Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP
Tonix Pharmaceuticals — Investor Presentation (March 2019)
103 slides from Tonix Pharmaceuticals's investor presentation, Mar 18, 2019
Slide 1: Investor Presentation March 2019
Investor Presentation March 2019 Version P0167 3-18-19 (Doc 0451) © 2019 Tonix Pharmaceuticals Holding Corp.
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
Slide 3: Tonix Pharmaceuticals
Tonix Pharmaceuticals 3 Who we are: • A clinical stage pharmaceutical company dedicated to developing innovative treatments for patients and making meaningful contributions to society What we do: • Target therapeutics with high need for improvement Conditions with no or ineffective treatments Signif
Slide 4: Tonix Development Highlights
Tonix Development Highlights 4 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
Slide 5: Lead Program: TNX-102 SL – Product Concept
Lead Program: TNX 102 SL – Product Concept 5 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 disorders The focus of TNX-102 SL development is both
Slide 6: Candidates in Development Pipeline
Candidates in Development 6 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
Slide 7: Tonmya: a Potential Bedtime Treatment for PTSD
Tonmya: a Potential Bedtime Treatment for PTSD 7 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 •
Slide 8: No Recognized Abuse Potential in Clinical Studies
No Recognized Abuse Potential in Clinical Studies 8 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
Slide 9: TNX-102 SL Intellectual Property – U.S. Protection
TNX 102 SL Intellectual Property – U.S. Protection until 2034 9 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 201 7U.S. Patent No. 9,956,188 in May 2018 and U.S. Patent No. 10,117,936 in Nove
Slide 10: TNX-102 SL: Sublingual Formulation Designed for Bedtime Administration
TNX 102 SL: Sublingual Formulation is Designed for Bedtime Administration 10 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 d
Slide 11: Proprietary Cyclobenzaprine Eutectic Mixture Stabilizes Sublingual Tablet
Proprietary Cyclobenzaprine Hydrochloride Eutectic Mixture Stabilizes Sublingual Tablet Formulation 11 Cyclobenzaprine-HCl Protectic™ (CBP-HCl) Eutectic formulation 1 ANGSTRO-TECHNOLOGY™ Mannitol (inactive) Base particle Base particle (K 2 HPO 4 ) (K 2 HPO 4 ) Base particle Cyclobenzaprine (K 2 HPO
Slide 12: Tonmya: Hypothesized Novel Mechanism Targets Sleep Quality
Tonmya: Hypothesized Novel Mechanism Targets Sleep Quality for Recovery from PTSD 12 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 esse
Slide 13: Proposed Mechanism of Action of Tonmya in PTSD
Proposed Mechanism of Action of Tonmya in the Treatment of PTSD: The Effects of Nocturnal Neuroreceptor Blockade on Sleep 13 Cyclobenzaprine is a functional antagonist at serotonergic 5-HT 2A receptors, noradrenergic 1 receptors, and histaminergic H 1 receptors Histaminergic projections from the tub
Slide 14: Focus on Nocturnal 5-HT2A Receptor Blockade in REM
Proposed Mechanism of Action of Tonmya in the Treatment of PTSD: Focus on Nocturnal HT 2A Receptor Blockade in REM 14 • Generally, serotonin (5-HT) activity promotes the awake state and inhibits REM sleep; whereas once in REM sleep, the 5-HT system is normally quiescent • Extinction learning is crit
Slide 15: Fear Extinction Memory Consolidation
Fear Extinction Memory Consolidation: The Proposed Role of Waves, REM Sleep, and Serotonergic Neuroreceptor Activity 15 • Increased P-wave activity • Serotonergic activity during REM sleep is critical for normally inhibits P-wave release during REM sleep 2 fear extinction memory • This is thought to
Slide 16: Overview of Posttraumatic Stress Disorder (PTSD)
Overview of Posttraumatic Stress Disorder (PTSD) 16 PSTD is a chronic disabling disorder in response to experiencing traumatic event(s) Symptoms of PTSD fall into four clusters: 1. Intrusion (aversive memories, nightmares, flashbacks) 2. Avoidance (avoiding persons, places or situations) 3. Mood/cog
Slide 17: Impact of PTSD on People
Impact of PTSD on People 17 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 factor for: • Depression • Alcohol or substance abuse
Slide 18: PTSD: U.S. Prevalence and Index Traumas
PTSD: U.S. Prevalence and Index Traumas 18 PTSD is 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 PTSD 1 Adult Civilians: • Lifetime
Slide 19: PTSD Prevalence and Market Characteristics
PTSD Prevalence and Market Characteristics 19 Prevalent Population (U.S.) Diagnosed population ~12 million 1 Large population (~1.8 million) (civilians plus veterans) Receive Rx ~620k Veterans Majority receive drug treatment 495,500 Diagnosed Civilians: ~75% 3 in Veterans Veterans: ~80% 4 No Rx Admi
Slide 20: What Drug Classes are Used to Treat PTSD?
What Drug Classes are Used to Treat PTSD? 20 Market highly fragmented, with benzodiazepines widely prescribed (but not indicated) 1 • Multiple medications per patient (or “Polypharmacy”) is the norm • Approximately 55% of patients receive a benzodiazepine, and 53% receive a selective serotonin reupt
Slide 21: PTSD: Not Well Served by Approved Treatments
PTSD: Not Well Served by Approved Treatments 21 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
Slide 22: Why Initially Target Military Related PTSD?
Why Initially Targeted Military Related PTSD? 22 Military-related PTSD not well-served by existing FDA-approved therapies • No clear treatment response observed in U.S. military population Sertraline: failed to show efficacy in a large multicenter trial in U.S. military (placebo numerically better)
Slide 23: Prevalence of PTSD Among Civilians and Veterans
Prevalence of PTSD Among Civilians and Veterans 23 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
Slide 24: Growing Economic and Social Burden of Veterans with PTSD
Growing Economic and Social Burden to Care for Veterans with PTSD 24 Health care costs associated with PTSD for OEF/OIF/OND veterans: Direct costs Indirect costs $3,000 5,000 $2 3 billion per patient per year for estimated yearly cost OEF/OIF Veterans 1 to society 2 ~ 1.9M Veterans out of 2.7M Famil
Slide 25: P201/AtEase Study in Military Related PTSD
Phase 2 P201/AtEase Study in Military Related PTSD 25 • 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.
Slide 26: P201/AtEase Study
P201/AtEase Study 26 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
Slide 27: P201/AtEase Study – Summary of Primary and Secondary Analyses
P201/AtEase Study – Summary of Primary and Secondary Analyses (Week 12) 27 © 2019 Tonix Pharmaceuticals Holding Corp.
Slide 28: P301/HONOR Study
P301/HONOR Study Evidence of Efficacy at Week 4 Discontinued Due to High Placebo Response at Week 12 28 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
Slide 29: P301/HONOR Study Primary Analysis in mITT Population
P301/HONOR Study Primary Analysis in mITT Population 29 MMRM with Multiple Imputation In P301 study both TNX-102 SL and placebo-treated groups improved but the greater improvement on TNX-102 SL compared with placebo diminished over time • TNX-102 SL did not separate from placebo at primary endpoint
Slide 30: TNX-102 SL: Sublingual Formulation Designed for Bedtime Administration
TNX 102 SL: Sublingual Formulation is Designed for Bedtime Administration 30 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 d
Slide 31: Differences Between P201/AtEase and P301/HONOR Studies
Differences Between P201/AtEase and P301/HONOR Studies Design 31 Phase 2 and 3 studies were very similar – both studied military related PTSD at multiple sites in the US • CAPS-5 33 entry criteria used in Phase 3 BDI-II= Beck Depression Inventory-II; CGI-I=Clinical Global Impression – Improvement; M
Slide 32: P201/AtEase and P301/HONOR Demographics and Characteristics
P201/AtEase and P301/HONOR Demographics and Characteristics 32 The striking difference between P201 and P301 was time since trauma • Phase 2 P201 study recruited many participants from the surge in Iraq who were mostly <9 years since trauma © 2019 Tonix Pharmaceuticals Holding Corp.
Slide 33: Tonmya Dose Effect in Military Related PTSD
Tonmya Phase 2 Dose Effect in Military Related PTSD 1 33 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
Slide 34: Primary Outcome in Phase 3 and Time Since Trauma Subgroups
Primary Outcome (CAPS 5) in Phase 3 mITT) and 9 Years Time Since Trauma (TST) Subgroups 34 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, mixed model repeat
Slide 35: 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) 35 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
Slide 36: CAPS-5 Difference from Placebo in TST Subgroups in P301
CAPS 5 Mean Change from Baseline Difference from Placebo of Tonmya 5.6 mg in TST Subgroups in P301 1 36 • 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
Slide 37: 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 37 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, *
Slide 38: 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 38 Remission is a clinical state that is essentially asymptomatic In order to confirm remission: • Determined rates of participants who met remission status at b
Slide 39: Sustained Remission in P201/AtEase With and Without Oral AEs
Sustained Remission in P201/AtEase Study Retrospective Analyses of Phase 2 Subgroups with and without Oral AE’s (ON/OT/NT) 39 Oral numbness (ON), oral tingling (OT) and noticeable taste (NT) are local administration site reactions that are potentially unblinding • Subgroups with and without ON/OT/NT
Slide 40: Retrospective Analyses of Time Since Trauma on Endpoints in P301
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
Slide 41: Time Since Trauma Subgroup on Key Secondary Endpoints in P301
Retrospective Analyses of 9 Years Since Trauma Subgroup on Key Secondary Endpoints in P301/HONOR Study 41 Key secondary endpoints showed strong treatment effects • CGI-I, PGIC and PROMIS SD were pre-specified secondary analyses • Supports CAPS-5 results and similar to Phase 2 P201 Study results CGI-
Slide 42: Adverse Events in P201/AtEase and P301/HONOR Studies
Adverse Events (AEs) in P201/AtEase and P301/HONOR Studies 42 #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
Slide 43: Time Since Trauma – Review of Published Studies
Time Since Trauma – Review of Published Studies 43 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
Slide 44: Time Since Trauma – Remitting and Persistent Phases of PTSD
Time Since Trauma – Remitting and Persistent Phases of PTSD 44 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
Slide 45: Response to Tonmya for Female Participants in P301/HONOR
Response to Tonmya for Female Participants in P301/HONOR Study 1 45 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
Slide 46: Response to Tonmya for Non-Combat Traumas in P301/HONOR
Response to Tonmya for Non Combat Traumas in P301/HONOR Study in 9 Years Time Since Trauma Subgroup 1 46 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,
Slide 47: Summary of Clinical Experience with Tonmya in PTSD
Summary of Clinical Experience with Tonmya/ TNX 102 SL in PTSD 47 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
Slide 48: New Phase 3 P302/RECOVERY Study – Initiated 1Q 2019
New Phase 3 P302/RECOVERY Study –Initiated 1Q 2019 48 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
Slide 49: Late Stage PTSD Drug Candidates
Late Stage PTSD Drug Candidates 49 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
Slide 50: Commercialization Options
Commercialization Options 50 Tonix is exploring a variety of options to commercialize TNX-102 SL, including commercializing on our own or partnering all or some indications in specific regions of the world Tonix has participated in numerous partnering meetings Commercial Considerations: • Primary ph
Slide 51: TNX-102 SL – Multi-Functional Mechanism Involves Antagonism at 3 Receptors
TNX 102 SL – Multi Functional Mechanism Involves Antagonism at 3 Neuronal Receptors 51 Active ingredient, cyclobenzaprine, interacts with 3 receptors • Antagonist at 5-HT2A receptors • Similar activity to trazodone and Nuplazid® (pimivanserin) • Antagonist at α1-adrenergic receptor • Similar activit
Slide 52: Cyclobenzaprine is a Multi-Functional Drug – SNARI
52 Cyclobenzaprine is a multi-functional drug - SNARI - inhibits serotonin and norepinephrine reuptake - blocks serotonin 5-HT2A and norepinephrine α1 receptors Untreated Effects of TNX-102 SNARI = Serotonin and Norepinephrine receptor Antagonist and Reuptake Inhibitor © 2019 Tonix Pharmaceuticals H
Slide 53: Trazodone, Prazosin and Tonmya
53 Trazodone (disordered sleep), prazosin (night terrors) - Trazodone inhibits serotonin 5HT2A receptors and serotonin reuptake (SARI) - Prazosin blocks norepinephrine α1 receptors Tonmya Trazodone Prazosin SARI – Serotonin Receptor Antagonist & Reuptake Inhibitor (Stahl SM, CNS Spectrums, 2009;14:5
Slide 54: Opportunities to Expand to Other Indications
Opportunities to Expand to Other Indications 54 Role of sleep disturbance more established in common psychiatric and neurological/pain disorders • Recognized as a core symptom of many of these disorders • Traditional sleep medications, which increase sleep quantity, may not provide benefit (benzodia
Slide 55: TNX-102 SL – Bedtime Treatment for Multiple Potential Indications
TNX 102 SL – Bedtime Treatment for Multiple Potential Indications 55 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
Slide 56: What is Agitation in Alzheimer's Disease?
What is Agitation in Alzheimer’s Disease? 56 Agitation is one of the most distressing and debilitating of the behavioral complications of Alzheimer’s disease • Includes emotional lability, restlessness, irritability and aggression1 Link between disturbed sleep and agitation in Alzheimer’s1-3 • Agita
Slide 57: Consequences of Agitation in Alzheimer's Disease
Consequences of Agitation in Alzheimer’s Disease 57 Outcomes • Agitation is associated with significant poor outcomes for Alzheimer’s patients and challenges for their caregivers Common reason for institutionalization • Development of agitation, or its worsening, is one of the most common reasons fo
Slide 58: Agitation in Alzheimer's Disease – Additional Indication for TNX-102 SL
Agitation in Alzheimer’s Disease – Additional Indication Being Developed for TNX 102 SL 58 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
Slide 59: Regulatory Status and Registration Strategy for Agitation in Alzheimer's
TNX 102 SL for Agitation in Alzheimer’s –Regulatory Status and Registration Strategy 59 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
Slide 60: TNX-102 SL Addresses Challenges in Treating Agitation in Alzheimer's
TNX 102 SL Potentially Addresses Some of the Challenges in Treating Agitation in Alzheimer’s 60 Sublingual route of administration (no swallowing) • Swallowing can be an issue for a significant number of Alzheimer’s patients Low dose taken daily at bedtime • Potentially minimize daytime anticholiner
Slide 61: Scientific Rationale for Developing TNX-102 SL for Agitation in Alzheimer's
Scientific Rationale for Developing TNX 102 SL for Agitation in Alzheimer’s Disease 61 Connection between Sleep Disturbance and Agitation • Agitation in Alzheimer’s Disease is associated with sleep disturbance1,2 • Evidence that improving sleep could improve agitation3 Supported by Potential Mechani
Slide 62: Protective Barriers in the Central and Peripheral Nervous Systems
Protective Barriers in the Central and Peripheral Nervous Systems 62 Glial cells are cells that reside in the central nervous system and can provide protective barriers between the central and peripheral nervous systems1,2 Blood–Brain Barrier: Cerebrospinal Fluid (CSF)–Brain supplies nutrients to th
Slide 63: During Wakefulness, Proteins Accumulate in the Brain's Extracellular Space
During Wakefulness, Proteins Linked to Neuronal Death and Neurodegeneration Accumulate in the Brain’s Extracellular Space 63 The pathways of interchanging CSF and ISF depend on aquaporin-4 (AQP4) water channels on astrocytes1 Ependymal glial cells line the ventricle1 AQP4 localized to astrocyte proc
Slide 64: During Sleep, the CSF–Brain Barrier Is More Permeable
During Sleep, the CSF–Brain Barrier Is More Permeable, Allowing Debris to Clear 64 Extracellular volume increases Astrocytes change shape, promoting fluid exchange1 during sleep2 Permeability of CSF–brain barrier is increased during sleep2 Aβ = β-amyloid CSF = Cerebrospinal Fluid 1. Bellesi M, et al
Slide 65: Sleep-Wake Cycles Alter Permeability of the CSF–Brain Barrier
Sleep Wake Cycles Alter Permeability of the CSF–Brain Barrier 65 Fluid exchange at the CSF–brain barrier allows for clearance of toxic proteins called β–amyloids (Aβ).1 Glial cells in the brain work to facilitate this fluid exchange.2 Sleep–wake cycles alter glial cell morphology, which may affect f
Slide 66: Agitation in Alzheimer's – Competitive Landscape of Select Drugs
Agitation in Alzheimer’s – Competitive Landscape of Select Drugs in Development 66 Competitive landscape • 5HT2A Antagonists/inverse agonists • Nelotanserin (Axovant) • Atypical Antipsychotics (also have 5HT2A antagonism) • Rexulti® brexpiprazole (Otsuka/Lundbeck) • Lumateperone (Intra-Cellular) • D
Slide 67: Candidates in Development Pipeline
Candidates in Development 67 Pipeline Product Indication Preclinical Phase 1 Phase 2 Phase 3 NDA1/BLA2 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 Fibromyal
Slide 68: TNX-601 (Tianeptine Oxalate): A Potential Clinical Candidate for PTSD
TNX 601 Tianeptine Oxalate): A Potential Clinical Candidate for PTSD 68 Targeted as a 1st 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 Pr
Slide 69: Structural Comparison: TNX-102 and TNX-601
Structural Comparison: TNX 102 and TNX 601 69 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-chlorodibenzothiazepine nucleus with an aminoheptanoic side
Slide 70: TNX-801: A Smallpox Preventing Vaccine Candidate
TNX 801 (Synthesized Live Horsepox Virus): A Smallpox Preventing Vaccine Candidate 70 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
Slide 71: TNX-801: A Smallpox Preventing Vaccine Candidate
TNX 801 (Synthesized Live Horsepox Virus): A Smallpox Preventing Vaccine Candidate 71 Synthesis1 from sequence of a 1976 Mongolian isolate2 In mice, TNX-801 behaved like attenuated vaccinia virus • Vaccinia is the term used to classify the live poxviruses that are used as smallpox vaccines, includin
Slide 72: The Currently Licensed Smallpox Vaccine ACAM2000
The Currently Licensed Smallpox Vaccine ACAM2000 is a Live Vaccinia Virus (VACV) Vaccine 72 ACAM2000 is sold to the U.S. Strategic National Stockpiles1 • Sold by Emergent BioSolutions • Sanofi divested ACAM2000 to Emergent BioSolutions in 2017 for $97.5 M upfront plus milestones • ACAM2000 was devel
Slide 73: HPXV and its Relationship to Other Orthopoxviruses
HPXV and its Relationship to Other Orthopoxviruses 73 HSPV074 – fragmented homolog of VACV I4L (ribonucleotide reductase) HSPV200 – 216 kDa protein probably regulates T-cell activation with homologs still present in variola, cowpox, and monkeypox viruses Evans, D. U. of Alberta (2018) with permissio
Slide 74: Genome Assembly by Synthesis of Fragments and Construction of Telomeres
Genome Assembly (212 kbp) by Synthesis of Fragments and Construction of Telomeres 74 Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453 Sequence: GenBank entry DQ792504; DNA: GeneArt © 2019 Tonix Pharmaceuticals Holding Corp.
Slide 75: HPXV Produces Small Plaques More Like Cowpox Than Vaccinia
HPXV Produces Small Plaques that are More Like Cowpox Than Vaccinia (VACV) 75 Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453 © 2019 Tonix Pharmaceuticals Holding Corp.
Slide 76: Production of Cell-Associated and Extracellular Virus
Production of Cell-Associated and Extracellular Virus 76 Cell-associated virus Virus in the media Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453 © 2019 Tonix Pharmaceuticals Holding Corp.
Slide 77: HPXV Growth Characteristics
HPXV Growth Characteristics 77 Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453 © 2019 Tonix Pharmaceuticals Holding Corp.
Slide 78: Testing Vaccine Protective Activity of HPXV in Mice Model
Testing Vaccine Protective Activity of HPXV in Mice Model 78 Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453 © 2019 Tonix Pharmaceuticals Holding Corp.
Slide 79: Biological Properties of HPXV: Less Virulent but Protective
Biological Properties of HPXV: Less Virulent than a Dryvax Clone, but Produces Protective Immunity 79 PBS VACV WR (5x103 PFU) Dryvax clone (107 PFU) HPXV (107 PFU) Challenge (106 PFU VAC strain WR) Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.
Slide 80: HPXV Vaccine Protection Activity Observed at Low PFU
HPXV Vaccine Protection Activity Observed As Low As 105 PFU* 80 PBS HPXV (105 PFU) HPXV (106 PFU) HPXV (107 PFU) Challenge (106 PFU VAC strain WR) *PFU = plaque forming units Noyce, RS, Lederman S, Evans DH. PLoS ONE. 2018; 13(1): e0188453 https://doi.org/10.1371/journal.pone.0188453 © 2019 Tonix Ph
Slide 81: No Overt Clinical Sign in HPXV Vaccinated Mice After VACV Challenge
No Overt Clinical Sign Observed in HPXV Vaccinated Mice After VACV Challenge 81 No challenge PBS VACV (106 PFU) VACV* (5x103 PFU) VACV (106 PFU) HPXV (105 PFU) VACV (106 PFU) HPXV (106 PFU) VACV (106 PFU) HPXV (107 PFU) VACV (106 PFU) * VACV (strain WR) Noyce, RS, Lederman S, Evans DH. PLoS ONE. 201
Slide 82: TNX-801 May Have an Improved Safety Profile
HPXV or TNX 801– May Have an Improved Safety Profile as a Smallpox Preventing Vaccine 82 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 cardiotoxicity1 HPXV has potential for
Slide 83: An Improved Smallpox Preventing Vaccine is Important and Necessary
An Improved Smallpox Preventing Vaccine is Important and Necessary for a Potential Public Health Issue 83 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 of smallpox do
Slide 84: Current Needs to Vaccinate Against Smallpox
Current Needs to Vaccinate Against Smallpox 84 Ongoing vaccination of U.S. troops • Troops in the Global Response Force Threat of smallpox re-introduction • Strategic National Stockpile & public health policy Re-emergence of monkey pox1 • Believed to resurgent because of vaccinia-naïve populations i
Slide 85: TNX-801: A Potential Medical Countermeasure
TNX 801: A Potential Medical Countermeasure 85 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: • Biological, chemical, radiological, or nuclea
Slide 86: TNX-801: A Smallpox Preventing Vaccine Candidate
TNX 801 (Synthesized Live Horsepox Virus): A Smallpox Preventing Vaccine Candidate 86 TNX-801 (HPVX) • Synthesized live horsepox virus • Shares structural characteristics with vaccinia-based smallpox vaccines • Unique properties that suggest lower toxicity Live virus vaccines stimulate cross-reactiv
Slide 87: Evidence of Effectiveness for Smallpox Vaccine
Evidence of Effectiveness for Smallpox Vaccine 87 Given that smallpox is eradicated the only evidence of effectiveness for modern vaccines is from historical use when smallpox was endemic • Stimulates interest in the evolution of vaccinia Vaccinia stocks around the world diverged from Jenner’s 1798
Slide 88: ACAM2000 – Best Technology of its Time
ACAM2000 – Best Technology of its Time 88 Single clone picked from “swarm” of Dryvax® 1 • Some rationale for selection2 Growth in serum free Vero cells • Eliminates risk of Bovine Spongiform Encephalopathy (BSE)/prion contamination – safety concerns in Wyeth’s Dryvax (grown in calf lymph) In 2000, t
Slide 89: Rationale for Developing a Potentially Improved New Smallpox Vaccine
Rationale for Developing a Potentially Improved New Smallpox Vaccine 89 Toxicity concern of modern vaccinia (VACV) vaccines limit wildly administration • Not recommended for use, even in first responders • U.S. soldiers in the Global Response Force are immunized Modern VACV vaccination safety studie
Slide 90: Proposed Evolution of Vaccinia Vaccines
Proposed Evolution of Vaccinia Vaccines 90 Postulated Divergence of Historical Strains of Vaccinia Horsepox-like ancestral strain RPXV NYCBH/European IHD-J TianTan precursor stocks Dryvax® Ankara Tashkent LIVP WR IHD-J=International Health Department-Japan LIVP=Lister Vaccine Strain Copenhagen NYCBH
Slide 91: Proposed Evolution of Vaccinia Vaccines and Smallpox Incidence
Proposed Evolution of Vaccinia Vaccines 91 Relationship to Smallpox Incidence and Eradication SMALLPOX CASES IN US/EUROPE* ACAM2000™ Dryvax® Jenner’s swarm Vaccine (Horsepox -like) Mulford Clonal Diversity Vaccine Eradication 1798 1902 1931 1977 2007 TIME *Rough approximation (not data derived) © 20
Slide 92: What's the Evidence of Effectiveness of Smallpox Vaccines?
What’s the Evidence of Effectiveness of Smallpox Vaccines for Preventing Smallpox? 92 Theoretical effectiveness of modern vaccinia vaccines are based on extrapolation from older vaccines • Newer/modern vaccines were not widely used when smallpox was endemic MVA ( Modified Virus Ankara) which has lar
Slide 93: Possible Smallpox Prevention and Treatment Strategies
Possible Smallpox Prevention and Treatment Strategies 93 Preventing Vaccine • Jenner’s vaccine, HPXV (upon licensure), Vaccinia Post-exposure vaccination1 • Jenner’s vaccine Priming of the immune system • Imvamune® (MVA) and DNA vaccines2 Pharmacotherapy for infected or exposed individuals • Arestvy
Slide 94: Viral Replication Proficiency is Critical to Immunogenicity but May Compromise Safety
Viral Replication Proficiency is Critical to Human Immunogenicity but May Compromise Safety 94 Pox vaccines with low or no replication appear safer than vaccines replicate fast in human cells • Canarypox and Imvamune® (Modified Virus Ankara/MVA) appear to have good tolerability • Relatively safe in
Slide 95: Manufacturing and Dosing Requirements
Manufacturing and Dosing Requirements 95 TNX-801 (HPXV) is expected to have similar scalability for mass production as ACAM2000 • TNX-801 grows well in cell lines – immunity is expected after single administration (immunization) • Only a small dose (replicating live virus) is required for immunizati
Slide 96: Rationale for Developing a Potentially Improved Vaccine Based on Jenner's Vaccine
Rationale for Developing a Potentially Improved New Smallpox Vaccine Based on Jenner’s Vaccine 96 Vaccination protects against smallpox – both individuals and populations at risk • Use of Jenner’s vaccine resulted in eradication of smallpox Vaccination can protect AFTER smallpox infection • Vaccinia
Slide 97: Potential for Use of HPXV as a Vector for Vaccines
Potential for Use of HPXV as a Vector for Vaccines to Infectious Disease or Cancer 97 Poxviruses like HPXV can be engineered to express foreign genes and are well recognized platforms for vaccine development • Large packaging capacity for exogenous DNA inserts (i.e. encoding antigens) • Precise viru
Slide 98: Financial Overview
Financial Overview 98 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.
Slide 99: Management Team
Management Team 99 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.
Slide 100: Board of Directors
Board of Directors 100 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
Slide 101: Milestones – Recently Completed and Upcoming
Milestones – Recently Completed and Upcoming 101 ✓ 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
Slide 102: Summary
Summary 102 Phase 3 development of new bedtime treatment for PTSD, including military-related PTSD • Major unmet need; ~12 million Americans annually • Benefited from FDA 505(b)(2) NDA approval requirement Complimentary day-time PTSD treatment in development • Leverages development expertise in PTSD
Slide 103: Thank you!
NASDAQ: TNXP Thank you ! © 2019 Tonix Pharmaceuticals Holding Corp.
Tonix Pharmaceuticals Holding — Investor Presentation (March 2019) on 6ix