Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP
Tonix Pharmaceuticals — Investor Presentation (March 2017)
47 slides from Tonix Pharmaceuticals's investor presentation, Mar 20, 2017
Slide 1: Investor Presentation
Investor Presentation TONIX PHARMACEUTICALS Version P0054 3-15-17
Slide 2: Cautionary Note on Forward-Looking Statements
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 Litigation Reform Act of 1995. These statements may be i
Slide 3: Tonix (TNXP): Developing Innovative Pharmaceutical Products
Tonix (TNXP): Developing Innovative Pharmaceutical Products to Address Current and Emerging Public Health Challenges Targeting central nervous system conditions + In Phase 3 development, TNX-102 SL* for posttraumatic stress disorder (PTSD) with Breakthrough Therapy designation from the U.S. Food and
Slide 4: Product Pipeline
Product Pipeline ee ee a Bedtime PTSD TNX-102 SL_ awed Cyclobenzaprine HCI sublingual tablets Phase 2 results reported May 2016 Phase 3 study initiation in 192017 Tianeptine oxalate oral formulation Live HPXV virus vaccine from cell culture, ‘Novel polymorph and salt discovered and ‘characterized Ho
Slide 5: Tonix Pharmaceuticals PTSD Program
Tonix Pharmaceuticals PTSD Program TNX-102 SL (cyclobenzaprine HCI sublingual tablets) + Aunique, innovative product designed for bedtime administration Phases + Targeting a chronic and serious psychiatric disorder: PTSD pavalapiient ¥ Therapeutic dose identified in Phase 2 study Phase 3 clinical an
Slide 6: PTSD Characteristics
PTSD Characteristics Unmet medical need + PTSD is a serious condition and the prevalence is increasing, especially combat PTSD + Military-related PTSD is not satisfactorily treated by existing FDA-approved therapies + Two selective serotonin reuptake inhibitors (SSRIs) are approved for PTSD, but hav
Slide 7: Breakthrough Therapy Designation
Breakthrough Therapy Designation + FDA granted TNX-102 SL Breakthrough Therapy designation - reported December 19, 2016 PTSD is a serious condition + TNX-102 SL has potential advantages over existing therapies in military-related PTSD + Benefits of Breakthrough Therapy designa n Eligibility for prio
Slide 8: What is PTSD?
What is PTSD? A chronic response to traumatic event(s) + A majority of people will experience a traumatic event at some point in their lifetime* + 20% of women and 8% of men in the U.S. who experience significant trauma develop PTSD! + Lifetime prevalence: 6.8%? (~ 17 million adults in the U.S.) + P
Slide 9: What Are the Symptoms of PTSD?
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 others) 4. Hyperarousal (anxiety, agitation &
Slide 10: What Are the Consequences of PTSD?
What Are the Consequences of PTSD? 10 Consequences: + Impaired daily function and substan + Reckless or destructive behavior + Increased health care utilization and greater medical mort interference with work and social interactions PTSD as a risk factor for: + Depression + Alcohol or substance abus
Slide 11: Prevalent Population (U.S.)
Prevalent Population (U.S.) ~8.6 million? _ % 26 Undiagnosed 6,788,000 798% re 10% EDs 4. Kessler, et a, 2005; Prevalence rate of 3.5% applied to U.S. Census estimate of 247 PTSD Prevalence and Market Characteristics 510,000 No Rx 128,000 872,000 288,000 Diagnosed population Veterans Large populatio
Slide 12: What Drug Classes are Used to Treat PTSD?
What Drug Classes are Used to Treat PTSD? Market ighly fragmented, with benzodiazepines being widely prescribed (but not indicated)* Multiple medications per patient (or “Polypharmacy”) is the norm + Approximately 55% of patients receive a benzodiazepine, and 53% receive an SSRI SSRIs are the only F
Slide 13: Sleep Disturbances Are a Core Feature Of PTSD
Sleep Disturbances Are a Core Feature Of PTSD? Sleep disturbances are a core feature of PTSD and a component of three of the four major symptom clusters: Di SW |. Presence of one (or more) intrusion symptoms ._ Persistent avoidance of stimuli associated with traumatic event jostic Criteria for P |.
Slide 14: What Is Restorative Sleep?
(65) What Is Restorative Sleep? Restorative Sleep Hypothesis: Sleep is an active, necessary state for processing emotionally charged memories, replenishing energy, and resetting homeostasis to circuitry in the brain DL ENeRCY e 7. Depression, Chronic Sleep Deprivation oN Pain, Anxiety, and PTSD Slee
Slide 15: Relevance of Sleep Disturbances for PTSD
Relevance of Sleep Disturbances for PTSD 15 Sleep disturbances: + Core symptom of PTSD (component of intrusion and hyperarousal symptom clusters) + Believed to play roles in the pathophysiology of PTSD Sleep Pharmacological | Therapeutic As a Core Pathophysiology Action Benefit Symptom. 2° Clinical
Slide 16: TNX-102 SL: Proprietary Patented Formulation
TNX-102 SL: Proprietary Patented’ Formulation 16 Active Pharmaceutical Ingredient (API) is cyclobenzaprine (CBP), is structurally related to tricyclic antidepressants (TCAs) + TCAs and their metabolites differ widely in their receptor binding and pharmacokinetic profiles? ~ CBP is more selective for
Slide 17: High Prevalence of PTSD Among Combat Veterans
High Prevalence of PTSD Among Combat Veterans 17 3-9% 19-31% >19% General population’ Vietnam veterans? Operation Enduring Freedom (OEF; Afghanistan) / Operation Iraqi Freedom @BK_8.6 million American adults affected! (Gir) veterans / Operation: New Dawn (OND)? QC Women more likely to develop than m
Slide 18: Growing Economic and Social Burden to Care for Veterans with PTSD
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 $3,000-5,000 ion estimated yearly cost to society? ~ 2.7 million troops depl I 10/1/2001 and 3/3. js ystem? Veterans, ‘rough 2nd Qtr FY Bis a
Slide 19: Why Initially Target Military-Related PTSD?
Why Initially Target Military-Related PTSD? 19 itary-related PTSD not well-served by existing FDA-approved therapies Sertraline: failed to show efficacy in a large multicenter trial in U.S. military (placebo numerically better)! Paroxetine: no large trials conducted with predominantly military traum
Slide 20: Phase 2 AtEase Study in Military-Related PTSD
Phase 2 AtEase Study in Military-Related PTSD Randomized, double-blind, placebo-__*_Enrolled patients with baseline controlled trial in military-related PTSD CAPS-5 2 29 + Analysis from 231 patients; 24 U.S. clinical sites TNX-102 SL at bedtime once-daily + TNX-102 SL was active at 5.6 mg dose 2.8 m
Slide 21: AtEase Study Demographics and Characteristics
AtEase Study Demographics and Characteristics 24 © 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. military distribution © Current Major
Slide 22: AtEase Study: Traumas Associated with PTSD
AtEase Study: Traumas Associated with PTSD ‘Index Trauma During Military Service Patient Count™ Being Involved in an TED explosion or suicide bombing 35 Witness death or Injury of fellow sol Witnessing IED explosion 30 Receiving Incoming artillery, rocket, or mortar fire 29 Being wounded or injured
Slide 23: AtEase Study - Summary of Primary and Secondary Analyses
AtEase Study - Summary of Primary and Secondary Analyses (week 12) ‘Assessment Domain ‘Analysis p-Values 2.8 mg (N=90) | 5.6 mg (N=49) CAPSS [Total [MRM 0.259% 0.053 [rotal IMMRM with Multiple imputation 211 0.031" lrotal lMMRM w/ Hybrid LOCF/BOCF 0.172 0.037" lrotal lANCOVA 0.090 0.038" [CAPS-5 clu
Slide 24: AtEase Study: Safety and Tolerability Profile
AtEase Study: Safety and Tolerability Profile No serious adverse events reported with TNX-102 SL deemed related to treatment Systemic Adverse ventas acaho TWXHOESL28mg TWX-1G2SL5.6 mg ‘Somnolence 6.4% 11.8% 16.0% Dry Mouth 10.6% 4.3% 16.0% Headache 43% 4% 12.0% Insormia 85% 75% 6.0% Sedation 1.1% 2.
Slide 25: AtEase: Retrospective Analysis for TNX-102 SL 5.6 mg
AtEase: Retrospective Analysis for TNX-102 SL 5.6 mg Prior pharmacotherapy trials in PTSD used earlier versions of CAPS (e.g. CAPS-2) + Different scoring range from CAPS-5 + Most frequently used a score of > 50 for entry (similar to CAPS-5 > 33%) + FDA has accepted this higher entry criteria (CAPS-5
Slide 26: Retrospective Analysis of CAPS-5 in Patients with Entry CAPS-5 ≥33
Retrospective Analysis of CAPS-5 in Patients with Entry CAPS-5 2 331 WkKO | Wk2Wk4 Wk6 WKB W100 Wk 12 0.0 Placebo 2 g so -+TNX-102 SL.2.8 mg g “+-TNX-102 SL5.6 mg B 10.0 § 15.0 3 g * B 20.0 8 point difference in CAPS-5 ra thange from baseline between § * placebo and TNX-102 SL 5.6 mg £ aso * Erect s
Slide 27: Retrospective Analyses of Week 12 Outcome Measures
Retrospective Analyses of Week 12 Outcome Measures for TNX-102 SL 5.6 mg vs. Placebo ‘ary-related or in M Combat PTSD Subset and for CAPS-5 2 29 and CAPS-5 2 33 at Baseline 27 Total Cluster B (intrusion) Cluster € (avoidance) Cluster D (mood/cognition) ‘Cluster € (arousal and reactivity) 6 (Sleep it
Slide 28: Phase 2 AtEase Study Conclusions
Phase 2 AtEase Study Conclusions 28 t large multi-center trial demonstrating efficacy of an Investigat New Drug (IND) in military-related PTSD ¥ TINX-102 SL therapeutic dose (5.6 mg) identified ¥ Symptom reduction (CAPS-5) ¥ Functional improvement (Sheehan Disability Scale domains) ¥ Clinical global
Slide 29: Planned Phase 3 HONOR Study in PTSD
Planned Phase 3 HONOR Study in PTSD 29 To confirm AtEase findings in military- General study characteristics: related PTSD: + Randomized, double-blind, placebo-controlled, entrance CAPS-S 233 + Larger adaptive design study + Targeting start in 19 2017 ‘One unblinded interim analysis (IA) by an indep
Slide 30: Commercialization Options
Commercialization Options 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. Commercial considerations: + Primary physician audience is well defined: psychiatrists (~30,000
Slide 31: Intellectual Property
Intellectual Property TN 02 SL Portfolio of international patents filed under the Patent Cooperation Treaty (PCT) Composition-of-matter (eutectic) + Notice of Allowance issued by U.S. Patent and Trademark Office + Additional claims and jurisdictions pending + Protection expected to 2034 Pharmacokine
Slide 32: Proprietary Cyclobenzaprine Hydrochloride Eutectic Mixture
© Proprietary Cyclobenzaprine Hydrochloride Eutectic Mixture Stabilizes Tablet Formulation (CBP-HCI) pats i PAA » ee Eutectic eee eee On - sollicice a « ot “HPO, @ é (K,HPO,) Vv & Vv < ooo Desiariie . Soe SE Peg & fReebece om ® o eo § PRB CO He: PMeMoPeed o> fore PH hearts wth base imc ton tnt CSI r
Slide 33: Product Pipeline
Product Pipeline Candidate Indication =e 33 Bedtime PTSD TNX-102 SL_ awed Cyclobenzaprine HCI sublingual tablets Tianeptine oxalate oral formulation Live HPXV virus vaccine from cell culture, [erent fre nee 2 ne 3 Phase 2 results reported May 2016 Phase 3 study initiation in 192017 ‘Novel polymorph
Slide 34: TNX-601 - A Potential Clinical Candidate for PTSD
TNX-601 - TNX-601 (tianep' A Potential Clinical Candidate for PTSD e oxalate oral formulation) a Pre-IND Candidate ga Health Challenge Targeted as a 1* line monotherapy for PTSD: daytime dosing v Leverages expertise in PTSD (clinical and regulatory experience, market analysis, etc.) ¥ Mechanism of A
Slide 35: Structural Comparison: TNX-102 SL and TNX-601
Structural Comparison: TNX-102 SL 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-chlorodibenzothiazepine nucleus with an aminoheptanoic side
Slide 36: TNX-601: A Potential Clinical Candidate for PTSD
TNX-601: A Potential Clinical Candidate for PTSD + APL is a novel oxalate salt of tianeptine + Shares structural features with tricyclic antidepressants, but has unique pharmacological and neurochemical properties! + Tianeptine modulates the glutamatergic system indirectly, + Does not have significa
Slide 37: TNX-801: A Potential Smallpox-Preventing Vaccine
TNX-801: A Potential Smallpox-Preventing Vaccine 37 Pre-IND Candidate Targeting a Public Health Issue 1. aes, Act al Ong design, development and Therapy: 4:71:79 (2010) TNX-801 (live virus vaccine - synthetic Horsepox (HPXV) vaccine) + Potential improvement over current methods for biodefense agains
Slide 38: TNX-801: Synthetic Live Horsepox Virus (HPXV)
TNX-801: Synthetic Live Horsepox Virus (HPXV) Synthesis from sequence of a 1976 Mongolian isolate In mice, TNX-801 behaved like attenuated vaccinia virus (vaccinia virus is foundation of current smallpox vaccines) How is horsepox related to modern vaccines? + Multiple sources? indicate that the smal
Slide 39: Horsepox - Better Tolerability as a Vaccine?
65) Horsepox - Better Tolerability as a Vaccine? + Horsepox is caused by HPXV and is characterized by mouth and skin eruptions * HXPV isolate from the 1976 outbreak later sequenced * Modern vaccinia virus smallpox vaccines are associated with cardiotoxicity; may have acquired undesirable properties
Slide 40: A Better Smallpox-preventing Vaccine is Important and Necessary Today
© 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 of smallpox does not require a natural dis
Slide 41: TNX-801: A Potential Medical Countermeasure
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 or vaccines intended to treat: + Biological, chemical, radiological, or nuclear agents that presen
Slide 42: TNX-801: A Potential Smallpox-Preventing Vaccine
TNX-801: A Potential Smallpox-Preventing Vaccine 42 ‘Synthetic live virus HPXV TNX-801 + Shares structural characteristics with vaccinia-based vaccines + Unique properties that suggest lower toxicity + Smallpox has a ~30% mortality rate in vaccine-naive populations Live virus vaccines stimulate cros
Slide 43: Management Team
Management Team 43 ‘Seth Lederman, MD President & CEO TARSENT™ &Fusiley’ vela. Gregory Sullivan, MD Chief Medical Officer Cowmata Univesity New York State Department of Psychiatry Psychiatric Institute Bradley Saenger, CPA Chief Financial Officer Ghire veftex a wi a Jessica Morris EVP, Operations, A
Slide 44: Board of Directors
© Board of Directors ‘Seth Lederman, MD Ernest Mario, PhD Chairman ALZA, Glaxo, Reliant Pharma Stuart Davidson Charles Mather Labrador Ventures, Alkermes, Combion BIIG, Janney, Jefferies, Cowen, Smith Barney Patrick Grace John Rhodes Apollo Philanthropy, WR Grace, Chered NYSERDA, NRDC, Booz Allen Ha
Slide 45: Milestones - recent and upcoming
Milestones - recent and upcoming INX-102 SL - Posttraumatic Stress Disorder © May 2016 Reported results from AtEase study & August 2016 End-of Phase 2 meeting with FDA - Proposed Phase 3 clinical and NDA plan accepted @& December 2016 _ Breakthrough Therapy designation granted by FDA & January 2017
Slide 46: Summary
Summary 46 Strong position for value growth Phase 3 development in a major medical indication: PTSD including military-related PTSD + Phase 3 asset not previously well-known to the investor marketplace ‘TNX-102 SL for PTSD is designated as a Breakthrough Therapy by FDA + Accelerated development and
Slide 47: Thank you!
TONIX PHARMACEUTICALS NASDAQ: TNXP Thank you! © 2017 Tonix Pharmaceuticals Holding Corp.
Tonix Pharmaceuticals Holding — Investor Presentation (March 2017) on 6ix