Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Investor Presentation (June 2019)

120 slides from Tonix Pharmaceuticals's investor presentation, Jun 3, 2019

1. Slide 1: Investor Presentation June 2019

   © 2019 Tonix Pharmaceuticals Holding Corp. June 2019 Version P0185 6 - 3 - 19 (Doc 0496) Investor Presentation

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

   © 2019 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, what we do

   © 2019 Tonix Pharmaceuticals Holding Corp. 3 Tonix Pharmaceuticals Who we are: • A clinical stage biopharmaceutical company dedicated to developing innovative treatments for patients and making meaningful contributions to society • Focusing on small molecules and biologics to treat psychiatric, pain

4. Slide 4: CNS Candidates in Development

   © 2019 Tonix Pharmaceuticals Holding Corp. 4 CNS Candidates in Development Psychiatry, Pain and Addiction Preclinical Phase 2 NDA 3 /BLA 4 Market Pipeline Product Indication Phase 3 TNX - 102 SL 1 Bedtime Treatment for PTSD – Tonmya ®2 Daytime Treatment for PTSD TNX - 601 Novel salt discovered and c

5. Slide 5: Biodefense Candidates in Development

   © 2019 Tonix Pharmaceuticals Holding Corp. 5 Biodefense Candidates in Development 1 NDA - New Drug Application; 2 BLA – Biologic Licensing Application Biodefense programs owned outright with no royalties due Preclinical Phase 2 NDA 1 /BLA 2 Market Pipeline Product Indication Phase 3 TNX - 801 Horsep

6. Slide 6: Lead Program: TNX-102 SL Product Concept

   © 2019 Tonix Pharmaceuticals Holding Corp. 6 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

7. Slide 7: Improving Sleep Quality Across Indications

   © 2019 Tonix Pharmaceuticals Holding Corp. 7 A unique and innovative approach (improving sleep quality), to potentially address a constellation of disorders in a variety of therapeutic areas where sleep disturbances are co - morbid and believed to have a role in the onset, progression and severity o

8. Slide 8: TNX-102 SL Intellectual Property

   © 2019 Tonix Pharmaceuticals Holding Corp. 8 TNX - 102 SL Intellectual Property – U.S. Protection until 2034 • United States Patent and Trademark Office (USPTO) issued U.S. Patent No. 9,636,408 in May 2017, U.S. Patent No. 9,956,188 in May 2018 and U.S. Patent No. 10,117,936 in Nov 2018 • Japanese P

9. Slide 9: Overview of PTSD

   © 2019 Tonix Pharmaceuticals Holding Corp. 9 Overview of Posttraumatic Stress Disorder (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

10. Slide 10: Impact of PTSD on People

    © 2019 Tonix Pharmaceuticals Holding Corp. 10 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

11. Slide 11: PTSD: U.S. Prevalence and Index Traumas

    © 2019 Tonix Pharmaceuticals Holding Corp. 11 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

12. Slide 12: Prevalence of PTSD Among Civilians and Veterans

    © 2019 Tonix Pharmaceuticals Holding Corp. 12 Prevalence of PTSD Among Civilians and Veterans 1 Goldstein et al., 2016 (adjusted for 2019) ; 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

13. Slide 13: PTSD Prevalence and Market Characteristics

    © 2019 Tonix Pharmaceuticals Holding Corp. 13 PTSD Prevalence and Market Characteristics 1 Goldstein et al., 2016 (adjusted for 2019) 2 Veterans: VA/DOD Clinical Practice Guidelines for the Managements of PTSD and Acute Stress Disorder, 2017, page 15 (619,493 vets diagnosed with PTSD in VA for 2016)

14. Slide 14: What Drug Classes are Used to Treat PTSD?

    © 2019 Tonix Pharmaceuticals Holding Corp. 14 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

15. Slide 15: PTSD: Not Well-Served by Approved Treatments

    © 2019 Tonix Pharmaceuticals Holding Corp. 15 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 male PTSD patients unresponsive or intolerant

16. Slide 16: Why Initially Target Military-Related PTSD?

    © 2019 Tonix Pharmaceuticals Holding Corp. 16 Why Initially Targeted 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 we

17. Slide 17: Economic and Social Burden of Veterans with PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 17 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

18. Slide 18: Tonmya: Potential Bedtime Treatment for PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 18 Tonmya : a Potential Bedtime Treatment for PTSD First investigational new drug to show treatment effect in military - related PTSD in two potential pivotal efficacy studies • Phase 2 study (P201/ AtEase ) showed Tonmya 5.6 mg had a strong signal of treat

19. Slide 19: No Recognized Abuse Potential in Clinical Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 19 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

20. Slide 20: Sublingual Formulation Designed for Bedtime Administration

    © 2019 Tonix Pharmaceuticals Holding Corp. 20 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

21. Slide 21: Proprietary Eutectic Mixture Stabilizes Sublingual Tablet

    © 2019 Tonix Pharmaceuticals Holding Corp. 21 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 -

22. Slide 22: Hypothesized Novel Mechanism Targets Sleep Quality

    © 2019 Tonix Pharmaceuticals Holding Corp. 22 Tonmya: Hypothesized 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 me

23. Slide 23: Proposed Mechanism: Nocturnal 5-HT2A Receptor Blockade

    © 2019 Tonix Pharmaceuticals Holding Corp. 23 • 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

24. Slide 24: Effects of Nocturnal Neuroreceptor Blockade on Sleep

    © 2019 Tonix Pharmaceuticals Holding Corp. 24 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

25. Slide 25: Fear Extinction Memory Consolidation and P-Waves

    © 2019 Tonix Pharmaceuticals Holding Corp. 25 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

26. Slide 26: Phase 2 P201/AtEase Study Design

    © 2019 Tonix Pharmaceuticals Holding Corp. 26 Phase 2 P201/AtEase 1 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 2 ≥ 29 •

27. Slide 27: P201/AtEase Study Results

    © 2019 Tonix Pharmaceuticals Holding Corp. 27 P201/AtEase Study P201 was a large adequate well - controlled Phase 2 study in military - related PTSD • Primary endpoint (Week 12 CAPS - 5) did not separate from placebo for TNX - 102 SL 2.8 mg • No safety or tolerability issue discovered • Retrospectiv

28. Slide 28: P201/AtEase Summary of Primary and Secondary Analyses

    © 2019 Tonix Pharmaceuticals Holding Corp. 28 P201/AtEase Study – Summary of Primary and Secondary Analyses (Week 12)

29. Slide 29: P301/HONOR Study Design and Interim Result

    © 2019 Tonix Pharmaceuticals Holding Corp. 29 P301/HONOR 1 Study – Evidence of Efficacy at Week 4 Discontinued Due to High Placebo Response at Week 12 Primary e ndpoint CAPS - 5 2 : • Mean change from baseline at W eek 12 (Tonmya 5.6 mg vs. placebo ) Unblinded interim analysis at 274 randomized part

30. Slide 30: P301/HONOR Primary Analysis in mITT Population

    © 2019 Tonix Pharmaceuticals Holding Corp. 30 P301/HONOR Study - Primary Analysis in mITT Population In P301 study both TNX - 102 SL and placebo - treated groups improved but the greater improvement on TNX - 102 SL compared with placebo diminished over time • TNX - 102 SL did not separate from place

31. Slide 31: Differences Between P201 and P301 Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 31 Differences Between P201/AtEase and P301/HONOR Studies Design Phase 2 and 3 studies were very similar – both studied military related PTSD at multiple sites in the US • CAPS - 5 ≥ 33 entry criteria used in Phase 3 BDI - II= Beck Depression Inventory - II

32. Slide 32: P201 and P301 Demographics and Characteristics

    © 2019 Tonix Pharmaceuticals Holding Corp. 32 P201/AtEase and P301/HONOR Demographics and Characteristics The striking difference between P201 and P301 was time since trauma • Phase 2 P201 study recruited many participants from the surge in Iraq who were mostly <9 years since trauma

33. Slide 33: Tonmya Dose-Effect in Military-Related PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 33 Tonmya Phase 2 Dose - Effect in Military - Related PTSD 1 1 Completed Phase 2 P201/AtEase study: Retrospective analysis of Tonmya 5.6 mg on CAPS - 5 ≥33 (high - moderate) subgroup. Primary analysis of P 201/ AtEase , based on Tonmya 2.8 mg in participant

34. Slide 34: Primary Outcome in mITT and ≤9 Years Subgroups

    © 2019 Tonix Pharmaceuticals Holding Corp. Primary Outcome (CAPS - 5) in Phase 3 ( mITT ) and ≤9 Years Time Since Trauma Subgroups Modified intent to treat ( mITT ) population Phase 3 P301/HONOR Study 1 ** p=0.004, * p=0.039, # p=0.069, TNX - 102 SL 5.6 mg group v. placebo, using MMRM with MI ~50% m

35. Slide 35: Time Since Trauma in P201 versus P301

    © 2019 Tonix Pharmaceuticals Holding Corp. 35 Retrospective Comparison of Time Since Trauma in P201/AtEase versus P301/HONOR (Tonmya 5.6 mg Groups) P301 study was initiated approximately two years later than Phase 2 P201 • The median time since trauma in P301 was 9.5 years compared to the median tim

36. Slide 36: CAPS-5 Difference from Placebo by Time Since Trauma

    © 2019 Tonix Pharmaceuticals Holding Corp. 36 CAPS - 5 Mean Change from Baseline Difference from Placebo of Tonmya 5.6 mg in TST Subgroups in P301 1 MCFB=mean change from baseline; ‘N’=number of participants in group; PBO=placebo; TST=time since trauma • The mITT population was divided into subgroup

37. Slide 37: PTSD Treatment Response in Phase 2 and Phase 3 Subgroups

    © 2019 Tonix Pharmaceuticals Holding Corp. P201 Baseline CAPS - 5 ≥33 (majority TST 1 ≤9 yr ) **p<0.01, *p=0.017, TNX - 102 SL 5.6 mg group v. placebo, using mixed model repeated measures (MMRM) with multiple imputation (MI) P301 TST ≤9 yr ** p=0.004, * p=0.039, # p=0.069 TNX - 102 SL 5.6 mg group v

38. Slide 38: Sustained Remission in Phase 2 and Phase 3 Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 38 Sustained Remission in Phase 2 and Phase 3 Studies: Retrospective Analyses of P201 Entry CAPS - 5 ≥33 and P301 ≤9 Years Since Trauma Subgroups Remission is a clinical state that is essentially asymptomatic In order to confirm remission: • Determined rate

39. Slide 39: Sustained Remission in P201 With and Without Oral AEs

    © 2019 Tonix Pharmaceuticals Holding Corp. 39 Sustained Remission in P201/ AtEase Study Retrospective Analyses of Phase 2 Subgroups with and without Oral AE’s (ON/OT/NT) Oral numbness (ON), oral tingling (OT) and noticeable taste (NT) are local administration site reactions that are potentially unbl

40. Slide 40: ≤9 Years Subgroup on Primary and Secondary Endpoints

    © 2019 Tonix Pharmaceuticals Holding Corp. BOLDED p - values are all p<0.05; BDI - II=Beck Depression CAPS - 5=Clinician - Administered PTSD Scale for DSM - 5; CGI - I=Clinical Global Impression – Improvement scale; mITT =modified Intent - to - Treat sample; MMRM=mixed model repeated measures analys

41. Slide 41: ≤9 Years Subgroup on Key Secondary Endpoints

    © 2019 Tonix Pharmaceuticals Holding Corp. 41 Retrospective Analyses of ≤9 Years Since Trauma Subgroup on Key Secondary Endpoints in P301/HONOR Study Key secondary endpoints showed strong treatment effects • CGI - I, PGIC and PROMIS SD were pre - specified secondary analyses • Supports CAPS - 5 resu

42. Slide 42: Adverse Events in P201 and P301 Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 42 Adverse Events (AEs) in P201/AtEase and P301/HONOR Studies No serious or unexpected AEs in P201 or P301 related to Tonmya • Systemic AEs comparable between studies and also consistent with those described in approved oral cyclobenzaprine product labeling

43. Slide 43: Time Since Trauma: Review of Published Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 43 Time Since Trauma – Review of Published Studies Published studies of prazosin suggested effects in military - PTSD prior to 9 years • Loss of treatment effect >9 years Paroxetine and sertraline studies supporting FDA approval were conducted on PTSD > 9 y

44. Slide 44: Remitting and Persistent Phases of PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 44 Time Since Trauma – Remitting and Persistent Phases of PTSD Kessler et al 1 studied remission in PTSD with and without therapy • Identified remitting and persistent phase of PTSD – with transition at approximately 6 years post trauma • Supported by other

45. Slide 45: Response for Female Participants in P301

    © 2019 Tonix Pharmaceuticals Holding Corp. 45 Response to Tonmya for Female Participants in P301/HONOR Study 1 Females made up only 11% of the P301/HONOR study mITT population Difference in mean change from baseline in CAPS - 5 in females between placebo (N=17) and Tonmya 5.6 mg (N=10) was: • At 4 w

46. Slide 46: Response for Non-Combat Traumas in P301

    © 2019 Tonix Pharmaceuticals Holding Corp. 46 Non - combat traumas studied are similar to traumas experienced in civilian populations with PTSD To determine the therapeutic effects of Tonmya 5.6 mg in a mixed civilian and military population, difference in MCFB in CAPS - 5 was assessed in non - comb

47. Slide 47: Summary of Clinical Experience in PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 47 Summary of Clinical Experience with Tonmya/ TNX - 102 SL in PTSD Median time since trauma (TST) in TNX - 102 SL 5.6 mg group in the P301/HONOR study (9.5 years) was longer than P201/AtEase study (6 years) • Both studied military - related PTSD • Time has

48. Slide 48: New Phase 3 P302/RECOVERY Study

    © 2019 Tonix Pharmaceuticals Holding Corp. 48 New Phase 3 P302/RECOVERY Study – Initiated 1Q 2019 Primary e ndpoint: • CAPS - 5 1 mean change from baseline at Week 4 ( Tonmya 5.6 mg vs. placebo) Key Secondary e ndpoint s include: • CAPS - 5 m ean change from baseline at W eek 12 (Tonmya 5.6 mg vs. p

49. Slide 49: Late-Stage PTSD Drug Candidates

    © 2019 Tonix Pharmaceuticals Holding Corp. 49 Late - Stage PTSD Drug Candidates Tonmya • Phase 3 development focused on military - related and civilian PTSD; showed activity in treatment of military - related PTSD in large multi - center trials MDMA - assisted psychotherapy • Indication – “drug assi

50. Slide 50: Commercialization Options

    © 2019 Tonix Pharmaceuticals Holding Corp. 50 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 mee

51. Slide 51: Multi-Functional Mechanism: Antagonism at 3 Neuronal Receptors

    © 2019 Tonix Pharmaceuticals Holding Corp. 51 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

52. Slide 52: Effects of Cyclobenzaprine as a Multi-Functional Drug

    © 2019 Tonix Pharmaceuticals Holding Corp. 52 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

53. Slide 53: Tonmya, Trazodone and Prazosin Comparison

    © 2019 Tonix Pharmaceuticals Holding Corp. 53 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

54. Slide 54: Opportunities to Expand to Other Indications

    © 2019 Tonix Pharmaceuticals Holding Corp. 54 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

55. Slide 55: Bedtime Treatment for Multiple Potential Indications

    © 2019 Tonix Pharmaceuticals Holding Corp. 55 TNX - 102 SL – Bedtime Treatment for Multiple Potential Indications Ma nagement of Fibromyalgia (FM) – chronic pain condition • TNX - 102 SL 2.8 mg (half the dose being developed for PTSD) studied in Phase 2/3 trials – did not separate from placebo on pr

56. Slide 56: Fibromyalgia as a Pain Alarm Disorder

    © 2019 Tonix Pharmaceuticals Holding Corp. 56 Volkswagen Check Engine [Photograph]. (2011, October 14). Wikipedia • Pain is a sensor system in the brain similar to a check engine light on a car’s dashboard • When the check engine light malfunctions, the light is on even though the car is not malfunc

57. Slide 57: Fibromyalgia: Market Characteristics

    © 2019 Tonix Pharmaceuticals Holding Corp. 57 Fibromyalgia: Market Characteristics Undiagnosed ~2.7 million Drug Treated 85% 3 2,366,400 No Drug 15%3 353,600 U.S. Prevalence Rate 2 - 4% 1 (~5 - 10 million adults) Diagnosed 2 ~2.7 million Market Characteristics Prevalence • One of the more common chr

58. Slide 58: Fewer than Half Benefit from FDA-Approved Fibromyalgia Drugs

    © 2019 Tonix Pharmaceuticals Holding Corp. 58 Fewer than Half of Those Treated for Fibromyalgia Receive Sustained Benefit from the Three FDA - Approved Drugs 1 • The treatment objective is to restore functionality and quality of life by broadly improving symptoms while avoiding significant side effe

59. Slide 59: Need for New Fibromyalgia Therapies

    © 2019 Tonix Pharmaceuticals Holding Corp. 59 Large Need for New Fibromyalgia Therapies that Provide Broad Symptom Improvement with Better Tolerability • Currently - approved medications may have side effects that limit long - term use 1 • Many patients skip doses or discontinue altogether within mo

60. Slide 60: Fibromyalgia Phase 3 F301 Study Summary

    © 2019 Tonix Pharmaceuticals Holding Corp. 60 TNX - 102 SL for Fibromyalgia: Summary of a completed Phase 3 F301 study General s tudy c haracteristics: • Randomized, 12 - week, double - blind, placebo - controlle d Phase 3 study of TNX - 102 SL 2.8 mg (half the dose being developed for PTSD) taken d

61. Slide 61: F301 Study Results and Program Updates

    © 2019 Tonix Pharmaceuticals Holding Corp. 61 TNX - 102 SL for Fibromyalgia: F301 Study Results and Program Updates Safety results: • Good tolerability and low rates of systemic AEs. • The most common AEs were generally mild and transient events related to the sublingual administration of the study

62. Slide 62: What is Agitation in Alzheimer's Disease?

    © 2019 Tonix Pharmaceuticals Holding Corp. 62 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

63. Slide 63: Consequences of Agitation in Alzheimer's Disease

    © 2019 Tonix Pharmaceuticals Holding Corp. 63 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

64. Slide 64: Agitation in Alzheimer's: Additional Indication for TNX-102 SL

    © 2019 Tonix Pharmaceuticals Holding Corp. 64 Agitation in Alzheimer’s Disease – Additional Indication Being Developed for TNX - 102 SL FDA designated Fast Track development program Significant unmet need • No FDA approved drugs for the treatment of agitation in Alzheimer’s Mechanism of improving sl

65. Slide 65: Regulatory Status and Registration Strategy for AAD

    © 2019 Tonix Pharmaceuticals Holding Corp. 65 TNX - 102 SL for Agitation in Alzheimer’s – Regulatory Status and Registration Strategy FDA confirmed no additional study was needed prior to IND submission • Pre - IND meeting established open dialogue with the FDA on pivotal clinical study design and e

66. Slide 66: TNX-102 SL Addresses Challenges in Treating Agitation

    © 2019 Tonix Pharmaceuticals Holding Corp. 66 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

67. Slide 67: Scientific Rationale for TNX-102 SL in Agitation

    © 2019 Tonix Pharmaceuticals Holding Corp. 67 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

68. Slide 68: Protective Barriers in the Nervous Systems

    © 2019 Tonix Pharmaceuticals Holding Corp. 68 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 n

69. Slide 69: Protein Accumulation in Extracellular Space During Wakefulness

    © 2019 Tonix Pharmaceuticals Holding Corp. 69 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

70. Slide 70: CSF-Brain Barrier More Permeable During Sleep

    © 2019 Tonix Pharmaceuticals Holding Corp. 70 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

71. Slide 71: Sleep-Wake Cycles Alter CSF-Brain Barrier Permeability

    © 2019 Tonix Pharmaceuticals Holding Corp. 71 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 – wa

72. Slide 72: Agitation in Alzheimer's Competitive Landscape

    © 2019 Tonix Pharmaceuticals Holding Corp. 72 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

73. Slide 73: CNS Candidates in Development

    © 2019 Tonix Pharmaceuticals Holding Corp. 73 CNS Candidates in Development Psychiatry, Pain and Addiction Preclinical Phase 2 NDA 3 /BLA 4 Market Pipeline Product Indication Phase 3 TNX - 102 SL 1 Bedtime Treatment for PTSD – Tonmya ®2 Daytime Treatment for PTSD TNX - 601 Novel salt discovered and

74. Slide 74: Biodefense Candidates in Development

    © 2019 Tonix Pharmaceuticals Holding Corp. 74 Biodefense Candidates in Development 1 NDA - New Drug Application; 2 BLA – Biologic Licensing Application Biodefense programs owned outright with no royalties due Preclinical Phase 2 NDA 1 /BLA 2 Market Pipeline Product Indication Phase 3 TNX - 801 Horse

75. Slide 75: About TNX-1300

    © 2019 Tonix Pharmaceuticals Holding Corp. 75 About TNX - 1300 Produced through rDNA technology in non - disease - producing strain of E. coli. • Cocaine Esterase ( CocE ) was identified in bacteria ( Rhodococcus ) that use cocaine as its sole source of carbon and nitrogen and that grow in soil surr

76. Slide 76: About Cocaine and Cocaine Intoxication

    © 2019 Tonix Pharmaceuticals Holding Corp. 76 About Cocaine and Cocaine Intoxication Cocaine: an illegal recreational drug taken for its pleasurable effects and associated euphoria. • Cocaine blocks the reuptake of the neurotransmitter dopamine (DA) in the CNS • Results in accumulation of DA within

77. Slide 77: Cocaine Action

    © 2019 Tonix Pharmaceuticals Holding Corp. 77 Cocaine Action • Cocaine acts to inhibit the Dopamine Reuptake Transporter • Binds to transporter and blocks reuptake of dopamine from synapse • No antagonist has been developed for cocaine • Unlike situation for opiates which can be blocked by naloxone

78. Slide 78: Cocaine Action: Lack of Antidote

    © 2019 Tonix Pharmaceuticals Holding Corp. 78 Cocaine Action – Lack of “Antidote” • Cocaine binding site on Dopamine Reuptake Transporter is too small or simple for a blocker • Antagonists of cocaine binding have the same function as cocaine • Naltrexone exploits the complexity of the opiate binding

79. Slide 79: CocE Breaks Cocaine Down into Less Toxic Metabolites

    © 2019 Tonix Pharmaceuticals Holding Corp. 79 CocE is a Catalyst that Breaks Cocaine Down into Less Toxic Metabolites 1 - 4 Cocaine Ecgonine Methyl Ester Benzoic Acid • Metabolites ecgonine methyl ester and benzoic acid are neither pleasurable nor addictive 1 Bresler MM et al, Appl Environ Microbiol

80. Slide 80: Prevalence of Cocaine Usage and Overdose

    © 2019 Tonix Pharmaceuticals Holding Corp. 80 The Prevalence of Cocaine Usage and Overdose (U.S.) Cocaine Usage in the U.S. 5.07 million individuals estimated to have used cocaine in past year 1 • 2.2 million “current” (i.e. users in the past month) of cocaine (2017) 2 • 966,000 had cocaine use diso

81. Slide 81: Mortality Due to Cocaine Overdose

    © 2019 Tonix Pharmaceuticals Holding Corp. 81 Mortality Due to Cocaine Overdose Cocaine is involved in 20% of overdose deaths in the U.S. • In 2016, 10,375 deaths due to cocaine overdose 1 • In 2017, about 13,900 deaths occurred in the U.S. due to cocaine overdose. 2 Overdose deaths involving cocain

82. Slide 82: Treatment for Cocaine Intoxication

    © 2019 Tonix Pharmaceuticals Holding Corp. 82 Treatment for Cocaine Intoxication Current Standard of Care • Patients present with acute agitation, hyperthermia, tachycardia, arrhythmias, and hypertension • Potential life - threatening sequalae of myocardial infarction, cerebrovascular accident, rhab

83. Slide 83: Value of TNX-1300 to Tonix

    © 2019 Tonix Pharmaceuticals Holding Corp. Value of TNX - 1300 to Tonix Features of the Acquired Asset: • Full rights to the IP and to develop and commercialize TNX - 1300 worldwide • FDA Breakthrough Therapy Designated product • An inventory of investigational drug product • Clinical trial results

84. Slide 84: CNS Candidates in Development

    © 2019 Tonix Pharmaceuticals Holding Corp. 84 CNS Candidates in Development Psychiatry, Pain and Addiction Preclinical Phase 2 NDA 3 /BLA 4 Market Pipeline Product Indication Phase 3 TNX - 102 SL 1 Bedtime Treatment for PTSD – Tonmya ®2 Daytime Treatment for PTSD TNX - 601 Novel salt discovered and

85. Slide 85: Biodefense Candidates in Development

    © 2019 Tonix Pharmaceuticals Holding Corp. 85 Biodefense Candidates in Development 1 NDA - New Drug Application; 2 BLA – Biologic Licensing Application Biodefense programs owned outright with no royalties due Preclinical Phase 2 NDA 1 /BLA 2 Market Pipeline Product Indication Phase 3 TNX - 801 Horse

86. Slide 86: TNX-601 (Tianeptine Oxalate): Potential Clinical Candidate for PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 86 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

87. Slide 87: Structural Comparison: TNX-102 and TNX-601

    © 2019 Tonix Pharmaceuticals Holding Corp. 87 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

88. Slide 88: TNX-801 Synthesized Live Horsepox Virus Vaccine Candidate

    © 2019 Tonix Pharmaceuticals Holding Corp. 88 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

89. Slide 89: TNX-801: Synthesis and Relation to Modern Vaccines

    © 2019 Tonix Pharmaceuticals Holding Corp. 89 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

90. Slide 90: ACAM2000 Currently Licensed Smallpox Vaccine

    © 2019 Tonix Pharmaceuticals Holding Corp. 90 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

91. Slide 91: HPXV and Its Relationship to Other Orthopoxviruses

    91 © 2019 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

92. Slide 92: HPXV Sequence and Genome Assembly

    92 © 2019 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

93. Slide 93: HPXV Produces Small Plaques Like Cowpox

    93 © 2019 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

94. Slide 94: Production of Cell-Associated and Extracellular Virus

    94 © 2019 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

95. Slide 95: HPXV Growth Characteristics

    95 © 2019 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

96. Slide 96: Testing Vaccine Protective Activity of HPXV in Mice

    96 © 2019 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

97. Slide 97: HPXV Less Virulent than Dryvax Clone, Protective Immunity

    97 © 2019 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):

98. Slide 98: HPXV Vaccine Protection Observed at Low Doses

    98 © 2019 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.

99. Slide 99: No Overt Clinical Signs in HPXV Vaccinated Mice

    99 © 2019 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

100. Slide 100: HPXV May Have Improved Safety Profile

     © 2019 Tonix Pharmaceuticals Holding Corp. 100 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 associa

101. Slide 101: Improved Smallpox Vaccine Important for Public Health

     © 2019 Tonix Pharmaceuticals Holding Corp. 101 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 Accid

102. Slide 102: Current Needs to Vaccinate Against Smallpox

     © 2019 Tonix Pharmaceuticals Holding Corp. 102 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 popula

103. Slide 103: TNX-801: Potential Medical Countermeasure

     © 2019 Tonix Pharmaceuticals Holding Corp. 103 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: •

104. Slide 104: TNX-801 Mechanism of Action and Possible Advantages

     © 2019 Tonix Pharmaceuticals Holding Corp. 104 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 ex

105. Slide 105: Evidence of Effectiveness for Smallpox Vaccine

     © 2019 Tonix Pharmaceuticals Holding Corp. 105 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 vac

106. Slide 106: ACAM2000: Best Technology of its Time

     © 2019 Tonix Pharmaceuticals Holding Corp. 106 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

107. Slide 107: Rationale for Developing Improved Smallpox Vaccine

     © 2019 Tonix Pharmaceuticals Holding Corp. 107 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 [

108. Slide 108: Postulated Divergence of Historical Vaccinia Strains

     © 2019 Tonix Pharmaceuticals Holding Corp. 108 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=I

109. Slide 109: Relationship to Smallpox Incidence and Eradication

     © 2019 Tonix Pharmaceuticals Holding Corp. 109 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 V

110. Slide 110: Evidence of Effectiveness of Smallpox Vaccines

     © 2019 Tonix Pharmaceuticals Holding Corp. 110 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

111. Slide 111: Possible Smallpox Prevention and Treatment Strategies

     © 2019 Tonix Pharmaceuticals Holding Corp. 111 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 ® /

112. Slide 112: Viral Replication Critical to Immunogenicity but May Compromise Safety

     © 2019 Tonix Pharmaceuticals Holding Corp. 112 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 m

113. Slide 113: Manufacturing and Dosing Requirements

     © 2019 Tonix Pharmaceuticals Holding Corp. 113 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

114. Slide 114: Rationale for Improved Smallpox Vaccine Based on Jenner's Vaccine

     © 2019 Tonix Pharmaceuticals Holding Corp. 114 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 Vac

115. Slide 115: HPXV as a Vector for Vaccines

     © 2019 Tonix Pharmaceuticals Holding Corp. 115 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 ins

116. Slide 116: Management Team

     © 2019 Tonix Pharmaceuticals Holding Corp. 116 Management Team Seth Lederman, MD President & CEO Jessica Morris Chief Operating Officer Gregory Sullivan, MD Chief Medical Officer Bradley Saenger, CPA Chief Financial Officer

117. Slide 117: Board of Directors

     © 2019 Tonix Pharmaceuticals Holding Corp. 117 Board of Directors Seth Lederman, MD Chairman Adeoye “Oye” Olukotun, MD Squibb, BMS, Mallinckrodt, Esperion John Rhodes Chair, NYS Public Service Commission, CEO, NYS Dept. of Public Service, Booz Allen James Treco First Chicago, Salomon Brothers/Citigr

118. Slide 118: Milestones: Recently Completed and Upcoming

     © 2019 Tonix Pharmaceuticals Holding Corp. 118 Milestones – Recently Completed and Upcoming □ July 201 8 Completed P301/HONOR study interim analysis - result did not support study continuation but strengthened new Phase 3 study □ August 201 8 Presentation of P301/HONOR study results at Military Heal

119. Slide 119: Summary

     © 2019 Tonix Pharmaceuticals Holding Corp. 119 Summary Two Phase 3 Programs in indications affecting millions of Americans • Tonmya for PTSD: affects 12 million adults in U.S.; currently in Phase 3 with data expected next year; bedtime treatment • TNX - 102 SL for Fibromyalgia: affects between 5 - 1

120. Slide 120: Thank you!

     © 2019 Tonix Pharmaceuticals Holding Corp. Thank you ! NASDAQ: TNXP

Tonix Pharmaceuticals Holding — Investor Presentation (June 2019) on 6ix