Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Technical Presentation (December 2023)

41 slides from Tonix Pharmaceuticals's technical presentation, Dec 20, 2023

  1. Slide 1: TNX-102 SL Fibromyalgia Phase 3 RESILIENT Study Topline

    © 2023 Tonix Pharmaceuticals Holding Corp. Tonix Pharmaceuticals TNX - 102 SL (sublingual cyclobenzaprine) Fibromyalgia Phase 3 RESILIENT Study ( TNX - CY - F307 ) Topline December 20, 2023 Version P0512 December 18 , 2023 (Doc 1357 )

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

    2 © 2023 Tonix Pharmaceuticals Holding Corp. 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: TNX-102 SL Cyclobenzaprine HCl (Protectic)

    © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL* Cyclobenzaprine HCl ( Protectic ® ) Fibromyalgia Status: Two potential pivotal Phase 3 studies completed • P ositive Phase 3 study (RELIEF) completed • Second Phase 3 study (RALLY) missed primary endpoint • Positive confirmatory Phase 3 study

  4. Slide 4: Phase 3 RESILIENT Study Design

    4 © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL: Phase 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 defined by 2016 Revisions t

  5. Slide 5: F307 Primary Outcome Measure Reduction in Widespread Pain

    5 © 2023 Tonix Pharmaceuticals Holding Corp. F307 Primary Outcome Measure Reduction in Widespread Pain Weekly Average of Daily Diary NRS Ratings of Average Pain Over Prior 24 Hours -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) Change in NRS Pain

  6. Slide 6: Pre-Specified Primary Endpoint Summary

    6 © 2023 Tonix Pharmaceuticals Holding Corp. Pre - Specified Primary Endpoint Summary • TNX - 102 SL demonstrated statistically significant improvement in mean weekly pain scores over placebo at Week 14 • p - value of 0.00005 is highly statistically significant Additional Findings • Effect size 0.38

  7. Slide 7: F307 Continuous Pain Responder Graph

    7 © 2023 Tonix Pharmaceuticals Holding Corp. F307 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 r c e n t o f S u b

  8. Slide 8: Summary of All Key Pre-Specified Secondary Outcome Measures

    8 © 2023 Tonix Pharmaceuticals Holding Corp. Summary of ALL Key Pre - Specified Secondary Outcome Measures *In order of statistical serial gate - keeping hierarchy (or, “waterfall”) to control overall Type 1 error **Statistical significance met Met** Week 14 Rating Scale  p < 0.001 Patient Global I

  9. Slide 9: F307 Patient Global Impression of Change

    9 © 2023 Tonix Pharmaceuticals Holding Corp. F307 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 differenc

  10. Slide 10: F307 FIQ-R Symptoms Domain

    10 © 2023 Tonix Pharmaceuticals Holding Corp. F307 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

  11. Slide 11: F307 FIQ-R Function Domain

    11 © 2023 Tonix Pharmaceuticals Holding Corp. F307 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 Mul

  12. Slide 12: F307 PROMIS Sleep Disturbance Inventory

    12 © 2023 Tonix Pharmaceuticals Holding Corp. F307 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 Meas

  13. Slide 13: F307 PROMIS Fatigue Inventory

    13 © 2023 Tonix Pharmaceuticals Holding Corp. F307 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 Mu

  14. Slide 14: F307 Sleep Quality by Daily Diary

    14 © 2023 Tonix Pharmaceuticals Holding Corp. F307 Sleep Quality by Daily Diary Key Secondary Outcome Measure 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 # Weekly Average of Daily Diary NRS Ratings

  15. Slide 15: F307 Subject Disposition

    15 © 2023 Tonix Pharmaceuticals Holding Corp. F307 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%) Lack of Efficacy

  16. Slide 16: F307 Safety Summary

    16 © 2023 Tonix Pharmaceuticals Holding Corp. F307 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 • N

  17. Slide 17: F307 Safety Summary - Continued

    17 © 2023 Tonix Pharmaceuticals Holding Corp. F307 Safety Summary - Continued Total* N=457 Placebo N=226 TNX - 102 SL N=231 System Organ Class Preferred Term Oral Cavity Adverse Events 56 (12.3%) 1 (0.4%) 55 (23.8%) Hypoaesthesia oral 29 (6.3%) 2 (0.9%) 27 (11.7%) Product taste abnormal 18 (3.9%) 2

  18. Slide 18: Phase 3 RESILIENT Demographics and Baseline Characteristics

    18 © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL: Phase 3 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

  19. Slide 19: F307 Prior Medication Use

    19 © 2023 Tonix Pharmaceuticals Holding Corp. F307 Prior Medication Use Total* N=457 Placebo N=226 TNX - 102 SL N=231 System Organ Class Preferred Term 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

  20. Slide 20: F307 Washout Medications

    20 © 2023 Tonix Pharmaceuticals Holding Corp. F307 Washout Medications Total* N=457 Placebo N=226 TNX - 102 SL N=231 System Organ Class Preferred Term 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%) G

  21. Slide 21: F307 Characteristics of Study Population

    21 © 2023 Tonix Pharmaceuticals Holding Corp. F307 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 me

  22. Slide 22: Fibromyalgia Development Program Profile

    22 © 2023 Tonix Pharmaceuticals Holding Corp. PROFILE DEVELOPMENT PROGRAM Patents Issued TNX - 102 SL*: Fibromyalgia Cyclobenzaprine Protectic ® Sublingual Tablets Fibromyalgia (FM) is a chronic pain disorder resulting from amplified sensory and pain signaling within the CNS • Afflicts an estimated

  23. Slide 23: Thank You

    © 2023 Tonix Pharmaceuticals Holding Corp. THANK YOU Confidential

  24. Slide 24: Overview of Scientific Rationale for Protectic Formulation

    24 © 2023 Tonix Pharmaceuticals Holding Corp. Overview of TNX - 102 SL Scientific Rationale for Protectic ® Formulation • Engenders unique pharmacokinetic and pharmacodynamic properties that emphasize sleep properties of cyclobenzaprine while minimizing undesirable properties • Potential therapeutic

  25. Slide 25: Differentiation from Oral Forms of Cyclobenzaprine

    25 © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL - Differentiation from Oral Forms of Cyclobenzaprine

  26. Slide 26: Experience in Muscle Spasm

    26 © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL – Experience in Muscle Spasm • Flexeril ® approval in 1977 received by Merck for the treatment of muscle spasm ‒ 10 mg T.I.D. for acute use (2 - 3 weeks) ‒ 1999 OTC AdCom Briefing Package noted original NDA included “ 8 long term safety stud

  27. Slide 27: Proprietary Eutectic Formulation

    27 © 2023 Tonix Pharmaceuticals Holding Corp. 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 n z a p r i n e - HCl

  28. Slide 28: Sublingual Administration and Transmucosal Delivery

    28 © 2023 Tonix Pharmaceuticals Holding Corp. 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 ac

  29. Slide 29: 5.6 mg Fibromyalgia Three Phase 3 Trials Completed

    29 © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL 5.6 mg: Fibromyalgia Three Phase 3 Trials Completed Phase 3 Study, RESILIENT, compared TNX - 102 SL 5.6 mg and placebo • First patient enrolled in April 2022, completed p - value = 0.00005 • Parallel design, double - blind, randomized placeb

  30. Slide 30: Fibromyalgia Program Update

    30 © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL: Fibromyalgia Program Update Phase 3 Study, RELIEF, compared TNX - 102 SL 5.6 mg and placebo • First patient enrolled in December 2019, completed p - value = 0.010 • Parallel design, double - blind, randomized placebo - controlled study, all

  31. Slide 31: 5.6 mg Phase 3 Study Comparisons on Primary Pain Endpoint

    31 © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL 5.6 mg Phase 3 Study Comparisons on Primary Pain Endpoint Significance Met? p - value** LSMD (SE)* Study Yes p = 0.010 - 0.4 (0.16) F304 No p = 0.115 - 0.2 (0.16) F306 Yes p = 0.0005 - 0.7 (0.16) F307 *LSMD (SE) – Least Squared Means Differe

  32. Slide 32: 5.6 mg Key Secondaries - Study Comparison

    32 © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL 5.6 mg Key Secondaries – Study Comparison F307 F304 Rating Scale p < 0.001 p = 0.058 Patient Global Impression of Change (PGIC) p < 0.001 p = 0.007 Fibromyalgia Impact Questionnaire - Symptoms p = 0.001 p = 0.009 Fibromyalgia Impact Question

  33. Slide 33: 2.8 mg Studies in Fibromyalgia

    33 © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL 2.8 mg Studies in Fibromyalgia Completed Trials in FM: • Phase 2 (F202 BESTFIT) – 205 patients randomized • Phase 3 (F301 AFFIRM) – 519 patients randomized Topline Efficacy Results: • Studies did not achieve statistical significance in the p

  34. Slide 34: Summary of 2.8 mg Trials

    34 © 2023 Tonix Pharmaceuticals Holding Corp. Summary of TNX - 102 SL 2.8 mg Trials p=0.005 p=0.038 P<0.001 P<0.001 P<0.001 Phase 3 F301 (AFFIRM) Dose: 2.8 mg Responder analysis ≥ 30% pain reduction (Logistic regression) • Imbalance in missing data and individuals with missing data treated as ‘non -

  35. Slide 35: Dose Response

    35 © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL Dose Response Response Dosage Dose - Response Inconsistent response No clear response Consistent response Consistent but trade - offs* (AEs) Basic Pharmacology • Dose can make the difference in the strength of the response

  36. Slide 36: Chronic Overlapping Pain Conditions

    36 © 2023 Tonix Pharmaceuticals Holding Corp. 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 • Irritable bow

  37. Slide 37: Role of Infections in Triggering Fibromyalgia or CFS-Like Illnesses

    37 © 2023 Tonix Pharmaceuticals Holding Corp. 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 of these condit

  38. Slide 38: New Classification for Central Pain: Nociplastic Pain

    38 © 2023 Tonix Pharmaceuticals Holding Corp. New Classification for Central Pain: Nociplastic Pain 1 Nociplastic pain Nociceptive pain Neuropathic pain Pain due to the activation of nociceptors that arises from actual or threatened damage to non - neural tissue Pain that arises from altered nocicep

  39. Slide 39: Central Sensitization: A Feature of Many Nociplastic Pain Syndromes

    39 © 2023 Tonix Pharmaceuticals Holding Corp. 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 (hyperalges

  40. Slide 40: Central Sensitization Can Occur in a Range of Diseases

    40 © 2023 Tonix Pharmaceuticals Holding Corp. 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.

  41. Slide 41: Thank You

    © 2023 Tonix Pharmaceuticals Holding Corp. THANK YOU

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