Aim Immunotech Inc. · AMEX:AIM
Aim Immunotech — Investor Presentation (February 2020)
51 slides from Aim Immunotech's investor presentation, Feb 18, 2020
Slide 1: Ampligen As An Antiviral
S AIM ImmunoTech Ampligen As An Antiviral February 2020
Slide 2: Forward Looking Statements
Forward Looking Statements This corporate presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate" and similar expressions (as well as other words or expressions referencin
Slide 3: Table of Contents
Table of Contents [section ice Overview 4 Ampligen’s Safety Profile 7 Ampligen and Alphaviruses 16 Ampligen and Ebola 22 Ampligen and HIV 39 A Summary of Antiviral Activity of Ampligen, Including Other Viruses 43 The Synergistic Activities of Ampligen 47
Slide 4: Overview
Overview
Slide 5: Ampligen as a Therapy for Viral Diseases
Ampligen as a Therapy for Viral Diseases = Ampligen is the only known specific TLR3 agonist based on synthetic double-stranded RNA (dsRNA) with a well-developed , v intravenous, intraperitoneal and intranasal safety profile a Poly 1:C12U i Ampuigene 2009 5 g r , ii & Injectable Form Stability: 7 yea
Slide 6: Ampligen is a Broad-Spectrum Antiviral
Ampligen is a Broad-Spectrum Antiviral e Ampligen has demonstrated antiviral activity against a broad spectrum of viruses, including Herpes viruses, Alphaviruses Coronaviruses and Filoviruses ° Ampligen has shown a survival benefit in Alphaviruses, Coronaviruses, Filoviruses and Paramyxoviruses in a
Slide 7: Ampligen's Safety Profile
Ampligen’s Safety Profile
Slide 8: Overview of Ampligen's Safety Profile
Overview of Ampligen’s Safety Profile e e e Administered by intravenous (IV) infusion over 30 to 60 minutes Generally well-tolerated with ~100,000 doses administered Extensive exposure to drug (>600 patient treatment years), including two placebo-controlled pivotal studies Favorable safety profile o
Slide 9: Clinical Safety Profile Related to Molecular Structure of Ampligen
Clinical Safety Profile Related to Molecular Structure of Ampligen (Poly I: Poly C,,U) Mis-paired regions of base pair hydrogen bonding accelerate chain hydrolysis while preserving biological activity Decreased toxicity and improved safety compared to the absence of mis- pairing No development of an
Slide 10: No Significant Difference in Number or Relationship of SAEs to Study Drug
AMP 502 & AMP 516: No Significant Difference in the Number or Relationship of SAEs to Study Drug as Determined by Blinded Investigators Relationship Number of Serious Adverse Events to Study Drug Ampligen Placebo Not Related 16 16 Remote 4 3 Possible 2 2 Probable 0 1 Definite 0 ) Total 22 22 Note: D
Slide 11: All SAEs in the Ampligen CFS Program
All SAEs in the Ampligen CFS Program — No Significant Difference’ Between Ampligen and Placebo Groups in Relationship of SAEs to Study Drug All CFS Studies? Ampligen Group Placebo Group ™@ 1=None © 2=Remote ™ 3=Possible @ 4=Probable @ 5=Definite Percent of Patients 7.7% <—— withSAEs -——> 8.6% ‘Fishe
Slide 12: Safety Findings from Two Well-Controlled Pivotal Studies
Safety Findings from Two Well-Controlled Pivotal Studies (502 and 516) e e e No Evidence of new Autoimmune Disease No Evidence for Induction of Autoantibodies No Increase of Treatment Emergent Depression or Suicide Attempts No Increase Incidence of Cancer 5.6 % increase in SGOT (AST) or SGPT (ALT) >
Slide 13: Important Differences Between Ampligen and Poly I:Poly C / Poly ICLC
Important Differences Between Poly I:Poly C,,U (Ampligen®) and Poly | : Poly C / Poly ICLC * Ampligen is a selective TLR-3 agonist (i.e. it does not activate the TLR-3 independent pathways using RNA helicase sensors such as MDAS or retinoic acid-inducible protein | (RIG-1) « Ampligen does not induce
Slide 14: Poly I:Poly C Induces High Levels of TNF-a
Poly | : Poly C Induces High Levels of TNF-a; Poly | : Poly C,,U Does Not 10000 4 1000 4 100 4 TNF (pg/ml) 104 1 T T T T ; 0 poly poly poly Fe, hey 1Oi,U TNF-a expression was measured in the supernatant of dendritic cells (DCs) cultured overnight with the 3 TLR agonists. Data represent mean +SEM fro
Slide 15: Why is Induction of TNF-a a Problem for Poly I:Poly C
Why is the Induction of TNF-a by Poly | : Poly C a Problem for Poly |: Poly C / Poly ICLC? e TNF-a is a tumor promoter e TNF-a has been linked to the carcinogenic effects of: ° Nickel compound and lung cancer (Current Cancer Drug Targets 2009; 9:81-90) ° Helicobacter pylori and stomach cancer (BBRC
Slide 16: Ampligen and Alphaviruses
Ampligen and Alphaviruses
Slide 17: Western Equine Encephalitis Virus: Independent Studies Show Increased Survival
Western Equine Encephalitis Virus: Independent Studies Show Ampligen Increases Survival « Ampligen consistently increased survival 2-5 fold over placebo controls in animal models ¢ Ampligen administered intraperitoneally (ip) protected against WEEV ¢ Intranasally administered Ampligen may be importa
Slide 18: Percent Survival with Ampligen Treatment of WEEV Infection
Percent Survival with Ampligen (ip) Treatment of WEEV (VR-70) Infection (ip) Compared to Placebo in Mice and Hamsters Mice Hamsters Percent Survival Percent Survival placebo favipiravr — Ampligen Julander (2007) (T-705a) Julander (2009) Institute for Antiviral Research, Utah State University _—_ “
Slide 19: Five-Fold Increase in Survival with Ampligen
Five-Fold Increase in Survival with Ampligen Treatment of WEEV (VR-70) Compared to Placebo Percent Survival 100 90 80 70 60 50 —— ee Ampligen* ~—| bas ay ae i i 1 i — 1 iT ! = 1 1 : -- 1 1 1 i] Favipiravir** Sa ~~ ~~ - Placebo 6 7 8 9 10 11 12 13 #14 Days *p<0,004; **p<0.04 (Wileaxon log-rank surviv
Slide 20: Ampligen Increased Survival of Mice and Hamsters in WEEV Models
Ampligen (ip) Increased Survival of Mice and Hamsters in WEEV (VR-70) Models Dose Dosing Schedule 7 i MST Dru Alive / Total % Survival (mg/kg) (days) (days) Julander (2007) Hamsters. Ampligen 3.2 -Ah and 2 dpi 15/15 100** 22" Placebo. 0 4h to 6 dpi 9/40 22.5: oJ. Julander (2009) Mice (C57BL/6) Ampli
Slide 21: WEEV Mouse Experiment: Ampligen and Favipiravir Dosing Schedules
WEEV Mouse Experiment: Comparison of Ampligen and Favipiravir (T-705) Dosing Schedules Daily Dose | Administration (mg/kg) Frequency * Ampligen -4 hours and 2 (Poly I: Poly d C20) m -4 hours and twice daily for 8 days Favipiravir (T-705a) 1, dpi= days post-infection 2, survival of placebo control= 2
Slide 22: Ampligen and Ebola
Ampligen and Ebola
Slide 23: Potential Benefits of Ampligen with Respect to Ebola Disorders
Potential Benefits of Ampligen with Respect to Ebola Disorders (a Risk/Benefit Analysis) qT. N Ww Uniquely addresses the primary molecular defect conveyed to the body's antiviral/immune defenses due to Ebola infection. Secondary molecular deficiencies (lack of interferon induction and viral protein
Slide 24: Potential Benefits of Ampligen with Respect to Ebola Disorders
Potential Benefits of Ampligen with Respect to Ebola Disorders (a Risk/Benefit Analysis) 4. Ampligen is a broad-spectrum antiviral (multiple classes of RNA and DNA viruses are susceptible) in animals. 5. May demonstrate efficacy against mutated Ebola which may become resistant to protein or nucleic
Slide 25: Ampligen Clinical Safety
Ampligen Clinical Safety ® Mispaired regions accelerate hydrolysis while preserving activity ® Decreased toxicity and improved safety profile ® No development of antibodies to Ampligen - In contrast to 40-60% antibody formation in poly ICLC and poly ICL patients (J. of IFN Research 3,281 (1983)] © A
Slide 26: Anti-Ebola Activity of Ampligen Confirmed at Three Independent Laboratories
Anti-Ebola Activity of Ampligen Confirmed at Three Independent Laboratories « Ampligen inhibits Ebola virus replication using human Hela cells (Rekha G. Panchal, PhD, United States Army Medical Research Institute of Infectious Diseases (USAMRIID) Frederick, MD) « Ampligen binds to Ebola VP35 and dis
Slide 27: The USAMRIID Report February 2, 2015
The USAMRIID Report February 2, 2015 The report indicates that Prophylactic Ampligen (rintatolimod) has High Activity Against the Ebola Virus in Cell Culture (Hela Cells) EC50 =~4 pg/ml Cmax (Humans) “65 pg/ml
Slide 28: Mean Ampligen Serum Levels vs. Time (Humans)
Mean Ampligen Serum Levels vs. Time (Humans) 0.08 AmpligenEC50 Against Ebola = .004 mg/ml (Hela Cells, USAMRIID 0.07 Ampligen IV Dose 0.05 Levels in Humans © 200 mg (n=10) A 400 mg (n=10) 3 700 mg (n=11) Ampligen (mg/ml) o & e 20 40 60 80 100 120 Time After Infusion (min) _— ;
Slide 29: Lethality of Ebola Virus Attributed Primarily to a Single Mechanism
The Overwhelming Lethality of Ebola Virus is Attributed Primarily to a Single Mechanism Structure of dsRNA EBOV VP35 Binding Complex Binding to dsRNA and IFN inhibition is dependent on a VP35 complex in which two \P35 molecules are paired in binding to a single RNA strand. Illustrated are the arysta
Slide 30: Ampligen Competes with dsRNA for Ebola VP35 Binding
Ampligen Competes with dsRNA for Ebola VP35 Binding with an IC50=1.1 pg/ml* 120 % of control of VP35 binding to dsRNA 01 4 10 Ampligen Concentration (ug/ml) Recent unpublished data from Dr, Enzo Tramantano (University of Cagfiari, Italy) 30
Slide 31: Presence of Functional VP35 in Ebola Infection
Presence of Functional VP35 in Ebola Infection == strand v == | viral dh [dsRNA Excess VP35 Vv iral reten — —> OO 5 Ha Available $ -O ¢ dsRNA Receptor Ebola Viral RNA ¢ T and B Cells Active IFN Antiviral Cascades q ¢ Immunity Not Enhanced Ebola Proteins Proliferate ——> Death ee e
Slide 32: Ampligen Binds to VP35 and Releases Viral dsRNA
Ampligen Binds to VP35 and Releases Viral dsRNA* ©-3—O-@- 7 hes Binding VP35 +Ampligen + meng Excess > v == | Ampligen & | Binding vp35 == | Viral dsRNA y a [Released dsRNA Receptors IFN -_— NA Vv T and B Cells Active IFN Antiviral Cascades Vv Antiviral State Enhanced Immunity Enhanced Blocks Synthe
Slide 33: Ampligen Induces a 90% Inhibition of EBOV in a Minigenome Model
Ampligen Induces a 90% Inhibition of EBOV ina Minigenome Model: Experimental Results of Dr. Sergei Nekhai, Howard University, WDC 450000 8 3 30000) 30000) soon 4 ooo 4 150000 + 100000 + Luciferase activity (arbitrary units) 50000 + 0 90% Inhibition of EBOV (25 pg/ml Ampligen) Phillip, et al. J Biol
Slide 34: Molecular Structure of Hiltonol Significantly Different Compared to Ampligen
Molecular Structure of Hiltonol (poly ICLC) is Significantly Different Compared to Ampligen (Poly | : Poly C,,U) Ampligen | DsRNA Parameter (Poly 1: Poly C. Uracil residues incorporated into Yes poly C strand Half-life Toxicity Poly L-lysine bound to No phosphodiester backbone Carboxymethylcellulose
Slide 35: Explanation of the Lack of Activity of Hiltonol in the NHP Model of Ebola
Explanation of the Lack of Activity of Hiltonol in the NHP Model of Ebola e Hiltonol [poly ICLC] is poly IC stabilized with poly L-lysine and carboxymethylcellulose (LC) in order to increase its half-life by protecting it from enzymatic attack e Both LC compounds bind to the phosphodiester “backbone
Slide 36: Anti-EBOV Activity of Ampligen Evaluated by USAMRIID in a Rodent Challenge Model
Anti-EBOV Activity of Ampligen Evaluated by USAMRIID in a Rodent Challenge Model e Balb/c mice (10 per group) infected with 1,000 pfu of mouse adapted EBOV given i.p., 4 hours later © Treated with Ampligen (0, 6, 12, or 18 mg/kg) i.p. every other day for 7 doses e Last Ampligen dose on Day 12 e Mice
Slide 37: Increased Survival Observed in Ampligen Treated Mice
Increased Survival (90-100%) Observed Up to Day 21 in Ampligen Treated Mice (Data from USAMRIID) 100 75 —*-Control g - —® Ampligen (6 mg/kg) iS —*-Ampligen (12 mg/kg) p<0.0001 x ——Ampligen (18 mg/kg) 25 ie) 0 3 6 9 1220 °«15 «18 Days post infection —_— »
Slide 38: Mice Treated with Low Dose Ampligen Did Not Lose Weight
Mice Treated with Low Dose Ampligen (6mg/kg) Did Not Lose Weight (Recent Data from USAMRIID) 250 200 150 —- Control 100 —m-Ampligen (6 mg/kg) \ —t—Ampligen (12 mg/kg) ——Ampligen (18 mg/kg) Total Group Weights of Surviving Mice (gms) Days post infection ee Total grou weights of Dead mice = 0 gms 2
Slide 39: Ampligen and HIV
Ampligen and HIV
Slide 40: Evidence for Ampligen's Immuno-Enhancement in Human Subjects
Evidence for Ampligen’s Immuno-Enhancement Clinically in Immuno-Deficient or Immuno-Naive Human Subjects ¢« Ampligen augments DTH response in patients with HIV disease with decreased progression to AIDS ¢« Ampligen plus seasonal influenza vaccine induces mucosal immunity against highly pathogenic in
Slide 41: Effect of Ampligen on Delayed Type Hypersensitivity in Human HIV Disease
Effect of Ampligen on Delayed Type Hypersensitivity in Human HIV Disease (Baseline CD4+ > 300)* 100 @ PLACEBO @ ANP 400&700mg % Reactive Subjects 0-8 16-48 WEEKS * AMP 700 Randomized, Placebo-Controlled, Multicenter Study (Thompson, et al. 1996) ae < 0.05, Placebo vs, Ampligen, logistic regression a
Slide 42: Progression to AIDS-Defining Event In Ampligen Trial
Progression to AIDS-Defining Event In Ampligen Randomized, Placebo-Controlled, Multicenter, Double Blind Trial (Baseline CD4+ > 300) Proportion without Progression to AIDS S os A Serer fees Rw Ro DN & & pope — Placebo (n=7) -@ Ampligen (n=9) o Thompson, et al. 1996 _— «
Slide 43: A Summary of Antiviral Activity of Ampligen, Including Other Viruses
A Summary of Antiviral Activity of Ampligen, Including Other Viruses
Slide 44: Antiviral Activity of Ampligen: Double-Stranded DNA Viruses
Antiviral Activity of Ampligen: Double-Stranded DNA Viruses Herpes Simplex Type 2 Hepatitis Cytom egalovirus, strain AD 169 Human Herpes Virus Type 6 (HHV-6) Vaccinia Mouse, in vivo protection Duck, in vivo treatm ent Human fibroblast, in vitro protection Human blood cells, in vitro protection Mouse
Slide 45: Antiviral Activity of Ampligen: Single-Stranded (+) RNA Viruses
Antiviral Activity of Ampligen: Single-Stranded (+) RNA Viruses Banzi Virus Mouse Hepatitis Virus Type 3 Encephalom yocarditis SARS-CoV (coronavirus) Enterovirus (coxsackie B3) Mouse, in vivo protection Mouse, in vivo protection Mouse, in vivo protection Mouse, in vivo protection Mouse, in vivo prot
Slide 46: Antiviral Activity of Ampligen: Single-Stranded (-) RNA Viruses
Antiviral Activity of Ampligen: Single-Stranded (-) RNA Viruses Punta Toro Bunyavirus Caraparu Bunyavirus Vesicular Stomatitis Virus Nipah Virus (param yxcovirus) Ebala Virus (Zaire) Ebola Virus (mouse adapted) Mouse, in vivo treatment Mouse, in vivo protection Human fibroblasts, in vitro protection
Slide 47: The Synergistic Activities of Ampligen
The Synergistic Activities of Ampligen
Slide 48: Ampligen Potential to Enhance Efficacy of Antiproliferative and Antiviral Drugs
Ampligen Has The Potential To Enhance The Efficacy Of A Broad Spectrum of Antiproliferative and Antiviral Drugs Ampligen is synergistic with small molecule antiviral drugs: * Influenza? — oseltamivir — zanamivir HIV/AIDS? abacavir zidovudine zalcitabine didanosine stavudine efavirenz indinavir riton
Slide 49: Synergistic Inhibition of HIV by Ampligen Combined with NRTIs
Synergistic Inhibition of HIV by Ampligen (polyl-poly C,,U) Combined with Nucleoside Reverse Transcriptase Inhibitors (NRTI} Mixed dose effect analysis of polyl-polyC,;U with NRTI Drug Experimental drug ratio® Mean” Synergy® Abacavir Sulfate 1:16 L49 1146 EC 0.799 (0.128) 0.79 (0.065) 1.052 (0.176)
Slide 50: Synergy of Poly I:Poly C12U and Oseltamivir
SYNERGY OF POLY I: POLY C,,U AND OSELTAMIVIR Poly |: Combination Index (Cl) * Poly C,,U : Oseltamivir Ratio 32:1 100:1 320:1 1000:1 3200:1 * Combination Indices < 0.90 Indicate Some Degree of Synergism ‘HHH = very strong synergism, ++++= strong synergism, +++= synergism ee 50
Slide 51: Synergy of Poly I:Poly C12U and Zanamivir
SYNERGY OF POLY 1: POLY C,,U AND ZANAMIVIR Poly |: Combination Index (Cl) * Poly C,,U : Zanamivir Ratio 3:1 10:1 32:1 100:1 * Combination Indices < 0.90 Indicate Some Degree of Synergism HHH = very strong synergism, ++++= strong synergism, +++= synergism ee 51
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