Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP
Tonix Pharmaceuticals — Investor Presentation (April 2018)
93 slides from Tonix Pharmaceuticals's investor presentation, Apr 3, 2018
Slide 1: Investor Presentation April 2018
© 2018 Tonix Pharmaceuticals Holding Corp. April 2018 Version P0106 4 - 3 - 18 (Doc 0334) Investor Presentation
Slide 2: Cautionary Note on Forward-Looking Statements
© 2018 Tonix Pharmaceuticals Holding Corp. 2 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 Litigat
Slide 3: Tonix Development Highlights
© 2018 Tonix Pharmaceuticals Holding Corp. 3 Lead Program Tonmya ®1 - FDA Breakthrough Therapy in PTSD 2 • Phase 3 HONOR study enrolling - bedtime treatment for PTSD TNX - 102 SL 3 - Bedtime treatment for agitation in Alzheimer’s disease • Phase 2 IND submitted in March 2018 TNX - 601 4 - Pre - IND
Slide 4: Pipeline program summaries
© 2018 Tonix Pharmaceuticals Holding Corp. 4 Tonmya ®1 (cyclobenzaprine HCl sublingual tablets) = bedtime treatment for posttraumatric stress disorder (PTSD) • Phase 3 HONOR study in military - related PTSD enrolling • Breakthrough Therapy designation granted by the U.S. Food and Drug Administration
Slide 5: Candidates in Development
© 2018 Tonix Pharmaceuticals Holding Corp. 5 Candidates in Development Preclinical Phase 2 NDA 1 /BLA 2 Market Pipeline Product Indication/ Description Phase 3 Tonmya Bedtime Treatment for PTSD Daytime Treatment for PTSD TNX - 601 Novel polymorph and salt discovered and characterized TNX - 801 Horse
Slide 6: Tonmya for PTSD: Phase 3 HONOR study
© 2018 Tonix Pharmaceuticals Holding Corp. 6 Tonmya (Cyclobenzaprine HCl Sublingual Tablets) for PTSD Phase 3 HONOR study in military - related PTSD enrolling • Encouraging evidence of safety and efficacy was demonstrated in Phase 2 • CAPS - 5 1 ≥ 33 is entry criteria in Phase 3, CAPS - 5 ≥ 29 was u
Slide 7: Phase 3 HONOR Study Enrolling
© 2018 Tonix Pharmaceuticals Holding Corp. 7 Phase 3 HONOR Study Enrolling • General s tudy c haracteristics: • Randomized, double - blind, placebo - controlled . • ~ 550 participants in approximately 40 U.S. sites . • Unblinded interim analysis will be reviewed by IDMC* to determine: ( i ) Early st
Slide 8: Go to HONOR study website
© 2018 Tonix Pharmaceuticals Holding Corp. 8 Go to: https://thehonorstudy.com/
Slide 9: Breakthrough Therapy Designation
© 2018 Tonix Pharmaceuticals Holding Corp. 9 Breakthrough Therapy Designation FDA granted Tonmya Breakthrough Therapy designation – reported December 19, 2016 • PTSD is a serious condition • Tonmya has potential advantages over existing therapies in military - related PTSD Benefits of Breakthrough T
Slide 10: No Recognized Abuse Potential in Clinical Studies
© 2018 Tonix Pharmaceuticals Holding Corp. 10 No Recognized Abuse Potential in Clinical Studies Active ingredient is cyclobenzaprine, which is structurally related to tricyclic antidepressants • Cyclobenzaprine interacts with receptors that regulate sleep quality: 5 - HT 2A ; a 1 - adrenergic and hi
Slide 11: TNX-102 SL Intellectual Property
© 2018 Tonix Pharmaceuticals Holding Corp. 11 TNX - 102 SL Intellectual Property – U.S. Protection until 2034 Composition of matter (eutectic) • U.S. Patent No. 9,636,408 issued in May 2017 by U.S. Patent and Trademark Office (USPTO) • Protection expected to 2034 • Japan Patent Office (JPO) issued N
Slide 12: Proprietary Cyclobenzaprine Eutectic Mixture
© 2018 Tonix Pharmaceuticals Holding Corp. 12 Proprietary Cyclobenzaprine Hydrochloride Eutectic Mixture Stabilizes Sublingual Tablet Formulation Base particle (K 2 HPO 4 ) Base particle (K 2 HPO 4 ) Base particle (K 2 HPO 4 ) Eutectic formulation 1 ANGSTRO - TECHNOLOGY™ Cyclobenzaprine - HCl (CBP -
Slide 13: Sublingual Formulation Designed for Bedtime Administration
© 2018 Tonix Pharmaceuticals Holding Corp. 13 TNX - 102 SL: Sublingual Formulation is Designed for Bedtime Administration TNX - 102 SL: Proprietary sublingual formulation of cyclobenzaprine (CBP) with transmucosal absorption • Innovation by design with patent protected CBP/mannitol eutectic • Rapid
Slide 14: Novel Mechanism Targets Sleep Quality
© 2018 Tonix Pharmaceuticals Holding Corp. 14 Tonmya: Novel Mechanism Targets Sleep Quality for Recovery from PTSD PTSD is a disorder of recovery • Most people exposed to extreme trauma recover over a few weeks • In PTSD, recovery process impeded due to insufficient sleep - dependent memory processi
Slide 15: Proposed Mechanism of Action in PTSD
© 2018 Tonix Pharmaceuticals Holding Corp. 15 Proposed Mechanism of Action of Tonmya in the Treatment of PTSD: The Effects of Nocturnal Neuroreceptor Blockade on Sleep Cyclobenzaprine is a functional antagonist at serotonergic 5 - HT 2A receptors , noradrenergic α 1 receptors , and histaminergic H 1
Slide 16: Focus on Nocturnal 5-HT2A Receptor Blockade
© 2018 Tonix Pharmaceuticals Holding Corp. 16 • Generally, serotonin (5 - HT) activity promotes the awake state and inhibits REM sleep; whereas once in REM sleep, the 5 - HT system is normally quiescent • Extinction learning is critical to recovery from trauma, and such new learning is consolidated
Slide 17: Fear Extinction Memory Consolidation and P-Waves
© 2018 Tonix Pharmaceuticals Holding Corp. 17 Fear Extinction Memory Consolidation: The Proposed Role of P - Waves, REM Sleep, and Serotonergic Neuroreceptor Activity Serotonergic projections from the dorsal raphe nuclei pons Site of release of phasic waves called pontine or P - waves P - wave activ
Slide 18: What are the Consequences of PTSD?
© 2018 Tonix Pharmaceuticals Holding Corp. 18 What are the Consequences of PTSD? Consequences: • Impaired daily function and substantial interference with work and social interactions • Reckless or destructive behavior • Increased health care utilization and greater medical morbidity PTSD as a risk
Slide 19: What are the Symptoms of PTSD?
© 2018 Tonix Pharmaceuticals Holding Corp. 19 What are the Symptoms of PTSD? Symptoms of PTSD fall into four clusters: 1. Intrusion (aversive memories, nightmares, flashbacks) 2. Avoidance (avoiding persons, places or situations) 3. Mood/cognitions (memory block, emotional numbing, detachment from o
Slide 20: What are the Consequences of PTSD?
© 2018 Tonix Pharmaceuticals Holding Corp. 20 What are the Consequences of PTSD? Consequences: • Impaired daily function and substantial interference with work and social interactions • Reckless or destructive behavior • Increased health care utilization and greater medical morbidity PTSD as a risk
Slide 21: PTSD: U.S. Prevalence and Index Traumas
© 2018 Tonix Pharmaceuticals Holding Corp. 21 PTSD: U.S. Prevalence and Index Traumas A chronic response to traumatic event(s) • A majority of people will experience a traumatic event at some point in their lifetime 1 • 20% of women and 8% of men in the U.S. who experience significant trauma develop
Slide 22: PTSD Prevalence and Market Characteristics
© 2018 Tonix Pharmaceuticals Holding Corp. 22 PTSD Prevalence and Market Characteristics 1 Kessler, et al., 2005; Prevalence rate of 3.5% applied to U.S. Census estimate of 247 million U.S. adult ( > 18) population in 2015 (www.census.gov/quickfacts/table/PST045215/00) 2 IMS Consulting, Market Sizin
Slide 23: What Drug Classes are Used to Treat PTSD?
© 2018 Tonix Pharmaceuticals Holding Corp. 23 What Drug Classes are Used to Treat PTSD? * TRx = Total prescriptions 1 VA/DoD Clinical Practice Guideline for the Management of Post - Traumatic Stress, Version 2, 2010 2 IMS Consulting, Market Sizing & Treatment Dynamics: “Post - Traumatic Stress Disor
Slide 24: PTSD: Not Well-Served by Approved Treatments
© 2018 Tonix Pharmaceuticals Holding Corp. 24 PTSD: Not Well - Served by Approved Treatments FDA - approved SSRIs, paroxetine and sertraline, have not shown efficacy in military - related PTSD Majority of patients unresponsive or intolerant to current treatments • Side effects relating to sexual dys
Slide 25: Why Initially Target Military-Related PTSD?
© 2018 Tonix Pharmaceuticals Holding Corp. 25 Why Initially Target Military - Related PTSD? 1 Friedman et al., J Clin Psychiatry 2007; 68:711 2 Zoloft Package Insert, August, 2014 3 Paxil Package Insert, June, 2014 4 Fava et al., Psychother Psychosom 84:72 - 81, 2015 Military - related PTSD not well
Slide 26: High Prevalence of PTSD Among Combat Veterans
© 2018 Tonix Pharmaceuticals Holding Corp. 26 High Prevalence of PTSD Among Combat Veterans 1 Kessler et al., Arch Gen Psych 2005; Prevalence rate of 3.5% applied to U.S. Census estimate of 247M U.S. adult ( > 18) population in 2015 ( www.census.gov/quickfacts/table/PST045215/00 ) ; 2 Norris, PTSD R
Slide 27: Economic and Social Burden of Veterans with PTSD
© 2018 Tonix Pharmaceuticals Holding Corp. 27 Growing Economic and Social Burden to Care for Veterans with PTSD Health care costs associated with PTSD for OEF/OIF/OND veterans: Direct costs Indirect costs 1 CBO Report 2012; 2 Tanielan , Invisible Wounds of War . 2005; 3 Analysis of VA Health Care Ut
Slide 28: Phase 2 AtEase Study in Military-Related PTSD
© 2018 Tonix Pharmaceuticals Holding Corp. 28 Phase 2 AtEase Study in Military - Related PTSD • Randomized, double - blind, placebo - controlled trial in military - related PTSD • Efficacy analysis from 231 patients; 24 U.S. clinical sites • Enrolled patients with baseline CAPS - 5 ≥ 29 • Primary Ef
Slide 29: Results of Phase 2 AtEase Study
© 2018 Tonix Pharmaceuticals Holding Corp. 29 Results of Phase 2 AtEase Study in Military - Related PTSD Tonmya 5.6 mg showed clinical benefit in military - related PTSD • CAPS - 5 scale, was statistically significant by Mixed - effect Model Repeated Measures, or MMRM, with Multiple Imputation, or M
Slide 30: AtEase Study Demographics and Characteristics
© 2018 Tonix Pharmaceuticals Holding Corp. 30 AtEase Study Demographics and Characteristics 93% of the randomized patients were male 98% had trauma during military service Deployed an average of 2.3 times Mean time since index trauma was 7 years Race and ethnicity generally consistent with U.S. mili
Slide 31: AtEase Study: Traumas Associated with PTSD
© 2018 Tonix Pharmaceuticals Holding Corp. 31 AtEase Study: Traumas Associated with PTSD *Some patients experienced more than one trauma 0 5 10 15 20 25 30 35 40 Other Knowing someone seriously injured or killed Being responsible for the death of an enemy combatant Seeing dead bodies or human remain
Slide 32: AtEase Study Summary of Primary and Secondary Analyses
© 2018 Tonix Pharmaceuticals Holding Corp. 32 AtEase Study – Summary of Primary and Secondary Analyses (week 12)
Slide 33: AtEase Primary Endpoint CAPS-5 Total Score
© 2018 Tonix Pharmaceuticals Holding Corp. 33 AtEase Study Results: Primary Endpoint CAPS - 5 Total Score by MMRM with MI # -25 -20 -15 -10 -5 0 Wk 0 Wk 2 Wk 4 Wk 6 Wk 8 Wk 10 Wk 12 Placebo Tonmya 2.8 mg Tonmya 5.6 mg * # Primary analysis MMRM (mixed - effect model repeated measures), * p=0.031, com
Slide 34: AtEase Safety and Tolerability Profile
© 2018 Tonix Pharmaceuticals Holding Corp. 34 AtEase Study: Safety and Tolerability Profile No serious adverse events reported with Tonmya deemed related to treatment Systemic Adverse Events* Placebo (N=94) Tonmya 2.8 mg (N=93) Tonmya 5.6 mg (N=50) Somnolence 6.4% 11.8% 16.0% Dry Mouth 10.6% 4.3% 16
Slide 35: Assessing CAPS-5 Entry Threshold in AtEase
© 2018 Tonix Pharmaceuticals Holding Corp. 35 Assessing CAPS - 5 Entry Threshold in AtEase Score of ≥29 on CAPS - 5 (20 items for severity score) required at screening and baseline • >50 on prior versions of CAPS (17 items) typical in previous drug registration trials • Extrapolation from prior vers
Slide 36: AtEase Retrospective Analysis for Subgroup CAPS-5 ≥33
© 2018 Tonix Pharmaceuticals Holding Corp. 36 AtEase Total CAPS - 5 for Intention - to - Treat Population and Retrospective Analysis for Subgroup with Entry CAPS - 5 ≥33 A baseline CAPS - 5 score ≥33 was set as the PTSD severity inclusion criterion in Phase 3 HONOR study Intention - to - Treat Popul
Slide 37: AtEase Effect Sizes for CAPS-5 and Symptom Clusters
© 2018 Tonix Pharmaceuticals Holding Corp. 37 0.53 0.46 0.12 0.39 0.52 0 0.1 0.2 0.3 0.4 0.5 0.6 Effect Size AtEase Effect Sizes for Total CAPS - 5 and Symptom Clusters for Intention - to - Treat Population and Subgroup with Entry CAPS - 5 ≥33 Effect Sizes in Tonmya 5.6 mg in AtEase Subgroup with En
Slide 38: AtEase Retrospective Analysis: Remission
© 2018 Tonix Pharmaceuticals Holding Corp. 38 AtEase Study Retrospective Analysis: Remission in Subgroup with Entry CAPS - 5 ≥33 Remission = Loss of Diagnosis and CAPS - 5 < 11 Asterisk and hashmark represent pairwise comparisons between Tonmya and Placebo; # p=0.08, Odds Ratio 3.01 (0.89, 10.18) *p
Slide 39: Multi-Functional Mechanism: Antagonism at 3 Receptors
© 2018 Tonix Pharmaceuticals Holding Corp. 39 TNX - 102 SL – Multi - Functional Mechanism Involves Antagonism at 3 Neuronal Receptors Active ingredient, cyclobenzaprine, interacts with 3 receptors • Antagonist at 5 - HT 2A receptors • Similar activity to trazodone and Nuplazid ® ( pimivanserin ) • A
Slide 40: Cyclobenzaprine is a Multi-Functional Drug (SNARI)
© 2018 Tonix Pharmaceuticals Holding Corp. 40 Untreated Effects of TNX - 102 Cyclobenzaprine is a multi - functional drug - SNARI - inhibits serotonin and norepinephrine reuptake - blocks serotonin 5 - HT 2A and norepinephrine a 1 receptors SNARI = S erotonin and N orepinephrine receptor A ntagonist
Slide 41: Tonmya Compared with Trazodone and Prazosin
© 2018 Tonix Pharmaceuticals Holding Corp. 41 Tonmya Trazodone Trazodone (disordered sleep ), prazosin (night terrors) - Trazodone inhibits serotonin 5HT 2A receptors and serotonin reuptake (SARI) - Prazosin blocks norepinephrine a 1 receptors Prazosin SARI – S erotonin Receptor A ntagonist & R eupt
Slide 42: Opportunities to Expand to Other Indications
© 2018 Tonix Pharmaceuticals Holding Corp. 42 v Opportunities to Expand to Other Indications Growing recognition that there is a constellation of disorders where sleep disturbances may have a role in the pathophysiology (cardiovascular, metabolic, neurologic) • Homeostatic role of sleep quality in s
Slide 43: TNX-102 SL Multiple Potential Indications
© 2018 Tonix Pharmaceuticals Holding Corp. 43 TNX - 102 SL – Multiple Potential Indications Management of Fibromyalgia (FM) – chronic pain condition • TNX - 102 SL clinical development in FM was halted after near miss in Phase 3 at low dose (2.8 mg) – half the dose being developed for PTSD • Imbalan
Slide 44: What is Agitation in Alzheimer's Disease?
© 2018 Tonix Pharmaceuticals Holding Corp. 44 What is Agitation in Alzheimer’s Disease? Agitation is one of the most distressing and debilitating of the behavioral complications of Alzheimer’s disease • Includes emotional lability, restlessness, irritability and aggression 1 Link between disturbed s
Slide 45: Consequences of Agitation in Alzheimer's Disease
© 2018 Tonix Pharmaceuticals Holding Corp. 45 Consequences of Agitation in Alzheimer’s Disease Outcomes • Agitation is associated with significant poor outcomes for Alzheimer’s patients and challenges for their caregivers Common reason for institutionalization • Development of agitation, or its wors
Slide 46: Agitation in Alzheimer's: Potential New Indication
© 2018 Tonix Pharmaceuticals Holding Corp. 46 Agitation in Alzheimer’s Disease – Potential New Indication for TNX - 102 SL Successful pre - IND meeting in November, 2017 • Phase 2 IND submitted March 2018 Significant unmet need • No FDA approved drugs for the treatment of agitation in Alzheimer’s Me
Slide 47: Regulatory Status and Registration Strategy for Alzheimer's Agitation
© 2018 Tonix Pharmaceuticals Holding Corp. 47 TNX - 102 SL for Agitation in Alzheimer’s – Regulatory Status and Registration Strategy FDA confirmed no additional study is needed prior to IND submission • Pre - IND meeting established open dialogue with the FDA on pivotal clinical study design and ef
Slide 48: Scientific Rationale for Agitation in Alzheimer's
© 2018 Tonix Pharmaceuticals Holding Corp. 48 Scientific Rationale for Developing TNX - 102 SL for Agitation in Alzheimer’s Disease Connection between Sleep Disturbance and Agitation • Agitation in Alzheimer’s Disease is associated with sleep disturbance 1,2 • Evidence that improving sleep could imp
Slide 49: Addressing Challenges in Treating Agitation in Alzheimer's
© 2018 Tonix Pharmaceuticals Holding Corp. 49 TNX - 102 SL Potentially Addresses Some of the Challenges in Treating Agitation in Alzheimer’s Sublingual route of administration (no swallowing) • Swallowing can be an issue for a significant number of Alzheimer’s patients Low dose taken daily at bedtim
Slide 50: Protective Barriers in the Central and Peripheral Nervous Systems
© 2018 Tonix Pharmaceuticals Holding Corp. Protective Barriers in the Central and Peripheral Nervous Systems Glial cells are cells that reside in the central nervous system and can provide protective barriers between the central and peripheral nervous systems 1,2 Blood – Brain Barrier: supplies nutr
Slide 51: During Wakefulness, Proteins Accumulate in Extracellular Space
© 2018 Tonix Pharmaceuticals Holding Corp. 51 During Wakefulness, Proteins Linked to Neuronal Death and Neurodegeneration Accumulate in the Brain’s Extracellular Space CSF = Cerebrospinal Fluid ISF = Interstitial Fluid 1. Papadopoulos MC, et al. Nat Rev Neurosci . 2013;14(4):265 - 277. During wakefu
Slide 52: During Wakefulness, Proteins Accumulate in Extracellular Space
© 2018 Tonix Pharmaceuticals Holding Corp. 52 During Wakefulness, Proteins Linked to Neuronal Death and Neurodegeneration Accumulate in the Brain’s Extracellular Space AQP4 = A quaporin - 4 CSF = Cerebrospinal Fluid ISF = Interstitial Fluid 1. Papadopoulos MC, et al. Nat Rev Neurosci . 2013;14(4):26
Slide 53: During Wakefulness, Proteins Accumulate in Extracellular Space
© 2018 Tonix Pharmaceuticals Holding Corp. 53 During Wakefulness, Proteins Linked to Neuronal Death and Neurodegeneration Accumulate in the Brain’s Extracellular Space Aβ = β - amyloid CSF = Cerebrospinal Fluid ISF = Interstitial Fluid 1. Xie L, et al. Science. 2013;342(6156):373 - 377. Permeability
Slide 54: During Sleep, CSF-Brain Barrier More Permeable
© 2018 Tonix Pharmaceuticals Holding Corp. 54 During Sleep, the CSF – Brain Barrier Is More Permeable, Allowing Debris to Clear Aβ = β - amyloid CSF = Cerebrospinal Fluid 1. Bellesi M, et al. BMC Biol. 2015;13:66. 2. Xie L, et al. Science. 2013;342(6156):373 - 377. Permeability of CSF – brain barrie
Slide 55: During Sleep, CSF-Brain Barrier More Permeable
© 2018 Tonix Pharmaceuticals Holding Corp. 55 Aβ = β - amyloid CSF = Cerebrospinal Fluid ISF = Interstitial Fluid 1. Xie L, et al. Science. 2013;342(6156):373 - 377. During Sleep, the CSF – Brain Barrier Is More Permeable, Allowing Debris to Clear CSF interchanging with ISF removes interstitial prot
Slide 56: Sleep-Wake Cycles Alter Permeability of CSF-Brain Barrier
© 2018 Tonix Pharmaceuticals Holding Corp. Sleep – Wake Cycles Alter Permeability of the CSF – Brain Barrier Fluid exchange at the CSF – brain barrier allows for clearance of toxic proteins called β – amyloids (A β ). 1 Glial cells in the brain work to facilitate this fluid exchange. 2 Sleep – wake
Slide 57: Agitation in Alzheimer's: Competitive Landscape
© 2018 Tonix Pharmaceuticals Holding Corp. 57 Agitation in Alzheimer’s – Competitive Landscape of Select Drugs in Development Competitive landscape • 5HT 2A Antagonists/inverse agonists • Nelotanserin ( Axovant ) • Atypical Antip sychotics (also have 5HT 2A antagonism) • Rexulti ® brexpiprazole (Ots
Slide 58: Candidates in Development
© 2018 Tonix Pharmaceuticals Holding Corp. 58 Candidates in Development Preclinical Phase 2 NDA 1 /BLA 2 Market Pipeline Product Indication/ Description Phase 3 Tonmya Bedtime Treatment for PTSD Daytime Treatment for PTSD TNX - 601 Novel polymorph and salt discovered and characterized TNX - 801 Hors
Slide 59: TNX-601 (Tianeptine Oxalate): Potential Clinical Candidate for PTSD
© 2018 Tonix Pharmaceuticals Holding Corp. 59 TNX - 601 ( Tianeptine Oxalate): A Potential Clinical Candidate for PTSD Pre - IND Candidate Targeted as a 1 st line monotherapy for PTSD: oral formulation for daytime dosing x Leverages expertise in PTSD (clinical and regulatory experience, market analy
Slide 60: Structural Comparison: TNX-102 and TNX-601
© 2018 Tonix Pharmaceuticals Holding Corp. 60 Structural Comparison: TNX - 102 and TNX - 601 Cyclobenzaprine and tianeptine share structural similarities with classic tricyclic antidepressants (TCAs) and to each other, but each has unique pharmacological properties • Tianeptine has a 3 - chlorodiben
Slide 61: TNX-801 Synthesized Live Horsepox Virus Smallpox Vaccine Candidate
© 2018 Tonix Pharmaceuticals Holding Corp. 61 TNX - 801 (Synthesized Live Horsepox Virus): A Smallpox - Preventing Vaccine Candidate Pre - IND Stage Potential improvement over current biodefense tools against smallpox ✓ Leverages Tonix’s government affairs effort ✓ Collaboration with Professor David
Slide 62: TNX-801: Synthesis and Relationship to Vaccinia
© 2018 Tonix Pharmaceuticals Holding Corp. 62 TNX - 801 (Synthesized Live Horsepox Virus): A Smallpox - Preventing Vaccine Candidate Synthesis 1 from sequence of a 1976 Mongolian isolate 2 In mice, TNX - 801 behaved like attenuated vaccinia virus • Vaccinia is the term used to classify the live poxv
Slide 63: Currently Licensed Smallpox Vaccine ACAM2000
© 2018 Tonix Pharmaceuticals Holding Corp. 63 ACAM2000 is sold to the U.S. Strategic National Stockpiles 1 • Sold by Emergent BioSolutions • Sanofi divested ACAM2000 to Emergent BioSolutions in 2017 for $97.5 M upfront plus milestones • ACAM2000 was developed by Acambis which was acquired by Sanofi
Slide 64: HPXV and its Relationship to Other Orthopoxviruses
64 © 2018 Tonix Pharmaceuticals Holding Corp. HSPV074 – fragmented homolog of VACV I4L (ribonucleotide reductase) HSPV200 – 216 kDa protein probably regulates T - cell activation with homologs still present in variola , cowpox, and monkeypox viruses HPXV and its Relationship to Other Orthopoxviruses
Slide 65: HPXV Sequence and Synthesis
65 © 2018 Tonix Pharmaceuticals Holding Corp. Sequence: GenBank entry DQ792504; DNA: GeneArt Genome Assembly (212 kbp ) by Synthesis of Fragments and Construction of Telomeres Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453
Slide 66: HPXV Produces Small Plaques
66 © 2018 Tonix Pharmaceuticals Holding Corp. HPXV Produces Small Plaques that are More Like Cowpox Than Vaccinia (VACV) Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453
Slide 67: Production of Cell-Associated and Extracellular Virus
67 © 2018 Tonix Pharmaceuticals Holding Corp. Cell - associated virus Virus in the media Production of Cell - Associated and Extracellular Virus Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453
Slide 68: HPXV Growth Characteristics
68 © 2018 Tonix Pharmaceuticals Holding Corp. HPXV Growth Characteristics Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453
Slide 69: Testing Vaccine Protective Activity of HPXV in Mice
69 © 2018 Tonix Pharmaceuticals Holding Corp. Testing Vaccine Protective Activity of HPXV in Mice Model Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453
Slide 70: HPXV Less Virulent than Dryvax Clone, Protective Immunity
70 © 2018 Tonix Pharmaceuticals Holding Corp. PBS VACV WR (5x10 3 PFU) Dryvax clone (10 7 PFU) HPXV (10 7 PFU) Challenge (10 6 PFU VAC strain WR) Biological Properties of HPXV: Less Virulent than a Dryvax Clone, but Produces Protective Immunity Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1):
Slide 71: HPXV Vaccine Protection Activity at Low Doses
71 © 2018 Tonix Pharmaceuticals Holding Corp. PBS HPXV (10 5 PFU) HPXV (10 6 PFU) HPXV (10 7 PFU) Challenge (10 6 PFU VAC strain WR) HPXV Vaccine Protection Activity Observed As Low As 10 5 PFU* *PFU = plaque forming units Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.
Slide 72: No Overt Clinical Signs in HPXV Vaccinated Mice
72 © 2018 Tonix Pharmaceuticals Holding Corp. No challenge PBS ➔ VACV (10 6 PFU) VACV* (5x10 3 PFU) ➔ VACV (10 6 PFU) HPXV (10 5 PFU) ➔ VACV (10 6 PFU) HPXV (10 6 PFU) ➔ VACV (10 6 PFU) HPXV (10 7 PFU) ➔ VACV (10 6 PFU) * VACV (strain WR) No Overt Clinical Sign Observed in HPXV Vaccinated Mice After
Slide 73: HPXV May Have an Improved Safety Profile
© 2018 Tonix Pharmaceuticals Holding Corp. 73 HPXV or TNX - 801 – May Have an Improved Safety Profile as a Smallpox Preventing Vaccine Horsepox is caused by HPXV and is characterized by mouth and skin eruptions HXPV isolate from the 1976 outbreak later sequenced Modern smallpox vaccines are associat
Slide 74: Improved Smallpox Vaccine is Important for Public Health
© 2018 Tonix Pharmaceuticals Holding Corp. 74 An Improved Smallpox - Preventing Vaccine is Important and Necessary for a Potential Public Health Issue Smallpox was eradicated as a result of global public health campaigns No cases of naturally - occurring smallpox have been reported since 1977 Accide
Slide 75: Current Needs to Vaccinate Against Smallpox
© 2018 Tonix Pharmaceuticals Holding Corp. 75 Ongoing vaccination of U.S. troops • Troops in the Global Response Force Threat of smallpox re - introduction • Strategic National Stockpile & public health policy Re - emergence of monkey pox 1 • Believed to resurgent because of vaccinia - naïve populat
Slide 76: TNX-801: A Potential Medical Countermeasure
© 2018 Tonix Pharmaceuticals Holding Corp. 76 TNX - 801: A Potential Medical Countermeasure 21st Century Cures Act (2016), Section 3086 • Encouraging treatments for agents that present a national security threat Medical countermeasures are drugs, biologics (vaccines) or devices intended to treat: •
Slide 77: TNX-801: Smallpox-Preventing Vaccine Candidate Advantages
© 2018 Tonix Pharmaceuticals Holding Corp. 77 Live virus vaccines stimulate cross - reactive immunity • Protects from possible infection with smallpox virus • Renders recipient “immune” • Provides indirect protection to non - immunized population “herd immunity” Potential safety improvement over exi
Slide 78: Evidence of Effectiveness for Smallpox Vaccine
© 2018 Tonix Pharmaceuticals Holding Corp. 78 Given that smallpox is eradicated the only evidence of effectiveness for modern vaccines is from historical use when smallpox was endemic • Stimulates interest in the evolution of vaccinia Vaccinia stocks around the world diverged from Jenner’s 1798 vacc
Slide 79: ACAM2000: Best Technology of its Time
© 2018 Tonix Pharmaceuticals Holding Corp. 79 Single clone picked from “swarm” of Dryvax ® 1 • Some rationale for selection 2 Growth in serum free Vero cells • Eliminates risk of Bovine Spongiform Encephalopathy (BSE)/prion contamination – safety concerns in Wyeth’s Dryvax (grown in calf lymph) In 2
Slide 80: Rationale for Developing a Potentially Improved Smallpox Vaccine
© 2018 Tonix Pharmaceuticals Holding Corp. 80 Toxicity concern of modern vaccinia (VACV) vaccines limit wildly administration • Not recommended for use, even in first responders • U.S. soldiers in the Global Response Force are immunized Modern VACV vaccination safety studied in 1081 VACV ( Dryvax [6
Slide 81: Postulated Divergence of Historical Strains of Vaccinia
© 2018 Tonix Pharmaceuticals Holding Corp. 81 Postulated Divergence of Historical Strains of Vaccinia Proposed Evolution of Vaccinia Vaccines NYCBH/European precursor stocks Horsepox - like ancestral strain Lister/Evans/USSR Dryvax ® IHD - J WR Copenhagen Tashkent RPXV TianTan Ankara LIVP IHD - J=In
Slide 82: Relationship to Smallpox Incidence and Eradication
© 2018 Tonix Pharmaceuticals Holding Corp. 82 Relationship to Smallpox Incidence and Eradication Proposed Evolution of Vaccinia Vaccines TIME *Rough approximation (not data derived) 1977 Eradication SMALLPOX CASES IN US/EUROPE* ACAM2000™ 1798 1902 1931 2007 Dryvax ® swarm Mulford Vaccine Jenner’s Va
Slide 83: Evidence of Effectiveness of Smallpox Vaccines
© 2018 Tonix Pharmaceuticals Holding Corp. 83 Theoretical effectiveness of modern vaccinia vaccines are based on extrapolation from older vaccines • Newer/modern vaccines were not widely used when smallpox was endemic MVA ( Modified Virus Ankara) which has large deletions also produces different T c
Slide 84: Possible Smallpox Prevention and Treatment Strategies
© 2018 Tonix Pharmaceuticals Holding Corp. 84 Preventing Vaccine • Jenner’s vaccine, HPXV (upon licensure), Vaccinia Post - exposure vaccination 1 • Jenner’s vaccine Priming of the immune system • Imvamune ® (MVA) and DNA vaccines 2 Pharmacotherapy for infected or exposed individuals • Arestvyr ® /T
Slide 85: Viral Replication Proficiency, Immunogenicity and Safety
© 2018 Tonix Pharmaceuticals Holding Corp. 85 Pox vaccines with low or no replication appear safer than vaccines replicate fast in human cells • Canarypox and Imvamune ® (Modified Virus Ankara/MVA) appear to have good tolerability • Relatively safe in immunocompromised hosts • Rapidly replicating mo
Slide 86: Manufacturing and Dosing Requirements
© 2018 Tonix Pharmaceuticals Holding Corp. 86 TNX - 801 (HPXV) is expected to have similar scalability for mass production as ACAM2000 • TNX - 801 grows well in cell lines – immunity is expected after single administration (immunization) • Only a small dose (replicating live virus) is required for i
Slide 87: Rationale for Improved Smallpox Vaccine Based on Jenner's Vaccine
© 2018 Tonix Pharmaceuticals Holding Corp. 87 Vaccination protects against smallpox – both individuals and populations at risk • Use of Jenner’s vaccine resulted in eradication of smallpox Vaccination can protect AFTER smallpox infection • Vaccinia can be administered 1 - 3 days after infection Vacc
Slide 88: HPXV as a Vector for Vaccines
© 2018 Tonix Pharmaceuticals Holding Corp. 88 Potential for Use of HPXV as a Vector for Vaccines to Infectious Disease or Cancer Poxviruses like HPXV can be engineered to express foreign genes and are well recognized platforms for vaccine development • Large packaging capacity for exogenous DNA inse
Slide 89: Management Team
© 2018 Tonix Pharmaceuticals Holding Corp. 89 Management Team Seth Lederman, MD President & CEO Jessica Morris Chief Operating Officer Gregory Sullivan, MD Chief Medical Officer Bradley Saenger, CPA Chief Financial Officer
Slide 90: Board of Directors
© 2018 Tonix Pharmaceuticals Holding Corp. 90 Board of Directors Seth Lederman, MD Chairman Ernest Mario, PhD ALZA, Glaxo, Reliant Pharma John Rhodes Chair, NYS Public Service Commission, CEO, NYS Dept. of Public Service, Booz Allen Samuel Saks, MD Jazz Pharma, ALZA, Johnson & Johnson Charles Mather
Slide 91: Milestones: Recently Completed and Upcoming
© 2018 Tonix Pharmaceuticals Holding Corp. 91 Milestones – Recently Completed and Upcoming T onmya – Posttraumatic Stress Disorder □ May 2016 Report ed results from Phase 2 AtEase study □ August 2016 End - of - Phase 2 meeting with FDA - Proposed Phase 3 clinical and NDA plan accepted □ December 201
Slide 92: Summary
© 2018 Tonix Pharmaceuticals Holding Corp. 92 Summary Near term milestones in Phase 3 program PTSD focused on military - related PTSD • Major unmet need; 8.6 Million Americans affected • Potential for NDA approval based on one study New indication for agitation in Alzheimer’s Disease • Phase 2 IND s
Slide 93: Thank you!
© 2018 Tonix Pharmaceuticals Holding Corp. Thank you ! NASDAQ: TNXP
Tonix Pharmaceuticals Holding — Investor Presentation (April 2018) on 6ix