Tonix Pharmaceuticals Holding Corp.

Tonix Pharmaceuticals Holding Corp. 8-K

2020 Tonix Pharmaceuticals Holding Corp. 1 Seth Lederman, CEO June 8 - 11, 2020 Version P0232 5 - 27 - 20 (Doc 0640) Bio International - 2020 NASDAQ:TNXP

2020 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 Litigation Reform Act of 1995 . These statements may be identified by the use of forward - looking words such as "anticipate," "believe," "forecast," "estimate" and "intend," among others . These forward - looking statements are based on Tonix's current expectations and actual results could differ materially . There are a number of factors that could cause actual events to differ materially from those indicated by such forward - looking statements . These factors include, but are not limited to, risks related to failure to obtain U . S . Food and Drug Administration clearances or approvals and noncompliance with its regulations ; our need for additional financing ; substantial competition ; uncertainties of patent protection and litigation ; uncertainties of government or third party payor reimbursement ; limited research and development efforts and dependence upon third parties . As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products . The forward - looking statements in this presentation are made as of the date of this presentation, even if subsequently made available by Tonix on its website or otherwise . Tonix does not undertake an obligation to update or revise any forward - looking statement, except as required by law . Investors should read the risk factors set forth in the Annual Report on Form 10 - K for the year ended December 31 , 2018 , as filed with the Securities and Exchange Commission (the "SEC") on March 18 , 2019 , and periodic reports and current reports filed with the SEC on or after the date thereof . All of Tonix's forward - looking statements are expressly qualified by all such risk factors and other cautionary statements .

2020 Tonix Pharmaceuticals Holding Corp. 3 Tonix Pharmaceuticals 2020 Tonix Pharmaceuticals Holding Corp. Developing novel therapies for humanity A clinical - stage biopharmaceutical company committed to discovering and developing innovative and proprietary new therapeutics that address the needs of patients We focus on developing small molecules and biologics: CNS (pain, neurology, psychiatry, addiction) Immunology (vaccines, immunosuppression, oncology, autoimmune disease) 3

2020 Tonix Pharmaceuticals Holding Corp. 4 Our Pipeline CANDIDATES INDICATION STATUS CNS Portfolio TNX - 102 SL Fibromyalgia (FM) - Lead Program Phase 3 - ongoing PTSD Phase 3 - ongoing Agitation in Alzheimer's Phase 2 ready Alcohol Use Disorder Pre - IND TNX - 1300 Cocaine Intoxication / Overdose Phase 2 TNX - 601 CR Major depression Phase 1 PTSD Phase 1 Neurocognitive Dysfunction from Corticosteroids Phase 1 TNX - 1600 Depression, PTSD and ADHD Preclinical Immunology Portfolio TNX - 1800 Covid - 19 vaccine - Prioritized Program Pre - clinical TNX - 801 Smallpox and monkeypox preventing vaccine Preclinical TNX - 1200 Smallpox and monkeypox preventing vaccine Preclinical TNX - 1500 Organ Transplant Rejection/Autoimmune Conditions Preclinical TNX - 1700 Gastric and pancreatic cancers Preclinical

2020 Tonix Pharmaceuticals Holding Corp. 5 Overview of TNX - 102 SL Protectic proprietary formulation of cyclobenzaprine that supports sublingual administration Scientific Rationale for Protectic Formulation Engenders unique pharmacokinetic and pharmacodynamic properties that emphasize sleep properties of cyclobenzaprine while minimizing undesirable properties Potential therapeutic value in a constellation of disorders where sleep disturbances are: Co - morbid Involved in the onset, progression and severity of the disease *TNX - 102 SL is in clinical stage of development and not approved for any indication

2020 Tonix Pharmaceuticals Holding Corp. 6 TNX - 102 SL: Differentiation from Oral Formulations FEATURE BENEFIT ADVANTAGE Cyclobenzaprine 40+ years as oral medication Established safety record Formulation: Protectic Allows submucosal absorption Not achievable with oral formulation Administration: sublingual Bypasses gut Avoids first - pass metabolism; reduced formation of "activating" metabolite Pharmcaokinetic profile Rapid absorption (peak at ~4 hours, low trough levels 8 - 24 hours) Desired profile for nighttime action Dose: low (2.8 to 5.6 mg) Recruitment of high affinity receptors (5 - HT 2A , 1 , H 1 ) Complimentary trimodal mechanism of action with less risk of off - target interference

2020 Tonix Pharmaceuticals Holding Corp. 7 TNX - 102 SL: Results from Completed FM Trials Completed Trials in FM: Phase 2 (F202 BESTFIT) - 205 patients randomized Phase 3 (F301 AFFIRM) - 519 patients randomized Topline Efficacy Results: Studies did not achieve statistical significance in the primary efficacy endpoint More In - Depth Results: Both studies showed efficacy signals justifying continued development in FM Safety: Well tolerated; side effects consistent with known side effects of cyclobenzaprine

2020 Tonix Pharmaceuticals Holding Corp. 8 p=0.005 p=0.038 P<0.001 P<0.001 P<0.001 Phase 3 F301 (AFFIRM) Dose: 2.8 mg Responder analysis 30% pain reduction (Logistic regression) Imbalance in missing data and individuals with missing data treated as non - responder' Current FDA statistical guidance on handling missing data: analysis with MMRM with MI* p=0.005 p=0.038 P<0.001 P<0.001 P<0.001 Trend: p=0.095 Phase 2b F202 (BESTFIT) Dose: 2.8 mg Primary Endpoint: Pain Relief at Week 12 Pre - specified pain endpoint Change in daily pain score (ANCOVA with JTC/MI*) Post hoc analysis Responder analysis > 30% pain reduction (Logistic Regression) Key Secondary Endpoints: Global improvement or improvement in symptoms and function Patient Global Impression of Change (PGIC) Fibromyalgia Impact Questionnaire - Revised (FIQ - R) total score PROMIS Sleep Disturbance instrument FIQ - R Pain Item Trend: p=0.172 p=0.033 p=0.025 p=0.015 (ANCOVA) p=0.004 (ANCOVA) p=0.004 TNX - 102 SL 2.8 mg: Efficacy Signal in Completed FM Trials * MI=multiple imputation; JTC = jumpt to control; MMRM = Multiple measures repeated models

2020 Tonix Pharmaceuticals Holding Corp. 9 Results from F301 (AFFIRM) Using Current FDA Statistical Guidance on Handling of Missing Data A retrospective analysis conducted using Mean Pain Analysis, MMRM with MI demonstrated a significant effect on pain, even though the dose was 2.8 mg -1.8 -1.6 -1.4 -1.2 -1.0 -0.8 -0.6 -0.4 -0.2 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 LS Mean Difference (SE) in NRS Pain Score Study Week Change in Pain Scores Over 12 Weeks: MMRM with MI Placebo (N=257) TNX-102 SL 2.8 mg (N=262) * * * ** As will be the case for the RELIEF F304 primary analysis, all discontinuations due to Adverse Event and Lack of Efficacy are imputed using MI based on baseline values; all other discontinuations assumed to be Missing at Random and are imputed with MI using weekly data of subjects. *p<.05; **p<.01

2020 Tonix Pharmaceuticals Holding Corp. 10 Where Are We on the Dose - Response Curve? Basic Pharmacology Dose can make the difference in the strength of the response Response Dosage Dose - Response Inconsistent response No clear response Consistent response Consistent but trade - offs (AEs) *Trade off's are increases in adverse events, side - effects and drug - drug interactions

2020 Tonix Pharmaceuticals Holding Corp. 11 Dose Response from Phase 2 PTSD Study * Placebo 5.6 mg 2.8 mg * P < 0.05 Consistent Dose - response Across Primary and Key Secondary Endpoints at Week 12 Clinician Administered PTSD Scale for DSM - 5 (CAP - 5) * Phase 2 study (AtEase), a randomized, placebo - controlled study of 231 patients with PTSD at 25 U.S. clinical sites, receiving a sublingual dose of either 2.8 mg TNX - 102 SL (n=90) or 5.6 mg TNX - 102 SL (n=49) compared to placebo (n=92) -1.6 -1.4 -1.2 -1 -0.8 -0.6 -0.4 -0.2 0 CAPS - 5 Sleep Item -25 -20 -15 -10 -5 0 Change from Baseline CAPS - 5 (Primary) p= 0.053 * p= 0.26 Improvement Improvement

2020 Tonix Pharmaceuticals Holding Corp. 12 Dose Response from Phase 2 PTSD Study Placebo 5.6 mg 2.8 mg * P < 0.05 Consistent Dose - response Across Primary and Key Secondary Endpoints at Week 12 Sheehan Disability Score (SDS) -3 -2.5 -2 -1.5 -1 -0.5 0 SDS Work/School -4 -3.5 -3 -2.5 -2 -1.5 -1 -0.5 0 SDS Social/Leisure * * Improvement Improvement Change from Baseline

2020 Tonix Pharmaceuticals Holding Corp. 13 Dose Response from Phase 2 PTSD Study 0% 10% 20% 30% 40% 50% 60% 70% Percent Responders CGI - I Responders 2.45 2.5 2.55 2.6 2.65 2.7 2.75 2.8 2.85 2.9 2.95 Mean Score PGIC Improvement Placebo 5.6 mg 2.8 mg * P < 0.05 * * Improvement Improvement Consistent Dose - response Across Primary and Key Secondary Endpoints at Week 12 Clinical Global Impression - Improvement (CGI - I) Patients' Global Impression of Change (PGIC)

2020 Tonix Pharmaceuticals Holding Corp. 14 Effect of Dose on Adverse Events (AEs) in the P201/ AtEase and P301/HONOR PTSD Studies # 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% P201 P301 Placebo (N=94) 2.8 mg (N=93) 5.6 mg (N=50) Placebo (N=134) 5.6 mg (N=134) Systemic Adverse Event * # Somnolence 6.4% 11.8% 16.0% 9.0% 15.7% Dry Mouth 10.6% 4.3% 16.0% Headache 4.3% 5.4% 12.0% Insomnia 8.5% 7.5% 6.0% Sedation 1.1% 2.2% 12.0% Local Administration Site Reaction * # Hypoaesthesia oral 2.1% 38.7% 36.0% 1.5% 37.3% Paresthesia oral 3.2% 16.1% 4.0% 0.7% 9.7% Glossodynia 1.1% 3.2% 6.0% Product Taste Abnormal 3.0% 11.9% Dose - related AEs: AE profiles are comparable between FM and PTSD studies at 2.8 mg No serious and unexpected AEs in PTSD at either 2.8 or 5.6 mg doses No unique systemic AEs observed for 5.6 mg dose (but generally, a modest increase in frequency) Severity and incidence of oral hypoesthesia (oral numbness) are not dose related

2020 Tonix Pharmaceuticals Holding Corp. 15 TNX - 102 SL: On - going Phase 3 Study in FM (F304/RELIEF) 2020 Tonix Pharmaceuticals Holding Corp. Key changes to protocol from previous Phase 3 trial in FM Exclusive use of higher dose of 5.6 mg (2 x 2.8 mg) Primary endpoint: mean pain improvement Analysis: MMRM with MI Clear guidance from FDA to advance fibromyalgia program using higher dose (5.6 mg) Long - term safety of 5.6 mg dose from PTSD studies expected to support FM NDA Study is progressing on schedule First patient enrolled in the new Phase 3 RELIEF study in December 2019 Achieved 50% enrollment in April 2020 Optional interim analysis results expected September 2020; topline results in 1Q 2021 if no delays Potential pivotal efficacy study to support NDA approval 15

2020 Tonix Pharmaceuticals Holding Corp. 16 TNX - 1800 1 , a SARS - CoV - 2 Vaccine Utilizes Tonix's proprietary horsepox virus as a vector Designed to express a protein from SARS - CoV - 2, the cause of COVID - 19 Collaboration with Southern Research Status of Vaccines for COVID - 19 No vaccines are currently available Many vaccines are being developed However, uncertainty exists around efficacy, and importantly, safety Global response will require multiple vaccines developed in parallel Contingencies are needed *TNX - 1800 is at the pre - IND stage of development

2020 Tonix Pharmaceuticals Holding Corp. 17 Why Use a Horsepox Platform for a Vaccine? Horsepox can be engineered to express foreign genes Lack of persistence or genomic integration in the host Strong immunogenicity as a vaccine Readily manufacture at scale Live, replicating vaccine - direct antigen presentation Potential advantages of horsepox over vaccinia Maintains strong immunogenicity with potentially improved tolerability Relative to non - replicating vaccinia, horsepox's replication in human cells provides direct antigen presentation by Class I MHC Horsepox may behave differently as a vector, in part because of its different repertoire of genes that modulate immune responses and host range

2020 Tonix Pharmaceuticals Holding Corp. 18 TNX - 1800 is Based on a Horsepox Virus (HPXV) Vector Designed to Express SARS - CoV - 2 S Protein *TNX - 1800 is at the pre - IND stage of development Horsepox sHPXV ~200,000 Bp TNX - 1800 * rHPXV/SARS - CoV - 2S ~200,000 Bp Homologous Recombination

2020 Tonix Pharmaceuticals Holding Corp. 19 TNX - 1800 is Designed to Induce Robust T H 1 Cellular Immunity 1. Fulginiti VA, et al. Clin Infect Dis. 2003;37(2):241 - 250. 2. Liu L, et al. Nature Med. 2010;16(2):224 - 228. 3. Centers for Disease Control and Prevention. Accessed April 15, 2020. https://phil.cdc.gov/Details.aspx?pid=3276 TNX - 1800 Host skin cells *Example of major cutaneous reaction, or "take," resulting from a replication - competent live - virus vaccine delivered via scarifi cation, indicating successful vaccination 1,3 5 mm Vaccine Vaccination by scarification 1 Inactive CD4 T cell Dendritic cell (DC) Memory B cell Memory CD8 T cell Memory CD4 T cell Neutrophil Macrophage NK cell IFNs IL - 4 T H 2 CD4 T cell B cell Antibodies * CD8 T cell Inactive CD8 T cell DC T H 1 CD4 T cell IFNs Scarification with live replicating orthopoxviruses evokes innate and adaptive immunity, including T H 1 and strong CD8 T cell responses 1,2

2020 Tonix Pharmaceuticals Holding Corp. 20 TNX - 1800 Development Status Southern Research will address two key questions: Will vaccination of animals elicit an immune response to the S protein? 4th Quarter 2020 - Small animal response expected 1 Will immune response protect non - human primates against a challenge with SARS - CoV - 2 virus? 4th Quarter 2020 - Primate testing results expected 1 Manufacturing development for GMP virus initiated Clinical development will require manufacturing for clinical supplies 2 1 1 We cannot predict whether the global COVID - 19 pandemic will impact the timing of these milestones

2020 Tonix Pharmaceuticals Holding Corp. 21 Tonix Pharmaceuticals: Lead Programs 1 2020 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL for fibromyalgia (FM) Phase 3 clinical development - RELIEF study enrolling Sublingual cyclobenzaprine tablets at higher dose of 5.6 mg Milestones: September 2020 - Optional interim analysis results expected 5 1 st Quarter 2021 - Topline data expected 5 TNX - 1800 potential vaccine for COVID - 19 2,3 Pre - clinical stage Live virus vaccine designed on our horsepox vaccine platform 4 to express the SARS - CoV - 2 Spike (S) protein Milestones: 4 th Quarter 2020 - Small animal response expected 5 4 th Quarter 2020 - Primate testing results expected 5 1 Experimental new medicines and biologics, not approved for any indication 2 Collaboration with Southern Research 3 COVID - 19 = Coronavirus disease 2019 4 TNX - 801 is unmodified horsepox virus, which is in development as a vaccine to protect against smallpox and monkeypox 5 We cannot predict whether the global COVID - 19 pandemic will impact the timing of these milestones 21

2020 Tonix Pharmaceuticals Holding Corp. 22 Management Team Seth Lederman, MD President & CEO Jessica Morris Chief Operating Officer Gregory Sullivan, MD Chief Medical Officer Bradley Saenger , CPA Chief Financial Officer

2020 Tonix Pharmaceuticals Holding Corp. 23 Thank You!