 31,2024,there were 6 patients enrolled in this open-label expanded ac

56、cess treatment protocol(including twopatients with Post-COVID Conditions).To date,there have been eight such Post-COVID patients treated in the study.AIM previously reported positive preliminary results basedon data from the first four Post-COVID Condition patients enrolled in the study.The data sho

57、w that,by week 12,compared to baseline,there was what the investigatorsconsidered a clinically significant decrease in fatigue-related measures and improvement in cognition.We plan on a comprehensive follow-up with the FDA regarding the use of Ampligen as a treatment for ME/CFS.We have learned a gre

58、at deal since the FDAs CRL andplan 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 teamand consultants.In January 2025,we announced that the final Clinical Study results from AMP-518 had been

59、posted to ClinicalTrials.gov.The results support our belief in Ampligen as apotential therapeutic for people with the moderate-to-severe Post-COVID condition of fatigue,and that this would be the likely subject population for AIMs planned follow-upclinical trial.Please see Ampligen as a Treatment fo

60、r ME/CFS and Post-Covid Conditions”below.Atlas Equity Line of Credit On March 28,2024,we entered into a purchase agreement(the Purchase Agreement”)and a registration rights agreement(the Registration Rights Agreement”)withAtlas Sciences,LLC,a Utah limited liability company(Atlas”),pursuant to which

61、Atlas has committed to purchase up to$15 million of our Common Stock.Under the terms and subject to the conditions of the Purchase Agreement,we have the right,but not the obligation,to sell to Atlas,and Atlas is obligated to purchase upto$15 million of our Common Stock(the Commitment Amount”).Such s

62、ales by us,if any,will be subject to certain limitations,and may occur from time to time,at our solediscretion,over the 24-month period commencing on the date that a registration statement covering the resale of shares that have been and may be issued under the PurchaseAgreement.We have filed a regi

63、stration statement with the SEC which has been declared effective and filed a final prospectus with the SEC in connection therewith.Atlas has no right to require us to sell any shares to Atlas,but Atlas is obligated to make purchases as we direct,subject to certain conditions.There are no upper limi

64、tson the price per share that Atlas must pay for shares of Common Stock.Actual sales of shares to Atlas will depend on a variety of factors to be determined by us from time to time,including,among others,market conditions,the trading price of the Common Stock and determinations by us as to the appro

65、priate sources of funding for us and our operations.The net proceeds under the Purchase Agreement will depend on the frequency and prices at which we sell shares to Atlas.We expect that any proceeds received by uswill be used for working capital and general corporate purposes.We cannot sell shares b

66、elow the Minimum Price(as defined by the NYSE American)under the Purchase Agreement that would represent,in the aggregate,more than19.99%of the outstanding shares on the date that the Purchase Agreement was executed or more than one percent of such shares to Substantial Security Holders(as defined b

67、ythe NYSE American).Before we could do that,we would need to obtain stockholder approval.We have agreed with Atlas that we will not enter into any variable rate”transactions with any third party for a period defined in the Purchase Agreement.Atlas hascovenanted not to cause or engage in any manner w

68、hatsoever,any direct or indirect short selling or hedging of the Companys shares.As consideration for Atlass irrevocable commitment to purchase shares upon the terms of and subject to satisfaction of the conditions set forth in the PurchaseAgreement,upon execution of the Purchase Agreement,the Compa

69、ny agreed to pay Atlas an initial commitment fee in shares equal to 1.0%of the Commitment Amount.The initialcommitment fee was paid upon execution of the Purchase Agreement through the issuance of 338,600 shares of Common Stock.5 The Purchase Agreement and the Registration Rights Agreement contain c

70、ustomary representations,warranties,conditions and indemnification obligations of the parties.The Company has the right to terminate the Purchase Agreement at any time,at no cost or penalty.During any period where bankruptcy,insolvency,reorganization or liquidation proceedings or other proceedings,v

71、oluntary or involuntary,for relief under anybankruptcy law or any law for the relief of debtors shall be instituted or anticipated by or against the Company or any subsidiary of the Company,and in the case of such aproceeding being involuntary or commenced against the Company,which is not dismissed

72、within 60 days,the Company may not initiate any purchase of shares by Atlas.The foregoing descriptions of the Purchase Agreement and the Registration Rights Agreement are qualified in their entirety by reference to the full text of suchagreements,copies of which incorporated by reference as Exhibits

73、 hereto,and each of which is incorporated herein in its entirety by reference.The representations,warranties andcovenants contained in such agreements were made only for purposes of such agreements and as of specific dates,were solely for the benefit of the parties to such agreementsand may be subje

74、ct to limitations agreed upon by the contracting parties.Liquidity and Going Concern The accompanying audited consolidated financial statements have been prepared assuming the Company will continue as a going concern.The going concern basis ofpresentation assumes that the Company will continue in op

75、eration one year after the date these financial statements are issued and will be able to realize its assets and dischargeits liabilities and commitments in the normal course of business.Pursuant to the requirements of the Financial Accounting Standards Boards(the FASB”)Accounting Standards Codifica

76、tion(ASC”)Topic 205-40,Disclosure ofUncertainties about an Entitys Ability to Continue as a Going Concern,management must evaluate whether there are conditions or events,considered in the aggregate,that raisesubstantial doubt about the Companys ability to continue as a going concern for one year fro

77、m the date these financial statements are issued.This evaluation does not take intoconsideration the potential mitigating effect of managements plans that have not been fully implemented or are not within control of the Company as of the date the financialstatements are issued.When substantial doubt

78、 about the Companys ability to continue as a going concern exists,management evaluates whether the mitigating effect of its planssufficiently alleviates the substantial doubt.The mitigating effect of managements plans,however,is only considered if both(1)it is probable that the plans will be effecti

79、velyimplemented within one year after the date that the financial statements are issued,and(2)it is probable that the plans,when implemented,will mitigate the relevant conditions orevents that raise substantial doubt about the Companys ability to continue as a going concern within one year after the

80、 date that the financial statements are issued.The Companys principal source of liquidity is its cash and cash equivalents,marketable securities,and proceeds from financing activities to provide the necessaryfunding to meet our obligations as they become due.The Company has suffered losses from oper

81、ations and net cash used on operating activities for the year ended December 31,2024,and has a working capital deficit as of December 31,2024.Additionally,the Companys stockholders equity was below the minimum requirements for continued listing on theNew York Stock Exchange American(NYSE American”).

82、These conditions raise substantial doubt regarding the Companys ability to continue as a going concern for a period ofat least one year from the date of issuance of these audited consolidated financial statements.Management evaluated the conditions,and the significance of these conditionsrelated to

83、the Companys ability to meet its obligations and determined that the primary cause of the deficit was related to certain accounts payable to which the Company iscurrently in negotiations with the vendor.The Company is in negotiations to reduce the amount that is outstanding.These negotiations are on

84、going and could result in significantamounts which could partially alleviate the negative working capital.There is no assurance as to the timing or outcome of these efforts.If the Company is unable to implementsufficient mitigation efforts,the Company may be forced to limit its business activities o

85、r be unable to continue as a going concern,which would have a material adverse effect onits results of operations and financial condition.6 SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS AND SUMMARY RISK FACTORS Certain statements in this Report contain forward-looking statements within the meani

86、ng of Section 27A of the Securities Act and Section 21E of the Securities ExchangeAct of 1934,as amended,which we refer to as the Exchange Act.All statements,other than statements of historical fact,included or incorporated herein regarding our strategy,future operations,financial position,future re

87、venues,projected costs,plans,prospects and objectives are forward-looking statements.Words such as expect,”anticipate,”intend,”plan,”believe,”seek,”estimate,”think,”may,”could,”will,”would,”should,”continue,”potential,”likely,”opportunity”and similar expressions orvariations of such words are intend

88、ed to identify forward-looking statements but are not the exclusive means of identifying forward-looking statements and their absence does notmean that a statement is not forward-looking.Our forward-looking statements are not guarantees of performance,and actual results could vary materially from th

89、ose contained inor expressed by such statements due to risks and uncertainties.These statements are based on our managements current beliefs,expectations and assumptions about futureevents,conditions and results and on information currently available to us.Discussions containing these forward-lookin

90、g statements may be found,among other places,in thisReport in Part I,Item 1.Business”;Part II,Item 2.Managements Discussion and Analysis of Financial Condition and Results of Operations”;Part II,Item 1.LegalProceedings”;and Part II,Item 1A.Risk Factors”.Among other things,for those statements,we cla

91、im the protection of safe harbor for forward-looking statements contained inthe Private Securities Litigation Reform Act of 1995.Any forward-looking statements set forth in this presentation speak only as of the date of this presentation.We do notundertake to update any of these forward-looking stat

92、ements to reflect events or circumstances that occur after the date hereof.We are in various stages of seeking to determinewhether Ampligen will be effective in the treatment of multiple types of viral diseases,cancers,and immune-deficiency disorders and the presentation sets forth our current andan

93、ticipated future activities.These activities are subject to change for a number of reasons.Significant additional testing and trials will be required to determine whetherAmpligen will be effective in the treatment of these conditions.Results obtained in animal models do not necessarily predict resul

94、ts in humans.Human clinical trials will benecessary to prove whether or not Ampligen will be efficacious in humans.No assurance can be given as to whether current or planned clinical trials will be successful or yieldfavorable data and the trials are subject to many factors including lack of regulat

95、ory approval(s),lack of study drug,or a change in priorities at the institutions sponsoring othertrials.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.Among the studiesare clinical trial

96、s that provide only preliminary data with a small number of subjects,and no assurance can be given that the findings in these studies will prove true or that thestudy or studies will yield favorable results.Some of the worlds largest pharmaceutical companies and medical institutions are working on a

97、 treatment for COVID-19.Even ifAmpligen proves effective in combating the virus,no assurance can be given that our actions toward proving this will be given first priority or that another treatment thateventually proves capable will not make our efforts ultimately unproductive,as multiple vaccines,a

98、nd some treatments,are now available and major pharma companies are workingto develop their own disease treatments.No assurance can be given that future studies will not result in findings that are different from those reported in the studies referenced inthis Report.Operating in foreign countries c

99、arries with it a number of risks,including potential difficulties in enforcing intellectual property rights.In addition,many countries,including Argentina,are still dealing with COVID-19 outbreaks and have made that their primary focus.We believe that this along with a massive devaluation of the Arg

100、entinepeso may be delaying our commercialization of Ampligen in Argentina until COVID-19 is more under control.We cannot assure that our potential foreign operations will notbe adversely affected by these risks.Our filings are available at .The information found on our website is not incorporated by

101、 reference into this Report and is included for referencepurposes only.SUMMARY RISK FACTORS Risks Related to Ownership of Our Securities We have a history of losses,expect to continue to incur losses in the near term and may not achieve or sustain profitability in the future,and as a result,there is

102、 asubstantial doubt about our ability to continue as a going concern.We are currently not in compliance with the Exchange continued listing requirements.If we are unable to regain compliance with the Exchanges listing requirements,oursecurities could be delisted,which could affect our common stock m

103、arket price and liquidity and reduce our ability to raise capital.If we are not able to comply with the applicable continued listing requirements or standards of the NYSE American,our common stock could be delisted from theExchange.We may seek to raise additional funds or develop strategic relations

104、hips by issuing securities that would dilute your ownership.Depending on the terms available to us,ifthese activities result in significant dilution,it may negatively impact the trading price of our common stock.An active,liquid and orderly trading market for our common stock may not develop,the pri

105、ce of our stock may be volatile,and you could lose all or part of yourinvestment.If our shares of common stock become subject to the penny stock rules,it would become more difficult to trade our shares.Proxy contests and related litigation by activist investors could cause significant fluctuations i

106、n our stock price based on temporary or speculative market perceptions orother factors that do not necessarily reflect the underlying fundamentals and prospects of our business.If we were to dissolve,the holders of our securities may lose all or substantial amounts of their investments.If securities

107、 or industry analysts do not publish or cease publishing research or reports about us,our business or our market,or if they change their recommendationsregarding our securities adversely,our stock price and trading volume could decline.Our business,financial condition and operating results could be

108、negatively affected as a result of actions by activist investors.7 General Risk Related to our Business We will require additional financing which may not be available.We may continue to incur substantial losses and our future profitability is uncertain.Our drug and related technologies are investig

109、ational and subject to regulatory approval.If we are unable to obtain regulatory approval in a timely manner,or at all,ouroperations will be materially harmed and our stock adversely affected.We may be subject to product liability claims from the use of Ampligen,Alferon N Injection,or other of our p

110、roducts which could negatively affect our future operations.We have limited product liability and clinical trial insurance.Uncertainty of health care reimbursement for our products.There are risks of liabilities associated with handling and disposing of hazardous materials.Failures of our informatio

111、n technology infrastructure could have a material adverse effect on operations.The loss of services of key personnel could hurt our chances for success.GAAP requires estimates,judgements and assumptions which inherently contain uncertainties.We currently,and may in the future,have assets held at fin

112、ancial institutions that may exceed the insurance coverage offered by the Federal Deposit InsuranceCorporation,and the loss of such assets would have a severe negative affect on our operations and liquidity.Risks Associated with Our Products The development of Ampligen is subject to significant risk

113、s.The development of Alferon N Injection is subject to significant risks.Possible side effects from the use of Ampligen or Alferon N Injection could adversely affect potential revenues and physician/patient acceptability of our product.Risks Related to our activities associated with Ampligens potent

114、ial effectiveness as a treatment for COVID-19 or Post-Covid Conditions It is not possible to predict the future of COVID-19,and related Post-COVID Conditions,as a global public health threat or the development of related therapies.Noassurance can be given that Ampligen will aid in or be applied to t

115、he treatment of this virus.Operating in foreign countries carries with it many risks.Risks Associated with Our Intellectual Property We may not be profitable unless we can protect our patents and/or receive approval for additional pending patents.The patent position of biotechnology and pharmaceutic

116、al firms is highly uncertain and involves complex legal and factual questions.There can be no assurance that we will be able to obtain necessary licenses if we cannot enforce patent license rights we may hold.In addition,the failure of third partiesfrom whom we currently license certain proprietary

117、information or from whom we may be required to obtain such licenses in the future,to adequately enforce their rightsto such proprietary information,could adversely affect the value of such licenses to us.There is no guarantee that our trade secrets will not be disclosed or known by our competitors.R

118、isks Associated with Our R&D We 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.In addition,w

119、e have no basis for estimating when material net cash inflowsmay commence.We have yet to generate significant revenues from the sale of these developmental products.Risks Associated with Our Manufacturing Our Alferon N Injection Commercial Sales were halted due to lack of finished goods inventory.If

120、 we are unable to gain the necessary FDA approvals related to Alferon NInjection,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.There are no long-term agreements with suppliers of required materia

121、ls and services for Ampligen and there are a limited number of raw material suppliers.If we are unableto obtain the required raw materials and/or services,we may not be able to manufacture Ampligen.There are limited number of organizations in the United States available to provide the final manufact

122、uring steps of formulation,fill,finish and packing sets for Alferon NInjection and Ampligen.There is no assurance that,upon success,manufacture of a drug on a limited-scale basis for investigational use would lead to a successful transition to commercial,large-scale production.We have limited manufa

123、cturing experience for Ampligen and Alferon N Injection.We may not be profitable unless we can produce Ampligen,Alferon N Injection or otherproducts in commercial quantities at costs acceptable to us.8 Risks Associated with Our Licensing/Collaborations/Joint Ventures If we are unable to achieve lice

124、nsing,collaboration and/or joint ventures,our marketing strategy for Ampligen will be part of the differing health care systems around theworld along with the different marketing and distribution systems that are used to supply pharmaceutical products to those systems.Risks Associated with Our Marke

125、ting and Distribution We have limited marketing and sales capability.If we are unable to obtain additional distributors and our current and future distributors do not market our productssuccessfully,we may not generate significant revenues or become profitable.Risks Associated with Our Competition R

126、apid technological change may render our products obsolete or non-competitive.Our products may be subject to substantial competition.Risks Associated with an Investment in Our Common Stock The market price of our stock may be adversely affected by market volatility.Sales of a significant number of s

127、hares of our common stock in the public markets,or the perception that such sales could occur,could depress the market price of ourcommon stock.Provisions of our Certificate of Incorporation and Delaware law could defer a change of our Management,which could discourage or delay offers to acquire us.

128、Our business,financial condition and operating results could be negatively affected as a result of actions by activist investors.AVAILABLE INFORMATION We file electronically with the United States Securities and Exchange Commission,or SEC,our annual reports on Form 10-K,quarterly reports on Form 10-

129、Q,currentreports 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 availableon our website at free of charge,copies of these reports as soon as reasonably practicable after filing these reports wi

130、th,or furnishing them to,the SEC.Weare subject to the information and periodic reporting requirements of the Exchange Act and,in accordance therewith,we file periodic reports,proxy statements and otherinformation with the SEC.Such periodic reports,proxy statements and other information are available

131、 for inspection and copying at the website of the SEC www.sec.gov.You alsomay 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 theday of filing with the SEC on our website at http:/ un

132、der the Investor Relations tab for SEC Filings or by contacting the Investor Relations Department bycalling(833)475-8247 or(352)448-7797 or sending an e-mail message to AIM.Our Internet website and the information contained on that website,or accessible from ourwebsite,is not intended to be incorpor

133、ated into this Annual Report on Form 10-K(this Annual Report”)or any other filings we make with the SEC.OUR PRODUCTS Our primary pharmaceutical product platform consists of Ampligen(rintatolimod),a first-in-class drug of large macromolecular double-stranded(ds)RNA(ribonucleicacid)molecules.Ampligen

134、is the only known TLR3 agonist to avoid helicase activation of NF-B.Natural dsRNAs and poly IC which activate NF-B in the tumormicroenvironment(TME)and have the potential to enhance cancer cell proliferation.Alferon Injection is an FDA-approved natural alpha-interferon product.Ampligen Ampligen is a

135、pproved for sale in Argentina(to 2026)for severe CFS and is an experimental drug in the United States currently undergoing clinical development for thetreatment of certain cancers,ME/CFS and Post-COVID Conditions.Over its developmental history,Ampligen has received various designations,including Orp

136、han Drug ProductDesignation(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 Q

137、uality).Based on the results ofpublished,peer-reviewed pre-clinical studies and clinical trials,we believe that Ampligen may have broad-spectrum antiviral and anti-cancer properties.We believe that nucleic acid compounds represent a potential new class of pharmaceutical products designed to act at t

138、he molecular level for treatment of many humandiseases.Ampligen represents the first drug in the class of large(macromolecular)dsRNA molecules to apply for NDA review.There are two forms of nucleic acids:deoxyribonucleic acid(DNA”)and ribonucleic acid(RNA”).DNA is a group of naturally occurring mole

139、cules found in chromosomes,the cells genetic machinery.RNA is agroup of naturally occurring informational molecules which orchestrate a cells behavior which,in turn,regulates the action of groups of cells,including the cells which comprisethe bodys immune system.RNA directs the production of protein

140、s and regulates certain cell activities including the activation of an otherwise dormant cellular defense againstviruses and tumors.Our drug technology utilizes specifically configured RNA and is a selective Toll-like Receptor 3(TLR3”)agonist that can be administered intravenously,intranasally and i

141、ntraperitoneally.Ampligen has been assigned the generic name rintatolimod by the United States Adopted Names Council(USANC”)and has the chemicaldesignation poly(I):poly(C12U).9 Expanded Access Program/Early Access Programs/clinical trials of Ampligen that have been conducted or that are ongoing incl

142、ude studies of the potential treatment ofpatients 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.We have received approval of our NDA fr

143、om ANMAT for the commercial sale of Ampligen in the Argentine Republic for the treatment of severe CFS.The product wouldbe marketed by GP Pharm,our commercial partner in Latin America.Shipment of the drug product to Argentina was initiated in 2018 to complete the release testing by ANMATneeded for c

144、ommercial distribution.In September 2019,we received clearance from the FDA to ship Ampligen to Argentina for the commercial launch and subsequent sales.InJune 2020,we received import clearance from ANMAT to import the first shipment of commercial grade vials of Ampligen into Argentina.Collaboration

145、 with GP Pharm continuesfor commercial launch of Ampligen in Argentina.Commercialization in Argentina will require,among other things,the establishment of disease awareness,medical education,creation of an appropriate reimbursement level,design of marketing strategies and completion of manufacturing

146、 preparations for launch and ANMAT conducting a final inspectionof the product and release tests before granting final approval to begin commercial sales.AIM has supplied GP Pharm with the Ampligen required for testing and ANMAT release.This testing and approval process is ongoing.Once final approva

147、l by ANMAT is obtained,the distributing of Ampligen in Argentina can begin.Argentina has experienced hyper-inflation and recently devalued its currency to the U.S.dollar by 50%.Contracts in Argentina are U.S.dollar contracts and the parties must evaluate the impact of the recentdevaluation on its re

148、lationship.The FDA has authorized an open-label expanded access treatment protocol(AMP-511)allowing patient access to Ampligen in a study under which severely debilitatedCFS patients have the opportunity to be on Ampligen to treat this serious and chronic condition.The AMP-511 protocol started in th

149、e 1990s and is ongoing.The data collectedfrom 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 ofclinical safety information which we believe will provide further documentation regarding

150、 the absence of autoimmune disease associated with Ampligen treatment.We believe thatcontinued 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 thedesign of future clinical studies that the F

151、DA requested in a CRL.The FDA approved an increased reimbursement level from$200 to$345 per 200 mg vial of Ampligen,due toincreased production costs;which was re-authorized in 2021,2022,2023 and 2024.At this time,we do not plan on passing this adjustment along to the patients in this program.InOctob

152、er 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 withSARS-CoV-2 following clearance of the virus,but who still demonstrate chronic fatigue-like symptoms that we refer to as Post-COVID conditio

153、ns.As of December 31,2024,therewere 6 patients enrolled in this open-label expanded access treatment protocol.In July 2022,AIM 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 baselin

154、e,the investigators observed what they considered a clinically significantdecrease in fatigue-related measures.To date,there have been eight such Post-COVID patients treated in this study.In May 2016,we entered into a five-year agreement with myTomorrows,a Netherlands-based company,for the commencem

155、ent and management of an Early AccessProgram(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 AccessPrograms in Europe,Canada,and Turkey to treat pancreatic cancer and ME/CFS patients.The agreement was

156、 automatically extended for a period of 12 months on May 20,2021;has been automatically extended for 12 months on each subsequent May 20;and will continue to be automatically extended for periods of 12 months every May 20 until terminatedor the terms of the agreement are met.In June 2018,Ampligen wa

157、s cited as outperforming two other TLR3 agonists poly IC and natural double stranded RNA in creating an enhanced tumormicroenvironment for checkpoint blockade therapy in the journal of Cancer Research.In a head-to-head study in explant culture models,Ampligen activated the TLR3 pathwayand promoted a

158、n 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 consideredimportant because they indicate that Ampligen selectively reprograms the tumor microenvironment by inducing the beneficial aspects of tumo

159、r inflammation(attracting killer Tcells),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”).I

160、n 2018,we completed production of two commercial-size batches of more than 16,000 vials of Ampligen,following its Fill&Finish”at Jubilant HollisterStier,the ContractManufacturing Organization.These lots passed all required testing for regulatory release for human use and are being used for multiple

161、programs,including:the treatment ofME/CFS;the pancreatic cancer EAP in the Netherlands;and will continue to be used for ongoing and future clinical studies in oncology.Lots of Ampligen were manufactured inDecember 2019,January 2020 and December 2023.Additionally,in December 2020,we added Pharmaceuti

162、cs International Inc.(Pii”)as a Fill&Finish”provider to enhance ourcapacity to produce Ampligen.This addition amplifies our manufacturing capability by providing redundancy and cost savings.The contracts augment our active and in-processfill and finish capacity.10 As to the production of additional

163、Ampligen when and if needed,the validation of the polymer production process with Sterling Pharma Solutions(Sterling”)is ongoing.This will need to be complete before we can manufacture more polymer,and thus more Ampligen.Alferon N Injection Alferon N Injection is the registered trademark for our inj

164、ectable formulation of natural alpha interferon.Alferon N Injection is the only natural-source,multi-species alphainterferon currently approved for sale in the United States and Argentina for the intralesional(within lesions)treatment of refractory(resistant to other treatment)or recurringexternal g

165、enital warts in patients 18 years of age or older.Alferon N Injection is also approved in Argentina for the treatment of refractory patients that failed or were intolerant totreatment with recombinant interferons.Argentina has experienced hyper-inflation and recently devalued its currency to the U.S

166、.dollar by 50%.Contracts in Argentina are in U.S.dollars and the parties must evaluate the impact of the recent devaluation on its relationship.Certain types of human papilloma viruses(HPV”)cause genital warts,a sexuallytransmitted disease(STD”).According to the CDC,HPV is the most common sexually t

167、ransmitted infection,with approximately 79 million Americans most in their late teensand 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,gen

168、ital warts commonly recur,causing significant morbidity and entail substantial health care costs.Interferons are a group of proteins produced and secreted by cells to combat diseases.Researchers have identified four major classes of human interferon:alpha,beta,gamma and omega.Alferon N Injection con

169、tains a multi-species form of alpha interferon.The worldwide market for injectable alpha interferon-based products has experienced rapidgrowth and various alpha interferon injectable products are approved for many major medical uses worldwide.Alpha interferons are manufactured commercially in three

170、ways:bygenetic 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 inter

171、feron over recombinant(i.e.,synthetic)interferon producedand marketed by other pharmaceutical firms may be based upon their respective molecular compositions.Natural alpha interferon is composed of a family of proteins containingmany molecular species of interferon.In contrast,commercial recombinant

172、 alpha interferon products each contain only a single species.Researchers have reported that the variousspecies of interferons may have differing antiviral activity depending upon the type of virus.Natural alpha interferon presents a broad complement of species,which we believemay account for its hi

173、gher activity in laboratory studies.Natural alpha interferon is also glycosylated(i.e.,partially covered with sugar molecules).Such glycosylation is notpresent on the currently U.S.-marketed recombinant alpha interferons.We believe that the absence of glycosylation may be in part responsible for the

174、 production of interferon-neutralizing antibodies seen in patients treated with recombinant alpha interferon.Although cell culture-derived interferon is also composed of multiple glycosylated alphainterferon species,the types and relative quantity of these species are different from our natural alph

175、a interferon.Alferon N Injection Interferon alfa-n3(human leukocyte derived)is a highly purified,natural-source,glycosylated,multi-species alpha interferon product.There areessentially no neutralizing antibodies observed against Alferon N Injection to date and the product has a relatively low side-e

176、ffect profile.The recombinant DNA derived alphainterferon formulations have been reported to have decreased effectiveness after one year of treatment,probably due to neutralizing antibody formation(See Manufacturing”andMarketing/Distribution”sections below for more details on the manufacture and mar

177、keting/distribution of Alferon N Injection).The production of new Alferon N Injection ActivePharmaceutical 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.Additionally,on May 9,2023,we were granted a U

178、.S.Patent for a method for preventing or reducing antigenic drift or viral reassortment in a host animal comprising determining if a host animalhas been exposed to or infected by an avian influenza virus and administering to the exposed host animal alpha-interferon.Given our focus on developing Ampl

179、igen as anoncology therapy and antiviral,alone and in combination with other drugs,at this time we are not focusing on developing Alferon N Injection.11 PATENTS AND NON-PATENT EXCLUSIVITY RIGHTS We consider patent exclusivity as a crucial component of our business.As of December 31,2024,we had 59 pa

180、tents worldwide with 71 additional pending patentapplications comprising our intellectual property.We continually review our patents to determine if they have continuing value.Please see Note 4:Patents,and Trademark Rights,Net”under Notes to the ConsolidatedFinancial Statements for more information

181、on these patents.There are no current patent litigation proceedings involving us.Orphan drug designation U.S.Orphan drug designation qualifies sponsors for incentives including:Tax credits for qualified clinical trials Exemption from user fees Potential seven years of market exclusivity after FDA ap

182、proval We have received Orphan Drug Designation(ODD)from the FDA for Ampligen used in the treatment of Chronic Fatigue Syndrome,HIV,Metastatic Melanoma,RenalCell Carcinoma,Pancreatic Adenocarcinoma and Ebola Virus Disease.In the European Union,ODD carries ten years of market exclusivity after receiv

183、ing marketing authorization.We have received ODD from the EU for Ampligen used in thetreatment of Ebola Virus Disease and Pancreatic Adenocarcinoma and for Alferon used in the treatment of Middle East Respiratory Syndrome.RESEARCH AND DEVELOPMENT(R&D”)Our general focus during the past several fiscal

184、 years has been on expanding the market potential of Ampligen through investigation of efficacy(in vitro and in vivo)indifferent immune-based disorders including cancer and CFS.We also have focused on research and development of potential prophylactic and therapeutic applications for thetreatment of

185、 COVID-19,including the long-term effects of COVID-19.Immuno-Oncology The potential of Ampligen as an immuno-oncology therapeutic has been a major focus of AIM since our current leadership took over in 2016.We have been working withthe University of Pittsburghs chemokine modulation research initiati

186、ve,which includes the use of Ampligen as a potential adjuvant to modify the tumor microenvironment(TME”)with the goal of increasing anti-tumor responses to check point inhibitors(CPI”).As part of this collaboration,we have supplied Ampligen to the University.The study,under the leadership of Robert

187、P.Edwards,MD,chair of gynecologic services at Magee-Womens Hospital of the University of Pittsburgh School of Medicine,and Professor ofSurgery Pawel Kalinski,M.D.,Ph.D.,at Roswell Park,Buffalo,N.Y.,involved the chemokine modulatory regimen developed by Dr.Kalinskis group and successfully completed t

188、hePhase 1 dose escalation in patients with resectable colorectal cancer.Multiple Ampligen clinical trials are underway or recently completed at major university cancer centers testing whether tumor microenvironments can be reprogrammed toincrease the effectiveness of cancer immunotherapy,including c

189、heckpoint inhibitors.The underway trials include:Pancreatic Cancer Trial The DURIPANC Study is a Phase 1b/2 clinical trial combining Ampligen with AstraZenecas anti-PD-L1 immune checkpoint inhibitor Imfinzi(durvalumab)for thetreatment of late-stage pancreatic cancer.The primary objective of the Phas

190、e 1b portion was to determine the safety of combination treatment.Investigators at ErasmusMedical Center(Erasmus MC”)in the Netherlands have completed the safety evaluation of subjects enrolled in the first dose level of the dose escalation design,findingthe combination therapy to be generally well-

191、tolerated with no severe treatment-related adverse events or dose-limiting toxicities.In February 2025,we announced that theErasmus MC Safety Committee had approved the clinical trial to move forward with Phase 2.Up to 25 patients are expected to be enrolled in the Phase 2 portion ofDURIPANC.Enrollm

192、ent and dosing is ongoing in Phase 2.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 incombination with standard of care(SOC)versus SOC alone following first-line therapy,such as FOLFIRINOX f

193、or subjects with locally advanced pancreaticadenocarcinoma.Secondary objectives include comparing safety and tolerability.AMP-270 is expected to enroll approximately 90 subjects in up to 30 centers across theU.S.and Europe.In March 2022,the FDA granted clearance to proceed with the study.In April 20

194、22,we executed a work order with Amarex to manage the clinical trial.InAugust 2022,we received IRB approval of the trial protocol and so announced the trials commencement.The authorization to proceed with the Phase 2 pancreatic cancerclinical trial has been received with potential sites in the Nethe

195、rlands at Erasmus MC,and also at major cancer research centers in the United States such as The BuffettCancer Center at the University of Nebraska Medical Center(UNMC).We sought FDA guidance on the expansion of inclusion criteria and treatment arms,thensubsequently amended the study protocol.We rece

196、ntly made a business decision to place screening/enrollment on hold and suspend the study.(https:/clinicaltrials.gov/ct2/show/NCT05494697).12 Advanced Recurrent Ovarian Cancer Results of the Phase 1 portion of a Phase 1/2 study of intraperitoneal chemo-immunotherapy in advanced recurrent ovarian can

197、cer were published in the AmericanAssociation for Cancer Research publication,Clinical Cancer Research(Clin Cancer Res January 19,2022 DOI:10.1158/1078-0432.CCR-21-3659).The study resultsrepresent an important extension of prior studies using human tumor explants that showed Ampligens potentially im

198、portant role as a TLR3 agonist acting synergisticallywith high-dose IFN and celecoxib to selectively enhance Teff cell-attractants while suppressing Treg-attractants in the tumor microenvironment with a concomitantincrease in the Teff/Treg ratio.The importance of boosting the Teff/Treg ratio in the

199、tumor microenvironment is that it is associated with the conversion of cold tumorsinto hot tumors,which have an increased sensitivity to chemo-immunotherapy and an improved chance of showing tumor regression.The Phase 1 portion was designedto establish intraperitoneal safety.The Phase 2 portion of t

200、he study is recruiting subjects.https:/clinicaltrials.gov/ct2/show/NCT02432378A Phase 2 study of advanced recurrent ovarian cancer using cisplatin,pembrolizumab,plus Ampligen;up to 45 patients to be enrolled;enrollment has commenced,andnumerous patients have commenced treatment.In April 2024,researc

201、hers released topline data that saw an Objective Response Rate(ORR”)of 45%in platinum-sensitivesubjects with recurrent ovarian cancer.ORR includes complete response(CR”)and partial response(PR”)to treatment.There was a total Clinical Benefit Rate(CBR”)of 55%when including patients who experienced st

202、able disease(SD”).Researchers also reported a median Progression-Free Survival(PFS”)of 7.8 months.Based onthese results and other research suggesting a similar effect in other solid tumor types,AIM sees an Ampligen combination therapy as having potential across multipletypes of cancers.Additional cl

203、inical studies are underway and planned in many of these types of tumors to further confirm these effects.”https:/clinicaltrials.gov/ct2/show/NCT03734692.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

204、Ampligen as acombination cancer therapy with checkpoint blockade inhibitors(e.g.pembrolizumab,nivolumab).We believe that the above positive data makes this patent have heightenedpotential.Similar patents are pending in other countries.Stage 4 Metastatic Triple Negative Breast Cancer-Phase 1 study of

205、 metastatic triple-negative breast cancer using chemokine modulation therapy,including Ampligen andpembrolizumab.Eight patients were enrolled and 6 patients were evaluable.https:/www.clinicaltrials.gov/ct2/show/NCT03599453.The key findings announced first in April 2022,and later published in Novembe

206、r 2023,included:The pre-determined primary endpoint of efficacy was met(increase in CD8 in TME).Uniform 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 andGZMB/FOXP3(5.7-fold;p=0.036,and 7.6-fold;p=0.024 respectively),

207、thus successfully meeting the pre-determined primary endpoint in the study(increase in CD8 inTME).In 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 attractantsCCL22 or CXCL12 were not enhanced.Three patient

208、s had stable disease lasting 2.4,2.5 and 3.8 months,as of data cut off September 1,2021.An additional patient(non-evaluable)had a partial response(breast tumor autoamputation)with massive tumor necrosis in the post-CKM biopsy.Stage 4 Colorectal Cancer Metastatic to the Liver-Phase 2a study of Amplig

209、en 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 keyfindings announced in April 2022 included:

210、The studys primary endpoint was met,evidenced by increased CD8a expression post-treatment(p=0.046).Saw increase in the CD8a/CD4(p=0.03),CD8a/FOXP3(p0.01)and GZMB/FOXP3(p0.01)ratios.The expression of CTL-attracting chemokines CCL5(p=0.08),CXCL9(p=0.05),and CXCL10(p=0.06)were increased,while expressio

211、n of the Treg/MDSC attractantCXCL12(p=0.07)was decreased post-treatment.Median 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.No tumor responses were seen.The treatment was well tolerated.Of all enrolled patients(N=19),adverse events were noted in 74%of patients,wi

212、th the most commonbeing fatigue(58%).Grade 3 or higher adverse events were rare(5%).Early-Stage Prostate Cancer-Phase 2 study investigating the effectiveness and safety of aspirin and Ampligen with or without interferon-alpha 2b(Intron A)compared to nodrug treatments in a randomized three-arm study

213、of patients with prostate cancer before undergoing radical prostatectomy.Patient enrollment has been initiated in this studydesigned for up to 45 patients.The study is temporarily suspended due to the Merck discontinuation of Intron-A production.Roswell Park has had a Type-C meeting with theFDA and

214、is currently performing the necessary experiments to replace Intron-A with a generic alpha-interferon.We expect this trial to resume in the near future.https:/clinicaltrials.gov/ct2/show/NCT03899987.13 Early-Stage Triple Negative Breast Cancer-The objective of this Phase 1 study is to evaluate the s

215、afety and tolerability of a combination of Ampligen,celecoxib with or withoutIntron A,when given along with chemotherapy in patients with early-stage triple negative breast cancer.The now completed(as of September 2022)topline results from the studyconfirm the positive findings that were previously

216、presented at the 2022 Society for Immunotherapy of Cancer(SITC)37th Annual Meeting in a poster presentation titled Safetyand efficacy of de-escalated neoadjuvant chemoimmunotherapy of triple negative breast cancer(TNBC)using chemokine-modulating regimen(rintatolimod,IFN-2b,celecoxib).The primary end

217、point of the study was safety and tolerability.The results demonstrated that treatment was well-tolerated with mostly grade 1 or 2 treatment-related adverse events(TRAEs)without dose-limiting toxicities(DLTs)or delayed or immune-related toxicities.DLT was defined as grade 3 or higher toxicities with

218、in the first 3 weeks.Secondaryendpoints included pCR rate where 5/9(56%)of patients attained pCR and 1 more patient attained ypTmic.Tumor and blood biomarkers were also analyzed in exploratory studies.https:/clinicaltrials.gov/ct2/show/NCT04081389.Refractory Melanoma Roswell Park Comprehensive Cance

219、r Center(Roswell Park”),in a clinical trial fully funded by the National Cancer Institute(NCI),has commenced patientenrollment in its Phase 2 study in subjects with primary PD-1/PD-L1 resistant melanoma.The Phase 2 study will evaluate type-1 polarized dendritic cell(DC1)vaccine incombination with tu

220、mor-selective chemokine modulation(CKM”)comprised of Interferon alpha 2b,Ampligen(rintatolimod)and Celecoxib.Up to 24 patients are to be enrolled.The study was temporarily suspended due to the Merck discontinuation of Intron-A production but has since resumed recruitment(See:https:/www.clinicaltrial

221、s.gov/show/NCT04093323).Metastatic or Unresectable Triple Negative Breast Cancer This phase 1/2a trial tests the safety,side effects,and best dose of chemokine modulation therapy(CKM)(rintatolimod,celecoxib,and interferon alpha 2b)in combination with pembrolizumab for the treatment of patients with

222、triple negative breast cancer that has spread from where itfirst started(primary site)to other places in the body(metastatic)or that cannot be removed by surgery(unresectable).The study is recruiting subjects.(See:https:/clinicaltrials.gov/study/NCT05756166).Additional Progress and Analysis Related

223、to Pancreatic Cancer In January 2017,the EAP established under our agreement with myTomorrows to enable access of Ampligen to ME/CFS patients was extended to pancreatic cancerpatients beginning in the Netherlands.myTomorrows is our exclusive service provider in Europe and Turkey and will manage all

224、EAP activities relating to the pancreatic cancerextension of the program.In February 2018,the agreement with myTomorrows was extended to cover Canada to treat pancreatic cancer patients,pending government approval.There have been no physician requests to date that would cause the program to move for

225、ward with the approval process.A total of 42 pancreatic cancer patients initially received treatment with Ampligen immuno-oncology therapy under the EAP program at Erasmus MC in the Netherlands,with more than 50 patients ultimately receiving treatment.Prof.C.H.J.van Eijck,MD,was the lead investigato

226、r.In March 2024,the team at Erasmus MC published a thorough dataanalysis in an article titled Rintatolimod in Advanced Pancreatic Cancer enhances Anti-Tumor Immunity through Dendritic Cell-Mediated T Cell Responses”in the journal ClinicalCancer Research.The positive clinical findings relate to chang

227、es in the tumor microenvironment after Ampligen use.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 processto provide all the mate

228、rials and information required to achieve fast-track status.A manuscript titled Rintatolimod in Advanced Pancreatic Cancer enhances Anti-Tumor Immunity through Dendritic Cell-Mediated T Cell Responses,”was published inthe print version of the journal Clinical Cancer Research in August 2024.Researche

229、rs at the Erasmus University Medical Center(Erasmus MC”)found that Ampligen treatment inpancreatic cancer patients enhances peripheral immune activity at the transcriptomic and proteomic levels,particularly involving type 1 conventional dendritic cells(cDC1s)and Tcells.Post-Ampligen,the increased pe

230、ripheral abundance of BTLA+XCR1+cDC1s and CD4+SELL+T cells correlated with improved clinical outcomes.Patients with stable diseaseexhibited pronounced overexpression of genes related to DC and T cell activation.Notably,the expression of immune checkpoints PD-L1 and PD-L2 decreased post-Ampligenacros

231、s all patients.14 Additionally:In December 2020,the FDA granted Ampligen Orphan Drug Designation status for the treatment of pancreatic cancer.The Orphan Drug Designation program providesorphan status to drugs and biologics which are defined as those intended for the treatment,prevention or diagnosi

232、s of a rare disease or condition,which is one thataffects less than 200,000 persons in the United States or meets cost recovery provisions of the act.The status helps incentivize the treatment of therapies to treat unmetmedical needs by providing a company with seven years of exclusivity rights once

233、 a drug reaches market.In February 2021,our subsidiary,NV Hemispherx Biopharma Europe(now AIM ImmunoTech Europe N.V./S.A.),received formal notification from the EuropeanCommission(EC”)granting Orphan Medicinal Product Designation for Ampligen as a treatment for pancreatic cancer.Orphan products,once

234、 commercially approved inthe European Union(EU”),receive benefits including up to ten years of protection from market competition from similar medicines with similar active component andindication for use that are not shown to be clinically superior.In June 2021,Ampligen was featured in a publicatio

235、n containing state-of-the-art methodologies in the peer-reviewed medical journal Cancers as a potential treatmentoption for cancer patients who are infected with SARS-CoV-2.The studys authors stated that Ampligen has the potential to reduce the severity of the deadly respiratory diseaseCOVID-19.Acco

236、rding to laboratory data presented in the publication,Rintatolimod Ampligen activated the innate and the adaptive immune systems by activating a cascade ofactions in human pancreatic cancer cells”,including:Stimulation of interferon regulatory factors and activation of the interferon signaling pathw

237、ay,Production of immunomodulatory activity and Induction of the expression of MHC class I and II histocompatibility The full journal article is titled:Rintatolimod Induces Antiviral Activities in Human Pancreatic Cancer Cells:Opening for an Anti-COVID-19 Opportunity in CancerPatients?”Cancers is a p

238、eer-reviewed,open access journal of oncology published semimonthly online by MDPI.The studys authors include Prof.C.H.J.van Eijck,MD,PhD,thelead investigator at Erasmus Medical Center in the Netherlands.In October 2021,we and Amarex submitted an IND application with the FDA for a planned Phase 2 stu

239、dy of Ampligen as a therapy for locally advanced or metastatic late-stage pancreatic cancer.In December 2021,the FDA responded with a Clinical Hold on the proposed study.We submitted our response to the FDA in February 2022.In March2022,we received notification from the FDA that the Clinical Hold wa

240、s released and cleared,meaning that we are now able to proceed with the study specifically to treat locallyadvanced pancreatic cancer patients.In August 2022,we received IRB approval of the trial protocol and so announced the trials commencement.A Type D meeting package seeking the FDA guidance on e

241、xpansion of inclusion criteria and treatment arms to be included was submitted to the FDA.We subsequentlyamended the study protocol.AIM recently made a business decision to place screening/enrollment on hold and suspend the study.Positive data was published in March 2022 in a manuscript titled,Rinta

242、tolimod(Ampligen)enhances numbers of peripheral B cells and is associated with longersurvival 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 Panc

243、reatic Cancer.In the single-center,named-patient program,patients with locally advanced pancreatic cancer(LAPC)or metastaticdisease 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.Thestud

244、ys primary endpoints were the Systemic Immune-Inflammation Index(SIII),the Neutrophils to Lymphocyte Ratio(NLR),and absolute counts of 18 different populations ofcirculating immune cells as measured by flow cytometry.Secondary endpoints were progression-free survival(PFS)and overall survival(OS).The

245、 median overall survival in theAmpligen group was 19 months,compared to a historical control group and subgroup(7.5 and 12.5,respectively)that did not receive Ampligen.Also in March 2022,we announced that study data evaluating the direct effects of Ampligen on human pancreatic ductal adenocarcinoma(

246、PDAC)cells was accepted forpresentation at the 15th Annual International Hepato-Pancreato-Biliary Association World Congress in New York,NY.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.Th

247、e proliferation and migration effects were examined using in-vitroassays 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 demons

248、trated Ampligen decreased the proliferation and migration ability of CFPAC-1 cells.In addition,it decreased theproliferation 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 highlyexpressed in CFPAC-1 cell

249、s,low expressed in MIAPaCa-2 and not expressed in PANC-1.Gene expression analysis revealed the upregulation of interferon-related genes,chemokines,interleukins and cell cycle regulatory genes.The heterogeneity of TLR3 expression was confirmed in human PDAC samples.Based on these results,treatingpanc

250、reatic cancer with Ampligen may have a direct anti-tumor effect in pancreatic cancer cells expressing TLR-3.15 Ampligen as a Potential Antiviral Following the SARS-CoV-1 outbreak in 2002-03,Ampligen exhibited excellent antiviral properties and protective survival effect in NIH-contracted studies of

251、SARS-CoV-1-infected mice,which is very similar to SARS-CoV-2,the novel virus that causes COVID-19.The Barnard 2006 study(https:/ that Ampligen reduced virus lung levels to below detectable limits.The Day 2009 study(https:/ that,instead of 100%mortality,there was 100%protective survivalusing Ampligen

252、.We compared key transcription regulatory sequences of SARS-CoV-1 to SARS-CoV-2 and found significant similarities,suggesting highly probable extension of theantiviral effects of Ampligen in the earlier NIH-contracted SARS experiments to COVID-19.The SARS-CoV-2 virus which causes COVID-19 shares imp

253、ortant genomic andpathogenic similarities with SARS-CoV-1(hence its name).Since Ampligen has shown antiviral activity against more distantly related coronaviruses,there was a reasonableprobability that the antiviral effects of Ampligen against SARS-CoV-1 will likely extend to SARS-CoV-2,and as discu

254、ssed below,recently,Ampligen has demonstrated ex vivoantiviral activity against SARS-CoV-2.We believe that this creates a compelling case for clinical trials to evaluate Ampligen as a potential tool in the fight against COVID-19.Since the late 2019 outbreak of SARS-CoV-2,we have been actively engage

255、d in determining whether Ampligen could be an effective treatment for this virus or could bepart of a vaccine.We believe that Ampligen has the potential to be both an early-onset treatment for and prophylaxis against SARS-CoV-2.We believe that prior studies ofAmpligen in SARS-CoV-1 animal experiment

256、ation may predict similar protective effects against the new virus.In February 2020,we filed three provisional patent applications related to Ampligen in our efforts toward joining the global health community in the fight against thedeadly coronavirus(See:https:/ three provisional patent application

257、s include:1)Ampligen as a therapy for the coronavirus;2)Ampligen as part of a proposed intranasal universalcoronavirus vaccine that combines Ampligen with inactivated coronavirus,conveying immunity and cross-protection and;3)a high-volume manufacturing process for Ampligen.Under the Patent Cooperati

258、on Treaty of 1970,which provides international protections for patents,these three provisional patent applications were converted into twointernational patent applications based on the date of their filings.In August 2020,we contracted Amarex to act as our Clinical Research Organization and provide

259、regulatory support with regard to a possible clinical trial testingAmpligens potential as a COVID-19 prophylaxis via intranasal delivery.Beginning in April 2020,we entered into confidentiality and non-disclosure agreements with numerous companies for the potential outsourcing of the production ofpol

260、ymer,enzyme,placebo as well as Ampligen.In 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-19infections.This clinical trial,sponsored by Roswell Park in collaboration with us,will test the s

261、afety of this combination regimen in patients with cancer and COVID-19,and theextent 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 willenroll up to 44 patients in two stages.Phase

262、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

263、 willreceive best available care.We 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 beenenrolled and treated.This study was amended to add 20 patients,with 10 randomized to receive a single dose of Amplige

264、n and 10 patients to receive current best therapies.(Seeclinicaltrials.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 criter

265、ia to include other diseases lethal to immuno-compromised cancer patients,such as influenza.Accordingly,thestudy is temporarily suspended while seeking said approvals.We also entered into a specialized services agreement with Utah State University and have supplied Ampligen to support the University

266、s Institute for Viral Research inits research into SARS-CoV-2.The Utah State results show that Ampligen was able to decrease SARS-CoV-2 infectious viral yields by 90%at clinically achievable intranasalAmpligen dosage levels.In October 2020,we received IRB approval for the expansion of the AMP-511 Ex

267、panded Access Program clinical trial for ME/CFS to include patients previously diagnosedwith SARS-CoV-2,but who still demonstrate chronic fatigue-like symptoms.Patients in the trial are treated with our flagship pipeline drug Ampligen.In January 2021,wecommenced with the treatment of the first previ

268、ously diagnosed COVID-19 patient with long-COVID symptoms(i.e.,Long Hauler)also known as Post-COVID Conditions in theAMP-511 study.Enrollment of post-COVID patients continues in the study.16 In January 2021,we entered into a Sponsor Agreement with CHDR to manage a Phase 1 randomized,double-blind stu

269、dy to evaluate the safety and activity of repeatedintranasal administration of Ampligen.AIM funded and sponsored the study.This study was designed to assess the safety,tolerability and biological activity of repeatedadministration of Ampligen intranasally.A total of 40 healthy subjects received eith

270、er Ampligen or a placebo in the trial,with the Ampligen given at four escalating dosages acrossfour cohorts,to a maximum level of 1,250 micrograms.The study was completed,and the Final Safety Report reported no Serious or Severe Adverse Events at any dosage level.We believe that the trial is a criti

271、cal 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,we filed two COVID-19-related provisional patent applications in the third quarter of

272、 2021.In August,we filed an application for Ampligen as both anintranasal and an intravenous therapy for what we describe as Post-COVID conditions.The people suffering from Post-COVID conditions,including some young adults,can beafflicted with severe difficulties in concentrating;serious memory prob

273、lems;and the inability to live an active lifestyle,to work and even to perform everyday tasks.Early data hasdemonstrated that patients with symptoms of Post-COVID conditions being treated with Ampligen in the ongoing AMP-511 Expanded Access Program have reportedimprovements in fatigue symptoms.Simil

274、arly,in ME/CFS,data supports the claim that Ampligen improves fatigue symptoms.Then in September 2022,we filed a patent applicationfor Ampligen as a potential early-onset intranasal therapy designed to enhance and expand infection-induced immunity,epitope spreading,cross-reactivity and cross-protect

275、ion inpatients exposed to a wide range of RNA respiratory viruses,such as influenza,Rhinoviruses and SARS-CoV-2.In addition to securing these two provisional patent applications,we also moved forward with proposed studies in these areas and with Pre-Investigational New DrugApplications in September

276、2021.One pre-IND was for a Phase 2,two-arm,randomized,double-blind,placebo-controlled,multicenter study to evaluate the efficacy and safety ofAmpligen in patients experiencing Post-COVID conditions(originally referred to as Post-COVID Cognitive Dysfunction(PCCD)and has been revised to Post-COVID con

277、ditions).Since the late 2019 outbreak of SARS-CoV-2,we have been actively engaged in determining whether Ampligen could be an effective treatment for this virus or could bepart of a vaccine.We believe that Ampligen has the potential to be both an early-onset treatment for and prophylaxis against SAR

278、S-CoV-2.We believe that prior studies ofAmpligen in SARS-CoV-1 animal experimentation may predict similar protective effects against the new virus.Ampligen as a Treatment for ME/CFS and Post-COVID Conditions In July 2023,we enrolled and dosed the first patient in our Phase 2 study evaluating Amplige

279、n as a potential therapeutic for people with post-COVID conditions(AMP-518”).We announced in August 2023 that the study had met the planned enrollment of 80 subjects ages 18 to 60 years who have been randomized 1:1 to receive twice-weeklyintravenous infusions of Ampligen or placebo for 12 weeks,with

280、 a follow-up phase of two weeks.All patients have completed the study and topline data was reported in February2024.In January 2025,we announced that the final Clinical Study results from AMP-518 had been posted to ClinicalTrials.gov.The results support our belief in Ampligen as apotential therapeut

281、ic for people with the moderate-to-severe Post-COVID condition of fatigue,and that this would be the likely subject population for AIMs planned follow-upclinical trial.Study subjects with Long COVID were,on average,able to walk farther in a Six-Minute Walk Test(6MWT”)when compared to subjects who re

282、ceived a placebo.The6MWT measured the distance a subject was able to walk in six minutes as a baseline and then again at 13 weeks.A clear signal of significant potential(p 0.02,two-tailed T-test)was observed in Ampligen-treated subjects with a baseline 6MWT less than 205 meters,who saw a mean improv

283、ement of 139 meters,compared to a mean improvement of 91meters in the corresponding part of the group who received the placebo.AIM therefore believes that any future trial design should focus on Ampligens therapeutic potential forsubjects whose Long COVID-related fatigue can be categorized as modera

284、te or worse.Myalgic Encephalomyelitis/Chronic Fatigue Syndrome(ME/CFS),also known as Chronic Fatigue Immune Dysfunction Syndrome(CFIDS”)and Chronic FatigueSyndrome(CFS),is a serious and debilitating chronic illness and a major public health problem.ME/CFS is recognized by both the government and pri

285、vate sector as a significantunmet medical need,including the U.S.National Institutes of Health(NIH”),FDA and the CDC.Many severe ME/CFS patients become completely disabled or totally bedridden and are afflicted with severe pain and mental confusion even at rest.ME/CFS ischaracterized by incapacitati

286、ng fatigue with profound exhaustion and extremely poor stamina,sleep difficulties and problems with concentration and short-term memory.It is alsoaccompanied by flu-like symptoms,pain in the joints and muscles,tender lymph nodes,sore throat and new headaches.A distinctive characteristic of the illne

287、ss is a worsening ofsymptoms following physical or mental exertion,which do not subside with rest.17 The high number of younger people being hospitalized for COVID-19 suggests considerable numbers of people in the prime of their lives may have a COVID-inducedME/CFS-like illness in their future.Accor

288、ding to a 2016 journal article,the estimated annual cost of lost productivity related to ME/CFS was$9-37 billion in the United States,andfor direct medical costs it was$9-14 billion.In June of 2020,we filed a provisional patent application for,among other discoveries,the use of Ampligen as a potenti

289、al early-onset therapy for the treatment of COVID-19-induced chronic fatigue.Many survivors of the first SARS-CoV-1 epidemic in 2003 continued to report chronic fatigue,difficulty sleeping and shortness of breath months after recovering from theacute illness.After one year,17%of patients had not ret

290、urned to work and 9%more had not returned to their pre-SARS work levels,”according to Simmaron Research.Now thereis increasing evidence that patients with COVID-19 can develop a similar,ME/CFS-like illness.These patients are commonly referred to as Long Haulers.”In October 2020,we received IRB appro

291、val for the expansion of the AMP-511 Expanded Access Program clinical trial for ME/CFS to include patients previously diagnosedwith SARS-CoV-2 following clearance of the virus,but who still demonstrate chronic fatigue-like symptoms.For more information on our AMP-511 Expanded Access Program,please s

292、ee OUR PRODUCTS:Ampligen”above.In November 2020,we announced the publication of statistically significant data detailing how Ampligen could have a considerable positive impact on people living withME/CFS when administered in the early stages of the disease.The data were published in PLOS ONE,a peer-

293、reviewed open access scientific journal published by the PublicLibrary of Science.AIM researchers found that the TLR3 agonist Ampligen substantially improved physical performance in a subset of ME/CFS patients.As noted above in Overview;General;Ampligen as a treatment for ME/CFS,we have long been fo

294、cused on seeking the FDAs approval for the use of Ampligen to treatME/CFS.In fact,in February 2013,we received a CRL from the FDA for our Ampligen NDA for ME/CFS.We believe Phase 3 results provided in the NDA were positive.The CRLindicated that we should conduct at least one additional clinical tria

295、l,complete various nonclinical studies and perform a number of data analyses.While 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 August2016,we received approval of an NDA from ANMAT for commercial sal

296、e of Ampligen in the Argentine Republic for the treatment of severe CFS.In September 2019,we receivedclearance from the FDA to ship Ampligen to Argentina for the commercial launch and subsequent sales.On June 10,2020,we received import clearance from ANMAT to importthe first shipment of commercial g

297、rade vials of Ampligen into Argentina.The next steps in the commercial launch of Ampligen include ANMAT conducting a final inspection of theproduct and release tests before granting final approval to begin commercial sales.This testing and approval process is currently delayed due to ANMATs internal

298、 processes.Once final approval by ANMAT is obtained,we will begin distributing Ampligen in Argentina.We plan on a comprehensive follow-up with the FDA regarding the use of Ampligen as a treatment for ME/CFS.We have learned a great deal since the FDAs CRL andplan to adjust our approach to concentrate

299、 on specific ME/CFS symptoms.Responses to the CRL and a proposed confirmatory trial are being worked on now by our R&D teamand consultants.Other Diseases In Europe,the EMA has approved the Orphan Medicinal Products Designation for Ampligen as a potential treatment of Ebola virus disease and for Alfe

300、ron N Injection asa potential treatment of MERS.We concluded our series of collaborations designed to determine the potential effectiveness of Ampligen and Alferon N Injection as potential preventive and/ortherapeutic treatments for Ebola-related disorders.Although we believe that the threat of both

301、 MERS and Ebola globally may reemerge in the future,it appears that the spread ofthese disorders has diminished.In April 2021,we entered into an MTA with the University of Cagliari Dipartimento di Scienze della Vita e dellAmbiente(UNICA”),an educational institution,under thelaws of Italy,located in

302、Monserrato(Cagliari),Italy.The MTA relates to the research and development of the effects of Ampligen and its ability to induce interferon production inseveral cell lines,and also on the ability of the Ebola virus protein VP35 to bind to viral dsRNA and impede interferons upregulation and activity,a

303、nd on Ampligens ability toreverse VP35 inhibition of interferon production in biological systems.The data analysis was published in the peer-reviewed journal Antiviral Research,in a manuscript titledEbola virus disease:In vivo protection provided by the PAMP restricted TLR3 agonist rintatolimod and

304、its mechanism of action.”We believe that the analysis supports a dualmechanism of action when Ampligen is used as a prophylactic therapy against Ebola Virus Disease.In May 2021,we filed a U.S.Provisional Patent Application for Ampligen as a potential therapeutic to possibly slow,halt,or reverse the

305、progression of Alzheimersdisease.18 In November 2022,we received notice that the FDA had granted Orphan Drug Designation to Ampligen for the treatment of Ebola virus disease.In October 2024,we were granted U.S.patent No.12,102,649,covering both compositions and methods comprising Ampligen in the tre

306、atment of endometriosis,a painfulchronic condition in which tissue similar to the lining of the uterus grows outside the uterus,causing severe pelvic pain and making it difficult or impossible to become pregnant.The patented method involves the administration of a therapeutically effective amount of

307、 a pharmaceutical composition containing our proprietary double-stranded RNA products.The versatile administration options offer flexibility for patient-specific needs and care.The patent also covers treatments targeting recurrent endometriosis and includes optionsfor co-administration with interfer

308、ons,including well-known types such as alpha and beta interferons.We announced in February 2025 our intention to pursue a study of a potential avian influenza combination therapy of Ampligen and AstraZenecas FluMist,a nasalspray vaccine that helps prevent seasonal influenza.The new proposed clinical

309、 trial would expand upon previous Company-sponsored clinical research at the University ofAlabama-Birmingham(UAB”),which indicated that intranasal delivery of Ampligen after the intranasal delivery of the FluMist seasonal influenza vaccine increased the immuneresponse to seasonal variants in the vac

310、cine by greater than four-fold and induced cross-reactive secretory Immunoglobulin A against highly pathogenic avian influenza virusstrains H5N1,H7N9 and H7N3.We are seeking collaborative grants from government and industry to defray the cost of the study.We believe that pre-clinical and clinical wo

311、rk todate combined with the ever-growing threat of Avian influenza strongly supports our decision to move forward with this second Ampligen and FluMist study in humans.MANUFACTURING ANMAT in Argentina approved Ampligen for commercial distribution for the treatment of CFS in 2016.Shipment of the drug

312、 product to Argentina was initiated in 2018 tocomplete the release testing by ANMAT needed for commercial distribution.In September 2019,we received clearance from the FDA to ship Ampligen to Argentina for thecommercial launch and subsequent sales.In June 2020,we received import clearance from ANMAT

313、 to import the first shipment of commercial grade vials of Ampligen intoArgentina.We are currently collaborating with GP Pharm on the commercial launch of Ampligen in Argentina(See Our Products;Ampligen”above).Following our approval in Argentina,in 2017 we engaged Jubilant HollisterStier(Jubilant”)t

314、o be our authorized CMO for Ampligen.Two lots of Ampligen consisting ofmore than 16,000 units were manufactured and released in 2018;these lots have been designated for human use in the United States in the cost recovery CFS program and forexpanded oncology clinical trials.The production of addition

315、al polymer(Ampligen intermediates)took place in 2019 at our New Brunswick facility.Additionally,Jubilantmanufactured three more lots of Ampligen in December 2019,January 2020 and December 2023.In addition,we have supplied GP Pharm with the Ampligen required for testing andANMAT release under the agr

316、eement that GP Pharm would be the eventual distributor in Argentina.In December 2020,we added Pii as a Fill&Finish”provider to enhance our capacity to produce Ampligen.This addition amplifies our manufacturing capability byproviding redundancy and cost savings.The contracts augment our existing fill

317、 and finish capacity.We are prepared to initiate the production of additional Ampligen when and ifneeded.In 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 NewJersey Bioscience Center(NJBC),pr

318、imarily consisting of two separate laboratory suites.The lease commenced on July 1,2022,and runs through August 31,2027,but can beextended for an additional five-year period.The facility is AIMs operations,research and development center.Our business plan calls for the utilization of one or more CMO

319、s 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,on December 5,2022,we entered into a Master ServiceAgreement and a Qualit

320、y Agreement with Sterling Pharma Solutions(Sterling”)for the manufacture of our Poly I and Poly C12U polynucleotides and transfer of associated testmethods at Sterlings Dudley,UK location to produce the polymer precursors to manufacture the drug Ampligen.We are utilizing Sterlings expertise to refin

321、e our approach topolymer production;the validation of the polymer production process with Sterling is ongoing.In March 2023,we submitted a purchase order for a total of$1,432,257 tomanufacture additional lots of Ampligen at Jubilant.An additional lot was manufactured by Jubilant in December 2023.19

322、Our second product,Alferon N Injection,is approved by the FDA for commercial sales in the United States for the treatment of genital warts.It is also approved byANMAT in Argentina for commercial sales for the treatment of genital warts and in patients who are refractory to treatment with recombinant

323、 interferons.Commercial sales ofAlferon N Injection in the United States will not resume until new batches of commercial filled and finished product are produced and released by the FDA.We will need the FDAsapproval to release commercial product once we have identified our new manufacturing approach

324、 and submitted satisfactory stability and quality release data.Currently,we are notmanufacturing Alferon N Injection and there is no definitive timetable to resume production.LICENSING/COLLABORATIONS/JOINT VENTURES To enable potential availability of Ampligen to patients on a worldwide basis,we have

325、 embarked on a strategy to license the product and/or to collaborate and/or create ajoint venture with companies that have the demonstrated capabilities and commitment to successfully gain approval and commercialize Ampligen in their respective globalterritories of the world.Ideal partners would hav

326、e the following characteristics:well-established global and regional experience and coverage;robust commercial infrastructure;astrong track record of successful development and registration of in-licensed products;and a therapeutic area fit(e.g.,ME/CFS,immuno-oncology).MARKETING/DISTRIBUTION In May

327、2016,we entered into a five-year,exclusive Renewed Sales,Marketing,Distribution and Supply Agreement(the Agreement”)with GP Pharm.Under thisAgreement,GP Pharm was responsible for gaining regulatory approval in Argentina for Ampligen to treat severe CFS in Argentina and for commercializing Ampligen f

328、or thisindication in Argentina.We granted GP Pharm the right to expand rights to sell this experimental therapeutic into other Latin America countries based upon GP Pharm achievingcertain performance milestones.We also granted GP Pharm an option to market Alferon N Injection in Argentina and other L

329、atin America countries(See Our Products;Ampligen”above).The GP Pharm contract was extended in May 2021 with an end date of May 24,2024.While we are in discussions with GP Pharm to extend the agreement,we are also opento the possibility of looking for a new partner.In August 2021,ANMAT granted a five

330、-year extension to a previous approval to sell and distribute Ampligen to treat severe CFS inArgentina.This extends the approval until 2026.In May 2016,we entered into a five-year agreement(the Impatients Agreement”)with Impatients,N.V.(myTomorrows”),a Netherlands-based company,for thecommencement a

331、nd management of an EAP in Europe and Turkey(the Territory”)related to ME/CFS.Pursuant to the agreement,myTomorrows,as our exclusive service providerand distributor in the Territory,is performing EAP activities.These activities will be directed to(a)the education of physicians and patients regarding

332、 the possibility of earlyaccess to innovative medical treatments not yet the subject of a Marketing Authorization(regulatory approval)through named-patient use,compassionate use,expanded accessand hospital exemption,(b)patient and physician outreach related to a patient-physician platform,(c)the sec

333、uring of Early Access Approvals(exemptions and/or waivers requiredby regulatory authorities for medical treatments prior to Marketing Authorization)for the use of such treatments,(d)the distribution and sale of such treatments pursuant to suchEarly Access Approvals,(e)pharmacovigilance(drug safety)activities and/or(f)the collection of data such as patient-reported outcomes,doctor-reported experien