Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Investor Presentation (August 2018)

92 slides from Tonix Pharmaceuticals's investor presentation, Aug 13, 2018

1. Slide 1: Investor Presentation August 2018

   © 2018 Tonix Pharmaceuticals Holding Corp. August 2018 Version P0123 8 - 13 - 18 (Doc 0377) Investor Presentation

2. 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

3. Slide 3: Tonix Pharmaceuticals: Who we are

   © 2018 Tonix Pharmaceuticals Holding Corp. 3 Tonix Pharmaceuticals Who we are: • A clinical stage pharmaceutical company dedicated to developing innovative treatments for patients and making meaningful contributions to society What we do: • Target therapeutics with high need for improvement − Condit

4. Slide 4: Candidates in Development

   © 2018 Tonix Pharmaceuticals Holding Corp. 4 Candidates in Development Preclinical Phase 2 NDA 1 /BLA 2 Market Pipeline Product Indication/D escription Phase 3 Tonmya Bedtime Treatment for PTSD Daytime Treatment for PTSD TNX - 601 Novel polymorph and salt discovered and characterized TNX - 801 Horse

5. Slide 5: Lead Program: TNX-102 SL Product Concept

   © 2018 Tonix Pharmaceuticals Holding Corp. 5 Lead Program: TNX - 102 SL – Product Concept Sleep disturbances are associated with a constellation of disorders • Considered co - morbid or a key symptom in these disorders • Believed to have a role in the onset, progression and severity of these disorde

6. Slide 6: Lead Program Tonmya: FDA Breakthrough Therapy in PTSD

   © 2018 Tonix Pharmaceuticals Holding Corp. 6 Lead Program Tonmya ®1 – FDA Breakthrough Therapy in posttraumatic stress disorder (PTSD) 2 – Bedtime treatment in Phase 3 Development • Results from 2 efficacy studies improve the new pivotal efficacy study design • FDA feedback and agreement are expecte

7. Slide 7: Tonmya for PTSD

   © 2018 Tonix Pharmaceuticals Holding Corp. 7 Tonmya for PTSD Breakthrough Therapy (BT) designation from the FDA • Expedited development and accelerated approval are expected One Phase 2 study completed and one Phase 3 study stopped early due to inadequate separation from placebo • Both studies were

8. Slide 8: Breakthrough Therapy Designation

   © 2018 Tonix Pharmaceuticals Holding Corp. 8 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

9. Slide 9: No Recognized Abuse Potential in Clinical Studies

   © 2018 Tonix Pharmaceuticals Holding Corp. 9 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 his

10. 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

11. Slide 11: TNX-102 SL Intellectual Property: U.S. Protection until 2034

    © 2018 Tonix Pharmaceuticals Holding Corp. 11 TNX - 102 SL Intellectual Property – U.S. Protection until 2034 Composition of matter (eutectic) : Protection expected to 2034 • United States Patent and Trademark Office (USPTO) issued U.S. Patent No. 9,636,408 in May 2017 and U.S. Patent No. 9,956,188

12. Slide 12: Sublingual Formulation Designed for Bedtime Administration

    © 2018 Tonix Pharmaceuticals Holding Corp. 12 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

13. Slide 13: Proprietary Cyclobenzaprine Eutectic Mixture Stabilizes Tablet

    © 2018 Tonix Pharmaceuticals Holding Corp. 13 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 -

14. Slide 14: Tonmya: Novel Mechanism Targets Sleep Quality for PTSD

    © 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

15. Slide 15: Proposed Mechanism of Action of Tonmya 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 1 receptors , and histaminergic H 1 r

16. Slide 16: Mechanism of Action: 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

17. Slide 17: Fear Extinction Memory Consolidation: P-Waves and REM Sleep

    © 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

18. Slide 18: Overview of PTSD

    © 2018 Tonix Pharmaceuticals Holding Corp. 18 Overview of PTSD PSTD is a chronic disabling disorder in response to experiencing traumatic event(s) Symptoms of PTSD fall into four clusters: 1. Intrusion (aversive memories, nightmares, flashbacks) 2. Avoidance (avoiding persons, places or situations)

19. Slide 19: Impact of PTSD on People

    © 2018 Tonix Pharmaceuticals Holding Corp. 19 Impact of PTSD on People 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 factor for

20. Slide 20: PTSD: U.S. Prevalence and Index Traumas

    © 2018 Tonix Pharmaceuticals Holding Corp. 20 PTSD: U.S. Prevalence and Index Traumas PTSD is 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

21. Slide 21: PTSD Prevalence and Market Characteristics

    © 2018 Tonix Pharmaceuticals Holding Corp. 21 PTSD Prevalence and Market Characteristics 1 Goldstein et al., 2016 (civilians) 2 Veterans: VA/DOD Clinical Practice Guidelines for the Managements of PTSD and Acute Stress Disorder, 2017, page 15 (619,493 v et s diagnosed with PTSD in VA for 2016) 3 IMS

22. Slide 22: What Drug Classes are Used to Treat PTSD?

    © 2018 Tonix Pharmaceuticals Holding Corp. 22 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

23. Slide 23: PTSD: Not Well-Served by Approved Treatments

    © 2018 Tonix Pharmaceuticals Holding Corp. 23 PTSD: Not Well - Served by Approved Treatments FDA - approved SSRIs, paroxetine and sertraline, are indicated as a treatment for PTSD • Neither drug has shown efficacy in military - related PTSD • Majority of patients unresponsive or intolerant to curren

24. Slide 24: Why Initially Target Military-Related PTSD?

    © 2018 Tonix Pharmaceuticals Holding Corp. 24 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

25. Slide 25: High Prevalence of PTSD Among Combat Veterans

    © 2018 Tonix Pharmaceuticals Holding Corp. 25 High Prevalence of PTSD Among Combat Veterans 1 Goldstein et al., 2016 ; 2 Norris, PTSD Res Quar . 2013; 3 Analysis of VA Health Care Utilization among Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn Vete ran s, from 1st Qtr F

26. Slide 26: Economic and Social Burden of Veterans with PTSD

    © 2018 Tonix Pharmaceuticals Holding Corp. 26 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

27. Slide 27: HONOR Study Design

    © 2018 Tonix Pharmaceuticals Holding Corp. 27 HONOR Study – Evidence of Efficacy at Week 4 Discontinued Due to High Placebo Response at Week 12 Primary e ndpoint CAPS - 5 1 : • Mean change from baseline at w eek 12 (Tonmya 5.6 mg vs. placebo ) Unblinded interim analysis (IA) at ~50% randomized parti

28. Slide 28: HONOR Study Stopped in July 2018

    © 2018 Tonix Pharmaceuticals Holding Corp. 28 HONOR Study Stopped in July 2018 HONOR was a large adequate well - controlled study in military - related PTSD • Separation on primary endpoint at Week 12 did not cross pre - specified study continuation threshold at Week 12 • No safety or tolerability i

29. Slide 29: AtEase Study in Military-Related PTSD

    © 2018 Tonix Pharmaceuticals Holding Corp. 29 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

30. Slide 30: Results of AtEase Study

    © 2018 Tonix Pharmaceuticals Holding Corp. 30 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

31. Slide 31: AtEase Study Demographics and Characteristics

    © 2018 Tonix Pharmaceuticals Holding Corp. 31 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

32. Slide 32: AtEase Study: Traumas Associated with PTSD

    © 2018 Tonix Pharmaceuticals Holding Corp. 32 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

33. Slide 33: AtEase Study: Summary of Primary and Secondary Analyses

    © 2018 Tonix Pharmaceuticals Holding Corp. 33 AtEase Study – Summary of Primary and Secondary Analyses (Week 12)

34. Slide 34: AtEase Primary Endpoint: CAPS-5 Total Score

    © 2018 Tonix Pharmaceuticals Holding Corp. 34 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

35. Slide 35: AtEase Study: Safety and Tolerability Profile

    © 2018 Tonix Pharmaceuticals Holding Corp. 35 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

36. Slide 36: Assessing CAPS Entry Threshold in AtEase

    © 2018 Tonix Pharmaceuticals Holding Corp. 36 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

37. Slide 37: AtEase Retrospective Analysis: Entry CAPS-5 ≥33 Subgroup

    © 2018 Tonix Pharmaceuticals Holding Corp. 37 AtEase Study 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

38. Slide 38: AtEase Effect Sizes for CAPS-5 and Symptom Clusters

    © 2018 Tonix Pharmaceuticals Holding Corp. 38 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 Study 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 w

39. Slide 39: AtEase Retrospective Analysis: Remission

    © 2018 Tonix Pharmaceuticals Holding Corp. 39 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

40. Slide 40: Commercialization Options

    © 2018 Tonix Pharmaceuticals Holding Corp. 40 Commercialization Options Tonix is exploring a variety of options to commercialize TNX - 102 SL, including commercializing on our own or partnering all or some indications in specific regions of the world. Tonix has participated in numerous partnering me

41. Slide 41: Multi-Functional Mechanism: Antagonism at 3 Receptors

    © 2018 Tonix Pharmaceuticals Holding Corp. 41 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

42. Slide 42: Cyclobenzaprine is a Multi-Functional Drug (SNARI)

    © 2018 Tonix Pharmaceuticals Holding Corp. 42 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

43. Slide 43: Tonmya Compared with Trazodone and Prazosin

    © 2018 Tonix Pharmaceuticals Holding Corp. 43 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

44. Slide 44: Opportunities to Expand to Other Indications

    © 2018 Tonix Pharmaceuticals Holding Corp. 44 v Opportunities to Expand to Other Indications Growing recognition that there are many disorders where sleep disturbances may have a role in the pathophysiology (cardiovascular, metabolic, neurologic) • Homeostatic role of sleep quality in several disord

45. Slide 45: TNX-102 SL Multiple Potential Indications

    © 2018 Tonix Pharmaceuticals Holding Corp. 45 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

46. Slide 46: What is Agitation in Alzheimer's Disease?

    © 2018 Tonix Pharmaceuticals Holding Corp. 46 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

47. Slide 47: Consequences of Agitation in Alzheimer's Disease

    © 2018 Tonix Pharmaceuticals Holding Corp. 47 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

48. Slide 48: Agitation in Alzheimer's: Potential New Indication

    © 2018 Tonix Pharmaceuticals Holding Corp. 48 Agitation in Alzheimer’s Disease – Potential New Indication for TNX - 102 SL Phase 2 IND cleared April 2018 Significant unmet need • No FDA approved drugs for the treatment of agitation in Alzheimer’s Mechanism of improving sleep quality • Sleep disturba

49. Slide 49: Regulatory Status and Registration Strategy for Alzheimer's Agitation

    © 2018 Tonix Pharmaceuticals Holding Corp. 49 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

50. Slide 50: Scientific Rationale for Agitation in Alzheimer's

    © 2018 Tonix Pharmaceuticals Holding Corp. 50 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

51. Slide 51: Addressing Challenges in Treating Agitation in Alzheimer's

    © 2018 Tonix Pharmaceuticals Holding Corp. 51 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

52. Slide 52: 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

53. 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 AQP4 = A quaporin - 4 CSF = Cerebrospinal Fluid ISF = Interstitial Fluid 1. Papadopoulos MC, et al. Nat Rev Neurosci . 2013;14(4):26

54. Slide 54: During Sleep, CSF-Brain Barrier Is 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

55. Slide 55: 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

56. Slide 56: Competitive Landscape in Alzheimer's Agitation

    © 2018 Tonix Pharmaceuticals Holding Corp. 56 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

57. Slide 57: Candidates in Development

    © 2018 Tonix Pharmaceuticals Holding Corp. 57 Candidates in Development Preclinical Phase 2 NDA 1 /BLA 2 Market Pipeline Product Indication/D escription Phase 3 Tonmya Bedtime Treatment for PTSD Daytime Treatment for PTSD TNX - 601 Novel polymorph and salt discovered and characterized TNX - 801 Hors

58. Slide 58: TNX-601 (Tianeptine Oxalate): Potential Clinical Candidate for PTSD

    © 2018 Tonix Pharmaceuticals Holding Corp. 58 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

59. Slide 59: Structural Comparison: TNX-102 and TNX-601

    © 2018 Tonix Pharmaceuticals Holding Corp. 59 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

60. Slide 60: TNX-801: Smallpox-Preventing Vaccine Candidate

    © 2018 Tonix Pharmaceuticals Holding Corp. 60 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

61. Slide 61: TNX-801 Synthesized Live Horsepox Virus

    © 2018 Tonix Pharmaceuticals Holding Corp. 61 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

62. Slide 62: ACAM2000 Is a Live Vaccinia Virus Vaccine

    © 2018 Tonix Pharmaceuticals Holding Corp. 62 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

63. Slide 63: HPXV and Its Relationship to Other Orthopoxviruses

    63 © 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

64. Slide 64: HPXV Sequence and Synthesis

    64 © 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

65. Slide 65: HPXV Produces Small Plaques Like Cowpox

    65 © 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

66. Slide 66: Production of Cell-Associated and Extracellular Virus

    66 © 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

67. Slide 67: HPXV Growth Characteristics

    67 © 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

68. Slide 68: Testing Vaccine Protective Activity of HPXV in Mice

    68 © 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

69. Slide 69: HPXV Less Virulent than Dryvax Clone, Produces Protective Immunity

    69 © 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):

70. Slide 70: HPXV Vaccine Protection Observed at Low Doses

    70 © 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.

71. Slide 71: No Overt Clinical Signs in HPXV-Vaccinated Mice After Challenge

    71 © 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

72. Slide 72: TNX-801 May Have an Improved Safety Profile

    © 2018 Tonix Pharmaceuticals Holding Corp. 72 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

73. Slide 73: Improved Smallpox-Preventing Vaccine Is Necessary

    © 2018 Tonix Pharmaceuticals Holding Corp. 73 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

74. Slide 74: Current Needs to Vaccinate Against Smallpox

    © 2018 Tonix Pharmaceuticals Holding Corp. 74 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

75. Slide 75: TNX-801: A Potential Medical Countermeasure

    © 2018 Tonix Pharmaceuticals Holding Corp. 75 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: •

76. Slide 76: TNX-801 Smallpox-Preventing Vaccine Candidate: Advantages

    © 2018 Tonix Pharmaceuticals Holding Corp. 76 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

77. Slide 77: Evidence of Effectiveness for Smallpox Vaccine

    © 2018 Tonix Pharmaceuticals Holding Corp. 77 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

78. Slide 78: ACAM2000: Best Technology of its Time

    © 2018 Tonix Pharmaceuticals Holding Corp. 78 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

79. Slide 79: Rationale for Developing an Improved Smallpox Vaccine

    © 2018 Tonix Pharmaceuticals Holding Corp. 79 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

80. Slide 80: Postulated Divergence of Historical Vaccinia Strains

    © 2018 Tonix Pharmaceuticals Holding Corp. 80 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

81. Slide 81: Relationship to Smallpox Incidence and Eradication

    © 2018 Tonix Pharmaceuticals Holding Corp. 81 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

82. Slide 82: Evidence of Effectiveness of Smallpox Vaccines

    © 2018 Tonix Pharmaceuticals Holding Corp. 82 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

83. Slide 83: Possible Smallpox Prevention and Treatment Strategies

    © 2018 Tonix Pharmaceuticals Holding Corp. 83 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

84. Slide 84: Viral Replication Proficiency: Immunogenicity vs. Safety

    © 2018 Tonix Pharmaceuticals Holding Corp. 84 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

85. Slide 85: Manufacturing and Dosing Requirements

    © 2018 Tonix Pharmaceuticals Holding Corp. 85 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

86. Slide 86: Rationale for Developing a Potentially Improved Smallpox Vaccine

    © 2018 Tonix Pharmaceuticals Holding Corp. 86 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

87. Slide 87: Potential for HPXV as a Vaccine Vector

    © 2018 Tonix Pharmaceuticals Holding Corp. 87 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

88. Slide 88: Management Team

    © 2018 Tonix Pharmaceuticals Holding Corp. 88 Management Team Seth Lederman, MD President & CEO Jessica Morris Chief Operating Officer Gregory Sullivan, MD Chief Medical Officer Bradley Saenger, CPA Chief Financial Officer

89. Slide 89: Board of Directors

    © 2018 Tonix Pharmaceuticals Holding Corp. 89 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

90. Slide 90: Milestones: Recently Completed and Upcoming

    © 2018 Tonix Pharmaceuticals Holding Corp. 90 Milestones – Recently Completed and Upcoming T onmya – Posttraumatic Stress Disorder □ July 201 8 HONOR study discontinued – interim analysis result did not support study continuation □ August 201 8 Presentation of HONOR study results at scientific meeti

91. Slide 91: Summary

    © 2018 Tonix Pharmaceuticals Holding Corp. 91 Summary Phase 3 Breakthrough Therapy development for PTSD focused on military - related PTSD • Major unmet need; ~11 million Americans affected • Potential single - study NDA submission New indication in development for agitation in Alzheimer’s Disease •

92. Slide 92: Thank you!

    © 2018 Tonix Pharmaceuticals Holding Corp. Thank you ! NASDAQ: TNXP

Tonix Pharmaceuticals Holding — Investor Presentation (August 2018) on 6ix