Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Investor Presentation (March 2019)

42 slides from Tonix Pharmaceuticals's investor presentation, Mar 18, 2019

  1. Slide 1: Investor Presentation March 2019

    Investor Presentation March 2019 Version P0166 3-11-19 (Doc 0450) © 2019 Tonix Pharmaceuticals Holding Corp.

  2. Slide 2: Cautionary Note on Forward Looking Statements

    Cautionary Note on Forward Looking Statements 2 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 Litigation Reform Act of 1995. These statements may be

  3. Slide 3: Tonix Development Highlights

    Tonix Development Highlights 3 Posttraumatic Stress Disorder (PTSD) – Lead program; new bedtime treatment - Tonmya ®1 • P302/RECOVERY Phase 3 clinical study initiated in March 2019 • Results from 2 efficacy studies improve the new Phase 3 study design New Phase Tablets • P302/RECOVERY study design f

  4. Slide 4: Candidates in Development Pipeline

    Candidates in Development 4 Pipeline Product Indication Preclinical Phase 1 Phase 2 Phase 3 NDA 1 /BLA 2 Market Bedtime Treatment TNX-102 SL for PTSD – Tonmya® P302/ RECOVERY study initiated 1Q2019 Cyclobenzaprine HCl sublingual tablets Bedtime Treatment for Phase 2 and 3 completed at 2.8 mg Fibromy

  5. Slide 5: Tonmya: a Potential Bedtime Treatment for PTSD

    Tonmya: a Potential Bedtime Treatment for PTSD 5 First investigational new drug to show treatment effect in military-related PTSD in two potential pivotal efficacy studies • Phase 2 study (P201/AtEase) showed Tonmya 5.6 mg had a strong signal of treatment effect at Week 12 as measured by CAPS-5 1 •

  6. Slide 6: No Recognized Abuse Potential in Clinical Studies

    No Recognized Abuse Potential in Clinical Studies 6 Active ingredient is cyclobenzaprine, which is structurally related to tricyclic antidepressants • Cyclobenzaprine interacts with receptors that regulate sleep quality: 5-HT 2A, 1 -adrenergic and histamine H 1 receptors • Cyclobenzaprine does NOT i

  7. Slide 7: TNX-102 SL Intellectual Property – U.S. Protection

    TNX 102 SL Intellectual Property – U.S. Protection until 2034 7 Composition of matter (eutectic) : Protection expected to 2034 • United States Patent and Trademark Office (USPTO) issued U.S. Patent No. 9,636,408 in May 2017 U.S. Patent No. 9,956,188 in May 2018 and U.S. Patent No. 10,117,936 in Nove

  8. Slide 8: Sublingual Formulation is Designed for Bedtime Administration

    TNX 102 SL: Sublingual Formulation is Designed for Bedtime Administration 8 TNX-102 SL: Proprietary sublingual formulation of cyclobenzaprine (CBP) with transmucosal absorption • Innovation by design with patent protected CBP/mannitol eutectic • Rapid systemic exposure • Increases bioavailability du

  9. Slide 9: Hypothesized Novel Mechanism Targets Sleep Quality for Recovery from PTSD

    Tonmya: Hypothesized Novel Mechanism Targets Sleep Quality for Recovery from PTSD 9 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-dependent memory processing 1,2 Memory processing is essen

  10. Slide 10: PTSD: Not Well Served by Approved Treatments

    PTSD: Not Well Served by Approved Treatments 10 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 to current treatments • Side effects relating to

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

    Prevalence of PTSD Among Civilians and Veterans 11 4.7% 19-31% >19% Adult population 1 Vietnam veterans 2 Iraq/Afghanistan 3 12 million American adults annually 1 Women more likely to develop than men 1 1 Goldstein et al., 2016 (adjusted for 2019); 2 Norris, PTSD Res Quar . 2013; 3 Analysis of VA He

  12. Slide 12: Phase 2 P201/AtEase Study in Military Related PTSD

    Phase 2 P201/AtEase Study in Military Related PTSD 12 • Randomized, double-blind, placebo-Placebo at bedtime once-daily controlled trial in military-related PTSD N= 92 * • Efficacy analysis from 231 * patients; 24 U.S. clinical sites Tonmya at bedtime once-daily • Enrolled patients with baseline 2.8

  13. Slide 13: P201/AtEase Study

    P201/AtEase Study 13 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 • Retrospective analyses showed TNX-102 SL 5.6 mg had a strong si

  14. Slide 14: P301/HONOR Study Discontinued Due to High Placebo Response at Week 12

    P301/HONOR Study Evidence of Efficacy at Week 4 Discontinued Due to High Placebo Response at Week 12 14 General study characteristics: Primary endpoint CAPS-5 2 : Randomized, double-blind, placebo-controlled, adaptive • Mean change from baseline at Week 12 (Tonmya 5.6 mg design, planned 550 military

  15. Slide 15: P301/HONOR Study Stopped After Interim Analysis (July 2018)

    P301/HONOR Study Stopped After Interim Analysis (July 2018) 15 P301 was a large adequate well-controlled Phase 3 study in military-related PTSD • Separation on primary endpoint at Week 12 did not cross pre-specified study continuation threshold at Week 12 (p=0.602) • No safety or tolerability issue

  16. Slide 16: Tonmya Dose Effect in Military Related PTSD

    Tonmya Phase 2 Dose Effect in Military Related PTSD 1 16 PTSD Symptoms (CAPS-5 2 Score) 30% Remission at Weeks 8 & 12 25% * 21.10% 20% Placebo (N=77) Tonmya 2.8 mg (N=70) # Tonmya 5.6 mg (N=38) 15% 14.30% 10% 5.20% 5% 7.2 points Percent in Remission 0% Weeks 8 & 12 Remission = Loss of Diagnosis and

  17. Slide 17: Primary Outcome in Phase 3 mITT and Time Since Trauma Subgroups

    Primary Outcome (CAPS 5) in Phase 3 mITT) and 9 Years Time Since Trauma (TST) Subgroups 17 Phase 3 P301/HONOR Study 1 Modified intent to treat Time Since Trauma (mITT) population 9 yrs ~50% mITT Population *p=0.019, TNX-102 SL 5.6 mg group v. placebo, using **p=0.004, *p=0.039, # p=0.069, TNX-102 SL

  18. Slide 18: Retrospective Comparison of Time Since Trauma in P201 versus P301

    Retrospective Comparison of Time Since Trauma in P201/AtEase versus P301/HONOR (Tonmya 5.6 mg Groups) 18 P301 study was initiated approximately two years later than Phase 2 P201 • The median time since trauma in Phase 3 was 9.5 years compared to the median time since trauma in Phase 2 of 6.0 years f

  19. Slide 19: CAPS-5 Mean Change Difference from Placebo in TST Subgroups

    CAPS 5 Mean Change from Baseline Difference from Placebo of Tonmya 5.6 mg in TST Subgroups in P301 1 19 • The mITT population was divided into subgroups based on TST (1.5-2 years each as well as 0-5 years and 13.5 years subgroups) • Graph shows the CAPS-5 differences in MCFB between TNX 5.6 mg and P

  20. Slide 20: PTSD Treatment Response to Tonmya: Retrospective Analyses

    PTSD Treatment Response to Tonmya in Phase 2 and Phase 3 Studies: Retrospective Analyses of P201 Entry CAPS 5 33 and P301 9 Years Since Trauma Subgroups 20 Change in CAPS-5 over course of treatment with Tonmya P201 Baseline CAPS-5 33 (majority TST 1 9 yr) CAPS-5 is a structured interview **p<0.01, *

  21. Slide 21: Sustained Remission in Phase 2 and Phase 3 Studies

    Sustained Remission in Phase 2 and Phase 3 Studies: Retrospective Analyses of P201 Entry CAPS 5 33 and P301 9 Years Since Trauma Subgroups 21 Remission is a clinical state that is essentially asymptomatic In order to confirm remission: • Determined rates of participants who met remission status at b

  22. Slide 22: Retrospective Analyses of Time Since Trauma Subgroup on Endpoints

    Retrospective Analyses of 9 Years Since Trauma Subgroup on Primary and Secondary Endpoints in P301/HONOR Study 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-Trea

  23. Slide 23: Adverse Events in P201/AtEase and P301/HONOR Studies

    Adverse Events (AEs) in P201/AtEase and P301/HONOR Studies 23 #only adverse events (AEs) are listed that are at a rate of 5% in any TNX-treated group *no values in a row for either study means the AE in the active group(s) in that study was at a rate of <5% No serious or unexpected AEs in P201 or P3

  24. Slide 24: Time Since Trauma – Review of Published Studies

    Time Since Trauma – Review of Published Studies 24 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 years • SSRIs have a benefit long after trauma

  25. Slide 25: Time Since Trauma – Remitting and Persistent Phases of PTSD

    Time Since Trauma – Remitting and Persistent Phases of PTSD 25 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 studies 2-6 1 Kessler et al. Arch Gen Psych

  26. Slide 26: Response to Tonmya for Female Participants in P301/HONOR Study

    Response to Tonmya for Female Participants in P301/HONOR Study 1 26 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 Tonmya 5.6 mg (N=10) was: • At 4 weeks -11.5 points • At 12 weeks -9.1 points I

  27. Slide 27: Response to Tonmya for Non-Combat Traumas in P301/HONOR Study

    Response to Tonmya for Non Combat Traumas in P301/HONOR Study in 9 Years Time Since Trauma Subgroup 1 27 Non-combat traumas studied are similar to traumas experienced in civilian populations with PTSD To determine the therapeutic effects of Tonmya 5.6 mg in a mixed civilian and military population,

  28. Slide 28: Summary of Clinical Experience with Tonmya in PTSD

    Summary of Clinical Experience with Tonmya/ TNX 102 SL in PTSD 28 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 • Time has passed since the surge in Iraq In retrospective

  29. Slide 29: New Phase 3 P302/RECOVERY Study – Initiated 1Q 2019

    New Phase 3 P302/RECOVERY Study –Initiated 1Q 2019 29 General study characteristics: Primary endpoint: • Randomized, double-blind, placebo-controlled study with • CAPS-5 1 mean change from baseline at Week 4 (Tonmya 5.6 mg baseline CAPS-5 1 33 in approximately 30 U.S. sites vs. placebo) • Enrollment

  30. Slide 30: Late Stage PTSD Drug Candidates

    Late Stage PTSD Drug Candidates 30 Tonmya • Phase 3 development focused on military-related and civilian PTSD; showed activity in treatment of military-related PTSD in large multi-center trials MDMA-assisted psychotherapy • Breakthrough therapy that is Phase 3-ready; showed activity in a Phase 2 stu

  31. Slide 31: TNX-102 SL – Bedtime Treatment for Multiple Potential Indications

    TNX 102 SL – Bedtime Treatment for Multiple Potential Indications 31 Management of Fibromyalgia (FM) – chronic pain condition • TNX-102 SL studied at low dose (2.8 mg) – half the dose being developed for PTSD – did not separate from placebo on primary endpoint, average pain improvement (responder an

  32. Slide 32: Agitation in Alzheimer's Disease – Additional Indication Being Developed

    Agitation in Alzheimer’s Disease – Additional Indication Being Developed for TNX 102 SL 32 FDA designated Fast Track development program Significant unmet need • No FDA approved drugs for the treatment of agitation in Alzheimer’s Mechanism of improving sleep quality • Sleep disturbance is a signific

  33. Slide 33: TNX-102 SL for Agitation in Alzheimer's – Regulatory Status and Registration Strategy

    TNX 102 SL for Agitation in Alzheimer’s –Regulatory Status and Registration Strategy 33 FDA confirmed no additional study was needed prior to IND submission • Pre-IND meeting established open dialogue with the FDA on pivotal clinical study design and efficacy endpoints to support product registratio

  34. Slide 34: Candidates in Development Pipeline

    Candidates in Development 34 Pipeline Product Indication Preclinical Phase 1 Phase 2 Phase 3 NDA 1 /BLA 2 Market Bedtime Treatment TNX-102 SL for PTSD – Tonmya® P302/ RECOVERY study initiated 1Q2019 Cyclobenzaprine HCl sublingual tablets Bedtime Treatment for Phase 2 and 3 completed at 2.8 mg Fibrom

  35. Slide 35: TNX-601 (Tianeptine Oxalate): A Potential Clinical Candidate for PTSD

    TNX 601 Tianeptine Oxalate): A Potential Clinical Candidate for PTSD 35 Targeted as a 1 st line monotherapy for PTSD: oral formulation for daytime dosing Leverages expertise in PTSD (clinical and regulatory experience, market analysis, etc.) Mechanism of Action (MOA) is different from TNX-102 SL Pre

  36. Slide 36: TNX-801 (Synthesized Live Horsepox Virus): A Smallpox Preventing Vaccine Candidate

    TNX 801 (Synthesized Live Horsepox Virus): A Smallpox Preventing Vaccine Candidate 36 Potential improvement over current biodefense tools against smallpox Leverages Tonix’s government affairs effort Collaboration with Professor David Evans and Dr. Ryan Noyce at University of Alberta Demonstrated pro

  37. Slide 37: Financial Overview

    Financial Overview 37 NASDAQ: TNXP Cash and cash equivalents, December 31, 2018 $25.0 million Common stock outstanding as of March 13, 2019 6.1 million © 2019 Tonix Pharmaceuticals Holding Corp.

  38. Slide 38: Management Team

    Management Team 38 Seth Lederman, MD President & CEO Gregory Sullivan, MD Chief Medical Officer Bradley Saenger, CPA Chief Financial Officer Jessica Morris Chief Operating Officer © 2019 Tonix Pharmaceuticals Holding Corp.

  39. Slide 39: Board of Directors

    Board of Directors 39 Seth Lederman, MD Donald Landry, MD, PhD Chairman Chair of Medicine, Columbia University Margaret Smith Bell Adeoye “Oye” Olukotun, MD Standard Life Investments, Putnam Squibb, BMS, Mallinckrodt, Esperion Investments, State Street Research Patrick Grace John Rhodes (qp) global

  40. Slide 40: Milestones – Recently Completed and Upcoming

    Milestones – Recently Completed and Upcoming 40 July 2018 Completed P301/HONOR study interim analysis - result did not support study continuation but strengthened new Phase 3 study August 2018 Presentation of P301/HONOR study results at Military Health System Scientific Symposium October 2018 Met wi

  41. Slide 41: Thank you!

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

  42. Slide 42: Tonix Pharmaceuticals

    TONIX PHARMACEUTICALS NASDAQ: TNXP

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