Aethlon Medical, Inc. · NASDAQ:AEMD

Aethlon Medical — 33rd Vicenza Course on Critical Care Nephrology (June 2015)

38 slides from Aethlon Medical's conference presentation, Jun 16, 2015

  1. Slide 1: Case Study using Lectin-Affinity Plasmapheresis in Treatment of Ebola Virus Disease

    A Case Study using Lectin - Affinity Plasmapheresis in the Treatment of Ebola Virus Disease Rod Kenley President, Aethlon Medical, Inc. 33rd Vicenza Course on Critical Care Nephrology June 12, 2015

  2. Slide 2: Affinity Plasmapheresis Device

    Affinity Plasmapheresis Device Design Tube Affini Sheet a Matrix Sealed Header Fibers Jacket Port Blood Inlet T Blood Outlet

  3. Slide 3: Aethlon Hemopurifier

    — Aet nlon Hemopurifier

  4. Slide 4: Lectin types and ligands

    Lectin Symbol Lectin name Source Ligand Mannose Binding Lectins ConA Concanavalin A Canavalia ensiformis α - D - mannosyl and α - D - glucosyl residues branched α - mannosidic structures (high α - mannose type, or hybrid type and biantennary complex type N - Glycans ) LCH Lentil lectin Lens culinari

  5. Slide 5: HIV Glycoprotein GP120

    HIV Glycoprotein GP120 Branched-chain Mannose BONIS D3 arm HO: HON, O pus 0, HO. pe -R AFM HO HO yo! ‘0 ky OHO" oy ‘ii on HOL7~027~00 FG. ©: o a a oe iehyy HO fu HO fag HO, ae Ho"? 1

  6. Slide 6: GNA forms a tetramer with sugar binding sites

    GNA forms a tetramer of four identical subunits each with 3 sugar binding sites each for a total of 12 sites • Bound sugars are shown in red • Primary amines ( lysines ) are shown in blue. These are used to chemically attach GNA to the silica matrix.

  7. Slide 7: Clearance of infectious viral pathogens and shed glycoproteins

    » Clearance of infectious viral pathogens » Clearance of shed glycoproteins

  8. Slide 8: Ebola virus structure

    modified after Cook et al . and Dolnik et al .

  9. Slide 9: GP1/2

    © visual - science.ru GP1/2

  10. Slide 10: Shed GP of Ebola Virus Triggers Immune Activation

    ‘OPEN @ ACCESS Freely available online IGEPLOS | rsswocens Shed GP of Ebola Virus Triggers Immune Activation and Increased Vascular Permeability ‘ Beatriz Escudero-Pérez, Valentina A. Volchkova, Olga Dolni oe Bas f Wal atogeney, OA, MSEM UIT CNRS UMASIEB, Univer Lyon yon Fane. lip Lawrence, Viktor E

  11. Slide 11: Capture of Ebola Virus by LAPD

    Ebola (mut) – Ebola Zaire strain mutant; Ebola (wt) – Ebola Zaire strain Wild Type; Ebola (mac) – Ebola Zaire strain cultivated in Macrophages Capture of Ebola Virus by LAPD Ebola Removal from Tissue Culture Fluid (RT-PCR) 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 6 12 18 24 Time (hours) Copies/

  12. Slide 12: Clearance of sGP by LAPD

    Clearance of sGP by LAPD 0% 20% 40% 60% 80% 100% 0 5 10 15 20 25 Time (h) % Initial Density 1% 10% 100% 0 2 4 6 8 Time (h) % Initial Density Figure 1. Clearance of sGP by GNA Microkros from Reduced SDS/12% NuPAGE Western Blot. EBOVZ cell culture supernatant 5 ml passaged over GNA Microkros Hemopurif

  13. Slide 13: Ebola removal from monkey plasma

    0% 50% 100% 150% 200% 250% 300% 0 5 10 15 20 25 % of Zero Time Time (hours) Expt Control Ebola removal from monkey plasma Studies were performed at CDC and USAMRIID

  14. Slide 14: Capture of West Nile virus on LAPD

    Capture of West Nile virus on LAPD Studies performed at Battelle Memorial Institute 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 5 10 15 20 25 % of virus remaining Time (hours) West Nile virus

  15. Slide 15: Capture of H5N1 virus by LAPD

    Capture of H5N1 virus by LAPD Studies performed at Battelle Memorial Institute 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 5 10 15 20 25 % of virus remaining Time (hours) H5N1 (Bird Flu) virus

  16. Slide 16: Capture of 1918 Flu virus by LAPD

    Capture of 1918 Flu virus by LAPD Studies performed at Battelle Memorial Institute 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 5 10 15 20 25 % of virus remaining Time (hours) Reconstructed 1918 Influenza virus

  17. Slide 17: Capture of Monkeypox virus by LAPD

    Capture of Monkeypox virus by LAPD Studies performed at Battelle Memorial Institute 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 5 10 15 20 25 % of virus remaining Time (hours) Monkeypox Virus

  18. Slide 18: Clearance of H1N1 from Human Plasma

    Clearance of H1N1 from Human Plasma Results: Pandemic H1N1/09 influenza virus was successfully removed from human plasma by the GNA - GAW lectin cartridge with a calculated half - time of 26.4 minutes. The control, in this case the regenerated cartridge re - filled with unmodified GAW 60 - 80 showed

  19. Slide 19: Patient history: Chief of Ebola therapy at Lakka Children's Hospital

    ▪ Dr. M., 38 yrs, Chief of Ebola therapy at Lakka Children's Hospital ▪ 09/28/2014 : Day 1 : Fever; EBOV - PCR+ ; Self - administered Amiodarone ▪ 9/29/2014 – 10/3/2014: Day 2 - 4 : Increasing vomiting, nausea, myalgia and malaise. ▪ 10/03/2014 = Day 5 : MedEvac to Frankfurt Lakka Children's Hospita

  20. Slide 20: German Treatment Network for Highly Contagious Diseases

    ▪ German Treatment Network for Highly Contagious and Life Threatening Diseases. ▪ 50 isolation unit beds (7 centers) ▪ 6 beds in Frankfurt (2 ICU ) Level A transport.

  21. Slide 21: Therapeutic Options

    Therapeutic Options ▪ Unchanged since the 1967 VHF German outbreak: ▪ Best supportive care: Hydration, electrolyte balance, intensive care, convalescent serum. ▪ Organ failure support: Mechanical Respiration, TPN, CRRT. ▪ Drug: e.g. ZMAPP, FX - 06, faviripavir . ▪ Device: Extracorporeal virus and vi

  22. Slide 22: Patient's Ebola-specific Medications

    • Amiodarone: EBOV d1 - d5 Inhibition of Ebola - and Marburg virus cell entry. Gehring et al., J Antimicrob Chemother. 2014 Aug;69(8):2123 - 31. • T - 705 ( Faviripavir ): EBOV d6 Ebola RNA polymerase inhibition (broad spectrum antiviral activity) Smither et al. Antiviral Res. 2014 Apr;104:153 - 5.

  23. Slide 23: The Frankfurt Patient - Timeline

    EBOV Day 1 5 6 7 9 10 11 12 13 16 17 The Frankfurt Patient - Timeline LAPD approval (BfArM) LAPD therapy 6.5 hrs. < FX06 -------- FX06> 200mg/d Viral load (Copies/ml) 10 7 10 7 10 7 4x10 5 Hb (g/dl) 12.6 8.1 Amiodarone < > 1,2 g/24h Faviripavir < > 800 mg/d Lakka Frankfurt CRRT Fever , Very weak , E

  24. Slide 24: Extracorporeal Treatment

    E xtracorporeal Treatment 1) MultiFiltrate - CiCa® 2) CiCa - CVVHDF: postdilution, Ultraflux dialyzer, RCA 3) LADP : Upstream of the dialyzer

  25. Slide 25: Machine set-up

    Machine set - up

  26. Slide 26: Initiating Treatment of EBOV Patient in Frankfurt

    Initiating Treatment of EBOV Patient in Frankfurt 9 - 10 - 14

  27. Slide 27: CRRT Rx settings

    CRRT Rx settings • Blood flow rate 100 ml/min • Dialysate flow 2500 ml/h • Substitution flow 1000 ml/h (postdilution) • Calcium - dose 3 mmol/l dialysat flow • Citrate - dose 5 mmol/l blood flow There was no change to the prescribed dialysis dose or mode ionized Ca 2+ : » pre - filter : > 1.0mmol/l

  28. Slide 28: LAPD Easily Extracted from Extracorporeal Circuit

    LAPD Easily Extracted from Extracorporeal Circuit Stefan Büttner, MD

  29. Slide 29: Philipps University BSL Facility Marburg Germany

    Phillips University BSL - 4 Facility Marburg Germany

  30. Slide 30: Philipps University BSL Facility Marburg Germany

    Phillips University BSL - 4 Facility Marburg Germany

  31. Slide 31: 6.5 hrs: removal of 253,000,000 Ebola copies

    6.5 hrs : removal of 253,000,000 Ebola copies Philipps University Marburg: (O. Dolnik/M . Eickmann/S . Becker) EBOV - Binding to LAPD Buffer CT - value Copies/ml PBS 1 27.89 9.63E+04 PBS 2 27.67 1.12E+05 PBS 3 27.74 1.07E+05 1.05E+05 aMM 1 28.15 7.96E+04 aMM 2 28.44 6.51E+04 aMM 3 28.54 6.03E+04 6.8

  32. Slide 32: Glycoprotein Elimination by LAP in vivo

    Glycoprotein - Elimination by LAP in vivo LAP Device Eluent Before LAP After LAP

  33. Slide 33: Viral Load as a Predictor of Outcome

    RNA copy levels of EVOD cases with fatal and nonfatal outcomes. Towner et al. J. Virol. 2004;78:4330 - 4341 McElroy et al., J Infect Dis. 2014;210:558 - 66 . Viral Load as a Predictor of Outcome

  34. Slide 34: The Frankfurt Patient - Timeline 2

    EBV Day ... 9 11 11 13 14 15 17 18... 27 29 48 The Frankfurt Patient - Timeline 2 LAPD CRRT< Out of level A isolation CRRT> pre - treatment 378,000 copies/ml intra - treatment 76,000 copies/ml next day 6,080 copies/ml Discharged Date ...10/06 10/08 10/10 10/11 10/14 10/15 10/16... 10/23 10/27 11/19

  35. Slide 35: Safety of the Treatment

    • No signs of hemolysis (low blood flow) • No clogging or clotting (regional citrate anticoagulation) • No allergic reaction • No adverse event during 6.5 hrs of treatment Safety of the Treatment

  36. Slide 36: Conclusions

    Conclusions » Lectin Affinity Plasmapheresis: – is safe and feasible – promising new supportive tool for severe Ebola infection » Hypotheses to explain therapeutic effect: – Reducing viral & glycoprotein load below “fatality threshold” reduces damage - buys time for supportive care/host defenses. –

  37. Slide 37: Acknowledgements

    Acknowledgements Olga Dolnik ( Marburg) Helmut Geiger Markus Eickmann ( Marburg) Benjamin Koch Stefan Büttner

  38. Slide 38: Slide 38

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