Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Investor Presentation (June 2024)

84 slides from Tonix Pharmaceuticals's investor presentation, Jun 10, 2024

  1. Slide 1: TNX-102 SL: Fibromyalgia, Long COVID, and Acute Stress Disorder

    © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL Fibromyalgia, Long COVID, and Acute Stress Disorder NASDAQ: TNXP Version P0572 June 10 , 2024 (Doc 1450)

  2. Slide 2: Tonmya (TNX-102 SL) program status and differentiators

    © 2024 Tonix Pharmaceuticals Holding Corp. Tonmya (TNX - 102 SL)* Cyclobenzaprine HCl ( Protectic ® ) Fibromyalgia Status: Two statistically significant Phase 3 studies completed • First pivotal Phase 3 study (RELIEF) completed • Second Phase 3 study (RALLY) missed primary endpoint • Confirmatory pi

  3. Slide 3: About Fibromyalgia

    3 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO About Fibromyalgia Fibromyalgia is considered a chronic overlapping pain condition (COPC) - the only COPC with any FDA - approved drugs 3 Fibromyalgia is the prototypic nociplastic syndrome Multisite pain Fatigue Non - Restorative Sleep Fibr

  4. Slide 4: Fibromyalgia is a Large, Underserved and Dissatisfied Population

    4 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Fibromyalgia is a Large, Underserved and Dissatisfied population 1 American College of Rheumatology ( www.ACRPatientInfo.org accessed May 7, 2019) – prevalence rate of 2 - 4% for U.S. adult population (~250 million) 2 Vincent A, et al. Arthr

  5. Slide 5: Poor Sleep and Pain have Bi-directional Reinforcing Effects

    5 © 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

  6. Slide 6: Fibromyalgia: Unrefreshing Sleep and Cyclobenzaprine Treatment

    6 © 2024 Tonix Pharmaceuticals Holding Corp. 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 – 4

  7. Slide 7: Fibromyalgia Program Status

    7 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Fibromyalgia Program Status Fibromyalgia Tonmya * (TNX - 102 SL) Cyclobenzaprine Protectic ® Sublingual Tablets Statistically Significant 2 nd Phase 3 Topline Results Reported 4Q’23 First pivotal Phase 3 study ( RELIEF ) reported – December

  8. Slide 8: Phase 3 RESILIENT Study Population

    8 © 2024 Tonix Pharmaceuticals Holding Corp. Phase 3 RESILIENT Study Population

  9. Slide 9: Phase 3 RESILIENT Study Design

    9 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tonmya (TNX - 102 SL): P hase 3 RESILIENT Study Design General s tudy c haracteristics: • Randomized, double - blind, multicenter, placebo - controlle d study in fibromyalgia • 33 U.S. sites enrolled 457 participants with fibromyalgia as def

  10. Slide 10: RESILIENT Demographics and Baseline Characteristics

    10 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Demographics and Baseline Characteristics 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

  11. Slide 11: RESILIENT Characteristics of Study Population Pain Scores

    11 © 2024 Tonix Pharmaceuticals Holding Corp. 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 ra

  12. Slide 12: RESILIENT Study Efficacy Findings

    12 © 2024 Tonix Pharmaceuticals Holding Corp. RESILIENT Study Efficacy Findings

  13. Slide 13: RESILIENT Summary of Primary and Key Secondary Endpoints

    13 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Summary of Primary and Key Secondary Endpoints *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

  14. Slide 14: RESILIENT Primary Outcome Measure: Reduction in Widespread Pain

    14 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Weekly Average of Daily Diary NRS Ratings of Average Pain Over Prior 24 Hours RESILIENT Primary Outcome Measure Reduction in Widespread Pain -2.2 -2 -1.8 -1.6 -1.4 -1.2 -1 -0.8 -0.6 -0.4 -0.2 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 LS Mean (SE

  15. Slide 15: RESILIENT Continuous Pain Responder Graph

    15 © 2024 Tonix Pharmaceuticals Holding Corp. 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 P e

  16. Slide 16: RESILIENT Patient Global Impression of Change

    16 © 2024 Tonix Pharmaceuticals Holding Corp. 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 - Sq

  17. Slide 17: RESILIENT FIQ-R Symptoms Domain

    17 © 2024 Tonix Pharmaceuticals Holding Corp. 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 Mi

  18. Slide 18: RESILIENT FIQ-R Function Domain

    18 © 2024 Tonix Pharmaceuticals Holding Corp. 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 Repeate

  19. Slide 19: RESILIENT PROMIS Sleep Disturbance Inventory

    19 © 2024 Tonix Pharmaceuticals Holding Corp. 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

  20. Slide 20: RESILIENT PROMIS Fatigue Inventory

    20 © 2024 Tonix Pharmaceuticals Holding Corp. 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 Repeat

  21. Slide 21: RESILIENT Sleep Quality by Daily Diary

    21 © 2024 Tonix Pharmaceuticals Holding Corp. 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 (0.1 7); p=0.0007 # RESILIENT Sleep Quality by Daily Diary Key Secondary Outcome Measure Weekly Average of Dail

  22. Slide 22: RESILIENT Summary of Primary Endpoint and Key Secondary Efficacy Endpoints

    22 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Summary of Primary Endpoint and Key Secondary Efficacy Endpoints Fibromyalgia is a syndrome composed of symptoms • Widespread pain • Fatigue • Sleep disturbance Efficacy across symptoms of pain, fatigue and sleep • Pain (primary e

  23. Slide 23: RESILIENT: CSFQ-Females

    23 © 2024 Tonix Pharmaceuticals Holding Corp. 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

  24. Slide 24: RESILIENT: FIQR Individual Items

    24 © 2024 Tonix Pharmaceuticals Holding Corp. 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 explora

  25. Slide 25: RESILIENT: Beck Depression Inventory-II

    25 © 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

  26. Slide 26: RESILIENT: Summary of Baseline Depression BDI-II and FIQR Item

    26 © 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

  27. Slide 27: RESILIENT Summary of Efficacy

    27 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Summary of Efficacy Primary Pain, and Key Secondaries • Pain (primary endpoint, daily pain diary): p - value = 0.00005 • Fatigue (PROMIS fatigue): p - value = 0.00009 • Sleep (PROMIS sleep disturbance): p - value = 0.0000001 • Glo

  28. Slide 28: RESILIENT Summary of Efficacy Conclusion

    28 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Summary of Efficacy Conclusion: Tonmya 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 to r

  29. Slide 29: RESILIENT Study Safety Findings

    29 © 2024 Tonix Pharmaceuticals Holding Corp. RESILIENT Study Safety Findings

  30. Slide 30: RESILIENT Subject Disposition

    30 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Subject Disposition 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

  31. Slide 31: RESILIENT Prior Medication Use

    31 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Prior Medication Use 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/Pregabalin 96 (21.0%) 50 (22.1%) 46 (19.9%) Gabape

  32. Slide 32: RESILIENT Washout Medications

    32 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Washout Medications 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 ( 1.3%) 1 ( 0.4%) 5 ( 2.2%) Gabapentin 3 ( 0

  33. Slide 33: RESILIENT Safety Summary

    33 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Safety Summary Among participants randomized to Tonmya (TNX - 102 SL) and to placebo, 81.0% and 79.6%, respectively, completed the study Tonmya ( TNX - 102 SL) was generally well tolerated with an adverse event (AE) profile compar

  34. Slide 34: RESILIENT Safety

    34 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Safety 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

  35. Slide 35: RESILIENT Analysis by Sensory Adverse Events

    35 © 2024 Tonix Pharmaceuticals Holding Corp. 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 pre

  36. Slide 36: RESILIENT Safety, Continued

    36 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Safety, Continued No clinically meaningful difference in mean systolic blood pressure between groups Week 14 mean (SD) change from baseline: TNX - 102 SL = 0.7 (12.38) mmHg Placebo = 0.5 (10.42) mmHg No clinically meaningful diffe

  37. Slide 37: RESILIENT Systolic Blood Pressure Safety Measure

    37 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Systolic blood pressure Safety Measure No clinically meaningful difference in mean systolic blood pressure between groups Week 14 mean (SD) change from baseline: TNX - 102 SL = 0.7 (12.38) mmHg P lacebo = 0.5 (10.42) mmHg Horizont

  38. Slide 38: RESILIENT Diastolic Blood Pressure Safety Measure

    38 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Diastolic blood pressure Safety Measure 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 P lacebo = 0.2 (8.22) mmHg Horizont

  39. Slide 39: RESILIENT Weight Safety Measure

    39 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Weight Safety Measure No clinically meaningful difference in mean weight between treatment groups Week 14 mean (SD) change from baseline: TNX - 102 SL = 0.02 (2.940) kg P lacebo = 0.20 (2.932) kg Horizontal lines are the mean for

  40. Slide 40: Fibromyalgia Market Characteristics

    40 © 2024 Tonix Pharmaceuticals Holding Corp. Fibromyalgia Market Characteristics

  41. Slide 41: Fibromyalgia: Market Characteristics

    41 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Fibromyalgia: Market Characteristics 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

  42. Slide 42: Fewer than Half of Those Treated Receive Sustained Benefit from Approved Drugs

    42 © 2024 Tonix Pharmaceuticals Holding Corp. 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 25% 35% 60% fa il ure rate 1 The three drugs with FDA approval for the

  43. Slide 43: Current FDA-Approved Fibromyalgia Drugs were Repurposed

    43 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Current FDA - Approved Fibromyalgia Drugs were Repurposed 1 1 The three drugs with FDA approval for the treatment of fibromyalgia: Pregabalin (Lyrica); Duloxetine (Cymbalta); Milnacipran ( Savella ) Cymbalta® - Lilly Savella ® - AbbVie Lyri

  44. Slide 44: Large Need for New Fibromyalgia Therapies

    44 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO 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 altoge

  45. Slide 45: Tonmya Showed Broad-Spectrum Activity and was Well Tolerated

    45 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tonmya Showed Broad - Spectrum Activity and was Well Tolerated Tonmya Cymbalta® Savella ® Lyrica® YES YES YES Pain Activity YES - YES Sleep YES YES - Fatigue - + - Insomnia Systemic Tolerability Issues - - + Fatigue - - + Weight - + - Blood

  46. Slide 46: ~50% of U.S. Fibromyalgia Patients are on Medicare

    46 © 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

  47. Slide 47: Prescribers Broadly Dissatisfied with Available Fibromyalgia Medications

    47 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Prescribers Interviewed are Broadly Dissatisfied with Available Fibromyalgia Medications: Results of Primary Research 1 Perspectives on FM Therapies from Prescribers Interviewed Negatives Positives Drug • Tolerability issues: worsening depr

  48. Slide 48: Opportunity for a New Fibromyalgia Treatment Option

    48 © 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

  49. Slide 49: Many Fibromyalgia Patients are Prescribed Off-Label Drugs

    49 © 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% 22.62% 25.50% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% Milnacipran Amitr

  50. Slide 50: Potential for Tonix to Launch and Market Tonmya

    50 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Potential for Tonix to Launch and Market Tonmya Decline in personal promotion (“Detailing”) of prescription drugs • The pandemic accelerated transition to non - personal promotion o Omnichannel is more important and more sophisticated • Tel

  51. Slide 51: Planning for Tonmya Launch and Marketing

    51 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Planning for Tonmya 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 Tonm

  52. Slide 52: About Cyclobenzaprine and Tonmya

    52 © 2024 Tonix Pharmaceuticals Holding Corp. About Cyclobenzaprine and Tonmya

  53. Slide 53: Cyclobenzaprine Long-Term Utilization

    53 © 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

  54. Slide 54: Sublingual Administration and Transmucosal Delivery

    54 © 2024 Tonix Pharmaceuticals Holding Corp. 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 par

  55. Slide 55: Formulation with Base Increases Systemic Absorption

    55 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Formulation with Base Increases Systemic Absorption of Sublingual Cyclobenzaprine 1 Concentration gradient increases diffusion of free base across oral mucosa (Le Chatelier’s Principle) CBP - HCl Cyclobenzaprine free base Oral mucosa CBP -

  56. Slide 56: Proprietary Eutectic Formulation

    56 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tonmya (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 ) C y cl o be

  57. Slide 57: Cyclobenzaprine Detected in Plasma Within Minutes

    57 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tonmya (TNX - 102 SL): Cyclobenzaprine Detected in Plasma Within Minutes Following Sublingual Administration 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 5

  58. Slide 58: Single Dose PK Differentiation from Oral IR CBP

    58 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tonmya ( TNX - 102 SL): Single Dose PK Differentiation from Oral IR CBP 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 A

  59. Slide 59: Multi-Dose PK Differentiation from Simulated Oral IR CBP

    59 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tonmya ( TNX - 102 SL): Multi - Dose PK Differentiation from Simulated Oral IR CBP Day 20 TNX - 102 SL 5.6 mg v. Simulated Oral IR 5 mg Day 20 TNX - 102 SL 5.6 mg v. Simulated Oral IR 10 mg Steady State Pharmacokinetics (after 20 days dosin

  60. Slide 60: Multi-Functional Mechanism Involves Antagonism at Four Neuronal Receptors

    60 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Multi - Functional Mechanism Involves Antagonism at Four Neuronal Receptors Active ingredient, cyclobenzaprine, interacts with four receptors • Antagonist at 5 - HT 2A receptors • Similar activity to trazodone and Nuplazid ® ( pimivanserin

  61. Slide 61: Cyclobenzaprine Binding Affinities for Receptor and Transporter

    61 © 2024 Tonix Pharmaceuticals Holding Corp. 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 CBP/nCBP Activity

  62. Slide 62: Cyclobenzaprine Effects on Nerve Cell Signaling

    62 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Cyclobenzaprine Effects on Nerve Cell Signaling Untreated Effects of TNX - 102 SL SNARI = S erotonin and N orepinephrine receptor A ntagonist and R euptake I nhibitor Cyclobenzaprine is a multi - functional drug – SNARI • inhibits serotonin

  63. Slide 63: No Recognized Abuse Potential in Clinical Studies

    63 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tonmya (TNX - 102 SL): 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

  64. Slide 64: Sublingual Formulation is Designed for Bedtime Administration

    64 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tonmya (TNX - 102 SL): Sublingual Formulation is Designed for Bedtime Administration Tonmya (TNX - 102 SL): Proprietary sublingual formulation of cyclobenzaprine (CBP) with transmucosal absorption • Innovation by design with patent protecte

  65. Slide 65: Patents and Patent Applications

    65 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tonmya (TNX - 102 SL): Patents and Patent Applications • 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

  66. Slide 66: Tonmya for Other Indications: Long COVID and Acute Stress Disorder

    66 © 2024 Tonix Pharmaceuticals Holding Corp. Tonmya for Other Indications In Development: Long COVID and Acute Stress Disorder

  67. Slide 67: About Fibromyalgia-Type Long COVID

    67 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO About Fibromyalgia - Type Long COVID Many Long - COVID symptoms overlap with core symptoms of fibromyalgia and are hallmarks of other chronic pain syndromes like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) Multisite pain Mem

  68. Slide 68: Phase 2 PREVAIL Study Design

    68 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL for Fibromyalgia - Type Long COVID: Phase 2 PREVAIL Study Design Study c haracteristics: • Randomized, double - blind, placebo - controlle d study of TNX - 102 SL in fibromyalgia - type Long COVID • U.S. sites only, completed e

  69. Slide 69: Phase 2 PREVAIL Topline Results

    69 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL: Phase 2 PREVAIL Topline Results 1 Did not meet the primary endpoint of multi - site pain reduction at Week 14 However, f indings fulfill the objectives of proof - of - concept study, supporting the decision to advance the prog

  70. Slide 70: Acute Stress Reaction / Acute Stress Disorder

    70 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO CNS PORTFOLIO Acute Stress Reaction (ASR)/ Acute Stress Disorder (ASD) ASR/ASD are acute stress conditions resulting from trauma which c an affect both civilian and military populations. Large unmet need: • According to National Center for

  71. Slide 71: TNX-102 SL for ASR/ASD: Program Status

    71 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL for ASR/ASD: Program Status Status: Expect to start Phase 2 in 2Q 2024 Phase 2 Trial Funded by DoD grant to University of North Carolina (UNC) • UNC Institute for Trauma Recovery awarded a $3M grant from the Department of Defen

  72. Slide 72: Phase 2 OASIS Study Design

    72 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL for ASR/ASD: Phase 2 OASIS Study Design General s tudy c haracteristics: • Randomized, double - blind, placebo - controlle d study in Acute Stress Reaction (ASR) / Acute Stress Disorder (ASD) • The proposed O ptimizing A cute S

  73. Slide 73: Thank You

    © 2023 Tonix Pharmaceuticals Holding Corp. THANK YOU

  74. Slide 74: Appendix

    © 2023 Tonix Pharmaceuticals Holding Corp. APPENDIX

  75. Slide 75: RALLY Study Increased Adverse Event-Related Discontinuations

    75 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tonmya (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 - 1

  76. Slide 76: RALLY Study Impact of Missing Data on p-Values

    76 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tonmya (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 F

  77. Slide 77: Chronic Overlapping Pain Conditions Result from Shared Brain Processes

    77 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Chronic Overlapping Pain Conditions (COPC) Believed to Result from Shared Brain Processes • COPC is a set of disorders that coaggregate ; these disorders can include but are not limited to 1,2 : • Temporomandibular disorder • Fibromyalgia •

  78. Slide 78: Role of Infections in Triggering Fibromyalgia or CFS-Like Illnesses

    78 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Role of Infections in Triggering Fibromyalgia or Chronic fatigue (CFS) - Like Illnesses Infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism 2 - 7 • Infections can trigger any o

  79. Slide 79: The Third Type of Pain: Nociplastic Pain

    79 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO The Third Type of Pain: Nociplastic Pain 1 1 Trouvin AP, et al. Best Pract Res Clin Rheumatol . 2019;33(3):101415. Nociplastic syndrome includes: (1) widespread pain (2) fatigue (3) sleep disturbances (4) cognitive dysfunction (“brain fog”)

  80. Slide 80: Fibromyalgia Believed to Result from Chronic Pain or Prior Stress

    80 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Fibromyalgia is Believed to Result from Chronic Pain or Prior Stress Experiences Stresses that may precede or precipitate FM include: Chronic nociceptive pain • e.g. , osteoarthritis Chronic neuropathic pain • e.g. , diabetic neuropathy Inf

  81. Slide 81: Common Chronic Conditions are a Challenge for Pharma

    81 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Common Chronic Conditions are a Challenge for Pharma Fibromyalgia is a common chronic disease 1 • Chronic pain syndrome that persists for years or decades No animal model is recognized for nociplastic syndromes or its component symptoms • W

  82. Slide 82: Common Chronic Conditions are a Challenge for Society

    82 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Common Chronic Conditions are a Challenge for Society The Opiate Crisis in the U.S. was driven by mistreatment of chronic pain, which was often nociplastic pain • The e pidemic of prescription pain killers was addressed by regulations which

  83. Slide 83: Central Sensitization: A Feature of Many Nociplastic Pain Syndromes

    83 © 2024 Tonix Pharmaceuticals Holding Corp. 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 individua

  84. Slide 84: Central Sensitization Can Occur in a Range of Diseases and Conditions

    84 © 2024 Tonix Pharmaceuticals Holding Corp. 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.

Tonix Pharmaceuticals Holding — Investor Presentation (June 2024) on 6ix