Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Investor Presentation (November 2019)

140 slides from Tonix Pharmaceuticals's investor presentation, Nov 4, 2019

1. Slide 1: Investor Presentation, November 2019

   © 2019 Tonix Pharmaceuticals Holding Corp. November 2019 Version P0203 11 - 4 - 19 (Doc 0549) 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

   © 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 Clinical Development

   © 2019 Tonix Pharmaceuticals Holding Corp. 4 CNS Candidates in Clinical Development Psychiatry, Pain and Addiction 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 7 TNX - 1300 6 Cocaine intoxic

5. Slide 5: Preclinical Pipeline

   © 2019 Tonix Pharmaceuticals Holding Corp. 5 Preclinical Pipeline 1 1 (Experimental new medicines and biologics, not approved for any indication 2 (2S,4R,5R) - 5 - (((2 - aminobenzo[d]thiazol - 6 - yl)methyl)amino) - 2 - (bis(4 - fluorophenyl)methyl)tetrahydro - 2H - pyran - 4 - ol) is an inhibitor

6. Slide 6: The focus of TNX-102 SL development is both unique and innovative

   © 2019 Tonix Pharmaceuticals Holding Corp. 6 The focus of TNX - 102 SL development is both unique and innovative • Testing the therapeutic benefit of sleep (‘sleep quality’) − Restorative sleep, in contrast to time spent sleeping (‘sleep quantity’) • Targeting clinical conditions for which improved

7. Slide 7: TNX-102 SL Intellectual Property

   © 2019 Tonix Pharmaceuticals Holding Corp. 7 TNX - 102 SL Intellectual Property – U.S. Protection expected until 2035 • United States Patent and Trademark Office (USPTO) issued U.S. Patent No. 9636408 in May 2017, U.S. Patent No. 9956188 in May 2018, U.S. Patent No. 10117936 in Nov 2018, and U.S. Pa

8. Slide 8: Overview of Posttraumatic Stress Disorder (PTSD)

   © 2019 Tonix Pharmaceuticals Holding Corp. 8 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

9. Slide 9: Impact of PTSD on People

   © 2019 Tonix Pharmaceuticals Holding Corp. 9 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:

10. Slide 10: PTSD: U.S. Prevalence and Index Traumas

    © 2019 Tonix Pharmaceuticals Holding Corp. 10 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

11. Slide 11: Prevalence of PTSD Among Civilians and Veterans

    © 2019 Tonix Pharmaceuticals Holding Corp. 11 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

12. Slide 12: PTSD Prevalence and Market Characteristics

    © 2019 Tonix Pharmaceuticals Holding Corp. 12 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)

13. Slide 13: What Drug Classes are Used to Treat PTSD?

    © 2019 Tonix Pharmaceuticals Holding Corp. 13 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

14. Slide 14: PTSD: Not Well-Served by Approved Treatments

    © 2019 Tonix Pharmaceuticals Holding Corp. 14 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

15. Slide 15: Why Initially Targeted Military-Related PTSD?

    © 2019 Tonix Pharmaceuticals Holding Corp. 15 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

16. Slide 16: Growing Economic and Social Burden to Care for Veterans with PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 16 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

17. Slide 17: TNX-102 SL: a Potential Bedtime Treatment for PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 17 TNX - 102 SL: 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 TNX - 102 SL 5.6 mg had a strong sign

18. Slide 18: No Recognized Abuse Potential in Clinical Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 18 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

19. Slide 19: Sublingual Formulation is Designed for Bedtime Administration

    © 2019 Tonix Pharmaceuticals Holding Corp. 19 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

20. Slide 20: Proprietary Cyclobenzaprine Eutectic Mixture Stabilizes Sublingual Tablet

    © 2019 Tonix Pharmaceuticals Holding Corp. 20 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 -

21. Slide 21: Hypothesized Novel Mechanism Targets Sleep Quality for Recovery from PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 21 TNX - 102 SL: 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 - depend

22. Slide 22: Serotonin, REM Sleep and Extinction Consolidation

    © 2019 Tonix Pharmaceuticals Holding Corp. 22 • 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

23. Slide 23: Proposed Mechanism of Action of TNX-102 SL in PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 23 Proposed Mechanism of Action of TNX - 102 SL 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 histaminerg

24. Slide 24: Fear Extinction Memory Consolidation and P-Waves

    © 2019 Tonix Pharmaceuticals Holding Corp. 24 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

25. Slide 25: Phase 2 P201/AtEase Study in Military-Related PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 25 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 •

26. Slide 26: P201/AtEase Study

    © 2019 Tonix Pharmaceuticals Holding Corp. 26 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

27. Slide 27: P201/AtEase Summary of Primary and Secondary Analyses

    © 2019 Tonix Pharmaceuticals Holding Corp. 27 P201/AtEase Study – Summary of Primary and Secondary Analyses (Week 12)

28. Slide 28: P301/HONOR Study

    © 2019 Tonix Pharmaceuticals Holding Corp. 28 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 (TNX - 102 SL 5.6 mg vs. placebo ) Unblinded interim analysis at 274 randomize

29. Slide 29: P301/HONOR Primary Analysis in mITT Population

    © 2019 Tonix Pharmaceuticals Holding Corp. 29 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

30. Slide 30: Differences Between P201/AtEase and P301/HONOR Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 30 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

31. Slide 31: P201 and P301 Demographics and Characteristics

    © 2019 Tonix Pharmaceuticals Holding Corp. 31 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

32. Slide 32: Phase 2 Dose-Effect in Military-Related PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 32 TNX - 102 SL Phase 2 Dose - Effect in Military - Related PTSD 1 1 Completed Phase 2 P201/AtEase study: Retrospective analysis of TNX - 102 SL 5.6 mg on CAPS - 5 ≥33 (high - moderate) subgroup. Primary analysis of P201/ AtEase , based on TNX - 102 SL 2.8

33. Slide 33: Primary Outcome in Phase 3 Study by Time Since Trauma

    © 2019 Tonix Pharmaceuticals Holding Corp. Primary Outcome (CAPS - 5) in Phase 3 Study: mITT and ≤9 Years Time Since Trauma Subgroup 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%

34. Slide 34: Retrospective Comparison of Time Since Trauma in P201 versus P301

    © 2019 Tonix Pharmaceuticals Holding Corp. 34 Retrospective Comparison of Time Since Trauma in P201/AtEase versus P301/HONOR (TNX - 102 SL 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 medi

35. Slide 35: CAPS-5 Change Difference from Placebo in TST Subgroups

    © 2019 Tonix Pharmaceuticals Holding Corp. 35 CAPS - 5 Mean Change from Baseline Difference from Placebo of TNX - 102 SL 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 su

36. Slide 36: PTSD Treatment Response in Phase 2 and Phase 3 Studies

    © 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

37. Slide 37: Sustained Remission in Phase 2 and Phase 3 Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 37 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

38. Slide 38: Sustained Remission in P201 with and without Oral AEs

    © 2019 Tonix Pharmaceuticals Holding Corp. 38 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

39. Slide 39: Retrospective Analyses of ≤9 Years Since Trauma Subgroup

    © 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

40. Slide 40: Adverse Events in P201 and P301 Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 40 Adverse Events (AEs) in P201/AtEase and P301/HONOR Studies No serious or unexpected AEs in P201 or P301 related to TNX - 102 SL • Systemic AEs comparable between studies and also consistent with those described in approved oral cyclobenzaprine product la

41. Slide 41: Time Since Trauma – Review of Published Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 41 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

42. Slide 42: Time Since Trauma – Remitting and Persistent Phases of PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 42 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

43. Slide 43: Response to TNX-102 SL for Female Participants in P301

    © 2019 Tonix Pharmaceuticals Holding Corp. 43 Response to TNX - 102 SL 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 TNX - 102 SL 5.6 mg (N=10) w

44. Slide 44: Non-combat traumas similar to civilian PTSD traumas

    © 2019 Tonix Pharmaceuticals Holding Corp. 44 Non - combat traumas studied are similar to traumas experienced in civilian populations with PTSD To determine the therapeutic effects of TNX - 102 SL 5.6 mg in a mixed civilian and military population, difference in MCFB in CAPS - 5 was assessed in non

45. Slide 45: Summary of Clinical Experience with TNX-102 SL in PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 45 Summary of Clinical Experience with TNX - 102 SL/ 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 • Ti

46. Slide 46: Phase 3 P302/RECOVERY Study

    © 2019 Tonix Pharmaceuticals Holding Corp. 46 TNX - 102 SL for PTSD: Phase 3 P302/RECOVERY Study Expecting Interim Analysis Results in 1Q 2020 Potential pivotal efficacy study to support NDA approval Primary e ndpoint: • CAPS - 5 1 mean change from baseline at Week 12 (TNX - 102 SL 5.6 mg vs. placeb

47. Slide 47: Commercialization Options

    © 2019 Tonix Pharmaceuticals Holding Corp. 47 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

48. Slide 48: Multi-Functional Mechanism Involves Antagonism at 3 Neuronal Receptors

    © 2019 Tonix Pharmaceuticals Holding Corp. 48 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

49. Slide 49: Cyclobenzaprine Effects on Nerve Cell Signaling

    © 2019 Tonix Pharmaceuticals Holding Corp. 49 Cyclobenzaprine Effects on Nerve Cell Signaling Untreated Effects of TNX - 102 SL Cyclobenzaprine is a multi - functional drug - SNARI - inhibits serotonin and norepinephrine reuptake - blocks serotonin 5 - HT 2A and norepinephrine a 1 receptors SNARI =

50. Slide 50: Comparison of TNX-102 SL with Drugs Used Off-Label in PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 50 Comparison of TNX - 102 SL with Drugs Used Off - Label in PTSD TNX - 102 SL Trazodone Trazodone (disordered sleep ), prazosin (night terrors) - Trazodone inhibits serotonin 5HT 2A receptors and serotonin reuptake (SARI) - Prazosin blocks norepinephrine a

51. Slide 51: Opportunities to Expand to Other Indications

    © 2019 Tonix Pharmaceuticals Holding Corp. 51 v Opportunities to Expand to Other Indications Psychiatric Disorders • Stress Disorders (PTSD) • Mood Disorders • Anxiety Disorders Chronic Pain States • Chronic wide - spread pain (fibromyalgia) • Osteoarthritis Role of sleep disturbance more establishe

52. Slide 52: Bedtime Treatment for Multiple Potential Indications

    © 2019 Tonix Pharmaceuticals Holding Corp. 52 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

53. Slide 53: Fibromyalgia as a pain alarm disorder

    © 2019 Tonix Pharmaceuticals Holding Corp. 53 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

54. Slide 54: Fibromyalgia: Market Characteristics

    © 2019 Tonix Pharmaceuticals Holding Corp. 54 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 (~6 - 12 million adults) Diagnosed 2 ~2.7 million Market Characteristics Prevalence • One of the more common ch

55. Slide 55: Fewer than Half of Those Treated Receive Complete Relief

    © 2019 Tonix Pharmaceuticals Holding Corp. 55 Fewer than Half of Those Treated for Fibromyalgia Receive Complete Relief 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 effect

56. Slide 56: Large Need for New Fibromyalgia Therapies

    © 2019 Tonix Pharmaceuticals Holding Corp. 56 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

57. Slide 57: Completed Phase 3 Study F301 Summary and Results

    © 2019 Tonix Pharmaceuticals Holding Corp. 57 TNX - 102 SL 2.8 mg for Fibromyalgia: Summary of Completed Phase 3 Study F301 and Results 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

58. Slide 58: F301 Study Results and Program Updates

    © 2019 Tonix Pharmaceuticals Holding Corp. 58 TNX - 102 SL 2.8 mg 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

59. Slide 59: Planned New Phase 3 F304 Study

    © 2019 Tonix Pharmaceuticals Holding Corp. 59 TNX - 102 SL 5.6 mg for Fibromyalgia: Planned New Phase 3 F304 Study Primary e ndpoint (week 14) : • Daily diary pain severity score change (TNX - 102 SL 5.6 mg vs. placebo) from Baseline in the weekly average by numerical rating scale (NRS) analyzed by

60. Slide 60: What is Agitation in Alzheimer's Disease?

    © 2019 Tonix Pharmaceuticals Holding Corp. 60 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

61. Slide 61: Consequences of Agitation in Alzheimer's Disease

    © 2019 Tonix Pharmaceuticals Holding Corp. 61 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

62. Slide 62: Agitation in Alzheimer's – Additional Indication for TNX-102 SL

    © 2019 Tonix Pharmaceuticals Holding Corp. 62 Agitation in Alzheimer’s Disease – Additional Indication Being Developed for TNX - 102 SL Significant unmet need • No FDA approved drugs for the treatment of agitation in Alzheimer’s Mechanism of improving sleep quality • Sleep disturbance is a significa

63. Slide 63: Regulatory Status and Registration Strategy

    © 2019 Tonix Pharmaceuticals Holding Corp. 63 TNX - 102 SL for Agitation in Alzheimer’s – Regulatory Status and Registration Strategy Proposed Phase 2 IND study can potentially serve as a pivotal efficacy study to support NDA approval • FDA comments on final protocol received October 2018 Registrati

64. Slide 64: Addressing Challenges in Treating Agitation in Alzheimer's

    © 2019 Tonix Pharmaceuticals Holding Corp. 64 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

65. Slide 65: Scientific Rationale for Agitation in Alzheimer's Disease

    © 2019 Tonix Pharmaceuticals Holding Corp. 65 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

66. Slide 66: Protective Barriers in the Central and Peripheral Nervous Systems

    © 2019 Tonix Pharmaceuticals Holding Corp. 66 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

67. Slide 67: Proteins Accumulate in Extracellular Space During Wakefulness

    © 2019 Tonix Pharmaceuticals Holding Corp. 67 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

68. Slide 68: During Sleep, CSF-Brain Barrier Allows Debris to Clear

    © 2019 Tonix Pharmaceuticals Holding Corp. 68 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

69. Slide 69: Sleep-Wake Cycles Alter Permeability of the CSF-Brain Barrier

    © 2019 Tonix Pharmaceuticals Holding Corp. 69 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

70. Slide 70: Competitive Landscape of Select Drugs in Development

    © 2019 Tonix Pharmaceuticals Holding Corp. 70 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

71. Slide 71: Potential Treatment for Alcohol Use Disorder

    © 2019 Tonix Pharmaceuticals Holding Corp. 71 TNX - 102 SL: Potential Treatment for Alcohol Use Disorder (AUD) AUD is a chronic relapsing brain disease • Characterized by compulsive alcohol use, loss of control over alcohol intake, and a negative emotional state when not using Sleep disturbance is e

72. Slide 72: CNS Candidates in Clinical Development

    © 2019 Tonix Pharmaceuticals Holding Corp. 72 CNS Candidates in Clinical Development Psychiatry, Pain and Addiction 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 7 TNX - 1300 6 Cocaine intoxi

73. Slide 73: Preclinical Pipeline

    © 2019 Tonix Pharmaceuticals Holding Corp. 73 Preclinical Pipeline 1 1 (Experimental new medicines and biologics, not approved for any indication 2 (2S,4R,5R) - 5 - (((2 - aminobenzo[d]thiazol - 6 - yl)methyl)amino) - 2 - (bis(4 - fluorophenyl)methyl)tetrahydro - 2H - pyran - 4 - ol) is an inhibitor

74. Slide 74: TNX-1300 for the Treatment of Cocaine Intoxication

    © 2019 Tonix Pharmaceuticals Holding Corp. TNX - 1300* for the Treatment of Cocaine Intoxication Recombinant protein that degrades cocaine in the bloodstream 1 • Double - mutant cocaine esterase Phase 2 study completed by Rickett Benckiser (TNX - 1300 was formerly RBP - 8000) 2 • Volunteer cocaine a

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 Mechanism of Action

    Cocaine Mechanism of Action (MOA) When dopamine is released into the synapse, it stimulates dopamine receptors and triggers feelings of reward. 1,2 Dopamine Dopamine receptor Dopamine transporter 1. Benowitz NL. Pharmacol Toxicol . 1993. 2. Stahl SM. 4th ed. New York, NY: Cambridge University Press;

78. Slide 78: Cocaine MOA

    Cocaine MOA Dopamine Dopamine receptor Dopamine transporter Subsequently, dopamine is removed from the synapse and recycled by dopamine transporters . 1,2 1. Benowitz NL. Pharmacol Toxicol . 1993. 2. Stahl SM. 4th ed. New York, NY: Cambridge University Press; 2013.

79. Slide 79: Cocaine MOA

    Cocaine MOA Cocaine blocks dopamine transporters , leading to an accumulation of dopamine in the synapse and excessive stimulation of dopamine receptors . 1,2 Cocaine Dopamine Dopamine receptor Dopamine transporter 1. Benowitz NL. Pharmacol Toxicol . 1993. 2. Stahl SM. 4th ed. New York, NY: Cambridg

80. Slide 80: Cocaine Intoxication Result of Activity at Multiple Targets

    Cocaine Intoxication is the Result of Cocaine’s Activity at Multiple Targets 1. Brim et al. Mol Pharmacol . 2011. Psychosis Seizures Arrythmia Hypertension Hyperthermia The effects of cocaine intoxication include 1 : In addition to dopamine transporters, cocaine also blocks other targets 1 Dopamine

81. Slide 81: Pharmacotherapies for Cocaine Intoxication Have Not Been Effective

    © 2019 Tonix Pharmaceuticals Holding Corp. 81 Pharmacotherapies for Cocaine Intoxication Have Not Been Effective 1. Brim et al. Mol Pharmacol . 2011. 2. Melichar et al. Eur J Phamacol . 2003. 3. Narasimhan et al. Future Medicinal Chemistry. 2012. Opiates Simple; mediated by opioid receptors 2 Agonis

82. Slide 82: TNX-1300 Is a Fast-acting Cocaine Antidote

    © 2019 Tonix Pharmaceuticals Holding Corp. 82 TNX - 1300 (Cocaine Esterase or CocE ) Is a Fast - acting Cocaine Antidote CocE Rhodococcus bacteria living in the roots of the coca plant use CocE to metabolize cocaine 1 CocE cleaves chemical bonds in cocaine and disintegrates it 800 times faster than

83. Slide 83: Pharmacotherapies for Cocaine Intoxication Have Not Been Effective

    Pharmacotherapies for Cocaine Intoxication Have Not Been Effective • While simple pharmacological agents such as naloxone (Narcan ® ) are effective for the treatment of opiate intoxication 1 , a similar approach to treat cocaine intoxication is hampered by cocaine’s complex mechanism of action, or M

84. Slide 84: TNX-1300 cleaves cocaine in humans

    © 2019 Tonix Pharmaceuticals Holding Corp. 84 TNX - 1300 cleaves cocaine in humans and removes it from the blood circulation 1 (N=29) Time Required to Return to Baseline (minutes) 120 0 240 Pulse Rate Diastolic Blood Pressure Systolic Blood Pressure 60 180 Time (minutes) 120 240 0 Cocaine Plasma Con

85. Slide 85: Prevalence of Cocaine Usage and Overdose (U.S.)

    © 2019 Tonix Pharmaceuticals Holding Corp. 85 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

86. Slide 86: Cocaine Intoxication Is a Growing Problem in the U.S.

    Cocaine Intoxication Is a Growing Problem in the U.S. National Drug Overdose Deaths Involving Cocaine 0 5000 10000 15000 Cocaine is involved in more emergency department (ED) visits than any other illicit substance 1 Drug overdose deaths involving cocaine have increased dramatically in recent years

87. Slide 87: Treatment for Cocaine Intoxication

    © 2019 Tonix Pharmaceuticals Holding Corp. 87 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

88. Slide 88: 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 • An inventory of investigational drug product • Clinical trial results from previous Phase 2 study in which TNX - 130

89. Slide 89: CNS Candidates in Clinical Development

    © 2019 Tonix Pharmaceuticals Holding Corp. 89 CNS Candidates in Clinical Development Psychiatry, Pain and Addiction 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 7 TNX - 1300 6 Cocaine intoxi

90. Slide 90: Preclinical Pipeline

    © 2019 Tonix Pharmaceuticals Holding Corp. 90 Preclinical Pipeline 1 1 (Experimental new medicines and biologics, not approved for any indication 2 (2S,4R,5R) - 5 - (((2 - aminobenzo[d]thiazol - 6 - yl)methyl)amino) - 2 - (bis(4 - fluorophenyl)methyl)tetrahydro - 2H - pyran - 4 - ol) is an inhibitor

91. Slide 91: TNX-601 (Tianeptine Oxalate CR): Potential Daytime Treatment for PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 91 TNX - 601 * (Tianeptine Oxalate CR): A Potential Daytime Treatment for PTSD Pre - IND Candidate Targeted as a 1 st line monotherapy for PTSD: oral formulation for daytime dosing • Tianeptine sodium (amorphous), first marketed for depression in France in

92. Slide 92: TNX-601 for PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. TNX - 601* for PTSD Pharmacokinetic and safety study (ex - U.S.) of controlled release (CR) formulations underway • Targeting CR formulation for once - daily dosing Pre - IND meeting with FDA expected first half 2020 • Discussion of clinical development pla

93. Slide 93: Structural Comparison: TNX-102 and TNX-601

    © 2019 Tonix Pharmaceuticals Holding Corp. 93 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

94. Slide 94: TNX-1600 (Triple Reuptake Inhibitor)

    © 2019 Tonix Pharmaceuticals Holding Corp. 94 TNX - 1600 1 (Triple Reuptake Inhibitor): A Potential Daytime Treatment for PTSD Pre - IND Candidate Targeted as a 1 st line monotherapy for PTSD: oral formulation for daytime dosing x Leverages internal expertise in PTSD (clinical and regulatory experie

95. Slide 95: TNX-1500 (anti-CD154 monoclonal antibody)

    © 2019 Tonix Pharmaceuticals Holding Corp. 95 TNX - 1500 (monoclonal antibody anti - CD154): A Potential Treatment for Autoimmune Conditions and Organ Transplant Rejection Pre - IND Candidate Targeted as a 1 st line monotherapy for autoimmunity and add - on therapy for preventing and treating organ

96. Slide 96: About CD40L (CD154)

    © 2019 Tonix Pharmaceuticals Holding Corp. 96 About CD40L (CD154) Transiently expressed T cell surface molecule also known as CD40 - ligand 1 - 4 • Predominantly expressed by T cells • Interacts with CD40 on B cells and macrophages Mediates T cell helper function 1 - 4 • Activates B cells for humora

97. Slide 97: TNFα Superfamily

    © 2019 Tonix Pharmaceuticals Holding Corp. 97 TNF α Superfamily CD154 is a member of the Tumor Necrosis Factor (TNF α ) Super Family 1 • No mAb against CD154 has been licensed anywhere in the world Other TNF α Super Family members have proven to be targets for antagonist (blocking) mAbs 2 • anti - T

98. Slide 98: TNX-1500 (anti-CD40L) Transplantation/Autoimmune Asset

    © 2019 Tonix Pharmaceuticals Holding Corp. 98 TNX - 1500 (anti - CD40L (CD154)) Transplantation/Autoimmune treatment development asset • 3 rd generation of monoclonal antibody ( mAb ) for a class that has had extensive animal and human testing • Effects on T cell function with lower potential for si

99. Slide 99: TNX-1500 – Potential Treatment for Organ Transplant Rejection

    © 2019 Tonix Pharmaceuticals Holding Corp. 99 TNX - 1500 – Potential Treatment for Organ Transplant Rejection Facilitates ‘transplant tolerance’ in multiple preclinical transplant models • anti - CD154 therapy has a unique activity in controlling the immune response to organ transplants 1 - 3 • Sign

100. Slide 100: TNX-1500 – Potential Treatment for Autoimmune Disease

     © 2019 Tonix Pharmaceuticals Holding Corp. 100 TNX - 1500 – Potential Treatment for Autoimmune Disease Treats autoimmune conditions in multiple preclinical transplant models • anti - CD154 therapy has a unique activity in controlling the immune response in autoimmune models 1 - 3 • Significant need

101. Slide 101: Third Generation anti-CD154 Engineered to Decrease Thrombosis Risk

     © 2019 Tonix Pharmaceuticals Holding Corp. 101 Third Generation anti - CD154: Engineered to Potentially Decrease Risk of Thrombosis First generation anti - CD154 mAbs • Constant fragment (Fc) domain interacted with FcγRIIA (CD32A), which suggested a mechanism for increased risk of thrombosis 1,2 Sec

102. Slide 102: TNX-1700 (rTFF2): Potential Treatment for Gastric and Pancreatic Cancers

     © 2019 Tonix Pharmaceuticals Holding Corp. 102 TNX - 1700 (rTFF2): A Potential Treatment for Gastric and Pancreatic Cancers Pre - IND Candidate Targeted as a treatment for Cancer x Particularly for gastric and pancreatic cancer x Mechanism of Action (MOA) is different from checkpoint inhibitors x Po

103. Slide 103: TNX-1700 (rTFF2) for Potential Cancer Treatment

     © 2019 Tonix Pharmaceuticals Holding Corp. 103 TNX - 1700 (rTFF2) for Potential Cancer Treatment • Oncology development program • Recombinant trefoil family factor 2 (rTFF2) has effects on cancer cells and the tumor microenvironment 1,2 • Potential synergy with α nti - PD - 1/PD - L1 mAbs (Keytruda

104. Slide 104: Cancer: Toxic Tumor Microenvironment

     © 2019 Tonix Pharmaceuticals Holding Corp. 104 Cancer: Toxic Tumor Microenvironment • Tumor microenvironment sabotages immune T cells • Made up of blood vessels, inflammatory cells, and structural proteins • Difficult for cancer - killing immune T cells to penetrate • T cells detect and destroy canc

105. Slide 105: Trefoil Family Factor (rTFF2) and Cancer Biology

     © 2019 Tonix Pharmaceuticals Holding Corp. 105 Trefoil Family Factor 2 (rTFF2) and Cancer Biology • TFF2 is a small secreted protein • Encoded by the TFF2 gene in humans • Expressed in gastrointestinal mucosa where it functions to protect and repair mucosa • TFF2 is also expressed at low levels in s

106. Slide 106: Published Research on TNX-1700 by Dr. Wang at Columbia

     © 2019 Tonix Pharmaceuticals Holding Corp. 106 Published Research on TNX - 1700 (rTFF2) by Dr. Wang at Columbia • Either TFF2 overexpression or adenovirus - delivered rTFF2 markedly suppresses tumor growth 1,2 • Curtailed the proliferation and expansion of myeloid progenitors that give rise to myelo

107. Slide 107: TNX-801: Potential Smallpox-Preventing Vaccine

     © 2019 Tonix Pharmaceuticals Holding Corp. 107 TNX - 801 (Synthesized Live Horsepox Virus): A Potential Smallpox - Preventing Vaccine Pre - IND Stage Potential improvement over current biodefense tools against smallpox ✓ Leverages Tonix’s government affairs effort ✓ Collaboration with Professor Davi

108. Slide 108: TNX-801 Synthesized Live Horsepox Virus

     © 2019 Tonix Pharmaceuticals Holding Corp. 108 TNX - 801 (Synthesized Live Horsepox Virus): A Potential Smallpox - Preventing Vaccine 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 pox

109. Slide 109: The Currently Licensed Smallpox Vaccine ACAM2000

     © 2019 Tonix Pharmaceuticals Holding Corp. 109 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

110. Slide 110: HPXV and its Relationship to Other Orthopoxviruses

     110 © 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 Orthopoxviruse

111. Slide 111: HPXV Sequence and Synthesis

     111 © 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

112. Slide 112: HPXV Produces Small Plaques

     112 © 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

113. Slide 113: Production of Cell-Associated and Extracellular Virus

     113 © 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

114. Slide 114: HPXV Growth Characteristics

     114 © 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

115. Slide 115: Testing Vaccine Protective Activity of HPXV in Mice

     115 © 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

116. Slide 116: HPXV Less Virulent than Dryvax Clone, Protective Immunity

     116 © 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)

117. Slide 117: HPXV Vaccine Protection Activity

     117 © 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

118. Slide 118: No Overt Clinical Sign in HPXV Vaccinated Mice

     118 © 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 Afte

119. Slide 119: HPXV May Have an Improved Safety Profile

     © 2019 Tonix Pharmaceuticals Holding Corp. 119 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

120. Slide 120: Improved Smallpox-Preventing Vaccine is Important

     © 2019 Tonix Pharmaceuticals Holding Corp. 120 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

121. Slide 121: Current Needs to Vaccinate Against Smallpox

     © 2019 Tonix Pharmaceuticals Holding Corp. 121 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

122. Slide 122: TNX-801: A Potential Medical Countermeasure

     © 2019 Tonix Pharmaceuticals Holding Corp. 122 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: •

123. Slide 123: Possible advantages of TNX-801

     © 2019 Tonix Pharmaceuticals Holding Corp. 123 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

124. Slide 124: Evidence of Effectiveness for Smallpox Vaccine

     © 2019 Tonix Pharmaceuticals Holding Corp. 124 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

125. Slide 125: ACAM2000 – Best Technology of its Time

     © 2019 Tonix Pharmaceuticals Holding Corp. 125 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

126. Slide 126: Rationale for Developing a Potentially Improved Smallpox Vaccine

     © 2019 Tonix Pharmaceuticals Holding Corp. 126 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 [

127. Slide 127: Postulated Divergence of Historical Strains of Vaccinia

     © 2019 Tonix Pharmaceuticals Holding Corp. 127 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

128. Slide 128: Relationship to Smallpox Incidence and Eradication

     © 2019 Tonix Pharmaceuticals Holding Corp. 128 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

129. Slide 129: Evidence of Effectiveness of Smallpox Vaccines

     © 2019 Tonix Pharmaceuticals Holding Corp. 129 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

130. Slide 130: Possible Smallpox Prevention and Treatment Strategies

     © 2019 Tonix Pharmaceuticals Holding Corp. 130 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 ® /

131. Slide 131: Viral Replication Proficiency, Immunogenicity and Safety

     © 2019 Tonix Pharmaceuticals Holding Corp. 131 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

132. Slide 132: Manufacturing and Dosing Requirements

     © 2019 Tonix Pharmaceuticals Holding Corp. 132 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

133. Slide 133: Rationale for Improved Smallpox Vaccine Based on Jenner's Vaccine

     © 2019 Tonix Pharmaceuticals Holding Corp. 133 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

134. Slide 134: Potential for Use of HPXV as a Vector

     © 2019 Tonix Pharmaceuticals Holding Corp. 134 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

135. Slide 135: Management Team

     © 2019 Tonix Pharmaceuticals Holding Corp. 135 Management Team Seth Lederman, MD President & CEO Jessica Morris Chief Operating Officer Gregory Sullivan, MD Chief Medical Officer Bradley Saenger, CPA Chief Financial Officer

136. Slide 136: Board of Directors

     © 2019 Tonix Pharmaceuticals Holding Corp. 136 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

137. Slide 137: Milestones – Recently Completed and Upcoming

     © 2019 Tonix Pharmaceuticals Holding Corp. 137 Milestones – Recently Completed and Upcoming □ March 2019 P302/RECOVERY study initiated □ April 2019 Received FDA formal minutes with clear guidance and support for new Phase 3 FM study using TNX - 102 SL 5.6 mg □ May 2019 In - licensed TNX - 1300, prod

138. Slide 138: Pipeline Summary – by Select Therapeutic Areas

     © 2019 Tonix Pharmaceuticals Holding Corp. 138 Pipeline Summary – by Select Therapeutic Areas • Psychiatry/PTSD: • TNX - 102 SL – (sublingual cyclobenzaprine) for PTSD • Phase 3 • TNX - 601 – (tianeptine) for PTSD • Phase 1 formulation development • TNX - 1600 – (triple reuptake inhibitor) for PTSD

139. Slide 139: Pipeline Summary – by Phase of Development

     © 2019 Tonix Pharmaceuticals Holding Corp. 139 Pipeline Summary – by Phase of Development Two Phase 3 Programs in indications affecting millions of Americans • TNX - 102 SL for PTSD: affects an estimated 12 million adults in U.S. • TNX - 102 SL for Fibromyalgia: affects an estimated 6 - 12 million a

140. Slide 140: Thank you!

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

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