Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Investor Presentation (December 2024)

85 slides from Tonix Pharmaceuticals's investor presentation, Dec 3, 2024

1. Slide 1: TNX-102 SL Lead Indication: Fibromyalgia; Additional Indication: Acute Stress Disorder

   TNX - 102 SL Lead Indication : Fibromyalgia Additional Indication: Acute Stress Disorder NASDAQ: TNXP December 2024 © 2024 Tonix Pharmaceuticals Holding Corp. PO6027 December 3, 2024 (Doc 1539)

2. Slide 2: Fibromyalgia Status and TNX-102 SL Overview

   Fibromyalgia Status: Two statistically significant Phase 3 studies completed; FDA granted Fast Track Designation • First pivotal Phase 3 study (RELIEF) completed • Second Phase 3 study (RALLY) missed primary endpoint • Confirmatory pivotal Phase 3 study (RESILIENT) completed • Submitted New Drug App

3. Slide 3: About Fibromyalgia

   3 CNS PORTFOLIO About Fibromyalgia Fibromyalgia is considered a chronic overlapping pain condition (COPC) 5 - the only COPC with any FDA - approved drugs 6 Fibromyalgia is the prototypic nociplastic syndrome Multisite pain Non - Restorative Sleep Fibromyalgia is a chronic pain disorder resulting fro

4. Slide 4: The Third Primary Type of Pain: Nociplastic Pain

   4 CNS PORTFOLIO The Third Primary Type of Pain: Nociplastic Pain 1 - 5 Nociplastic syndrome includes: (1) widespread pain (2) fatigue (3) sleep disturbances (4) cognitive dysfunction (“brain fog”) Nociplastic Pain Examples: Fibromyalgia CFS/ ME* Long COVID Migraine PCS** IBS*** Endometriosis Low Bac

5. Slide 5: Fibromyalgia Believed to Result from Chronic Pain or Prior Stress

   5 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Fibromyalgia is Believed to Result from Chronic Pain or Prior Stress Experiences 1 - 2 Stresses that may precede or precipitate FM include: Chronic nociceptive pain • e.g. , osteoarthritis Chronic neuropathic pain • e.g. , diabetic neuropath

6. Slide 6: Common Chronic Conditions are a Challenge for Pharma

   6 CNS PORTFOLIO Common Chronic Conditions are a Challenge for Pharma © 2024 Tonix Pharmaceuticals Holding Corp. Fibromyalgia is a common chronic disease 1 - 3 • Chronic pain syndrome that persists for years or decades No animal model is recognized for nociplastic syndromes or its component symptoms

7. Slide 7: Common Chronic Conditions are a Challenge for Society

   7 CNS PORTFOLIO Common Chronic Conditions are a Challenge for Society © 2024 Tonix Pharmaceuticals Holding Corp. The Opiate Crisis in the U.S. was driven by mistreatment of chronic pain, which was often nociplastic pain • The epidemic of prescription pain killers was addressed by regulations which l

8. Slide 8: Fibromyalgia is a Large, Underserved and Dissatisfied Population

   8 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Fibromyalgia is a Large, Underserved and Dissatisfied Population • More than 10 million U.S. adults are affected – predominantly women 1,2 ‒ Debilitating and life altering condition ‒ Significant economic impact • Patients have expressed dis

9. Slide 9: Poor Sleep and Pain have Bi-directional Reinforcing Effects

   9 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Poor Sleep and Pain have Bi - directional Reinforcing Effects 1 1 Moldofsky H, et al. J Rheumatol . 1996;23:529 – 533. 2 Grönbald M, et al. Clin Rheumatol . 1993;12(2):186 – 191 • Poor sleep and pain form a vicious cycle in driving fibromyal

10. Slide 10: Fibromyalgia: Unrefreshing Sleep and Cyclobenzaprine Treatment

    10 CNS PORTFOLIO Fibromyalgia: Unrefreshing Sleep and Cyclobenzaprine Treatment 1 Moldofsky H et al. Psychosom Med. 1975. 37:341 - 51. 2 Moldofsky H and Scarisbrick P. Psychosom Med. 1976. 38:35 - 44. 3 Bennett RM, et al. Arthritis Rheum 1988. 31:1535 – 42. 4 Quimby LG, et al . J Rheumatol Suppl, 19

11. Slide 11: Fibromyalgia Program Status

    11 CNS PORTFOLIO Fibromyalgia Program Status Fibromyalgia TNX - 102 SL Cyclobenzaprine Sublingual Tablets NDA Submitted to FDA in October 2024 1 Lederman S, et al. Arthritis Care Res (Hoboken) . 2023 Nov;75(11):2359 - 2368. doi: 10.1002. © 2024 Tonix Pharmaceuticals Holding Corp. First pivotal Phase

12. Slide 12: Phase 3 RESILIENT Study Population

    12 Phase 3 RESILIENT Study Population © 2024 Tonix Pharmaceuticals Holding Corp.

13. Slide 13: RESILIENT Study Design

    13 CNS PORTFOLIO TNX - 102 SL: P hase 3 RESILIENT Study Design General study characteristics: • Randomized, double - blind, multicenter, placebo - controlled study in fibromyalgia • 33 U.S. sites enrolled 457 participants with fibromyalgia as defined by 2016 Revisions to the 2010/2011 FM Diagnostic

14. Slide 14: RESILIENT Demographics and Baseline Characteristics

    14 CNS PORTFOLIO RESILIENT Demographics and Baseline Characteristics © 2024 Tonix Pharmaceuticals Holding Corp. Placebo (N=225) TNX - 102 SL (N=231) 49.5 (11.35)* 49.3 (10.45)* Age (years) 211 (93.8%) † 224 (97.0%) † Female 35 (15.6%) † 36 (15.6%) † Hispanic or Latino 192 (85.3%) † 194 (84.0%) † Whi

15. Slide 15: RESILIENT Characteristics of Study Population

    CNS PORTFOLIO RESILIENT Characteristics of Study Population Pain Scores • Patients are asked to record “their average pain” for each day ‒ ‘Average’ pain for the day will almost always be lower than ‘worst’ pain for a patient’s day • Baseline pain for randomization a) A mean pain intensity score ≥4

16. Slide 16: RESILIENT Study Efficacy Findings

    RESILIENT Study Efficacy Findings 16 © 2024 Tonix Pharmaceuticals Holding Corp.

17. Slide 17: Summary of Primary and Key Secondary Endpoints

    17 CNS PORTFOLIO RESILIENT Summary of Primary and Key Secondary Endpoints © 2024 Tonix Pharmaceuticals Holding Corp. *In order of statistical serial gate - keeping hierarchy (or, “waterfall”) to control overall Type 1 error **Statistical significance met Effect Size (ES) P - value Endpoint Primary E

18. Slide 18: Primary Outcome Measure: Reduction in Widespread Pain

    18 CNS PORTFOLIO RESILIENT Primary Outcome Measure Reduction in Widespread Pain Weekly Average of Daily Diary NRS Ratings of Average Pain Over Prior 24 Hours - 2 - 1.8 - 1.6 - 1.4 - 1.2 - 1 - 0.8 - 0.2 - 0.4 - 0.6 0 LS Mean (SE) Change in NRS Pain Score - 2.2 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Week

19. Slide 19: Continuous Pain Responder Graph

    19 CNS PORTFOLIO RESILIENT Continuous Pain Responder Graph # Analyses: Pearson’s Chi Squared test for equality of proportions Abbreviations: CI, confidence interval; DIP, difference in proportions ^pre - specified analyses but not key secondary analyses Percent of Subjects 100 90 80 70 60 50 40 30 2

20. Slide 20: Patient Global Impression of Change

    20 CNS PORTFOLIO RESILIENT Patient Global Impression of Change Key Secondary Outcome Measure Week 14 TNX - 102 SL responders 35.1%, and placebo responders 19.1%; difference in proportions (95% CI) 16% (7.9%, 24.0%); p=0.00013 # # Based on a Pearson Chi - Squared with differences in proportions 95% C

21. Slide 21: FIQ-R Symptoms Domain

    21 CNS PORTFOLIO RESILIENT FIQ - R Symptoms Domain Key Secondary Outcome Measure * *** *** *** Week 14 LS mean (SE) change from baseline for TNX - 102 SL - 16.0 (1.17) and for placebo - 8.4 (1.17); LSMD from placebo - 7.7 (1.62); p=0.000002 # # Based on Mixed Model Repeated Measures with Multiple Im

22. Slide 22: FIQ-R Function Domain

    CNS PORTFOLIO RESILIENT FIQ - R Function Domain Key Secondary Outcome Measure Week 14 LS mean (SE) change from baseline for TNX - 102 SL - 12.2 (1.19) and for placebo - 6.8 (1.21); LSMD from placebo - 5.4 (1.66); p=0.001 # # Based on Mixed Model Repeated Measures with Multiple Imputation, with fixed

23. Slide 23: PROMIS Sleep Disturbance Inventory

    CNS PORTFOLIO RESILIENT PROMIS Sleep Disturbance Inventory Key Secondary Outcome Measure Week 14 LS mean (SE) change from baseline for TNX - 102 SL - 8.4 (0.57) and for placebo - 4.2 (0.56); LSMD from placebo - 4.2 (0.79); p=0.0000001 # # Based on Mixed Model Repeated Measures with Multiple Imputati

24. Slide 24: PROMIS Fatigue Inventory

    CNS PORTFOLIO RESILIENT PROMIS Fatigue Inventory Key Secondary Outcome Measure Week 14 LS mean (SE) change from baseline for TNX - 102 SL - 7.2 (0.55) and for placebo - 4.2 (0.56); LSMD from placebo - 3.0 (0.77); p=0.00009 # # Based on Mixed Model Repeated Measures with Multiple Imputation, with fix

25. Slide 25: Sleep Quality by Daily Diary

    25 CNS PORTFOLIO Week 14 LS mean (SE) change from baseline for TNX - 102 SL - 1.77 (0.12) and for placebo - 1.20 (0.12); LSMD from placebo - 0.57 (0.17); p=0.0007 # RESILIENT Sleep Quality by Daily Diary Key Secondary Outcome Measure Weekly Average of Daily Diary NRS Ratings of Prior Night Sleep Qua

26. Slide 26: Summary of Primary Endpoint and Key Secondary Efficacy Endpoints

    26 CNS PORTFOLIO RESILIENT Summary of Primary Endpoint and Key Secondary Efficacy Endpoints © 2024 Tonix Pharmaceuticals Holding Corp. Fibromyalgia is a syndrome composed of symptoms • Widespread pain • Fatigue • Sleep disturbance Efficacy across symptoms of pain, fatigue and sleep • Pain (primary e

27. Slide 27: CSFQ - Females Exploratory Endpoint

    27 CNS PORTFOLIO RESILIENT : CSFQ - 14 Females Pre - specified exploratory endpoint Pleasure Desire/Frequency Desire/Interest Arousal/Excitement Orgasm/Completion Desire Total Total Score 0.1 [ - 0.0, 0.30] [192/201] 0.3 [0.10, 0.5] [192/204] 0.0 [ - 0.3, 0.4] [192/204] 0.3 [ - 0.10, 0.60] [192/204]

28. Slide 28: FIQR Individual Items

    28 CNS PORTFOLIO RESILIENT : FIQR Individual Items 1 Affective Symptoms, Sensory Sensitivity, Cognition, and Energy Pre - specified exploratory endpoint Selected Fibromyalgia Impact Questionnaire - Revised Symptoms Domain Item Scores Pre - specified exploratory endpoints Effect Size P - value^ 95% C

29. Slide 29: Beck Depression Inventory-II Exploratory Endpoint

    29 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT : Beck Depression Inventory - II Pre - specified Exploratory Endpoint Effect Size P - value 95% CI for Difference Difference in LS Means (SE) TNX LS MCFB (SE) TNX Mean (SD) Placebo LS MCFB (SE) Placebo Mean (SD) 9.6 (6.32) 10.0 (6

30. Slide 30: Summary of Baseline Depression BDI-II and FIQR Item

    30 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT : Summary of Baseline Depression BDI - II and FIQR Item • While the rate of current MDE diagnosis was ~2% of the ITT, ~25% ITT had experienced a lifetime MDE, and ~47% reported past 6 month depression on FM Dx* • Also, about 25% o

31. Slide 31: Summary of Efficacy: Primary Pain and Key Secondaries

    31 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Summary of Efficacy Primary Pain, and Key Secondaries • Pain (primary endpoint, daily pain diary): • Fatigue (PROMIS fatigue): • Sleep (PROMIS sleep disturbance): • Global (PGIC) • Symptoms (FIQR Symptoms • Function (FIQR Function

32. Slide 32: Summary of Efficacy Conclusion

    CNS PORTFOLIO RESILIENT Summary of Efficacy 32 © 2024 Tonix Pharmaceuticals Holding Corp. Conclusion: TNX - 102 SL has “broad spectrum” or “syndromal activity” • Broad spectrum: across several symptoms • Syndromal: improves the syndrome (most of the symptoms) • Potential for a broad - spectrum drug

33. Slide 33: RESILIENT Study Safety Findings

    RESILIENT Study Safety Findings 33 © 2024 Tonix Pharmaceuticals Holding Corp.

34. Slide 34: RESILIENT Subject Disposition

    CNS PORTFOLIO RESILIENT Subject Disposition 34 © 2024 Tonix Pharmaceuticals Holding Corp. Total TNX - 102 SL Placebo 457 231 226 Randomized 366 (80.1%) 187 (81.0%) 179 (79.2%) Completed 91 (19.9%) 44 (19.0%) 47 (20.8%) Discontinued 22 (4.8%) 14 (6.1%) 8 (3.5%) Adverse Event 10 (2.2%) 2 (0.9%) 8 (3.5

35. Slide 35: RESILIENT Prior Medication Use

    CNS PORTFOLIO RESILIENT Prior Medication Use **Indicated for management of fibromyalgia 35 © 2024 Tonix Pharmaceuticals Holding Corp. Total* N=457 Placebo N=226 TNX - 102 SL N=231 257 (56.2%) 133(58.8%) 124 (53.7%) At least one lifetime medication 147 (32.2%) 75 (33.2%) 72 (31.2%) Gabapentin/Pregaba

36. Slide 36: RESILIENT Washout Medications

    CNS PORTFOLIO RESILIENT Washout Medications **Indicated for management of fibromyalgia 36 © 2024 Tonix Pharmaceuticals Holding Corp. Total* N=457 Placebo N=226 TNX - 102 SL N=231 26 ( 5.7%) 12 ( 5.3%) 14 ( 6.1%) At least one washout medication 20 ( 4.4%) 10 ( 4.4%) 10 ( 4.3%) Nervous System Drug 6 (

37. Slide 37: RESILIENT Safety Summary

    CNS PORTFOLIO RESILIENT Safety Summary Among participants randomized to TNX - 102 SL and to placebo, 81.0% and 79.6%, respectively, completed the study TNX - 102 SL was generally well tolerated with an adverse event (AE) profile comparable to prior fibromyalgia studies • No new safety signals were o

38. Slide 38: Treatment-Emergent Adverse Events at Rate of 3% or More

    38 CNS PORTFOLIO RESILIENT Safety © 2024 Tonix Pharmaceuticals Holding Corp. Total* N=457 Placebo N=226 TNX - 102 SL N=231 System Organ Class Preferred Term Systemic Adverse Events 17 (3.7%) 7 (3.1%) 10 (4.3%) COVID - 19 10 (2.2%) 3 (1.3%) 7 (3.0%) Somnolence 11 (2.4%) 4 (1.8%) 7 (3.0%) Headache Ora

39. Slide 39: Analysis by Sensory Adverse Events

    39 CNS PORTFOLIO RESILIENT Analysis by Sensory Adverse Events (AEs) TNX - 102 SL group divided for presence/absence of 3 sensory AEs • AEs of oral numbness, oral tingling, and bitter aftertaste named ‘Sensory AEs’* • Graph shows negligible advantage for presence of sensory AEs • At Week 14: ‒ TNX -

40. Slide 40: Safety Continued: Blood Pressure and Weight

    40 CNS PORTFOLIO RESILIENT Safety, Continued © 2024 Tonix Pharmaceuticals Holding Corp. No Signals for Clinically Meaningful Changes in Systolic or Diastolic Blood Pressure or in Weight No clinically meaningful difference in mean systolic blood pressure between groups Week 14 mean (SD) change from b

41. Slide 41: Systolic Blood Pressure Safety Measure

    CNS PORTFOLIO RESILIENT Systolic blood pressure Safety Measure and vertical lines begin and end at the 5 th and 95 th percentiles. 41 © 2024 Tonix Pharmaceuticals Holding Corp. No clinically meaningful difference in mean systolic blood pressure between groups Week 14 mean (SD) change from baseline:

42. Slide 42: Diastolic Blood Pressure Safety Measure

    CNS PORTFOLIO RESILIENT Diastolic blood pressure Safety Measure 42 © 2024 Tonix Pharmaceuticals Holding Corp. No clinically meaningful difference in mean diastolic blood pressure between groups Week 14 mean (SD) change from baseline: TNX - 102 SL = 1.1 (8.60) mmHg Placebo = 0.2 (8.22) mmHg Horizonta

43. Slide 43: Weight Safety Measure

    CNS PORTFOLIO RESILIENT Weight Safety Measure and vertical lines begin and end at the 5 th and 95 th percentiles. 43 © 2024 Tonix Pharmaceuticals Holding Corp. No clinically meaningful difference in mean weight between treatment groups Week 14 mean (SD) change from baseline: TNX - 102 SL = 0.02 (2.9

44. Slide 44: Fibromyalgia Market Characteristics

    Fibromyalgia Market Characteristics 44 © 2024 Tonix Pharmaceuticals Holding Corp.

45. Slide 45: Fibromyalgia: Market Characteristics

    45 CNS PORTFOLIO Fibromyalgia: Market Characteristics © 2024 Tonix Pharmaceuticals Holding Corp. Prevalence • One of the more common chronic pain disorders (2 - 4% of US Population) 1 Diagnosed population • Large population but underdiagnosed 2 relative to prevalence rate • Majority receive drug tre

46. Slide 46: Fewer than Half of Those Treated Receive Sustained Benefit

    46 CNS PORTFOLIO Fewer than Half of Those Treated for Fibromyalgia Receive Sustained Benefit from the Three FDA - Approved Drugs 1 Respond, but intolerant of side effects Do not respond © 2024 Tonix Pharmaceuticals Holding Corp. 25% 35% 60% failure rate 1 The three drugs with FDA approval for the tr

47. Slide 47: Current FDA-Approved Fibromyalgia Drugs

    47 CNS PORTFOLIO Current FDA - Approved Fibromyalgia Drugs 1 © 2024 Tonix Pharmaceuticals Holding Corp. 1 The three drugs with FDA approval for the management of fibromyalgia are Pregabalin (Lyrica); Duloxetine (Cymbalta); Milnacipran (Savella) 2 Leung MTY, et al. JAMA Netw Open. 2024;7(11):e2444488

48. Slide 48: Large Need for New Fibromyalgia Therapies

    48 CNS PORTFOLIO Large Need for New Fibromyalgia Therapies that Provide Symptom Improvement with Better Tolerability 4 Berger A, Dukes E, Martin S, Edelsberg J, Oster G, Int J ClinPract, 2007; 61(9):1498 – 1508. © 2024 Tonix Pharmaceuticals Holding Corp. • Currently - approved medications may have s

49. Slide 49: Showed Activity on Pain, Sleep and Fatigue and Well Tolerated

    49 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL Showed Activity on Pain, Sleep and Fatigue and was Generally Well Tolerated in the RESILIENT Study 1 1 Flexeril® and Amrix® are oral formulations of cyclobenzaprine indicated for short term (2 - 3 weeks) treatment of muscle spa

50. Slide 50: ~50% of U.S. Fibromyalgia Patients are on Medicare

    50 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO ~50% of U.S. Fibromyalgia Patients are on Medicare: Prescription Coverage in Medicare Stands to Benefit from Changes in IRA Approximately 50% of fibromyalgia patients are on Medicare ‒ EVERSANA analysis of claims database consisting of 2.2M

51. Slide 51: Prescribers Expressed Broad Dissatisfaction with Available Medications

    51 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Prescribers Interviewed Expressed Broad Dissatisfaction with Available Fibromyalgia Medications: Results of Primary Research 1 Perspectives on FM Therapies from Prescribers Interviewed Negatives Positives Drug • Tolerability issues: worseni

52. Slide 52: Opportunity for a New, Unique Fibromyalgia Treatment Option

    52 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Opportunity for a New, Unique Fibromyalgia Treatment Option: Results of Primary Research from EVERSANA 1,2 • Prescribers indicate a very high unmet need in FM (ranked ≥4.0 on a 5 - point scale) • Prescribers report there is no standard of c

53. Slide 53: Many Patients Prescribed Off-Label Drugs

    53 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Many Fibromyalgia Patients are Prescribed Off - Label Drugs; ~53% FM Patients Prescribed Opioids Off - Label 1,2 1.04% 6.03% 11.74% 12.96% 13.23% 17.58% 19.45% 20.47% 25.50% 0% 5% 10% 25% 20% 15% 30% 50% 45% 40% 35% Milnacipran Amitriptylin

54. Slide 54: Potential for Tonix to Launch and Market

    54 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Potential for Tonix to Launch and Market TNX - 102 SL Decline in personal promotion (“Detailing”) of prescription drugs • The pandemic accelerated transition to non - personal promotion o Omnichannel is more important and more sophisticated

55. Slide 55: Planning for Launch and Marketing

    55 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Planning for TNX - 102 SL Launch and Marketing Several companies that successfully developed CNS drugs have launched them • Big Pharma wants the commercial launch de - risked before acquisition ( e.g. , Nurtec®) To prepare for the launch of

56. Slide 56: Milestones: Recently Completed and Upcoming

    56 © 2024 Tonix Pharmaceuticals Holding Corp. Milestones: Recently Completed and Upcoming TNX - 102 SL for the Management of Fibromyalgia Milestones x □ 4 th Quarter 2023 □ x 2 nd Quarter 2024 Statistically significant topline results of Phase 3 RESILIENT study – 2 nd statistically significant Phase

57. Slide 57: About Cyclobenzaprine and TNX-102 SL

    57 © 2024 Tonix Pharmaceuticals Holding Corp. About Cyclobenzaprine and TNX - 102 SL

58. Slide 58: Cyclobenzaprine Long-Term Utilization

    58 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Cyclobenzaprine Long - Term Utilization • Flexeril® approved in 1977 by Merck for the treatment of muscle spasm • 10 mg T.I.D. for acute use (2 - 3 weeks) • Original NDA included “ 8 long term safety studies in which patients with various n

59. Slide 59: Sublingual Administration and Transmucosal Delivery

    CNS PORTFOLIO TNX - 102 SL: Sublingual Administration and Transmucosal Delivery • Advantages of the sublingual route • Faster absorption provides PK that is ideal for bedtime dosing • Bypasses “first - pass” hepatic metabolism • Reduced metabolism of parent CBP to active metabolite norcyclobenzaprin

60. Slide 60: Formulation with Base Increases Systemic Absorption

    CNS PORTFOLIO Formulation with Base Increases Systemic Absorption of Sublingual Cyclobenzaprine 1 CBP - HCl Cyclobenzaprine free base Oral mucosa CBP - HCl Concentration gradient increases diffusion of free base across oral mucosa (Le Chatelier’s Principle) Low pH (acidic) High pH (basic) Systemic e

61. Slide 61: Proprietary Eutectic Formulation

    61 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL: Proprietary Eutectic Formulation • Proprietary Cyclobenzaprine HCL Eutectic Mixture Stabilizes Sublingual Tablet Formulation Base particle (K 2 HPO 4 ) Base particle (K 2 HPO 4 ) Base particle (K 2 HPO 4 ) Cyclobenzaprine - HC

62. Slide 62: Cyclobenzaprine Detected in Plasma Within Minutes

    62 CNS PORTFOLIO TNX - 102 SL: Cyclobenzaprine Detected in Plasma Within Minutes Following Sublingual Administration © 2024 Tonix Pharmaceuticals Holding Corp. Plasma Concentration Versus Time of TNX - 102 SL Compared to Cyclobenzaprine IR 0 0.5 1.0 1.5 Concentration (ng/L) 2500 1500 1000 500 2000 0

63. Slide 63: Single Dose PK Differentiation from Oral IR CBP

    63 CNS PORTFOLIO TNX - 102 SL: Single Dose PK Differentiation from Oral IR CBP © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL 2.8 mg v. Oral IR CBP 5 mg: Single Dose Pharmacokinetics PK = pharmacokinetics IR = immediate release CBP = cyclobenzaprine C max = maximum concentration AUC = Area

64. Slide 64: Multi-Dose PK Differentiation from Simulated Oral IR CBP

    CNS PORTFOLIO TNX - 102 SL: Multi - Dose PK Differentiation from Simulated Oral IR CBP 64 © 2024 Tonix Pharmaceuticals Holding Corp. Day 20 TNX - 102 SL 5.6 mg v. Simulated Oral IR 10 mg Steady State Pharmacokinetics (after 20 days dosing) Day 20 TNX - 102 SL 5.6 mg v. Simulated Oral IR 5 mg PK = ph

65. Slide 65: Multi-Functional Mechanism Involves Antagonism at Four Receptors

    CNS PORTFOLIO Multi - Functional Mechanism Involves Antagonism at Four Neuronal Receptors 65 © 2024 Tonix Pharmaceuticals Holding Corp. Active ingredient, cyclobenzaprine, interacts with four receptors • Antagonist at 5 - HT 2A receptors • Similar activity to trazodone and Nuplazid ® (pimivanserin)

66. Slide 66: Cyclobenzaprine Binding Affinities for Receptor and Transporter

    CNS PORTFOLIO Cyclobenzaprine Binding Affinities for Receptor and Transporter NET SERT M 1 α 1B α 1A 5 - HT 2A H 1 39 29 8.4 8 7.1 5.4 1.2 Cyclobenzaprine (CBP) 12.8 461 155 71 82 38 17.8 Norcyclobenzaprine (nCBP) Antagonist Inhibitor 66 © 2024 Tonix Pharmaceuticals Holding Corp. CBP/nCBP Activity

67. Slide 67: Cyclobenzaprine Effects on Nerve Cell Signaling

    CNS PORTFOLIO Cyclobenzaprine Effects on Nerve Cell Signaling Untreated Effects of TNX - 102 SL SNARI = Serotonin and Norepinephrine receptor Antagonist and Reuptake Inhibitor Cyclobenzaprine is a multi - functional drug – SNARI • inhibits serotonin and norepinephrine reuptake • blocks serotonin 5 -

68. Slide 68: No Recognized Abuse Potential in Clinical Studies

    CNS PORTFOLIO TNX - 102 SL: No Recognized Abuse Potential in Clinical Studies 68 © 2024 Tonix Pharmaceuticals Holding Corp. Active ingredient is cyclobenzaprine, which is structurally related to tricyclic antidepressants • Cyclobenzaprine interacts with receptors that regulate sleep quality: 5 - HT2

69. Slide 69: Sublingual Formulation Designed for Bedtime Administration

    69 CNS PORTFOLIO TNX - 102 SL: Sublingual Formulation is Designed for Bedtime Administration © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL: Proprietary sublingual formulation of cyclobenzaprine (CBP) with transmucosal absorption • Innovation by design with patent protected CBP/mannitol eut

70. Slide 70: Patents and Patent Applications

    70 CNS PORTFOLIO TNX - 102 SL: Patents and Patent Applications © 2024 Tonix Pharmaceuticals Holding Corp. • U.S. Composition:* • A 75:25 cyclobenzaprine HCl - mannitol eutectic (dependent claims add a basifying agent). • 5 US Patents (Expire November 2034) • 1 Pending US Application (Would expire No

71. Slide 71: TNX-102 SL for Other Indications In Development: Acute Stress Disorder

    71 TNX - 102 SL for Other Indications In Development: Acute Stress Disorder © 2024 Tonix Pharmaceuticals Holding Corp.

72. Slide 72: Acute Stress Reaction / Acute Stress Disorder

    72 CNS PORTFOLIO © 2024 Tonix Pharmaceuticals Holding Corp. Acute Stress Reaction (ASR)/ Acute Stress Disorder (ASD) ASR/ASD are acute stress conditions resulting from trauma which can affect both civilian and military populations. Large unmet need: • According to National Center for PTSD, about 60%

73. Slide 73: TNX-102 SL for ASR/ASD: Program Status

    73 CNS PORTFOLIO TNX - 102 SL for ASR/ASD: Program Status © 2024 Tonix Pharmaceuticals Holding Corp. Status: Expect to start investigator - initiated Phase 2 in 1Q 2025 Investigator - initiated Phase 2 Trial Funded by DoD grant to University of North Carolina (UNC) • UNC Institute for Trauma Recover

74. Slide 74: Phase 2 OASIS Study Design

    74 CNS PORTFOLIO TNX - 102 SL for ASR/ASD: Phase 2 OASIS Study Design General study characteristics: • Randomized, double - blind, placebo - controlled study in Acute Stress Reaction (ASR) / Acute Stress Disorder (ASD) • The proposed O ptimizing A cute S tress reaction Interventions with TNX - 102 S

75. Slide 75: Fibromyalgia and Long-COVID

    75 Fibromyalgia and Long - COVID © 2024 Tonix Pharmaceuticals Holding Corp.

76. Slide 76: Significant Overlap between Fibromyalgia and Long-COVID

    76 CNS PORTFOLIO Significant Overlap between Fibromyalgia and Long - COVID © 2024 Tonix Pharmaceuticals Holding Corp. National Institutes of Health (NIH) - sponsored RECOVER study found many Long COVID patients suffer from pain at multiple sites 1 • Suggests that many Long - COVID patients may meet

77. Slide 77: NASEM Definition of Long-COVID

    77 CNS PORTFOLIO NASEM Definition of Long - COVID © 2024 Tonix Pharmaceuticals Holding Corp. • In June 2024, the US National Academies of Sciences, Engineering and Medicine (NASEM) described fibromyalgia as a ‘ diagnosable condition’ in people suffering from Long COVID 1 • This definition provides g

78. Slide 78: NASEM Language Highlighted by Senate Appropriations Subcommittee

    78 CNS PORTFOLIO NASEM Language Highlighted by Senate Labor - HHS Appropriations Subcommittee (August 1, 2024) • Senate Appropriations Committee report on FY25 Labor, Health, and Human Services Appropriations Act includes language on Long COVID, fibromyalgia and nociplastic syndromes 1 1 FY25 Labor

79. Slide 79: Thank You

    THANK YOU © 2023 Tonix Pharmaceuticals Holding Corp.

80. Slide 80: Appendix

    APPENDIX © 2023 Tonix Pharmaceuticals Holding Corp.

81. Slide 81: RALLY Study Increased Adverse Event-Related Discontinuations

    81 CNS PORTFOLIO TNX - 102 SL: RALLY Study Increased Adverse Event - Related Discontinuations TEAE = treatment - emergent adverse event Increases in AE - Related discontinuations in RALLY study compared with RELIEF study in both placebo and TNX - 102 SL groups Adverse events in RALLY • TNX - 102 SL

82. Slide 82: RALLY Study Impact of Missing Data on p-Values

    82 CNS PORTFOLIO TNX - 102 SL: RALLY Study Impact of Missing Data on p - Values in RALLY MI missing data treatment attenuated p - values in RALLY • At the current time, we expect MI will be part of the statistical analysis for the RESILIENT trial FIQR = Fibromyalgia Impact Questionnaire - Revised; L

83. Slide 83: Chronic Overlapping Pain Conditions Believed to Result from Shared Brain Processes

    83 CNS PORTFOLIO Chronic Overlapping Pain Conditions (COPC) Believed to Result from Shared Brain Processes • COPC is a set of disorders that co - aggregate; these disorders can include but are not limited to 1,2 : • Temporomandibular disorder • Fibromyalgia • Irritable bowel syndrome • Vulvodynia •

84. Slide 84: Central Sensitization: A Feature of Many Nociplastic Pain Syndromes

    84 CNS PORTFOLIO Central Sensitization (CS) A Feature of Many Nociplastic Pain Syndromes • CS is caused by amplified neural signaling in CNS pain circuits 1 - 3 • Patients with CS perceive higher pain to a slightly noxious stimuli than in non - CS individuals (hyperalgesia) 1 • Severe CS can lead to

85. Slide 85: Central Sensitization Can Occur in a Range of Diseases and Conditions

    85 CNS PORTFOLIO Central Sensitization (CS) Can Occur in a Range of Diseases and Conditions Degree of central sensitization Nijs J, et al. Lancet . 2021;3(5):e383 - e392. © 2024 Tonix Pharmaceuticals Holding Corp.

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