Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — World Vaccine Congress 2024

47 slides from Tonix Pharmaceuticals's conference presentation, Apr 3, 2024

  1. Slide 1: Attenuation of the Horsepox Virus Platform as a Vaccine for Mpox/Smallpox

    1 Attenuation of the Horsepox Virus Platform as a Vaccine for Mpox/Smallpox (TNX-801) Farooq Nasar, Ph.D., M.P.H. Senior Principal Scientist World Vaccine Congress: April 3rd, 2024 © 2024 Tonix Pharmaceuticals Holding Corp.

  2. Slide 2: Cautionary Note on Forward-Looking Statements

    Cautionary Note on Forward-Looking Statements Certain statements in this presentation regarding strategic plans, expectations and objectives for future operations or results are “forward-looking statements” as defined by the Private Securities Litigation Reform Act of 1995. These statements may be i

  3. Slide 3: Outline of Talk

    Outline of Talk 1) Background 2) TNX-801 attenuation in vitro 3) TNX-801 attenuation in vivo 4) TNX-801 immunogenicity and efficacy in NHP model © 2024 Tonix Pharmaceuticals Holding Corp.

  4. Slide 4: Background: Poxviruses

    Background: Poxviruses  Family: Poxviridae  Two subfamilies: 1) Chordopoxvirinae 2) Entomopoxvirinae  22 Genera  Genome: Double stranded DNA, ∼128-456 kb size  Virions: enveloped, brick-shaped, ∼220 to 450 nm long × 140 to 260 nm wide × 140 to 260 nm thick  Infect vertebrate and invertebrate h

  5. Slide 5: Poxviruses

    Poxviruses Poxviruses are ubiquitous in the environment across the globe © 2024 Tonix Pharmaceuticals Holding Corp.

  6. Slide 6: Orthopox Viruses

    Orthopox Viruses © 2024 Tonix Pharmaceuticals Holding Corp.

  7. Slide 7: Monkeypox Virus

    Monkeypox Virus  Endemic in Central and West Africa  Two Clades: 1) Clade I (DRC) 2) Clade IIa (West Africa) and IIb (Nigeria)  Human Case Fatality Rate:  Clade I – ∼11%  Clade IIa – ∼3%  Clade IIb – <0.1%  Clade IIb – 2022 Outbreak  116 Countries  ∼93,000 Confirmed Cases © 2024 Tonix Pharm

  8. Slide 8: Variola Virus (Smallpox)

    Variola Virus (Smallpox)  Oldest written record – ∼3,500 years  Oldest sequences – ∼1,400 years  Human Case Fatality Rate: ∼ 30%  20th century – ∼250 to 500 million deaths  Eradication: 1980 © 2024 Tonix Pharmaceuticals Holding Corp.

  9. Slide 9: Orthopox Viruses

    Orthopox Viruses Monkeypox, Variola Vaccines: CPXV, HPXV, VACV © 2024 Tonix Pharmaceuticals Holding Corp.

  10. Slide 10: Phylogenetic Tree of Genus Orthopox

    Phylogenetic Tree of Genus Orthopox Cowpox close orthopox relative to smallpox (Variola) Conferred protection against Variola © 2024 Tonix Pharmaceuticals Holding Corp.

  11. Slide 11: In 1796, Edward Jenner Successfully Used Vaccination to Protect Against Smallpox

    In 1796, Edward Jenner Successfully Used Vaccination to Protect Against Smallpox  Jenner observed milkmaids were protected from smallpox, reasoned that infection with an illness similar to smallpox but less deadly could protect one against smallpox “Cowpox” was the name of a disease in cows that co

  12. Slide 12: Equination, Use of Vaccines From Horses, Was Also Effective Against Smallpox

    Equination, Use of Vaccines From Horses, Was Also Effective Against Smallpox  Equination, the use of vaccines from horses (equus in Latin), was successfully used in parallel with vaccination in Europe1  Vaccine producers may have propagated stocks by periodically supplementing or refreshing them w

  13. Slide 13: HPXV Was Used as Civil War-Era (1860s-1870s) Vaccine

    HPXV Was Used as Civil War-Era (1860s- 1870s) Vaccine VK05 has the highest identity to HPXV across the whole genome and represents a true HSPV strain TNX-801 212,688 bps VK05 212,633 bps 99.8% Identical Key Points Pre-Mulford vaccines: VK05, VK12, VK02, VK08, and VK01 99.7% Identical VK05 and TNX-80

  14. Slide 14: Smallpox Vaccines

    Smallpox Vaccines  Vaccine: Cowpox origin  Serial passaging: Humans, cows, and horses (143 years)  Vaccine: Vaccinia Virus (1939) closely related to cowpox but serologically distinct  Multiple Vaccinia virus-based vaccines developed  Smallpox eradication © 2024 Tonix Pharmaceuticals Holding Cor

  15. Slide 15: Balance of Tolerability and Reactogenicity for Pox-based Vaccines

    Balance of Tolerability and Reactogenicity for Pox-based Vaccines MVA NYVAC Focus Copenhagen Canarypox Dryvax Tashkent Fowlpox Generation of Replication Deficient Lister TianTan Well tolerated, Requires high dose, 2 vaccinations ~1 death ~10 deaths per million per million Non-propagating Robustly Pr

  16. Slide 16: Balance of Tolerability and Reactogenicity for Pox-based Vaccines

    Balance of Tolerability and Reactogenicity for Pox-based Vaccines MVA NYVAC Canarypox Optimal Replicative Capacity Dryvax Copenhagen Fowlpox Lister Tashkent TianTan Well tolerated, Requires high dose, 2 vaccinations Horsepox ~1 death ~10 deaths (TNX-801) per million per million Non-propagating Moder

  17. Slide 17: TNX-801 Core Genome Is Identical to the Published HPXV Strain MNR-76

    TNX-801 Core Genome Is Identical to the Published HPXV Strain MNR-76 MNR-76 genome (212,633 bp) Genbank accession DQ792504 The core genome of TNX-801 is identical to MNR-761 MNR-76 genome fragments 1B 4 1A 2 5 7 LITR 3 6 RITR Ten overlapping genome fragments were assembled based on sequence homology

  18. Slide 18: TNX-801 attenuation in vitro

    2) TNX-801 attenuation in vitro © 2024 Tonix Pharmaceuticals Holding Corp.

  19. Slide 19: TNX-801 Characterization in vitro

    TNX-801 Characterization in vitro  Investigate attenuation of TNX-801 in vitro relative to VACV strains  Positive Control: VACV-Western Reserve (WR)  Older vaccines used in smallpox eradication: 1) VACV-International Health Department (IHD) 2) VACV-Lister (Lis) 3) VACV-New York City Board of Heal

  20. Slide 20: TNX-801: Small plaque phenotype in BSC-40 Cells

    TNX-801: Small plaque phenotype in BSC-40 Cells

  21. Slide 21: TNX-801: Small plaque phenotype in Vero-E6 Cells

    TNX-801: Small plaque phenotype in Vero-E6 Cells

  22. Slide 22: TNX-801: Replication in BSC-40 and Vero-E6

    TNX-801: Replication in BSC-40 and Vero-E6 Plaque Assay qPCR TNX-801: >10- to 100-fold more attenuated than VACV based vaccines

  23. Slide 23: TNX-801: Replication in Primary Human Cells (Dermal Tract)

    TNX-801: Replication in Primary Human Cells (Dermal Tract) Plaque Assay qPCR TNX-801: ∼10- to 27-fold more attenuated than VACV based vaccines

  24. Slide 24: TNX-801: Replication Kinetics in Primary Human Cells (Dermal Tract)

    TNX-801: Replication Kinetics in Primary Human Cells (Dermal Tract) Plaque Assay qPCR TNX-801: >5- to 119-fold more attenuated than VACV based vaccines

  25. Slide 25: TNX-801: Replication Kinetics in Primary Human Cells (Respiratory Tract)

    TNX-801: Replication Kinetics in Primary Human Cells (Respiratory Tract) Plaque Assay qPCR TNX-801: ∼20- to 30-fold more attenuated than VACV based vaccines

  26. Slide 26: TNX-801: Replication Kinetics in Primary Human Cells (Respiratory Tract)

    TNX-801: Replication Kinetics in Primary Human Cells (Respiratory Tract) Plaque Assay qPCR TNX-801: >3- to 30-fold more attenuated than VACV based vaccines

  27. Slide 27: TNX-801 attenuation in vivo

    3) TNX-801 attenuation in vivo © 2024 Tonix Pharmaceuticals Holding Corp.

  28. Slide 28: TNX-801 Characterization in vivo

    TNX-801 Characterization in vivo  Investigate attenuation of TNX-801 in vivo relative to VACV based vaccines  Immunocompromised Mice (C57BL/6 ifnar-/- and C57BL/6 ifnar-/- /ifngr-/-) • Sensitive to virus infection  Positive Control: VACV-WR  Older vaccines: VACV-IHD, VACV-Lis, VACV-NYCBH  TNX-8

  29. Slide 29: TNX-801 Characterization C57BL/6 ifnar-/-

    TNX-801 Characterization C57BL/6 ifnar-/-  Parameters measured: 1) Clinical Score 2) Temperature 3) Weight loss 4) Survival © 2024 Tonix Pharmaceuticals Holding Corp.

  30. Slide 30: TNX-801 Infection of C57BL/6 ifnar-/- Mice

    TNX-801 Infection of C57BL/6 ifnar-/- Mice TNX-801 infection did not produce any clinical disease © 2024 Tonix Pharmaceuticals Holding Corp.

  31. Slide 31: TNX-801 Infection of C57BL/6 ifnar-/- Mice

    TNX-801 Infection of C57BL/6 ifnar-/- Mice TNX-801 infection did not produce any clinical disease © 2024 Tonix Pharmaceuticals Holding Corp.

  32. Slide 32: TNX-801 Infection of C57BL/6 ifnar-/-/ifngr-/- Mice

    TNX-801 Infection of C57BL/6 ifnar-/-/ifngr-/- Mice  Parameters measured: 1) Clinical Score 2) Temperature 3) Weight loss 4) Survival © 2024 Tonix Pharmaceuticals Holding Corp.

  33. Slide 33: TNX-801 Infection of C57BL/6 ifnar-/-/ifngr-/- Mice

    TNX-801 Infection of C57BL/6 ifnar-/-/ifngr-/- Mice TNX-801 infection did not produce any clinical disease © 2024 Tonix Pharmaceuticals Holding Corp.

  34. Slide 34: TNX-801 Infection of ifnar-/-/ifngr-/- Mice: >1,000-fold more Attenuated

    TNX-801 Infection of C57BL/6 ifnar-/-/ifngr-/- Mice: >1,000-fold more Attenuated TNX-801 infection did not produce any clinical disease © 2024 Tonix Pharmaceuticals Holding Corp.

  35. Slide 35: TNX-801 immunogenicity and efficacy in NHP model

    4) TNX-801 immunogenicity and efficacy in NHP model © 2024 Tonix Pharmaceuticals Holding Corp.

  36. Slide 36: TNX-801 Immunogenicity and Efficacy in NHPs: Study Design

    TNX-801 Immunogenicity and Efficacy in NHPs: Study Design rVACV = Plaque pick from ACAM2000 (Approved Vaccine) © 2024 Tonix Pharmaceuticals Holding Corp.

  37. Slide 37: Immunogenicity and Efficacy in NHPs – Study Design

    Immunogenicity and Efficacy in NHPs – Study Design © 2024 Tonix Pharmaceuticals Holding Corp.

  38. Slide 38: Immunogenicity: Total IgG (ELISA)

    Immunogenicity: Total IgG (ELISA) = 100% Seroconversion in TNX-801 vaccinated groups © 2024 Tonix Pharmaceuticals Holding Corp.

  39. Slide 39: Immunogenicity: Neutralizing Antibody (PRNT50 Assay)

    Immunogenicity: Neutralizing Antibody (PRNT50 Assay) = 88% NHPs in TNX-801 vaccinated groups had neutralizing antibody responses © 2024 Tonix Pharmaceuticals Holding Corp.

  40. Slide 40: Virus Shedding: Oral Swabs (qPCR)

    Virus Shedding: Oral Swabs (qPCR) TNX-801 (High Dose) TNX-801 (Low Dose) rVACV Mock Minimal or no virus shedding in TNX-801 vaccinated groups © 2024 Tonix Pharmaceuticals Holding Corp.

  41. Slide 41: Viremia (qPCR)

    Viremia (qPCR) TNX-801 (High Dose) TNX-801 (Low Dose) rVACV Mock Sporadic or no viremia in TNX-801 vaccinated groups © 2024 Tonix Pharmaceuticals Holding Corp.

  42. Slide 42: Clinical Disease: Lesions

    Clinical Disease: Lesions TNX-801 (High Dose) TNX-801 (Low Dose) rVACV Mock NO LESIONS in TNX-801 vaccinated groups © 2024 Tonix Pharmaceuticals Holding Corp.

  43. Slide 43: Clinical Disease: Lesions (Mock Group)

    Clinical Disease: Lesions (Mock Group) © 2024 Tonix Pharmaceuticals Holding Corp.

  44. Slide 44: Clinical Disease: Lethality

    Clinical Disease: Lethality NO LETHALITY in TNX-801 vaccinated groups © 2024 Tonix Pharmaceuticals Holding Corp.

  45. Slide 45: Conclusions

    Conclusions  TNX-801 is attenuated in vitro: 1) Plaque phenotype: VACV (∼3-4 mm) vs. TNX-801 (∼1-2 mm) 2) Multi-step growth kinetics:  Immortalized cell lines: ∼10- to 100-fold attenuation  Human primary cell lines: ∼5- to 100-fold attenuation  TNX-801 is attenuated in vivo: 1) Assessed TNX-801

  46. Slide 46: Conclusions (NHP Study)

    Conclusions (NHP Study)  A single dose of TNX-801 vaccination was well tolerated  No severe adverse events (no lesions) following vaccination  TNX-801 vaccination via traditional route (scarification) was immunogenic  Provided near complete protection against virus shedding, viremia, and weight

  47. Slide 47: Acknowledgements

    Acknowledgements  Tonix Pharmaceuticals  Tonix Pharmaceuticals  University of Alberta  Stephanie Trefry  Jennifer Cho  Ryan Noyce  Mayanka Awasthi  Dawn Myscofski  David Evans  Christy Raney  Tinoush Moulaei  Amy Cregger  Natasza Ziółkowska  Southern Research  Chase A Gonzales  Scott

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