Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP
Tonix Pharmaceuticals — AFSP/ASCP Workshop: Inclusion of Suicidal Individuals in Treatment Trials: Now is the Time (May 2018)
26 slides from Tonix Pharmaceuticals's conference presentation, May 31, 2018
Slide 1: Including Suicidal Individuals in Treatment Trials: Military-Related PTSD with TNX-102 SL
1 An AFSP/ASCP Workshop: Inclusion of Suicidal Individuals in Treatment Trials: Now is the Time Wed May 30 th 2:45 - 4:45PM Poinciana 1 - 2 © 2018 Tonix Pharmaceuticals Holding Corp Including Suicidal Individuals in Treatment Trials: Treatment of Military - Related PTSD with TNX - 102 SL, a Novel Su
Slide 2: Disclosures
2 © 2018 Tonix Pharmaceuticals Holding Corp Disclosures • Gregory Sullivan MD is an employee of Tonix Pharmaceuticals and owns stock and stock options in the company • TNX - 102 SL is an investigational new drug and has not been approved for any indication • Presentation contains mention of two off
Slide 3: Including Suicidal Individuals in Clinical Trials
3 © 2018 Tonix Pharmaceuticals Holding Corp Including Suicidal Individuals in Clinical Trials • Multiple psychiatric disorders are associated with increased risk of suicide • Examples: Major Depression, Bipolar Disorder, Schizophrenia, PTSD • Making an impact on these suicide rates requires inclusio
Slide 4: Pharmacological Treatment of Underlying Disorders May Decrease Suicidal Behaviors
4 © 2018 Tonix Pharmaceuticals Holding Corp Pharmacological Treatment of Underlying Disorders May Decrease Suicidal Behaviors Suicidal Behaviors PTSD Depression Schizophrenia Bipolar Clozapine effective for suicidal behaviors in schizophrenia Lithium* p ossibly effective for suicidal behaviors in bi
Slide 5: Studying Predictors of Suicide
5 © 2018 Tonix Pharmaceuticals Holding Corp Studying Predictors of Suicide • Limited body of work on death from suicide, in part explained by: • Suicides being relatively rare events at the population level • Difficulty in predicting who will die by suicide even in high risk samples • Necessity for
Slide 6: Suicide-PTSD Link Established but Controversy Remains
6 © 2018 Tonix Pharmaceuticals Holding Corp Suicide - PTSD Link Established but Controversy Remains Abundance of evidence suggests PTSD increases risk of death by suicide • Consistent evidence of a strong association while accounting for pre - existing psychiatric comorbidity 1 • Danish registry (n=
Slide 7: Suicides in the US Military
7 © 2018 Tonix Pharmaceuticals Holding Corp Suicides in the US Military • Suicide rate among active duty US Army personnel was increasing since 2004 1 • 2001: 9 per 100,000 • 2009: 22 per 100,000 • Surpassed comparable civilian rates in 2008 • Suicides in US military currently account for nearly 20%
Slide 8: Rising Suicide Risk and Rates in US Veterans since 2001
8 © 2018 Tonix Pharmaceuticals Holding Corp Rising Suicide Risk and Rates in US Veterans since 2001 • Retrospective multivariate analysis of 3.8 million US military personnel between 2001 - 2011 1 , with outcome of death by suicide in Cox proportional hazard models showed: • Hazard rate increased wi
Slide 9: Disturbed Sleep and Suicide Risk
9 © 2018 Tonix Pharmaceuticals Holding Corp Disturbed Sleep and Suicide Risk Abundance of evidence showing link between poor sleep and increased risk of suicidal ideation and behaviors • Large epidemiological studies showing sleep disturbance as risk for suicide death 1,2 • Specific sleep disturbanc
Slide 10: Rationale for Including Suicidal Individuals in the Clinical Trial of TNX-102 SL in PTSD
10 © 2018 Tonix Pharmaceuticals Holding Corp Rationale for Including Suicidal Individuals in the Clinical Trial of TNX - 102 SL in PTSD • More representative sample of the condition for evaluating the efficacy TNX - 102 SL (cyclobenzaprine HCl sublingual tablets) 2.8 mg and 5.6 mg, as a potential tr
Slide 11: Phase 2 AtEase Study in Military-Related PTSD
11 © 2018 Tonix Pharmaceuticals Holding Corp Phase 2 AtEase Study in Military - Related PTSD • Randomized, double - blind, placebo - controlled trial in military - related PTSD • Enrolled 245 participants at 24 US clinical sites • Enrolled patients with baseline CAPS - 5 score ≥ 29 • Primary Efficac
Slide 12: Design of AtEase Study: Inclusions and Exclusions Based on SI/SB
12 © 2018 Tonix Pharmaceuticals Holding Corp Design of Phase 2 AtEase Study: Inclusions and Exclusions Based on SI/SB • Exclusions based on Columbia - Suicide Severity Rating Scale (C - SSRS) • Five types of Suicidal Ideation (SI) rated as present or absent during lookback period • Type 1 – Wish to
Slide 13: Protocol Recommended Interventions for C-SSRS Types of Suicidal Ideation
13 © 2018 Tonix Pharmaceuticals Holding Corp Protocol Recommended Interventions for C - SSRS Types of Suicidal Ideation During Trial • Type 1: Standard clinical care • Types 2 and/or 3: Medical monitor recommended implementation of a Safety Planning Intervention (SPI) for any visit with these types
Slide 14: AtEase Study Demographics and Characteristics
14 © 2018 Tonix Pharmaceuticals Holding Corp AtEase Study Demographics and Characteristics Sex distribution - 93% male / 7% female Index traumas 98% had trauma during military service 85% combat traumas Mean (SD) time since index trauma was 7 (3.4) yrs Deployed an average of 2.3 times Racial distrib
Slide 15: Suicidal Ideation and Attempt History in AtEase: Screening C-SSRS Results
15 © 2018 Tonix Pharmaceuticals Holding Corp Suicidal Ideation and Attempt History in AtEase Study: Screening C - SSRS Results Suicidal Ideation (SI) and Behavior (B) at Screening (N=237) Lifetime Any Type of Suicidal Ideation 32.1% C - SSRS Type 1 SI 30.4% C - SSRS Type 2 SI 20.7% C - SSRS Type 3 S
Slide 16: Suicidal Ideation and Attempt History in AtEase: Screening MINI Module B Results
16 © 2018 Tonix Pharmaceuticals Holding Corp Suicidal Ideation and Attempt History in AtEase Study: Screening MINI Suicidality Module B Results MINI Module B Suicidality Rating at Screening Low Suicidality (score of 1 - 8) 15.6% Moderate Suicidality (score of 9 - 16) 2.1% High Suicidality (score of
Slide 17: AtEase Study Screen Fails versus Inclusion in Individuals with SI/SB
17 © 2018 Tonix Pharmaceuticals Holding Corp AtEase Study Screen Fails versus Inclusion in Individuals with SI/SB • 455 individuals were screened for the AtEase study • 210 of these were screen failed • 11 were screen failed due to SI/SB exclusions • 5 due to MINI Suicidality module score ≥ 17 • 4 d
Slide 18: AtEase Study Results: Safety and Tolerability
18 © 2018 Tonix Pharmaceuticals Holding Corp AtEase Study Results: Safety and Tolerability Systemic adverse events (AEs) and local administration site reactions occurring at ≥5% rate in either TNX - 102 SL group: Placebo TNX - 102 SL 2.8 mg TNX - 102 SL 5.6 mg Systemic Adverse Events (N=94)* (N=93)*
Slide 19: Approach Taken to SI/SB Adverse Event Reporting
19 © 2018 Tonix Pharmaceuticals Holding Corp Approach Taken to SI/SB Adverse Event Reporting • Any post screening increase in C - SSRS SI over Type 1 considered an adverse event • Any emergence of Type 4 and/or Type 5 SI post screening considered a serious adverse event (SAE) • Any emergence of C -
Slide 20: Suicidal Ideation in the AtEase Study at Baseline and Week 12
20 © 2018 Tonix Pharmaceuticals Holding Corp Suicidal Ideation in the AtEase Study at Baseline and Week 12 Suicidal Ideation (SI) and Behavior (B) at Baseline and Week 12 using Since Last Visit C - SSRS Baseline Week 12 Placebo TNX - 2.8mg TNX - 5.6mg Placebo TNX - 2.8mg TNX - 5.6mg N=94 N=93 N=50 N
Slide 21: TNX-102 SL 5.6 mg Provided Significant Improvement in Sleep Disturbance
21 © 2018 Tonix Pharmaceuticals Holding Corp TNX - 102 SL 5.6 mg Provided Significant Improvement in Sleep Disturbance in the AtEase Study » Mechanism of action of TNX - 102 SL is hypothesized to be through improvement in sleep quality » Sleep responded early in treatment with TNX - 102 SL, by Week
Slide 22: CAPS-5 Treatment Response in mITT Population and Retrospective Subgroup
22 © 2018 Tonix Pharmaceuticals Holding Corp CAPS - 5 Treatment Response in Modified Intention - to - Treat Population and in Retrospective Analysis for Subgroup with Entry CAPS - 5 ≥33 A baseline CAPS - 5 score ≥33 was set as entry criterion in ongoing Phase 3 HONOR study Modified Intention - to -
Slide 23: CAPS-5 Item E2: Reckless or Self-Destructive Behavior
23 © 2018 Tonix Pharmaceuticals Holding Corp CAPS - 5 Item 16 (E2) – New to DSM - 5/CAPS - 5 • Reckless or self - destructive behavior • Risk • “In the past month/week, have there been times when you were taking more risks or doing things that might have caused you harm? • Can you give me some examp
Slide 24: Reduction in Reckless or Self-Destructive Behavior Item Compared with Placebo
24 © 2018 Tonix Pharmaceuticals Holding Corp Reduction in Reckless or Self - Destructive Behavior Item Compared with Placebo Over 12 Weeks in Subjects with More Severe PTSD (Baseline CAPS - 5 total ≥ 33) • Placebo N=77 • For subgroup with baseline E2>0: • N = 25 of 77 • Change from Baseline in subje
Slide 25: Conclusions about Including Suicidal Individuals in Phase 2 Trial of Military-Related PTSD
25 © 2018 Tonix Pharmaceuticals Holding Corp Conclusions about Including Suicidal Individuals in Phase 2 Trial of Military - Related PTSD • AtEase military - related PTSD sample had higher lifetime rates of SI/B compared with non - deployed Army sample • Rates of since - last - visit SI and SB durin
Slide 26: Thank you
26 Thank you…! © 2018 Tonix Pharmaceuticals Holding Corp To our research participants for their collaboration in the AtEase study! To our site PIs and Staff! To Tonix personnel responsible for AtEase : » Seth Lederman, Judy Gendreau, Ashild Peters, Perry Peters, Gregory Sullivan And to key consultan