Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Symposium to Honor Prof. David Evans on His Retirement (September 2024)

49 slides from Tonix Pharmaceuticals's conference presentation, Sep 9, 2024

  1. Slide 1: Using Synthetic Biology to Battle Mpox

    © 2024 Tonix Pharmaceuticals Holding Corp. Using Synthetic Biology to Battle Mpox Symposium to Honor Prof. David Evans on His Retirement Seth Leder man, M.D. Version P0594 Sept 6, 2024 (Doc 1505)

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

    © 2024 Tonix Pharmaceuticals Holding Corp. 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 Litigatio

  3. Slide 3: In 1798, Dr. Edward Jenner Described the Virus that Causes Cow Pox

    3 © 2024 Tonix Pharmaceuticals Holding Corp. In 1798, Dr. Edward Jenner Described the “Virus” that Causes Cow Pox and Identified its Utility in Preventing Smallpox 3 • Jenner, E. (1798) “An Inquiry Into the Causes and Effects of the Variolae Vaccinae , a Disease Discovered in Some of the Western Cou

  4. Slide 4: Edward Jenner Successfully Used Vaccination to Protect Against Smallpox

    © 2024 Tonix Pharmaceuticals Holding Corp. • Jenner "vaccinated” healthy individuals with material from the lesions, which he called “vaccine” (from vacca , Latin for “cow”) • The p ustule matter from “cow pox” sores on a milkmaid’s hands; conferred protection against future challenges with smallpox

  5. Slide 5: First Live Virus Vaccine: Edward Jenner's Inquiry (1798) – 1/2

    © 2024 Tonix Pharmaceuticals Holding Corp. First Live Virus Vaccine: Edward Jenner’s Inquiry 1 (1798) – 1/2 “There is a disease to which the Horse from his state of domestication is frequently subject. The Farriers have termed it the Grease . It is an inflammation and swelling in the heel, from whic

  6. Slide 6: First Live Virus Vaccine: Edward Jenner's Inquiry (1798) – 2/2

    © 2024 Tonix Pharmaceuticals Holding Corp. First Live Virus Vaccine: Edward Jenner’s Inquiry 1 (1798) – 2/2 1 Jenner, E. “An Inquiry Into the Causes and Effects of the Variolae Vaccinae , a Disease Discovered in Some of the Western Counties of England, Particularly Gloucestershire, and Known by the

  7. Slide 7: Loy's Account of Some Experiments (1801)

    © 2024 Tonix Pharmaceuticals Holding Corp. Loy’s “ Account of some experiments 1 (1801) “This fact induces me to suspect, that two kinds of Grease exist, differing from each other in the power of giving disease to the human or brute animal: and there is another circumstance which renders this suppos

  8. Slide 8: Equination: Use of Smallpox Vaccines Directly from Horse Lesions

    © 2024 Tonix Pharmaceuticals Holding Corp. Equination 1 : Use of Smallpox Vaccines Directly from Horse Lesions (Without Passage Through Cows) Both Jenner and Loy used vaccine from horses; subsequently “ Equination ” was used in Europe in parallel with “vaccination” − Jenner believed that his “cowpox

  9. Slide 9: 2006 Sequence and Analysis of the Horsepox Genome

    © 2024 Tonix Pharmaceuticals Holding Corp. 2006 Sequence and Analysis of the Horsepox Genome 1 9 “ It is likely that a once naturally circulating but now rare VACV - like virus(s) from which current strains are derived was introduced as a vaccine virus, and the agent of horsepox has been surmised as

  10. Slide 10: 2015 Genetic Analysis of Vaccinia Vaccines: Horsepox-like Virus Ancestor?

    © 2024 Tonix Pharmaceuticals Holding Corp. 2015 Genetic Analysis of Vaccinia Vaccines: Horsepox - like Virus Ancestor? 1 10 “The biological origin of VACV is uncertain, although it has been suggested that a horsepox - like virus was an ancestor, even though a surviving horsepox virus (HPXV) genome h

  11. Slide 11: David Evans: Speciation and Gene Loss in Vaccinia

    © 2024 Tonix Pharmaceuticals Holding Corp. David Evans 1 : Speciation and Gene Loss in Vaccinia Evans in (Qin et al): , “…the process of speciation appears to be associated with gene loss. ” − Larger virus − “ Relationship between DPP25 and horsepox virus. An important aspect of poxvirus evolutionar

  12. Slide 12: Synthesis of Horsepox (HPXV, TNX-801) 2018

    © 2024 Tonix Pharmaceuticals Holding Corp. Synthesis of Horsepox (HPXV, TNX - 801) 2018 1 12 1 Noyce RS, Lederman S, Evans DH. PLoS One . 2018 Jan 19;13(1):e0188453. doi : 10.1371/journal.pone.0188453. PMID: 29351298; PMCID: PMC5774680.

  13. Slide 13: Genome Assembly (212 kbp): TNX-801 Core Genome Based on HPXV Strain MNR-76

    © 2024 Tonix Pharmaceuticals Holding Corp. Genome Assembly (212 kbp ): TNX - 801 Core Genome i s Based on HPXV Strain MNR - 76 1,2 13 Sequence: GenBank entry DQ792504; DNA: GeneArt 1 Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453 2 Tulma

  14. Slide 14: TNX-801 Live HPXV for Percutaneous Administration

    © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 801 (Live HPXV for Percutaneous Administration) 14 Vaccine based on sequence of isolated horsepox (HPXV) clone 1 − Synthesized 2 since 1976 isolate was not available outside of the U.S. Centers for Disease Control and Prevention (CDC) − No new gene el

  15. Slide 15: Vaccination with TNX-801: Protective Immunity with Low Reactogenicity

    © 2024 Tonix Pharmaceuticals Holding Corp. Vaccination with TNX - 801 ( horsepox ): Protective Immunity with Low Reactogenicity ( i.e. , Improved Tolerability) 15 100 80 60 40 20 0 0 3 6 9 12 15 Days post - infection Survival (%) TNX - 801 + LD of VACV Dryvax + LD of VACV LD of VACV 0 5 10 15 20 25

  16. Slide 16: Horsepox Compared to Cowpox and 20th Century Vaccinia Strains

    © 2024 Tonix Pharmaceuticals Holding Corp. Horsepox Compared to Cowpox and 20 th Century Vaccinia Strains 1 : Consistent with Near “Primordial” Strain Status 1 Evans, D. U. of Alberta (2018) with permission

  17. Slide 17: Evolution of the Vaccinia Genome

    © 2024 Tonix Pharmaceuticals Holding Corp. Evolution of the Vaccinia Genome 17 Recent studies (particularly from José Esparza & colleagues ) demonstrate that horsepox and horsepox - like viruses were used as smallpox vaccines in the 1800s 1 - 3 HPXV or HPXV - like Jenner’s vaccinia (cause of “ gease

  18. Slide 18: Horsepox: Relationship to Jenner's Vaccinia

    © 2024 Tonix Pharmaceuticals Holding Corp. Horsepox: Relationship to Jenner’s Vaccinia Horsepox environmental isolate sequenced in 2006 shares a common ancestor with vaccinia and could be considered a strain of vaccinia − Similar to cowpox with “intact” inverted terminal repeats (ITRs) – could be co

  19. Slide 19: Deduced Relationship of Horsepox with Jenner's Vaccinia and 20th Century Vaccinia

    © 2024 Tonix Pharmaceuticals Holding Corp. Deduced Relationship of Horsepox with “Jenner’s Vaccinia” and “20 th Century Vaccinia” Vaccines 1976 Mongolian Field Isolate Arm - to - arm Molecular Biology “Vaccine Farms” Cow production started ~1875: Selection for Growth, Reactivity or Increased Virulen

  20. Slide 20: TNX-801 Live-Virus Horsepox Vaccine for Percutaneous Administration

    © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 801 (Live - virus Horsepox Vaccine for Percutaneous Administration) 20 Vaccine based on sequence of isolated horsepox (HPXV) clone 1 − Synthesized 2 since 1976 isolate was not available outside of the U.S. Centers for Disease Control and Prevention (C

  21. Slide 21: TNX-801 Immunogenicity and Efficacy in Macaques - 2023

    © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 801 Immunogenicity and Efficacy in Macaques - 2023 21 Noyce RS, et al. Viruses . 2023 Jan 26;15(2):356. doi : 10.3390/v15020356. PMID: 36851570; PMCID: PMC9965234.

  22. Slide 22: 100% of TNX-801 Vaccinated Macaques Survived Lethal MPXV Clade 1 Challenge

    © 2024 Tonix Pharmaceuticals Holding Corp. Survival: 100% of TNX - 801 Vaccinated Macaques Survived Lethal MPXV Clade 1 Intratracheal Challenge 22 No deaths in TNX - 801 vaccinated groups Noyce et al . Viruses. 2023 Jan 26;15(2):356.

  23. Slide 23: No Lesions Observed After TNX-801 Vaccination

    © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 801 Vaccination/Monkeypox Clade 1 Challenge: No Lesions Were Observed After TNX - 801 Vaccination 23 TNX - 801 (High Dose) TNX - 801 (Low Dose) rVACV Mock Noyce et al . Viruses. 2023 Jan 26;15(2):356.

  24. Slide 24: TNX-801 Vaccination: Minimal Monkeypox Virus Shedding

    © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 801 Vaccination: Minimal Monkeypox Virus Shedding 24 TNX - 801 (High Dose) TNX - 801 (Low Dose) rVACV Mock Potential to Reduce Forward Transmission Noyce et al . Viruses. 2023 Jan 26;15(2):356.

  25. Slide 25: Conclusions from Macaque Monkeypox Challenge Study

    © 2024 Tonix Pharmaceuticals Holding Corp. Conclusions from Macaque Monkeypox Challenge Study 25 • A single dose of TNX - 801 (horsepox) vaccination was well tolerated ‒ No severe adverse events ‒ Tolerability compares favorably to ACAM2000 – recently approved by US FDA for mpox 1 • TNX - 801 vaccin

  26. Slide 26: TNX-801 in Primary Cell Lines and Immunocompromised Mice - 2023

    © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 801 in Primary Cell Lines and Immunocompromised Mice – 2023 ( BioRxiv ) 26 Trefry , SV et al. bioRxiv 2023.10.25.564033; doi : https://doi.org/10.1101/2023.10.25.564033

  27. Slide 27: TNX-801 Has Reduced Virulence Relative to 20th Century Vaccinia Vaccines

    © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 801 has Reduced Virulence Relative to “20 th Century Vaccinia Vaccines” 27 Comparisons in vitro: 1) Plaque phenotype: VACV (  3 - 4 mm) vs. TNX - 801 (  1 - 2 mm) 2) Multi - step growth kinetics: ▪ Immortalized cell lines: TNX - 801  10 - to 1 00 -

  28. Slide 28: Conclusion: TNX-801 Is 100- to 1000-fold Less Virulent than 20th Century Vaccinia

    © 2024 Tonix Pharmaceuticals Holding Corp. Conclusion: TNX - 801 is 10 - to - 1000 - fold Less Virulent than 20 th Century Vaccinia (VACV) Vaccines 28

  29. Slide 29: High Dose TNX-801 Unable to Cause Disseminated Infection in Double KO Mice

    © 2024 Tonix Pharmaceuticals Holding Corp. High Dose TNX - 801 is Unable to Cause Disseminated Infection in Double KO IFN - α R - / - and IFN - γ R - / - mice 29 IND strain was deposited by the US Army in 1963 Farooq Nasar et al, Tonix unpublished data

  30. Slide 30: Illustrative Safety Spectrum of Pox-based Vaccine Vectors

    30 © 2024 Tonix Pharmaceuticals Holding Corp. INFECTIOUS DISEASE PORTFOLIO Illustrative Safety Spectrum Of Pox - based Vaccine Vectors Optimizing Live Virus Vaccines ~1 death per million ~10 deaths per million 20 th century smallpox vaccines Dryvax Lister TianTan Copenhagen Tashkent MVA Canarypox Fo

  31. Slide 31: Horsepox Protection and Tolerability in Animals Potentially Decouples Protective Immunity from Reactogenicity

    © 2024 Tonix Pharmaceuticals Holding Corp. Horsepox Protection and Tolerability in Animals Potentially Decouples Protective Immunity from Reactogenicity Conventional view holds that reactogenicity correlates with protection Protective immunity is not necessarily related to reactogenicity − Reactogen

  32. Slide 32: Horsepox: More (Regulatory) Genes Confer Tolerability

    © 2024 Tonix Pharmaceuticals Holding Corp. Horsepox: More (Regulatory) Genes Confer Tolerability “20 th Century vaccinia vaccines” evolved through a process of “Passage” through cows or birds that was a primitive form of genetic engineering − “Passage” through cows resulted in gene deletions that ma

  33. Slide 33: Mpox Outbreak 2022-23: Clade IIb: WHO Declared PHEIC

    © 2024 Tonix Pharmaceuticals Holding Corp. Mpox Outbreak 2022 - 23: Clade IIb: WHO Declared a Public Health Emergency of International Concern (PHEIC) 33 Risk of Spread and Lethality of Clade IIb • Case Fatality Rate (CFR): 0.1% to 3.6%  Lower compared to Clade I • Primarily spread through sexual c

  34. Slide 34: Monkeypox Clade IIb is 10,000- to 100,000-fold More Attenuated Than Clade IIa

    © 2024 Tonix Pharmaceuticals Holding Corp. Monkeypox Clade IIb (U.S. Isolate) is 10,000 - to 100,000 - fold More Attenuated Than Clade IIa 34 *p <0.0001 *p <0.01 Farooq Nasar et al, Tonix unpublished data Double KO IFN - α R - / - and IFN - γ R - / - mice Clade IIb: MA - 2022 Clade IIa : WR 7 - 61 a

  35. Slide 35: Do We Need Additional One-Dose Mpox and Smallpox Vaccine?

    © 2024 Tonix Pharmaceuticals Holding Corp. Do We Need Additional One - Dose Mpox and Smallpox Vaccine? 35 ACIP Oct 25, 2023 U.S. Mpox Vaccine Coverage in High - Risk Groups (CDC) 1 - dose: 38.8% 2 - dose: 24.3% 37% Drop Out

  36. Slide 36: Mpox and Smallpox Reports by U.S. Agencies & Institutions

    © 2024 Tonix Pharmaceuticals Holding Corp. Mpox and Smallpox Reports by U.S. Agencies & Institutions • Multiple recent statements by U.S. Agencies warning about smallpox and monkeypox 1 - 6 • U.S. National Academy of Sciences Consensus Report (March, 2024) 6 ‒ “Additionally, safer, single - dose vac

  37. Slide 37: U.S. Recognizes Smallpox Preparedness as a Priority

    © 2024 Tonix Pharmaceuticals Holding Corp. U.S. Recognizes Smallpox Preparedness as a Priority National Stockpile Expansion is Recommended by Experts 37

  38. Slide 38: Mpox Outbreak 2023-24: Clade I and Current State of the Epidemic in Congo

    © 2024 Tonix Pharmaceuticals Holding Corp. Mpox Outbreak 2023 - 24: Clade I and Current State of the Mpox Epidemic in Congo 38 Risk of Spread and Lethality • Higher CFRs  1.4% to over 10% • From January 1, 2023, to April 14, 2024, DRC reported 19,919 suspected cases and 975 deaths (4.9% CFR) in 25

  39. Slide 39: Mpox Declared Public Health Emergency of International Concern on August 14, 2024

    © 2024 Tonix Pharmaceuticals Holding Corp. Mpox Declared Public Health Emergency of International Concern (PHEIC) by WHO* on August 14, 2024: New Clade I • Clade I - first wave in Democratic Republic of Congo (DRC) • ~10% mortality, • Affects children • Additional emerging mutation • Potentially low

  40. Slide 40: Live Virus Vaccine Platform: Recombinant Pox Vaccine (RPV) Platform

    © 2024 Tonix Pharmaceuticals Holding Corp. Live Virus Vaccine Platform: Recombinant Pox Vaccine (RPV) Platform 40 Monkeypox and Smallpox Future Pandemics & New Infectious Diseases (“Hard Targets”) COVID - 19 Biodefense Using Proven Science To Address Challenging Disease States, We Have Created A Pro

  41. Slide 41: TNX-1800 Immunogenicity in Hamsters and Rabbits - 2023

    © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 1800 (SARS - CoV - 2 spike – Expressing HPXV) Immunogenicity in Hamsters and Rabbits - 2023 41 Awasthi M, et al. Viruses . 2023 Oct 21;15(10):2131. doi : 10.3390/v15102131. PMID: 37896908; PMCID: PMC10612059.

  42. Slide 42: Recombinant SARS-CoV-2 Vaccine Generation (TNX-1800 Expresses Spike)

    © 2024 Tonix Pharmaceuticals Holding Corp. Recombinant SARS - CoV - 2 Vaccine Generation (TNX - 1800* Expresses Spike) 42 Development of HPXV as a recombinant Delivery Vector Platform Central General Region 36Kp - 146Kbp Left Terminal Region 60Kbp Right Terminal Region 147 - 212 kbp Essential Viral

  43. Slide 43: TNX-1800 Immunogenicity and Efficacy in NHPs - 2023

    © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 1800 Immunogenicity and Efficacy in NHPs - 2023 43 Awasthi M, et al. Viruses . 2023 Oct 21;15(10):2131. doi : 10.3390/v15102131. PMID: 37896908; PMCID: PMC10612059.

  44. Slide 44: Immunogenicity: All NHPs in TNX-1800 Group Had Neutralizing Antibody Response

    © 2024 Tonix Pharmaceuticals Holding Corp. T N X - 1 8 0 0 D i l u e n t T N X - 1 8 0 0 D i l u e n t T N X - 1 8 0 0 D i l u e n t T N X - 1 8 0 0 D i l u e n t T N X - 1 8 0 0 D i l u e n t T N X - 1 8 0 0 D i l u e n t 0 100 200 300 400 M i c r o n e u t r a l i z a t i o n T i t e r -1 Days Pos

  45. Slide 45: TNX-1800 Inhibits SARS-CoV-2 Replication in Vaccinated NHPs

    © 2024 Tonix Pharmaceuticals Holding Corp. Vaccination with TNX - 1800 results in the inhibition of SARS - CoV - 2 Replication in Vaccinated NHPs 45 NHPs were vaccinated day 0 and challenged day 41; “Day 47” is 6 days after challenge

  46. Slide 46: TNX-801 Is Potential Vaccine for Mpox and Smallpox

    © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 801 is Potential Vaccine for Mpox and Smallpox Platform to express other viral antigens Animal studies show TNX - 801 protects against mpox − Appears to provide mucosal immunity after percutaneous vaccination (May prevent forward transmission) Single

  47. Slide 47: Tonix Platform Selected by NIH/NIAID: Project NextGen COVID

    © 2024 Tonix Pharmaceuticals Holding Corp. Tonix Platform Selected by NIH/NIAID : Project NextGen COVID 47

  48. Slide 48: TNX-801: Pre-IND Ready Candidate Mpox Vaccine

    48 © 2024 Tonix Pharmaceuticals Holding Corp. INFECTIOUS DISEASE PORTFOLIO TNX - 801: Pre - IND Ready Candidate Mpox Vaccine • Based on synthetic horsepox - vector, believed related to first smallpox vaccine reported by Dr. Edward Jenner in 1798 • Single - dose percutaneous • Attenuated live virus f

  49. Slide 49: Contributors

    © 2024 Tonix Pharmaceuticals Holding Corp. Contributors 49 Tonix Christy Raney Amy Cregger Chase A. Gonzales Brittany Layton Robert Enamorado Nelson Martinez Deborah Gohegan Massoudeh Masoud - Bahamiri Jennifer Cho Dawn Myscofski Tinoush Moulaei Nastasza Ziółkowska Current Addresses 1 McKinsey 2 Uni

Tonix Pharmaceuticals Holding — Symposium to Honor Prof. David Evans on His Retirement (September 2024) on 6ix