Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Investor Presentation (June 2019)

61 slides from Tonix Pharmaceuticals's investor presentation, Jun 3, 2019

  1. Slide 1: Investor Presentation June 2019

    © 2019 Tonix Pharmaceuticals Holding Corp. June 2019 Version P0184 6 - 3 - 19 (Doc 0495) Investor Presentation

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

    © 2019 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: Tonix Pharmaceuticals: Who we are, what we do

    © 2019 Tonix Pharmaceuticals Holding Corp. 3 Tonix Pharmaceuticals Who we are: • A clinical stage biopharmaceutical company dedicated to developing innovative treatments for patients and making meaningful contributions to society • Focusing on small molecules and biologics to treat psychiatric, pain

  4. Slide 4: CNS Candidates in Development

    © 2019 Tonix Pharmaceuticals Holding Corp. 4 CNS Candidates in Development Psychiatry, Pain and Addiction Preclinical Phase 2 NDA 3 /BLA 4 Market Pipeline Product Indication Phase 3 TNX - 102 SL 1 Bedtime Treatment for PTSD – Tonmya ®2 Daytime Treatment for PTSD TNX - 601 Novel salt discovered and c

  5. Slide 5: Biodefense Candidates in Development

    © 2019 Tonix Pharmaceuticals Holding Corp. 5 Biodefense Candidates in Development 1 NDA - New Drug Application; 2 BLA – Biologic Licensing Application Biodefense programs owned outright with no royalties due Preclinical Phase 2 NDA 1 /BLA 2 Market Pipeline Product Indication Phase 3 TNX - 801 Horsep

  6. Slide 6: Lead Program: TNX-102 SL – Product Concept

    © 2019 Tonix Pharmaceuticals Holding Corp. 6 Lead Program: TNX - 102 SL – Product Concept Sleep disturbances are associated with a constellation of disorders • Considered co - morbid or a key symptom in these disorders • Believed to have a role in the onset, progression and severity of these disorde

  7. Slide 7: TNX-102 SL: Improving Sleep Quality across indications

    © 2019 Tonix Pharmaceuticals Holding Corp. 7 A unique and innovative approach (improving sleep quality), to potentially address a constellation of disorders in a variety of therapeutic areas where sleep disturbances are co - morbid and believed to have a role in the onset, progression and severity o

  8. Slide 8: TNX-102 SL Intellectual Property – U.S. Protection until 2034

    © 2019 Tonix Pharmaceuticals Holding Corp. 8 TNX - 102 SL Intellectual Property – U.S. Protection until 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 Nov 2018 • Japanese P

  9. Slide 9: Prevalence of PTSD Among Civilians and Veterans

    © 2019 Tonix Pharmaceuticals Holding Corp. 9 Prevalence of PTSD Among Civilians and Veterans 1 Goldstein et al., 2016 (adjusted for 2019) ; 2 Norris, PTSD Res Quar . 2013; 3 Analysis of VA Health Care Utilization among Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn Veter

  10. Slide 10: PTSD Prevalence and Market Characteristics

    © 2019 Tonix Pharmaceuticals Holding Corp. 10 PTSD Prevalence and Market Characteristics 1 Goldstein et al., 2016 (adjusted for 2019) 2 Veterans: VA/DOD Clinical Practice Guidelines for the Managements of PTSD and Acute Stress Disorder, 2017, page 15 (619,493 vets diagnosed with PTSD in VA for 2016)

  11. Slide 11: PTSD: Not Well-Served by Approved Treatments

    © 2019 Tonix Pharmaceuticals Holding Corp. 11 PTSD: Not Well - Served by Approved Treatments 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

  12. Slide 12: Tonmya: a Potential Bedtime Treatment for PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 12 Tonmya : a Potential Bedtime Treatment for PTSD 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 treat

  13. Slide 13: No Recognized Abuse Potential in Clinical Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 13 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, a 1 - adrenergic and his

  14. Slide 14: TNX-102 SL: Sublingual Formulation Designed for Bedtime Administration

    © 2019 Tonix Pharmaceuticals Holding Corp. 14 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

  15. Slide 15: Hypothesized Novel Mechanism Targets Sleep Quality for Recovery from PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 15 Tonmya: 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 - dependent me

  16. Slide 16: Phase 2 P201/AtEase Study in Military-Related PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 16 Phase 2 P201/AtEase 1 Study in Military - Related PTSD • Randomized, double - blind, placebo - controlled trial in military - related PTSD • Efficacy analysis from 231 * patients; 24 U.S. clinical sites • Enrolled patients with baseline CAPS - 5 2 ≥ 29 •

  17. Slide 17: P201/AtEase Study

    © 2019 Tonix Pharmaceuticals Holding Corp. 17 P201/AtEase Study 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 • Retrospectiv

  18. Slide 18: P301/HONOR Study

    © 2019 Tonix Pharmaceuticals Holding Corp. 18 P301/HONOR 1 Study – Evidence of Efficacy at Week 4 Discontinued Due to High Placebo Response at Week 12 Primary e ndpoint CAPS - 5 2 : • Mean change from baseline at W eek 12 (Tonmya 5.6 mg vs. placebo ) Unblinded interim analysis at 274 randomized part

  19. Slide 19: P301/HONOR Study Stopped After Interim Analysis

    © 2019 Tonix Pharmaceuticals Holding Corp. 19 P301/HONOR Study Stopped After Interim Analysis (July 2018) 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 Wee

  20. Slide 20: Tonmya Dose-Effect in Military-Related PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 20 Tonmya Phase 2 Dose - Effect in Military - Related PTSD 1 1 Completed Phase 2 P201/AtEase study: Retrospective analysis of Tonmya 5.6 mg on CAPS - 5 ≥33 (high - moderate) subgroup. Primary analysis of P 201/ AtEase , based on Tonmya 2.8 mg in participant

  21. Slide 21: Primary Outcome in Phase 3 and ≤9 Years Time Since Trauma Subgroups

    © 2019 Tonix Pharmaceuticals Holding Corp. Primary Outcome (CAPS - 5) in Phase 3 ( mITT ) and ≤9 Years Time Since Trauma Subgroups Modified intent to treat ( mITT ) population Phase 3 P301/HONOR Study 1 ** p=0.004, * p=0.039, # p=0.069, TNX - 102 SL 5.6 mg group v. placebo, using MMRM with MI ~50% m

  22. Slide 22: Retrospective Comparison of Time Since Trauma in P201 versus P301

    © 2019 Tonix Pharmaceuticals Holding Corp. 22 Retrospective Comparison of Time Since Trauma in P201/AtEase versus P301/HONOR (Tonmya 5.6 mg Groups) P301 study was initiated approximately two years later than Phase 2 P201 • The median time since trauma in P301 was 9.5 years compared to the median tim

  23. Slide 23: CAPS-5 Mean Change Difference from Placebo by Time Since Trauma

    © 2019 Tonix Pharmaceuticals Holding Corp. 23 CAPS - 5 Mean Change from Baseline Difference from Placebo of Tonmya 5.6 mg in TST Subgroups in P301 1 MCFB=mean change from baseline; ‘N’=number of participants in group; PBO=placebo; TST=time since trauma • The mITT population was divided into subgroup

  24. Slide 24: PTSD Treatment Response in Phase 2 and Phase 3 Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. P201 Baseline CAPS - 5 ≥33 (majority TST 1 ≤9 yr ) **p<0.01, *p=0.017, TNX - 102 SL 5.6 mg group v. placebo, using mixed model repeated measures (MMRM) with multiple imputation (MI) P301 TST ≤9 yr ** p=0.004, * p=0.039, # p=0.069 TNX - 102 SL 5.6 mg group v

  25. Slide 25: Sustained Remission in Phase 2 and Phase 3 Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 25 Sustained Remission in Phase 2 and Phase 3 Studies: Retrospective Analyses of P201 Entry CAPS - 5 ≥33 and P301 ≤9 Years Since Trauma Subgroups Remission is a clinical state that is essentially asymptomatic In order to confirm remission: • Determined rate

  26. Slide 26: Retrospective Analyses of ≤9 Years Since Trauma Subgroup

    © 2019 Tonix Pharmaceuticals Holding Corp. 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 - Treat sample; MMRM=mixed model repeated measures analys

  27. Slide 27: Adverse Events in P201/AtEase and P301/HONOR Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 27 Adverse Events (AEs) in P201/AtEase and P301/HONOR Studies No serious or unexpected AEs in P201 or P301 related to Tonmya • Systemic AEs comparable between studies and also consistent with those described in approved oral cyclobenzaprine product labeling

  28. Slide 28: Time Since Trauma – Review of Published Studies

    © 2019 Tonix Pharmaceuticals Holding Corp. 28 Time Since Trauma – Review of Published Studies 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 y

  29. Slide 29: Time Since Trauma – Remitting and Persistent Phases of PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 29 Time Since Trauma – Remitting and Persistent Phases of PTSD 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

  30. Slide 30: Response to Tonmya for Female Participants in P301/HONOR Study

    © 2019 Tonix Pharmaceuticals Holding Corp. 30 Response to Tonmya for Female Participants in P301/HONOR Study 1 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 w

  31. Slide 31: Response to Tonmya for Non-Combat Traumas

    © 2019 Tonix Pharmaceuticals Holding Corp. 31 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, difference in MCFB in CAPS - 5 was assessed in non - comb

  32. Slide 32: Summary of Clinical Experience with Tonmya in PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 32 Summary of Clinical Experience with Tonmya/ TNX - 102 SL in PTSD 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

  33. Slide 33: New Phase 3 P302/RECOVERY Study – Initiated 1Q 2019

    © 2019 Tonix Pharmaceuticals Holding Corp. 33 New Phase 3 P302/RECOVERY Study – Initiated 1Q 2019 Primary e ndpoint: • CAPS - 5 1 mean change from baseline at Week 4 ( Tonmya 5.6 mg vs. placebo) Key Secondary e ndpoint s include: • CAPS - 5 m ean change from baseline at W eek 12 (Tonmya 5.6 mg vs. p

  34. Slide 34: Late-Stage PTSD Drug Candidates

    © 2019 Tonix Pharmaceuticals Holding Corp. 34 Late - Stage PTSD Drug Candidates 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 • Indication – “drug assi

  35. Slide 35: Opportunities to Expand to Other Indications

    © 2019 Tonix Pharmaceuticals Holding Corp. 35 Opportunities to Expand to Other Indications Growing recognition that there are many disorders where sleep disturbances may have a role in the pathophysiology (cardiovascular, metabolic, neurologic) • Homeostatic role of sleep quality in several disorder

  36. Slide 36: Fibromyalgia: Pain Alarm Overview

    © 2019 Tonix Pharmaceuticals Holding Corp. 36 Volkswagen Check Engine [Photograph]. (2011, October 14). Wikipedia • Pain is a sensor system in the brain similar to a check engine light on a car’s dashboard • When the check engine light malfunctions, the light is on even though the car is not malfunc

  37. Slide 37: Fibromyalgia: Market Characteristics

    © 2019 Tonix Pharmaceuticals Holding Corp. 37 Fibromyalgia: Market Characteristics Undiagnosed ~2.7 million Drug Treated 85% 3 2,366,400 No Drug 15%3 353,600 U.S. Prevalence Rate 2 - 4% 1 (~5 - 10 million adults) Diagnosed 2 ~2.7 million Market Characteristics Prevalence • One of the more common chr

  38. Slide 38: Fewer than Half Treated for Fibromyalgia Receive Sustained Benefit

    © 2019 Tonix Pharmaceuticals Holding Corp. 38 Fewer than Half of Those Treated for Fibromyalgia Receive Sustained Benefit from the Three FDA - Approved Drugs 1 • The treatment objective is to restore functionality and quality of life by broadly improving symptoms while avoiding significant side effe

  39. Slide 39: Large Need for New Fibromyalgia Therapies

    © 2019 Tonix Pharmaceuticals Holding Corp. 39 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 altogether within mo

  40. Slide 40: TNX-102 SL for Fibromyalgia: Phase 3 F301 Study Summary

    © 2019 Tonix Pharmaceuticals Holding Corp. 40 TNX - 102 SL for Fibromyalgia: Summary of a completed Phase 3 F301 study General s tudy c haracteristics: • Randomized, 12 - week, double - blind, placebo - controlle d Phase 3 study of TNX - 102 SL 2.8 mg (half the dose being developed for PTSD) taken d

  41. Slide 41: TNX-102 SL for Fibromyalgia: F301 Results and Program Updates

    © 2019 Tonix Pharmaceuticals Holding Corp. 41 TNX - 102 SL for Fibromyalgia: F301 Study Results and Program Updates Safety results: • Good tolerability and low rates of systemic AEs. • The most common AEs were generally mild and transient events related to the sublingual administration of the study

  42. Slide 42: TNX-102 SL: Potential Treatment for Agitation in Alzheimer's Disease

    © 2019 Tonix Pharmaceuticals Holding Corp. 42 TNX - 102 SL: Potential Treatment for Agitation in Alzheimer’s Disease (AAD) Agitation is one of the most distressing and debilitating of the behavioral complications of Alzheimer’s disease • Includes emotional lability, restlessness, irritability and ag

  43. Slide 43: New Addition to Pipeline: TNX-1300 for Cocaine Intoxication

    © 2019 Tonix Pharmaceuticals Holding Corp. New Addition to Tonix’s Pipeline: TNX - 1300* for the Treatment of Cocaine Intoxication Recombinant protein that degrades cocaine in the bloodstream 1 • Double - mutant cocaine esterase In - licensed from Columbia University (Univ. of Kentucky and Univ. of

  44. Slide 44: About TNX-1300

    © 2019 Tonix Pharmaceuticals Holding Corp. 44 About TNX - 1300 Produced through rDNA technology in non - disease - producing strain of E. coli. • Cocaine Esterase ( CocE ) was identified in bacteria ( Rhodococcus ) that use cocaine as its sole source of carbon and nitrogen and that grow in soil surr

  45. Slide 45: About Cocaine and Cocaine Intoxication

    © 2019 Tonix Pharmaceuticals Holding Corp. 45 About Cocaine and Cocaine Intoxication Cocaine: an illegal recreational drug taken for its pleasurable effects and associated euphoria. • Cocaine blocks the reuptake of the neurotransmitter dopamine (DA) in the CNS • Results in accumulation of DA within

  46. Slide 46: Cocaine Action

    © 2019 Tonix Pharmaceuticals Holding Corp. 46 Cocaine Action • Cocaine acts to inhibit the Dopamine Reuptake Transporter • Binds to transporter and blocks reuptake of dopamine from synapse • No antagonist has been developed for cocaine • Unlike situation for opiates which can be blocked by naloxone

  47. Slide 47: Cocaine Action – Lack of Antidote

    © 2019 Tonix Pharmaceuticals Holding Corp. 47 Cocaine Action – Lack of “Antidote” • Cocaine binding site on Dopamine Reuptake Transporter is too small or simple for a blocker • Antagonists of cocaine binding have the same function as cocaine • Naltrexone exploits the complexity of the opiate binding

  48. Slide 48: CocE Breaks Cocaine Down into Less Toxic Metabolites

    © 2019 Tonix Pharmaceuticals Holding Corp. 48 CocE is a Catalyst that Breaks Cocaine Down into Less Toxic Metabolites 1 - 4 Cocaine Ecgonine Methyl Ester Benzoic Acid • Metabolites ecgonine methyl ester and benzoic acid are neither pleasurable nor addictive 1 Bresler MM et al, Appl Environ Microbiol

  49. Slide 49: Prevalence of Cocaine Usage and Overdose

    © 2019 Tonix Pharmaceuticals Holding Corp. 49 The Prevalence of Cocaine Usage and Overdose (U.S.) Cocaine Usage in the U.S. 5.07 million individuals estimated to have used cocaine in past year 1 • 2.2 million “current” (i.e. users in the past month) of cocaine (2017) 2 • 966,000 had cocaine use diso

  50. Slide 50: Mortality Due to Cocaine Overdose

    © 2019 Tonix Pharmaceuticals Holding Corp. 50 Mortality Due to Cocaine Overdose Cocaine is involved in 20% of overdose deaths in the U.S. • In 2016, 10,375 deaths due to cocaine overdose 1 • In 2017, about 13,900 deaths occurred in the U.S. due to cocaine overdose. 2 Overdose deaths involving cocain

  51. Slide 51: Treatment for Cocaine Intoxication

    © 2019 Tonix Pharmaceuticals Holding Corp. 51 Treatment for Cocaine Intoxication Current Standard of Care • Patients present with acute agitation, hyperthermia, tachycardia, arrhythmias, and hypertension • Potential life - threatening sequalae of myocardial infarction, cerebrovascular accident, rhab

  52. Slide 52: Value of TNX-1300 to Tonix

    © 2019 Tonix Pharmaceuticals Holding Corp. Value of TNX - 1300 to Tonix Features of the Acquired Asset: • Full rights to the IP and to develop and commercialize TNX - 1300 worldwide • FDA Breakthrough Therapy Designated product • An inventory of investigational drug product • Clinical trial results

  53. Slide 53: CNS Candidates in Development

    © 2019 Tonix Pharmaceuticals Holding Corp. 53 CNS Candidates in Development Psychiatry, Pain and Addiction Preclinical Phase 2 NDA 3 /BLA 4 Market Pipeline Product Indication Phase 3 TNX - 102 SL 1 Bedtime Treatment for PTSD – Tonmya ®2 Daytime Treatment for PTSD TNX - 601 Novel salt discovered and

  54. Slide 54: Biodefense Candidates in Development

    © 2019 Tonix Pharmaceuticals Holding Corp. 54 Biodefense Candidates in Development 1 NDA - New Drug Application; 2 BLA – Biologic Licensing Application Biodefense programs owned outright with no royalties due Preclinical Phase 2 NDA 1 /BLA 2 Market Pipeline Product Indication Phase 3 TNX - 801 Horse

  55. Slide 55: TNX-601 (Tianeptine Oxalate): Potential Clinical Candidate for PTSD

    © 2019 Tonix Pharmaceuticals Holding Corp. 55 TNX - 601 ( Tianeptine Oxalate): A Potential Clinical Candidate for PTSD Pre - IND Candidate Targeted as a 1 st line monotherapy for PTSD: oral formulation for daytime dosing x Leverages expertise in PTSD (clinical and regulatory experience, market analy

  56. Slide 56: TNX-801 (Synthesized Live Horsepox Virus): Smallpox-Preventing Vaccine

    © 2019 Tonix Pharmaceuticals Holding Corp. 56 TNX - 801 (Synthesized Live Horsepox Virus): A Smallpox - Preventing Vaccine Candidate Pre - IND Stage Potential improvement over current biodefense tools against smallpox ✓ Leverages Tonix’s government affairs effort ✓ Collaboration with Professor David

  57. Slide 57: Management Team

    © 2019 Tonix Pharmaceuticals Holding Corp. 57 Management Team Seth Lederman, MD President & CEO Jessica Morris Chief Operating Officer Gregory Sullivan, MD Chief Medical Officer Bradley Saenger, CPA Chief Financial Officer

  58. Slide 58: Board of Directors

    © 2019 Tonix Pharmaceuticals Holding Corp. 58 Board of Directors Seth Lederman, MD Chairman Adeoye “Oye” Olukotun, MD Squibb, BMS, Mallinckrodt, Esperion John Rhodes Chair, NYS Public Service Commission, CEO, NYS Dept. of Public Service, Booz Allen James Treco First Chicago, Salomon Brothers/Citigro

  59. Slide 59: Milestones – Recently Completed and Upcoming

    © 2019 Tonix Pharmaceuticals Holding Corp. 59 Milestones – Recently Completed and Upcoming □ July 201 8 Completed P301/HONOR study interim analysis - result did not support study continuation but strengthened new Phase 3 study □ August 201 8 Presentation of P301/HONOR study results at Military Healt

  60. Slide 60: Summary

    © 2019 Tonix Pharmaceuticals Holding Corp. 60 Summary Two Phase 3 Programs in indications affecting millions of Americans • Tonmya for PTSD: affects 12 million adults in U.S.; currently in Phase 3 with data expected next year; bedtime treatment • TNX - 102 SL for Fibromyalgia: affects between 5 - 10

  61. Slide 61: Thank you!

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

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