Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Sachs Conference (January 2025)

42 slides from Tonix Pharmaceuticals's conference presentation, Jan 12, 2025

  1. Slide 1: Corporate Presentation - Sachs Conference

    Corporate Presentation Sachs Conference January 12, 2025 NASDAQ: TNXP PO6034, January 12, 2025 (Doc 1550) © 2025 Tonix Pharmaceuticals Holding Corp.

  2. 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

  3. Slide 3: Key Clinical Programs

    Key Clinical Programs NDA Molecule* Indication Phase 1 Phase 2 Phase 3 Submission Fibromyalgia Granted FDA Fast Track PDUFA** goal date of August 15, 2025 TNX-102 SL Designation Cyclobenzaprine HCl Sublingual Tablets Phase 2 Study*** Start Acute Stress Disorder Expected 1Q’25 TNX-1300 Cocaine Intoxi

  4. Slide 4: TNX-102 SL (Cyclobenzaprine HCl Sublingual Tablets) 5.6 mg

    TNX-102 SL* (Cyclobenzaprine HCl Sublingual Tablets) 5.6 mg A unique, sublingual formulation of cyclobenzaprine (CBP) designed to optimize absorption and delivery • Non-opioid analgesic – Tertiary Amine Tricyclic (TAT) • Rapid drug exposure following once-nightly sublingual administration • Reductio

  5. Slide 5: TNX-102 SL: Sublingual Formulation Designed for Long-Term Bedtime Dosing

    TNX-102 SL: Sublingual Formulation is Designed for Long-Term Daily Administration at Bedtime and Transmucosal Absorption CNS PORTFOLIO • TNX-102 SL: Proprietary sublingual formulation of cyclobenzaprine (CBP) with transmucosal absorption ‒ Innovation by design with patent-protected eutectic formulat

  6. Slide 6: TNX-102 SL Fibromyalgia Pivotal Clinical Trial Results

    TNX-102 SL (5.6 mg) Fibromyalgia Pivotal Clinical Trial Results CNS PORTFOLIO • Activity • First pivotal Phase 3 study (RELIEF) reported – December 20201 ‒ Statistically significant reduction in daily pain compared to placebo (p = 0.010) • Second Phase 3 study (RALLY) missed primary endpoint – July

  7. Slide 7: TNX-102 SL Fibromyalgia Regulatory Status

    TNX-102 SL (5.6 mg) Fibromyalgia Regulatory Status CNS PORTFOLIO • NDA can be filed without abuse potential assessment studies ‒ April 2017 • Granted FDA Fast Track Designation ‒ July 2024 • Submitted NDA to FDA ‒ October 2024 • NDA assigned a PDUFA goal date of August 15, 20251 ‒ December 2024 Next

  8. Slide 8: About Fibromyalgia

    About Fibromyalgia CNS PORTFOLIO Fibromyalgia is a chronic pain disorder resulting from amplified sensory and pain signaling within the CNS – now recognized as nociplastic pain1-4 Fibromyalgia is a syndrome comprised of the symptoms: chronic widespread pain, nonrestorative sleep, and fatigue Fatigue

  9. Slide 9: Fibromyalgia is a Large, Underserved and Dissatisfied Population

    Fibromyalgia is a Large, Underserved and Dissatisfied Population CNS PORTFOLIO • More than 10 million U.S. adults are affected – predominantly women1,2 ‒ Debilitating and life altering condition ‒ Significant economic impact • Patients have expressed dissatisfaction, despite three FDA approved drugs

  10. Slide 10: Poor Sleep and Pain have Bi-directional Reinforcing Effects

    Poor Sleep and Pain have Bi-directional Reinforcing Effects1 CNS PORTFOLIO • Harvey Moldofsky – recognition of unrefreshing/non-restorative sleep in fibromyalgia • Poor sleep and pain form a vicious cycle in driving fibromyalgia decompensation • Can’t sleep → worse pain / In pain → can’t sleep • Poo

  11. Slide 11: Cyclobenzaprine as Oral IR Tablet for Muscle Spasm and Fibromyalgia

    Cyclobenzaprine (CBP) as an Oral Immediate Release (IR) Tablet for Muscle Spasm and Investigational Product for Fibromyalgia CNS PORTFOLIO AMRIX® controlled Flexeril® release oral approved in 1977 CBP for the treatment Postmarketing approved for of muscle surveillance muscle Tricyclic spasm1 program

  12. Slide 12: Oral CBP Undergoes First-Pass Metabolism

    Oral CBP Undergoes First-Pass Metabolism CNS PORTFOLIO CBP undergoes “first pass” hepatic metabolism and is CBP administered as a ~50% converted to the CBP and norCBP enter swallowed oral dose persistent active metabolite the brain norCyclobenzaprine (norCBP) CBP < norCBP tongue H3C N H3C N CH3 H A

  13. Slide 13: CBP Binding Affinities for Receptors and Transporters

    CBP Binding Affinities for Receptors and Transporters CNS PORTFOLIO H1 5-HT2A α1A α1B M1 SERT NET Cyclobenzaprine (CBP) 1.3 5.2 5.6 9.1 7.9 29 35 norCyclobenzaprine 5.6 13 34 11 30 91 2.6 (norCBP) CBP/norCBP Activity Antagonist Inhibitor CBP: more active (lower Kd) at the key receptors involved in s

  14. Slide 14: Oral Dosing of CBP IR: Simulated Pharmacokinetics

    Oral Dosing of CBP Immediate Release (IR) 10 mg In Simulated Pharmacokinetics (PK) of Day 20 Daily Bed-time Administration CNS PORTFOLIO Cyclobenzaprine (CBP) Tertiary Amine Tricyclic (TAT) Sleep Time Awake Time 14000 12000 Concentration [pg/mL] 10000 8000 H3C 6000 N 4000 CH3 2000 Dynamic pharmacoki

  15. Slide 15: ~50% of Oral CBP is Converted to norCBP by the Liver

    ~50% of Oral CBP is Converted to norCBP by the Liver norCBP has “Flat” PK and Accumulates with Chronic Dosing CNS PORTFOLIO Cyclobenzaprine (CBP) norCyclobenzaprine (norCBP) “First pass” hepatic metabolism H3C CH3 H3C N Tertiary N Secondary Amine tail demethylation Amine tail CH3 H Dynamic pharmacok

  16. Slide 16: norCBP has Flat Blood Levels Over Time With Chronic Dosing

    norCBP has “Flat” Blood Levels Over Time With Chronic Dosing of CBP IR 10mg Over 20 Days (Simulated) CNS PORTFOLIO Sleep Time Wake Time norCyclobenzaprine 14000 12000 Concentration [pg/mL] 10000 8000 6000 H3C N Secondary 4000 Amine tail 2000 H 0 0 6 12 18 24 “Flat” pharmacokinetics Time [hrs] Accumu

  17. Slide 17: Multi-Dose PK of Simulated Oral CBP-IR

    Multi-Dose PK of Simulated Oral CBP-IR 10 mg Steady State at Day 20 CNS PORTFOLIO Steady State PK (after 20 days dosing) Sleep Time Wake Time 14000 CBP Simulated 12000 norCBP Simulated Concentration [pg/mL] 10000 8000 6000 4000 2000 0 0 6 12 18 24 Time [hrs] 17 PK = pharmacokinetics IR = immediate r

  18. Slide 18: TNX-102 SL: Transmucosal CBP Bypasses First-Pass Metabolism

    TNX-102 SL: Transmucosal CBP Bypasses First-Pass Metabolism CNS PORTFOLIO The sublingual tablet rapidly disintegrates, dissolves and releases solubilized CBP into the saliva adjacent to the mucosal membrane. TNX-102 SL is CBP enters the brain administered sublingually The base drives formation of CB

  19. Slide 19: Basic Excipient Increases Systemic Absorption of Sublingual Cyclobenzaprine

    Formulation with Basic Excipient Increases Systemic Absorption of Sublingual Cyclobenzaprine1 CNS PORTFOLIO Concentration gradient increases diffusion of free base across oral mucosa (Le Chatelier’s Principle) Low pH (acidic) High pH (basic) Base (K2HPO4) CBP-HCl CBP-HCl + +f + + + + + + + + + + + +

  20. Slide 20: TNX-102 SL: Proprietary Eutectic Formulation

    TNX-102 SL: Proprietary Eutectic Formulation CNS PORTFOLIO Proprietary Cyclobenzaprine HCl Eutectic Mixture Stabilizes Sublingual Tablet Formulation Eutectic Cyclobenzaprine-HCl formulation1 (CBP-HCl) Mannitol (inactive) Base particle Base particle (K2HPO4) (K2HPO4) Base particle Cyclobenzaprine (K2

  21. Slide 21: TNX-102 SL: CBP Detected in Plasma Within Minutes

    TNX-102 SL: CBP Detected in Plasma Within Minutes Following Sublingual Administration CNS PORTFOLIO Plasma Concentration Versus Time of TNX-102 SL Compared to CBP-IR 2500 TNX-102 SL 2.8mg 2000 Concentration (ng/L) 1500 1000 CBP-IR 5mg 500 0 0 0.5 1.0 1.5 Time (h) 21 © 2025 Tonix Pharmaceuticals Hold

  22. Slide 22: Steady State PK of Daily Sublingual TNX-102 SL

    Stead State PK on Day 20 of Daily Sublingual TNX-102 SL (5.6mg) CNS PORTFOLIO Steady State PK (after 20 days dosing) Sleep Time Awake Time 14000 CBP norCBP 12000 Concentration [pg/mL] 10000 8000 6000 With repeat daily dosing of 4000 TNX-102 SL, dynamic peak levels of CBP exceed 2000 norCBP during sl

  23. Slide 23: TNX-102 SL: Multi-Dose PK Differentiation from Oral CBP-IR

    TNX-102 SL: Multi-Dose PK Differentiation from Simulated Oral CBP-IR CNS PORTFOLIO Steady State PK (after 20 days dosing) Day 20 TNX-102 SL 5.6 mg v. Simulated Oral IR 10 mg Sleep Time Awake Time 14000 CBP 5.6 sl F106 (Measured) CBP 10.0 po (Simulated) 12000 norCBP 5.6 sl F106 (Measured) norCBP 10.0

  24. Slide 24: TNX-102 SL: Sublingual Formulation for Long-Term Daily Administration

    TNX-102 SL: Sublingual Formulation is Designed for Long-Term Daily Administration at Bedtime and Transmucosal Absorption CNS PORTFOLIO • Cyclobenzaprine (CBP) - Tertiary Amine Tricyclic (TAT) ‒ Dynamic pharmacokinetics (PK)  Elimination by N-glucuronidation • Oral administration results in first-pa

  25. Slide 25: TNX-102 SL: Patents and Patent Applications

    TNX-102 SL: Patents and Patent Applications CNS PORTFOLIO • U.S. Composition:* • A 75:25 cyclobenzaprine HCl - mannitol eutectic (dependent claims add a basifying agent). • 5 US Patents (Expire November 2034) • 1 Pending US Application (Would expire November 2034) • A composition of a cyclobenzaprin

  26. Slide 26: Fibromyalgia Market Characteristics

    Fibromyalgia Market Characteristics 26 © 2025 Tonix Pharmaceuticals Holding Corp.

  27. Slide 27: Fibromyalgia: Market Characteristics

    Fibromyalgia: Market Characteristics CNS PORTFOLIO Prevalence • One of the more common chronic pain disorders (2-4% of US Population)1 Diagnosed population • Large population but underdiagnosed2 relative to prevalence rate • Majority receive drug treatment3 Treatment Pattern • Polypharmacy the norm

  28. Slide 28: Fewer than Half of Those Treated Receive Sustained Benefit

    Fewer than Half of Those Treated for Fibromyalgia Receive Sustained Benefit from the Three FDA-Approved Drugs1 CNS PORTFOLIO • The treatment objective is to restore functionality and quality of life while avoiding significant sideeffects • The majority fail therapy due to lack of a response or poor

  29. Slide 29: Current FDA-Approved Fibromyalgia Drugs

    Current FDA-Approved Fibromyalgia Drugs1 CNS PORTFOLIO Improvement in fibromyalgia pain was primary endpoint for approval • No current product addresses pain, poor sleep and fatigue • Tolerability issues limit long term use for many patients Drug Pregabalin Duloxetine Milnacipran Class Gabapentinoid

  30. Slide 30: Large Need for New Fibromyalgia Therapies

    Large Need for New Fibromyalgia Therapies that Provide Symptom Improvement with Better Tolerability CNS PORTFOLIO • Currently-approved medications may have side effects that limit long-term use1 • Many patients skip doses or discontinue altogether within months of treatment initiation • Medication-r

  31. Slide 31: Prescribers Expressed Broad Dissatisfaction with Available Medications

    Prescribers Interviewed Expressed Broad Dissatisfaction with Available Fibromyalgia Medications: Results of Primary Research1 CNS PORTFOLIO Perspectives on FM Therapies from Prescribers Interviewed Drug Positives Negatives Duloxetine • Relatively high efficacy (compared to alternatives) • Tolerabili

  32. Slide 32: Many Fibromyalgia Patients are Prescribed Off-Label Drugs

    Many Fibromyalgia Patients are Prescribed Off-Label Drugs; ~53% FM Patients Prescribed Opioids Off-Label1,2 CNS PORTFOLIO % FM Patients (after index3 date) 50% 45% 40% 35% Off-Label 30% Off-Label Off-Label FDA Approved 25.50% Opioid Opioid 25% 22.62% Off-Label 20.47% Off-Label 19.45% 20% Opioid 17.5

  33. Slide 33: TNX-102 SL Pre-Launch Activities

    TNX-102 SL Pre-Launch Activities 33 © 2025 Tonix Pharmaceuticals Holding Corp.

  34. Slide 34: Potential for Tonix to Launch and Market TNX-102 SL

    Potential for Tonix to Launch and Market TNX-102 SL CNS PORTFOLIO Decline in personal promotion (“Detailing”) of prescription drugs • The pandemic accelerated transition to non-personal promotion o Omnichannel is more important and more sophisticated • Tele-sales • Digital • Direct mail • Growth in

  35. Slide 35: Milestones and Summary

    Milestones and Summary 35 © 2025 Tonix Pharmaceuticals Holding Corp.

  36. Slide 36: Milestones: Recently Completed and Upcoming

    Milestones: Recently Completed and Upcoming TNX-102 SL for the Management of Fibromyalgia Milestones   4th Quarter 2023 Statistically significant topline results of Phase 3 RESILIENT study – 2nd statistically significant Phase 2 trial 2nd Quarter 2024  Type B CMC and clinical pre-NDA meetings wi

  37. Slide 37: TNX-102 SL Indications with Active Programs

    TNX-102 SL* Indications with Active Programs Cyclobenzaprine HCl Fibromyalgia Non-opiate analgesic Status: Two statistically significant Phase 3 studies completed; FDA granted Fast Track Designation A unique, sublingual formulation of cyclobenzaprine designed for bedtime • First pivotal Phase 3 stud

  38. Slide 38: Thank You

    THANK YOU © 2025 Tonix Pharmaceuticals Holding Corp.

  39. Slide 39: Zembrace Important Safety Information (1 of 2)

    Zembrace® Important Safety Information (1 of 2) CNS PORTFOLIO Zembrace SymTouch (Zembrace) can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop use and get emergency help if you have any signs of a heart attack: • Discomfort in the center of

  40. Slide 40: Zembrace Important Safety Information (2 of 2)

    Zembrace® Important Safety Information (2 of 2) CNS PORTFOLIO Zembrace may cause serious side effects including: • Changes in color or sensation in your fingers and toes; sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrh

  41. Slide 41: Tosymra Important Safety Information (1 of 2)

    Tosymra® Important Safety Information (1 of 2) CNS PORTFOLIO Tosymra® can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop Tosymra and get emergency medical help if you have any signs of heart attack: • Discomfort in the center of your chest

  42. Slide 42: Tosymra Important Safety Information (2 of 2)

    Tosymra® Important Safety Information (2 of 2) CNS PORTFOLIO Tosymra may cause serious side effects including: • Changes in color or sensation in your fingers and toes; sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrhea

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