Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — 3rd Annual Neuropsychiatric Drug Development Summit (November 2020)

27 slides from Tonix Pharmaceuticals's conference presentation, Nov 12, 2020

  1. Slide 1: TNX-102 SL Development for Posttraumatic Stress Disorder (PTSD)

    © 2020 Tonix Pharmaceuticals Holding Corp. November 12, 2020 3 rd Annual Neuropsychiatric Drug Development Summit Seth Lederman, MD - CEO Version P0255 11 - 12 - 20 (Doc 0731) TNX - 102 SL Development for Posttraumatic Stress Disorder (PTSD)

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

    © 2020 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: Team and Collaborators

    © 2020 Tonix Pharmaceuticals Holding Corp. 3 Team and Collaborators Tonix • Seth Lederman, MD • Greg Sullivan, MD • Herb Harris, MD, PhD • Perry Peters • Ashild Peters, RN • Mandy Ng, PhD • Candace Flint Philip Stark, PhD • Univ. of Calif , Berkeley Ben Vaughn • Rho Disclosures: • Tonix employees ho

  4. Slide 4: PTSD Candidates in Development

    © 2020 Tonix Pharmaceuticals Holding Corp. 4 PTSD Candidates in Development Phase 2 NDA 3 Market Pipeline Product Targeted Indication Phase 3 TNX - 102 SL 1 Bedtime treatment for PTSD Tonmya ®2 Daytime treatment for PTSD TNX - 601 CR 4 Cyclobenzaprine HCl sublingual tablets Protectic ® formulation t

  5. Slide 5: SL: Hypothesized Novel Mechanism Targets Sleep Quality for Recovery from PTSD

    © 2020 Tonix Pharmaceuticals Holding Corp. 5 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 - depende

  6. Slide 6: SL: Sublingual Formulation is Designed for Bedtime Administration

    © 2020 Tonix Pharmaceuticals Holding Corp. 6 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 s

  7. Slide 7: No Recognized Abuse Potential in Clinical Studies

    © 2020 Tonix Pharmaceuticals Holding Corp. 7 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, α 1 - adrenergic, histami

  8. Slide 8: Three Recent PTSD Trials Testing SL

    © 2020 Tonix Pharmaceuticals Holding Corp. 8 Three Recent PTSD Trials Testing TNX - 102 SL (cyclobenzaprine sublingual tablets) Phase 2 P201 “ AtEase ” – Military - related PTSD 1 • Reported May 2016 ( mITT , N=231) • 3 groups: Placebo (n= 92), TNX 2.8 mg (n= 90) and TNX 5.6 mg (n=49) • Primary endp

  9. Slide 9: Adverse Events in P201/AtEase and P301/HONOR Studies

    © 2020 Tonix Pharmaceuticals Holding Corp. 9 Adverse Events (AEs) in P201/AtEase and P301/HONOR Studies No serious and 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

  10. Slide 10: Highlights of Three Recent PTSD Trials Testing SL

    © 2020 Tonix Pharmaceuticals Holding Corp. 10 Highlights of Three Recent PTSD Trials Testing TNX - 102 SL Focus on rater training, patient retention and data quality • First studies to use CAPS - 5 • Rater training, certification, and reliability overseen by Frank Weathers PhD and associates • Perio

  11. Slide 11: Common Themes from Three Recent PTSD Trials Testing SL

    © 2020 Tonix Pharmaceuticals Holding Corp. 11 Common Themes from Three Recent PTSD Trials Testing TNX - 102 SL • Consistent nominal improvement on sleep item on CAPS - 5 • E6 sleep disturbance item • Supported by nominal benefits in PROMIS Sleep Disturbance • Evidence of “target engagement”, appropr

  12. Slide 12: Heterogeneity of Study Participants

    © 2020 Tonix Pharmaceuticals Holding Corp. 12 Heterogeneity of Study Participants • PTSD diagnosis may include a heterogeneous group of different stress disorders • Psychiatric nosology and diagnosis remain clinical and pre - molecular • No validated biomarkers for diagnosis or response • PTSD may b

  13. Slide 13: Placebo Response – "Hard to Beat"

    © 2020 Tonix Pharmaceuticals Holding Corp. 13 Placebo Response – “Hard to Beat” • Improvement of placebo group makes it difficult for any drug to separate • Dramatic placebo responses suggest measurement issue with primary endpoint • Such dramatic recoveries are not consistent with known natural his

  14. Slide 14: Placebo Responses in PTSD Trials

    © 2020 Tonix Pharmaceuticals Holding Corp. 14 Placebo Responses in PTSD Trials 1 Marshall et al. Am J Psychiatry 2001;158:1982 - 1988. 2 Tucker et al. J Clin Psychiatry 2001;62:860 - 868. 3 Davidson et al. Arch Gen Psychiatry 2001;58:485 - 492. 4 Brady et al. JAMA 2000;283:1837 - 1844. 5 Friedman et

  15. Slide 15: Randomization is Often Overlooked as an Element in RCTs

    © 2020 Tonix Pharmaceuticals Holding Corp. 15 Randomization is Often Overlooked as an Element in Randomized Clinical Trials (RCTs) 1 In our trials a population of patients defined by inclusion and exclusion criteria are randomized into treatment groups in complex processes • Attempts to balance drug

  16. Slide 16: Proposed Solution: Randomization Honoring (RH) Method

    © 2020 Tonix Pharmaceuticals Holding Corp. 16 Proposed Solution: Randomization Honoring (RH) Method 1 Respects the method in which study subjects are randomized into drug and placebo groups • Technically, randomization IS “The Experiment” Accounts for the dependence of the drug and placebo groups pr

  17. Slide 17: How Does CAPS-5 Dimensionality Affect Its Use as a Measure of Change

    © 2020 Tonix Pharmaceuticals Holding Corp. 17 How Does CAPS - 5 Dimensionality Affect Its Use as a Measure of Change in Symptoms or Syndrome CAPS - 5 consists of 20 items that can be considered dimensions • CAPS - 5 was developed as a diagnostic tool based on DSM - 5 PTSD criteria • Paxil® (paroxeti

  18. Slide 18: Multi-dimensional Analyses

    © 2020 Tonix Pharmaceuticals Holding Corp. 18 Multi - dimensional Analyses “21 st Century Cures Act” addressed use of novel trial designs, simulations and analyses • Requiring guidance and encouraging increased reliance on novel and adaptive clinical trial designs, including use of modeling and simu

  19. Slide 19: Proposed Solution: RH Non-Parametric Combination of Tests

    © 2020 Tonix Pharmaceuticals Holding Corp. 19 Proposed Solution: Randomization Honoring (RH) Non - Parametric (NP) Combination of Tests (COT) Each of the 20 individual items is treated as a separate measurement that contributes evidence about the null hypothesis • Randomization Honoring (RH) can inc

  20. Slide 20: First Stage of RHNPCOT Randomization

    © 2020 Tonix Pharmaceuticals Holding Corp. 20 First Stage of RHNPCOT Randomization Treatment codes are randomly allotted to the observed data 10,000 times by generating sets of randomization lists that simulate (and are valid under) the original randomization system used • The test statistic is calc

  21. Slide 21: Second Stage of RHNPCOT Randomization

    © 2020 Tonix Pharmaceuticals Holding Corp. 21 Second Stage of RHNPCOT Randomization The 20 p - values { p_i } are combined into a single summary statistic using Fisher’s combining function • െ ʹ σ Ž  ሺ ݌ ௜ ሻ ଶ଴ ௜ ୀ ଵ . • If the 20 p - values were continuous and independent, this statistic would ha

  22. Slide 22: Phase P301 Data: Histogram Values of the Combining Function

    © 2020 Tonix Pharmaceuticals Holding Corp. Phase 3 P301 Data: Hist ogram V alues of the Combining Function (for Random Reallocations) 1 D ensity (frequency per unit of the X axis) V alues of the Combining Function 1 Retrospective analysis of CAPS - 5 Week 12 change from baseline

  23. Slide 23: Phase P301 Study: Comparison of Primary Analysis with Retrospective Analysis

    © 2020 Tonix Pharmaceuticals Holding Corp. 23 Phase 3 P301 Study: Comparison of Primary Analysis with Retrospective Analysis of CAPS - 5 Week 12 Change from Baseline by RHNPCOT Primary analysis • MMRM 1 with MI 2 , P =0.6 (two - sided) Retrospective RHNPCOT analysis • RHNPCOT using Medians with MI,

  24. Slide 24: RHNPCOT

    © 2020 Tonix Pharmaceuticals Holding Corp. 24 RHNPCOT 1 Honors the actual randomization method of the study • Uses modern analyses and simulations which are advocated by 21 st Century Cures Act Preserves information from 20 dimensional CAPS - 5 • Unlike “total CAPS - 5” which collapses data into one

  25. Slide 25: Future Plans

    © 2020 Tonix Pharmaceuticals Holding Corp. 25 Future Plans Pharmacogenomics on study participants • P302 has high rate of consent for DNA collection • P301 has a subset of participant DNA available • Exome sequencing to focus on: • Drug metabolizing enzymes • Neurotransmitter receptors and transport

  26. Slide 26: Crisis in Psychiatry Randomized Controlled Trials

    © 2020 Tonix Pharmaceuticals Holding Corp. 26 Crisis in Psychiatry Randomized Controlled Trials (RCTs) Paradox: while clinical methods (particularly randomization) and data quality are improving, success in subsequent studies has become harder to predict • Randomization sequence typically attempts t

  27. Slide 27: Thank you!

    © 2020 Tonix Pharmaceuticals Holding Corp. Thank you ! NASDAQ: TNXP

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