Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP
Tonix Pharmaceuticals — World Vaccine Congress 2023
38 slides from Tonix Pharmaceuticals's conference presentation, Apr 6, 2023
Slide 1: The Development of Horsepox Virus as a Vaccine Platform: Evaluation of TNX-1800
1 The Development of Horsepox Virus as a Vaccine Platform: Evaluation of TNX-1800 as a SARS-CoV-2 Vaccine Farooq Nasar, Ph.D., M.P.H. Senior Principal Scientist World Vaccine Congress April 6, 2023 © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 2: Cautionary Note on Forward-Looking Statements
Cautionary Note on Forward-Looking Statements 2 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
Slide 3: Poxviruses
Poxviruses 3 • Family: Poxviridae • Two subfamilies: 1) Chordopoxvirinae 2) Entomopoxvirinae • 22 Genera • Double stranded DNA, enveloped, ∼128-380kb • Virions: brick-shaped, ∼250 x 350 nm • Infect vertebrate and invertebrate hosts © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 4: Poxviruses
Poxviruses 4 Poxviruses are ubiquitous in the environment across the globe © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 5: Orthopox Viruses
Orthopox Viruses 5 Smallpox Vaccine: CPXV, HPXV, VACV © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 6: In 1796, Edward Jenner Successfully Used Vaccination to Protect Against Smallpox
In 1796, Edward Jenner Successfully Used Vaccination to Protect Against Smallpox 6 • 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
Slide 7: Phylogenetic Tree of Genus Orthopox
Phylogenetic Tree of Genus Orthopox 7 Cowpox close orthopox relative to smallpox (Variola) Conferred protection against Variola © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 8: Orthopox Viruses; Poxvirus-based Vaccines
Orthopox Viruses; Poxvirus-based Vaccines 8 Vaccine: VACV © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 9: Recombinant Pox-based Vector Development Addressing Safety
Recombinant Pox-based Vector Development Addressing “Safety” minimization of Adverse Events 9 • Three decades pox-vector modifications and engineering focused on the generation of replication deficient (RD) vectors MVA Canarypox Focus Copenhagen Fowlpox Dryvax NYVAC Generation Replication Deficient
Slide 10: Recombinant Pox-based Vector Development Addressing Safety
Recombinant Pox-based Vector Development Addressing “Safety” minimization of Adverse Events 10 Considering the overall body of data from RD pox-based vectors Have we gone to far in vector engineering requiring RD? • Safety data is great but immunological responses are typically weak or suboptimal im
Slide 11: Equination, Use of Vaccines From Horses, Was Also Effective Against Smallpox
Equination, Use of Vaccines From Horses, Was Also Effective Against Smallpox 11 • 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 the
Slide 12: HPXV and HPXV-Like Viruses Were Used as Civil War-Era Vaccines
HPXV and HPXV-Like Viruses Were Used as Civil War-Era (1860s-1870s) Vaccines 12 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%
Slide 13: Evolution of the Vaccinia Genome
Evolution of the Vaccinia Genome 13 • Recent studies demonstrate that HPXV and HPXV-like viruses were used as smallpox vaccines in the 1800s1,2 HPXV or HPXV-like Jenner’s vaccinia 1902 Mulford Modern vaccinia (agent of “cowpox”) vaccine Civil War-era vaccines are genetically diverse, The 1902 Mulfor
Slide 14: 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 14 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 homol
Slide 15: Properties of TNX-801 Live HPXV Vaccine
Properties of TNX-801 Live HPXV Vaccine 15 • TNX-801 is a vaccine based on sequence of TNX-801 isolated HPXV clone MNR-761,2 The core genome of TNX-801 is identical to MNR-76, with ~70 bp terminal hairpin sequences from vaccinia added due to incomplete sequencing of MNR-761,2 Small plaque size in cu
Slide 16: SARS-CoV-2
SARS-CoV-2 16 • SARS-CoV-2 emerged from Wuhan, China in 2019/2020 • Family: Coronaviridae • Genus: Betacoronavirus • Positive sense, single stranded, RNA virus • Genome: ∼30kb © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 17: SARS-CoV-2
SARS-CoV-2 17 • SARS-CoV-2 emerged from Wuhan, China in 2019/2020 • Family: Coronaviridae • Genus: Betacoronavirus • Positive sense, single stranded, RNA virus • Genome: ∼30kb • Develop HPXV vaccine platform • Model system: SARS CoV-2 • “Proof of concept” • Encoding Spike protein (WA-2020) • TNX-180
Slide 18: Recombinant SARS-CoV-2 Vaccine Generation (TNX-1800)
Recombinant SARS-CoV-2 Vaccine Generation (TNX-1800*) 18 Development of HPXV as a recombinant Delivery Vector Platform Non-Essential Viral Genes Δ095 (TK) Non-Essential Viral Genes L-ITR Essential Viral Genes R-ITR Left Terminal Region 60Kbp Central General Region 36Kp -146Kbp Right Terminal Region
Slide 19: Recombinant Vaccine Expressing Heterologous Antigen: Spike Protein Expression
Recombinant Vaccine Expressing Heterologous Antigen (TNX-1800): Spike Protein Expression 19 TNX-1800 rapidly expresses SARS-CoV-2 spike protein 19 / PRESENTATION © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 20: Preliminary Immunogenicity Studies
Preliminary Immunogenicity Studies 20 Goal: Investigate immunogenicity and tolerability following administration of a single dose of TNX-1800 Two animal models: 1) Syrian Hamsters 2) New Zealand Rabbits © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 21: Preliminary Immunogenicity: Hamster Study Design
Preliminary Immunogenicity: Hamster Study Design 21 Vaccination in Hamsters Dose Group Vaccine Number (log10 Route PFU/animal) 1 TNX-1800 (HD) 2M/1F 6.5 Percutaneous 2 TNX-1800 (LD) 2M/1F 5.5 Percutaneous 3 Vehicle 1M/1F - Percutaneous © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 22: Preliminary Immunogenicity: SARS CoV-2 Spike Protein Specific ELISA Titers
Preliminary Immunogenicity: SARS CoV-2 Spike Protein Specific ELISA Titers 22 800 600 Total IgG Titer 400 200 0 Ve D Ve D Ve D Ve D 18 D 18 D 18 D 18 D e e e e cl cl cl cl L L L L X- 0 H X- 0 H X- 0 H X- 0 H hi hi hi hi 00 00 00 00 TN 1 8 0 TN 8 0 TN 1 8 0 TN 8 0 1 1 X- X- X- X- TN TN TN TN 1 14 21
Slide 23: Preliminary Immunogenicity: Rabbit Study Design
Preliminary Immunogenicity: Rabbit Study Design 23 Vaccination in Rabbits Dose Group Vaccine Number (log10 Route PFU/animal) 1 TNX-1800 (HD) 2M/1F 6.5 Percutaneous 2 TNX-1800 (LD) 2M/1F 5.5 Percutaneous 3 Vehicle 1M/1F - Percutaneous © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 24: Preliminary Immunogenicity: SARS CoV-2 Spike Protein Specific ELISA Titers
Preliminary Immunogenicity: SARS CoV-2 Spike Protein Specific ELISA Titers 24 1600 1200 ELISA Titer 800 400 0 Ve D Ve D Ve D Ve D 18 D 18 D 18 D 18 D e e e e cl cl cl cl L L L L X- 0 H X- 0 H X- 0 H X- 0 H hi hi hi hi 00 00 00 00 TN 1 8 0 TN 1 8 0 TN 1 8 0 TN 1 8 0 X- X- X- X- TN TN TN TN 1 14 21 28
Slide 25: Preliminary Immunogenicity Studies: Conclusion
Preliminary Immunogenicity Studies: Conclusion 25 1) 100% of animals generate an antibody response 2) Vaccine was well-tolerated No adverse events No disseminated horsepox virus infection Proceeded to efficacy studies in NHPs © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 26: Preliminary Efficacy Study Design: African Green Macaques
Preliminary Efficacy Study Design: African Green Macaques 26 © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 27: Immunogenicity: Neutralization Titers
Immunogenicity: Neutralization Titers 27 400 Microneutralization Titer 300 200 100 0 t t t t t t D 00 D 00 D 00 D 00 D 00 D 00 en en en en en en 18 18 18 18 18 18 ilu ilu ilu ilu ilu ilu X- X- X- X- X- X- TN TN TN TN TN TN -1 7 14/15 21 28/29 41 Days Post-Vaccination 100% NHPs in TNX-1800 vaccinated
Slide 28: Virus Replication/Shedding: Oropharyngeal Swabs
Virus Replication/Shedding: Oropharyngeal (OP) swabs 28 p = 0.0286 10 7 Genome Copies/Swab 10 6 10 5 10 4 10 3 10 2 10 1 10 0 t t t D 0 D 0 D 0 en en en 0 0 0 18 18 18 ilu ilu ilu X- X- X- TN TN TN 0 6 14 Days Post-Challenge 100% NHPs in TNX-1800 vaccinated group had no detectable SARS-CoV-2 genome
Slide 29: Virus Replication/Shedding: Tracheal Lavage
Virus Replication/Shedding: Tracheal Lavage 29 10 5 p = 0.0328 Genome Copies/mL 10 4 10 3 10 2 10 1 10 0 t t D 00 D 00 en en 18 18 ilu ilu X- X- TN TN -5 6 Days Post-Challenge 100% NHPs in TNX-1800 vaccinated group had no detectable SARS-CoV-2 genome © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 30: Preliminary Efficacy Study Design: Cynomolgus Macaques
Preliminary Efficacy Study Design: Cynomolgus Macaques 30 © 2023 Tonix Pharmaceuticals Holding Corp.
Slide 31: Immunogenicity: Total Anti-SARS-CoV-2 Spike Protein IgG1 Titer
Immunogenicity: Total Anti-SARS-CoV-2 Spike Protein IgG1 Titer (ELISA) 31 10 4 IgG1 Titer (U/mL) 10 3 10 2 10 1 10 0 ) ) ) 0 0 nt 0 0 nt 0 0 nt A A A 1 8 lue 1 8 lue 1 8 lue (W (W (W X- Di X- Di X- Di TN TN TN Pre 0 14 Days Post-Vaccination 100% NHPs in TNX-1800 vaccinated group had IgG1 antibody re
Slide 32: Immunogenicity: Neutralizing Antibody (PRNT50 Assay)
Immunogenicity: Neutralizing Antibody (PRNT50 Assay) 32 600 PRNT50 Titer 400 200 0 ) ) ) 00 t 00 t 00 t A A A 18 en 18 en 18 en (W (W (W X- ilu X- ilu X- ilu D D D TN TN TN 0 14 29 Days Post-Vaccination 100% NHPs in TNX-1800 vaccinated group had neutralizing antibody response © 2023 Tonix Pharmaceut
Slide 33: Immunogenicity: Cell Mediated Response
Immunogenicity: Cell Mediated Response 33 0.5 0.5 %IFNγ+/CD4+ T Cells %IL-4+/CD4+ T Cells 0.4 0.4 0.3 0.3 0.2 0.2 0.1 0.1 0.0 0.0 ) ) ) 0 0 nt 0 0 nt 0 0 nt ) ) ) 0 0 nt 0 0 nt 0 0 nt A A A A A A 1 8 lue 1 8 lue 1 8 lue 1 8 lue 1 8 lue 1 8 lue (W (W (W (W (W (W X- Di X- Di X- Di X- Di X- i X- Di D T
Slide 34: Virus Replication/Shedding: Bronchoalveolar lavage (BAL)
Virus Replication/Shedding: Bronchoalveolar lavage (BAL) (TCID50) 34 6 ✱✱✱✱ Titer (Log10 TCID50/mL) 5 4 3 2 ) ) 0 0 nt 0 0 nt A A 1 8 ue 1 8 ue (W (W X- Dil X- Dil TN TN 2 4 Days Post-Challenge Infectious virus declined rapidly by ∼100-fold in TNX-1800 vaccinated group © 2023 Tonix Pharmaceuticals H
Slide 35: Conclusions
Conclusions 35 TNX-1800 engineered to expressed heterologous antigen “Proof of concept” SARS-CoV-2 WA-2020 Spike protein 2 preliminary immunogenicity and 2 efficacy studies Animal models: Hamsters, Rabbits, Cynomolgus and African green macaques A single dose of TNX-1800 vaccination was well
Slide 36: Conclusions
Conclusions 36 TNX-1800 vaccination via route percutaneous was immunogenic 100% response in all 4 animal models Rapid generation of antibody response (Total IgG and/or neutralizing antibody) Induced CD4+ T-cell response Responses were skewed to TH1 Efficacy studies in cynomolgus and Africa
Slide 37: Conclusions
Conclusions 37 No longer continuing with clinical development of SARS-CoV-2 vaccine program 1) New variants (e.g., XBB) appear to be boosting pre-existing immunity resulting in “herd immunity” 2) Challenging regulatory hurdles for clinical evidence Additional vector development for heterologous ge
Slide 38: Acknowledgements
Acknowledgements 38 Tonix Pharmaceuticals University of Siobhan Fogarty Alberta Helen Stillwell Ryan Noyce Bruce Daugherty David Evans Seth Lederman Southern Research BIOQUAL © 2023 Tonix Pharmaceuticals Holding Corp.
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