Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP
Tonix Pharmaceuticals — Investor Presentation (December 2017)
63 slides from Tonix Pharmaceuticals's investor presentation, Dec 12, 2017
Slide 1: Investor Presentation December 2017
© 2017 Tonix Pharmaceuticals Holding Corp. December 2017 Version P0089 12 - 12 - 17 (Doc 0303) Investor Presentation
Slide 2: Cautionary Note on Forward-Looking Statements
© 2017 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
Slide 3: Portfolio of Potential Treatments for Important Public Health Challenges
© 2017 Tonix Pharmaceuticals Holding Corp. 3 Tonix is Developing a Portfolio of Potential Treatments for Important Public Health Challenges and Diseases with Significant Unmet Needs Tonmya ®1 (cyclobenzaprine HCl sublingual tablets) bedtime treatment for posttraumatric stress disorder (PTSD) • Phase
Slide 4: Products in Development
© 2017 Tonix Pharmaceuticals Holding Corp. 4 Products in Development Preclinical Phase 2 NDA 1 /BLA 2 Market Pipeline Product Indication/ Description Phase 3 Tonmya Bedtime Treatment for PTSD Daytime Treatment for PTSD TNX - 601 Novel polymorph and salt discovered and characterized TNX - 801 Horsepo
Slide 5: Tonmya for PTSD
© 2017 Tonix Pharmaceuticals Holding Corp. 5 Tonmya (Cyclobenzaprine HCl Sublingual Tablets) for PTSD Phase 3 HONOR study of Tonmya in military - related PTSD enrolling • Encouraging evidence of safety and efficacy was demonstrated in Phase 2 Breakthrough Therapy designation from the FDA • Expedited
Slide 6: Phase 3 HONOR Study in PTSD Enrolling
© 2017 Tonix Pharmaceuticals Holding Corp. 6 Phase 3 HONOR Study in PTSD Enrolling • General s tudy c haracteristics: • Randomized, double - blind, placebo - controlled, entrance CAPS - 5 * ≥ 33 • One unblinded interim analys i s (IA) by an independent data monitoring committee at 50% randomized • I
Slide 7: Breakthrough Therapy Designation
© 2017 Tonix Pharmaceuticals Holding Corp. 7 Breakthrough Therapy Designation FDA granted Tonmya Breakthrough Therapy designation – reported December 19, 2016 • PTSD is a serious condition • Tonmya has potential advantages over existing therapies in military - related PTSD Benefits of Breakthrough T
Slide 8: No Recognized Abuse Potential in Clinical Studies
© 2017 Tonix Pharmaceuticals Holding Corp. 8 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
Slide 9: TNX-102 SL Intellectual Property – U.S. Protection until 2034
© 2017 Tonix Pharmaceuticals Holding Corp. 9 TNX - 102 SL Intellectual Property – U.S. Protection until 2034 Composition of matter (eutectic) • U.S. Patent No. 9,636,408 issued May 2, 2017 by U.S. Patent and Trademark Office • Protection expected to 2034 • Additional claims and jurisdictions pending
Slide 10: Proprietary Cyclobenzaprine Eutectic Mixture Stabilizes Sublingual Tablet
© 2017 Tonix Pharmaceuticals Holding Corp. 10 Proprietary Cyclobenzaprine Hydrochloride Eutectic Mixture Stabilizes Sublingual Tablet Formulation Base particle (K 2 HPO 4 ) Base particle (K 2 HPO 4 ) Base particle (K 2 HPO 4 ) Eutectic formulation 1 ANGSTRO - TECHNOLOGY™ Cyclobenzaprine - HCl (CBP -
Slide 11: Sublingual Formulation Designed for Bedtime Administration
© 2017 Tonix Pharmaceuticals Holding Corp. 11 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
Slide 12: Novel Mechanism Targets Sleep Quality for Recovery from PTSD
© 2017 Tonix Pharmaceuticals Holding Corp. 12 Tonmya : 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 memory process
Slide 13: What are the Symptoms of PTSD?
© 2017 Tonix Pharmaceuticals Holding Corp. 13 What are the Symptoms of PTSD? Symptoms of PTSD fall into four clusters: 1. Intrusion (aversive memories, nightmares, flashbacks) 2. Avoidance (avoiding persons, places or situations) 3. Mood/cognitions (memory block, emotional numbing, detachment from o
Slide 14: What are the Consequences of PTSD?
© 2017 Tonix Pharmaceuticals Holding Corp. 14 What are the Consequences of PTSD? Consequences: • Impaired daily function and substantial interference with work and social interactions • Reckless or destructive behavior • Increased health care utilization and greater medical morbidity PTSD as a risk
Slide 15: PTSD: U.S. Prevalence and Index Traumas
© 2017 Tonix Pharmaceuticals Holding Corp. 15 PTSD: U.S. Prevalence and Index Traumas A chronic response to traumatic event(s) • A majority of people will experience a traumatic event at some point in their lifetime 1 • 20% of women and 8% of men in the U.S. who experience significant trauma develop
Slide 16: PTSD Prevalence and Market Characteristics
© 2017 Tonix Pharmaceuticals Holding Corp. 16 PTSD Prevalence and Market Characteristics 1 Kessler, et al., 2005; Prevalence rate of 3.5% applied to U.S. Census estimate of 247 million U.S. adult ( > 18) population in 2015 (www.census.gov/quickfacts/table/PST045215/00) 2 IMS Consulting, Market Sizin
Slide 17: What Drug Classes are Used to Treat PTSD?
© 2017 Tonix Pharmaceuticals Holding Corp. 17 What Drug Classes are Used to Treat PTSD? * TRx = Total prescriptions 1 VA/DoD Clinical Practice Guideline for the Management of Post - Traumatic Stress, Version 2, 2010 2 IMS Consulting, Market Sizing & Treatment Dynamics: “Post - Traumatic Stress Disor
Slide 18: PTSD: Not Well-Served by Approved Treatments
© 2017 Tonix Pharmaceuticals Holding Corp. 18 PTSD: Not Well - Served by Approved Treatments FDA - approved SSRIs, paroxetine and sertraline, have not shown efficacy in military - related PTSD Majority of patients unresponsive or intolerant to current treatments • Side effects relating to sexual dys
Slide 19: Why Initially Target Military-Related PTSD?
© 2017 Tonix Pharmaceuticals Holding Corp. 19 Why Initially Target Military - Related PTSD? 1 Friedman et al., J Clin Psychiatry 2007; 68:711 2 Zoloft Package Insert, August, 2014 3 Paxil Package Insert, June, 2014 4 Fava et al., Psychother Psychosom 84:72 - 81, 2015 Military - related PTSD not well
Slide 20: High Prevalence of PTSD Among Combat Veterans
© 2017 Tonix Pharmaceuticals Holding Corp. 20 High Prevalence of PTSD Among Combat Veterans 1 Kessler et al., Arch Gen Psych 2005; Prevalence rate of 3.5% applied to U.S. Census estimate of 247M U.S. adult ( > 18) population in 2015 ( www.census.gov/quickfacts/table/PST045215/00 ) ; 2 Norris, PTSD R
Slide 21: Growing Economic and Social Burden to Care for Veterans with PTSD
© 2017 Tonix Pharmaceuticals Holding Corp. 21 Growing Economic and Social Burden to Care for Veterans with PTSD Health care costs associated with PTSD for OEF/OIF/OND veterans: Direct costs Indirect costs 1 CBO Report 2012; 2 Tanielan , Invisible Wounds of War . 2005; 3 Analysis of VA Health Care Ut
Slide 22: Phase 2 AtEase Study in Military-Related PTSD
© 2017 Tonix Pharmaceuticals Holding Corp. 22 Phase 2 AtEase 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 ≥ 29 • Primary Ef
Slide 23: Results of Phase 2 AtEase Study
© 2017 Tonix Pharmaceuticals Holding Corp. 23 Results of Phase 2 AtEase Study in Military - Related PTSD Tonmya 5.6 mg showed clinical benefit in military - related PTSD • CAPS - 5 scale, was statistically significant by Mixed - effect Model Repeated Measures, or MMRM, with Multiple Imputation, or M
Slide 24: AtEase Study Demographics and Characteristics
© 2017 Tonix Pharmaceuticals Holding Corp. 24 AtEase Study Demographics and Characteristics 93% of the randomized patients were male 98% had trauma during military service Deployed an average of 2.3 times Mean time since index trauma was 7 years Race and ethnicity generally consistent with U.S. mili
Slide 25: AtEase Study: Traumas Associated with PTSD
© 2017 Tonix Pharmaceuticals Holding Corp. 25 AtEase Study: Traumas Associated with PTSD *Some patients experienced more than one trauma 0 5 10 15 20 25 30 35 40 Other Knowing someone seriously injured or killed Being responsible for the death of an enemy combatant Seeing dead bodies or human remain
Slide 26: AtEase Study – Summary of Primary and Secondary Analyses
© 2017 Tonix Pharmaceuticals Holding Corp. 26 AtEase Study – Summary of Primary and Secondary Analyses (week 12)
Slide 27: AtEase Study Results: Primary Endpoint CAPS-5 Total Score
© 2017 Tonix Pharmaceuticals Holding Corp. 27 AtEase Study Results: Primary Endpoint CAPS - 5 Total Score by MMRM with MI # -25 -20 -15 -10 -5 0 Wk 0 Wk 2 Wk 4 Wk 6 Wk 8 Wk 10 Wk 12 Placebo Tonmya 2.8 mg Tonmya 5.6 mg * # Primary analysis MMRM (mixed - effect model repeated measures), * p=0.031, com
Slide 28: AtEase Study: Safety and Tolerability Profile
© 2017 Tonix Pharmaceuticals Holding Corp. 28 AtEase Study: Safety and Tolerability Profile No serious adverse events reported with Tonmya deemed related to treatment Systemic Adverse Events* Placebo (N=94) Tonmya 2.8 mg (N=93) Tonmya 5.6 mg (N=50) Somnolence 6.4% 11.8% 16.0% Dry Mouth 10.6% 4.3% 16
Slide 29: Assessing CAPS-5 Entry Threshold in AtEase
© 2017 Tonix Pharmaceuticals Holding Corp. 29 Assessing CAPS - 5 Entry Threshold in AtEase Score of ≥29 on CAPS - 5 (20 items) required at screening and baseline • >50 on prior versions of CAPS (17 items) typical in previous drug registration trials • Extrapolation from prior versions of CAPS: ((50/
Slide 30: AtEase Retrospective Analysis: Effect Sizes
© 2017 Tonix Pharmaceuticals Holding Corp. 30 0.53 0.46 0.012 0.39 0.52 0 0.1 0.2 0.3 0.4 0.5 0.6 Effect Size AtEase Retrospective Analysis: Effect Sizes for Total CAPS - 5 and Cluster Scores * MMRM, mixed - effect model repeated measures, p<0.05 Effect sizes calculated for total CAPS - 5 and cluste
Slide 31: AtEase Retrospective Analysis: Sustained Remission
© 2017 Tonix Pharmaceuticals Holding Corp. 31 AtEase Study Retrospective Analysis: Sustained Remission in Subgroup with Entry CAPS - 5 ≥33 Remission = Loss of Diagnosis and CAPS - 5 < 11 Asterisk and hashmark represent pairwise comparisons between Tonmya and Placebo; # p=0.08, Odds Ratio 3.01 (0.89,
Slide 32: Multi-Functional Mechanism Involves Antagonism at 3 Neuronal Receptors
© 2017 Tonix Pharmaceuticals Holding Corp. 32 TNX - 102 SL – Multi - Functional Mechanism Involves Antagonism at 3 Neuronal Receptors Active ingredient is cyclobenzaprine, interacts with 3 receptors • Antagonist at 5 - HT 2A receptors • Similar activity to trazodone and Nuplazid ® ( pimivanserin ) •
Slide 33: Cyclobenzaprine is a Multi-Functional Drug – SNARI
© 2017 Tonix Pharmaceuticals Holding Corp. 33 Untreated Effects of TNX - 102 Cyclobenzaprine is a multi - functional drug - SNARI - inhibits serotonin and norepinephrine reuptake - blocks serotonin 5HT 2a and norepinephrine α 1 receptors SNARI = S erotonin and N orepinephrine receptor A ntagonist an
Slide 34: Tonmya Compared with Trazodone and Prazosin
© 2017 Tonix Pharmaceuticals Holding Corp. 34 Tonmya Trazodone Trazodone (disordered sleep ), prazosin (night terrors) - Trazodone inhibits serotonin 5HT 2a receptors and serotonin reuptake (SARI) - Prazosin blocks norepinephrine α 1 receptors Prazosin SARI – S erotonin Receptor A ntagonist & R eupt
Slide 35: Opportunities to Expand to Other Indications
© 2017 Tonix Pharmaceuticals Holding Corp. 35 v Opportunities to Expand to Other Indications Growing recognition that there is a constellation of disorders where sleep disturbances may have a role in the pathophysiology (cardiovascular, metabolic, neurologic) • Homeostatic role of sleep quality in s
Slide 36: TNX-102 SL – Multiple Potential Indications
© 2017 Tonix Pharmaceuticals Holding Corp. 36 TNX - 102 SL – Multiple Potential Indications Management of Fibromyalgia – chronic pain condition • Tonix’s Phase 3 program was halted after near miss in Phase 3 at low dose (2.8 mg) – half the dose being developed for PTSD • Imbalance in “withdrawal of
Slide 37: What is Agitation in Alzheimer's Disease?
© 2017 Tonix Pharmaceuticals Holding Corp. 37 What is Agitation in Alzheimer’s Disease? Agitation is one of the most distressing and debilitating of the behavioral complications of Alzheimer’s disease • Includes emotional lability, restlessness, irritability and aggression 1 Link between agitation i
Slide 38: Consequences of Agitation in Alzheimer's Disease
© 2017 Tonix Pharmaceuticals Holding Corp. 38 Consequences of Agitation in Alzheimer’s Disease Outcomes • Agitation is associated with significant negative outcomes for Alzheimer’s patients and their caregivers Common reason for confinement • Development of agitation, or its worsening, is one of the
Slide 39: Agitation in Alzheimer's – Potential New Indication for TNX-102 SL
© 2017 Tonix Pharmaceuticals Holding Corp. 39 Agitation in Alzheimer’s Disease – Potential New Indication for TNX - 102 SL Successful pre - IND meeting in November, 2017 • IND planned 1Q2018 to support a Phase 2 efficacy study Significant unmet need • No FDA approved drugs for the treatment of agita
Slide 40: Agitation in Alzheimer's – Regulatory Status and Registration Strategy
© 2017 Tonix Pharmaceuticals Holding Corp. 40 TNX - 102 SL for Agitation in Alzheimer’s – Regulatory Status and Registration Strategy FDA confirmed no additional study is needed prior to IND submission • Pre - IND meeting established open dialogue with the FDA on pivotal clinical study design and ef
Slide 41: Scientific Rationale for TNX-102 SL in Agitation in Alzheimer's
© 2017 Tonix Pharmaceuticals Holding Corp. 41 Scientific Rationale for Developing TNX - 102 SL for Agitation in Alzheimer’s Disease Connection between Sleep Disturbance and Agitation • Agitation in Alzheimer’s Disease is associated with sleep disturbance 1,2 Supported by Potential Mechanism of Actio
Slide 42: TNX-102 SL Addresses Challenges in Treating Agitation in Alzheimer's
© 2017 Tonix Pharmaceuticals Holding Corp. 42 TNX - 102 SL Potentially Addresses Some of the Challenges in Treating Agitation in Alzheimer’s Sublingual route of administration (no swallowing) • Swallowing can be an issue for a significant number of Alzheimer’s patients Low dose taken daily at bedtim
Slide 43: Agitation in Alzheimer's – Competitive Landscape of Select Drugs
© 2017 Tonix Pharmaceuticals Holding Corp. 43 Agitation in Alzheimer’s – Competitive Landscape of Select Drugs in Development Competitive landscape • 5HT2A Antagonists/inverse agonists • Pimavanserin (Acadia) • Nelotanserin ( Axovant ) • Atypical Antip sychotics (also have 5HT2A antagonism) • Rexult
Slide 44: Products in Development
© 2017 Tonix Pharmaceuticals Holding Corp. 44 Products in Development Preclinical Phase 2 NDA 1 /BLA 2 Market Pipeline Product Indication/ Description Phase 3 Tonmya Bedtime Treatment for PTSD Daytime Treatment for PTSD TNX - 601 Novel polymorph and salt discovered and characterized TNX - 801 Horsep
Slide 45: TNX-601 (Tianeptine Oxalate): A Potential Clinical Candidate for PTSD
© 2017 Tonix Pharmaceuticals Holding Corp. 45 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 an
Slide 46: Structural Comparison: TNX-102 and TNX-601
© 2017 Tonix Pharmaceuticals Holding Corp. 46 Structural Comparison: TNX - 102 and TNX - 601 Cyclobenzaprine and tianeptine share structural similarities with classic tricyclic antidepressants (TCAs) and to each other, but each has unique pharmacological properties • Tianeptine has a 3 - chlorodiben
Slide 47: TNX-601: A Potential Clinical Candidate for PTSD
© 2017 Tonix Pharmaceuticals Holding Corp. 47 • Tianeptine modulates the glutamatergic system indirectly • Does not have significant affinity (K i >10 μ M) for NMDA 2 or AMPA 3 receptors • Tianeptine is a weak µ - opioid receptor (MOR) agonist • Controlled substance in France, Bahrain and Singapore
Slide 48: TNX-801 (Synthesized Live Horsepox Virus): A Potential Smallpox-Preventing Vaccine
© 2017 Tonix Pharmaceuticals Holding Corp. 48 TNX - 801 ( Synthesized Live Horsepox Virus ): A Potential Smallpox - Preventing Vaccine Pre - IND Candidate Potential improvement over current methods for biodefense against smallpox x Leverages government affairs effort x Collaboration with Professor D
Slide 49: TNX-801 (Synthesized Live Horsepox Virus): A Potential Smallpox-Preventing Vaccine
© 2017 Tonix Pharmaceuticals Holding Corp. 49 TNX - 801 ( Synthesized Live Horsepox Virus ): A Potential Smallpox - Preventing Vaccine Synthesis from sequence of a 1976 Mongolian isolate 1 In mice, TNX - 801 behaved like attenuated vaccinia virus • Vaccinia is the term used to classify the live poxv
Slide 50: Horsepox – May Have Better Tolerability as a Smallpox Vaccine
© 2017 Tonix Pharmaceuticals Holding Corp. 50 Horsepox – May Have Better Tolerability as a Smallpox Preventing Vaccine? Horsepox is caused by HPXV and is characterized by mouth and skin eruptions HXPV isolate from the 1976 outbreak later sequenced Modern smallpox vaccines are associated with cardiot
Slide 51: A Better Smallpox-Preventing Vaccine is Important and Necessary Today
© 2017 Tonix Pharmaceuticals Holding Corp. 51 A Better Smallpox - Preventing Vaccine is Important and Necessary Today Smallpox was eradicated as a result of global public health campaigns No cases of naturally - occurring smallpox have been reported since 1977 Accidental or intentional transmission
Slide 52: TNX-801: A Potential Medical Countermeasure
© 2017 Tonix Pharmaceuticals Holding Corp. 52 TNX - 801: A Potential Medical Countermeasure 21st Century Cures Act (2016), Section 3086 • Encouraging treatments for agents that present a national security threat Medical countermeasures are drugs, biologics (vaccines) or devices intended to treat: •
Slide 53: TNX-801: Mechanism of Action and Important Benefits
© 2017 Tonix Pharmaceuticals Holding Corp. 53 Live virus vaccines stimulate cross - reactive immunity • Protects from consequences of infection with smallpox agent • Renders recipient “immune” • Provides additional protection of non - immunized population Potential safety advantage over existing vac
Slide 54: Vaccination Against Smallpox
54 © 2016 Tonix Pharmaceuticals Holding Corp. Ongoing vaccination of U.S. troops • Troops on the Korean Peninsula Threat of smallpox re - introduction • Strategic National Stockpile & public health policy Re - emergence of monkey pox 1 • Believed to resurgent because of vaccinia - naïve populations
Slide 55: Postulated Divergence of Historical Strains of Vaccinia
55 © 2016 Tonix Pharmaceuticals Holding Corp. Postulated Divergence of Historical Strains of Vaccinia Proposed Evolution of Vaccinia Vaccines NYCBH/European precursor stocks Horsepox - like ancestral strain Lister/Evans/USSR Dryvax ® IHDJ WR Copenhagen Tashkent RPXV TianTan Ankara LIVP IHD - J=Inter
Slide 56: Relationship to Smallpox Incidence and Eradication
56 © 2016 Tonix Pharmaceuticals Holding Corp. Relationship to Smallpox Incidence and Eradication Proposed Evolution of Vaccinia Vaccines TIME *Rough approximation (not data derived) 1977 Eradication SMALLPOX CASES IN US/EUROPE* ACAM2000™ 1798 1902 1931 2007 Dryvax ® swarm Mulford Vaccine Jenner’s Va
Slide 57: Jenner's Vaccine – Motivation to Study HPXV
57 © 2016 Tonix Pharmaceuticals Holding Corp. Vaccination protects against smallpox – both individuals and populations • Eradication based on Jenner’s vaccine Vaccination can protect AFTER infection • Vaccinia can be administered 1 - 3 days after infection Vaccination protects unvaccinated people in
Slide 58: Financial Overview
© 2017 Tonix Pharmaceuticals Holding Corp. 58 Financial overview NASDAQ: TNXP Cash, cash equivalents, and marketable securities reported at September 30, 2017 $29.3 million Gross proceeds from sale of common stock under purchase agreement with Lincoln Park Capital Fund, LLC through December 11, 2017
Slide 59: Management Team
© 2017 Tonix Pharmaceuticals Holding Corp. 59 Management Team Seth Lederman, MD President & CEO Jessica Morris EVP, Operations Gregory Sullivan, MD Chief Medical Officer Bradley Saenger, CPA Chief Financial Officer
Slide 60: Board of Directors
© 2017 Tonix Pharmaceuticals Holding Corp. 60 Board of Directors Seth Lederman, MD Chairman Ernest Mario, PhD ALZA, Glaxo, Reliant Pharma John Rhodes NYSERDA, NRDC, Booz Allen Hamilton Samuel Saks, MD Jazz Pharma, ALZA, Johnson & Johnson Charles Mather BTIG, Janney, Jefferies, Cowen, Smith Barney St
Slide 61: Milestones – Recently Completed and Upcoming
© 2017 Tonix Pharmaceuticals Holding Corp. 61 Milestones – Recently Completed and Upcoming T onmya – Posttraumatic Stress Disorder □ May 2016 Report ed results from Phase 2 AtEase study □ August 2016 End - of - Phase 2 meeting with FDA - Proposed Phase 3 clinical and NDA plan accepted □ December 201
Slide 62: Summary
© 2017 Tonix Pharmaceuticals Holding Corp. 62 Summary Strong position for value growth with Phase 3 development in a major medical indication: PTSD including military - related PTSD • PTSD is an important public health issue Tonmya for PTSD is designated as a Breakthrough Therapy by FDA • Accelerate
Slide 63: Thank you!
© 2017 Tonix Pharmaceuticals Holding Corp. Thank you ! NASDAQ: TNXP
Tonix Pharmaceuticals Holding — Investor Presentation (December 2017) on 6ix