Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — 11th Pharmaceutics and Novel Drug Delivery Systems (PDDS) Conference 2024

38 slides from Tonix Pharmaceuticals's conference presentation, Sep 23, 2024

  1. Slide 1: Pharmacokinetic Properties of TNX-102 SL, a Sublingual Formulation of Cyclobenzaprine HCl

    © 2024 Tonix Pharmaceuticals Holding Corp. Pharmacokinetic Properties of TNX - 102 SL, a Sublingual Formulation of Cyclobenzaprine Hydrochloride Bruce Daugherty, PhD 11 th Pharmaceutics and Novel Drug Delivery Systems (PDDS) Conference 2024 – Oral Presentation September 19, 2024 Rome, Italy Version

  2. Slide 2: Cautionary Note on Forward-Looking Statements

    2 © 2024 Tonix Pharmaceuticals Holding Corp. 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 Litigat

  3. Slide 3: Disclosure

    3 © 2024 Tonix Pharmaceuticals Holding Corp. Disclosure TONIX Seth Lederman* Gregory Sullivan* Mary Kelly* Jean Engels* Bruce Daugherty* Siobhan Fogarty* # # Poster : Friday, Sept 20 “The importance of in vitro discriminatory tests in the development of a sublingual dosage form of TNX - 102 SL (Cycl

  4. Slide 4: Outline

    4 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Outline □ Clinical Pharmacology of TNX - 102 SL □ Single dose □ Multiple dose □ Dose proportionality and food effect □ Phase 3 Efficacy and Safety of TNX - 102 SL in Fibromyalgia

  5. Slide 5: Cyclobenzaprine HCl and TNX-102 SL

    5 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Cyclobenzaprine - HCl and TNX - 102 SL* H Cl Cyclobenzaprine Hydrochloride TNX - 102 SL Tablet 2.8 mg Flexeril ® 10 mg T.I.D. approved for the treatment of muscle spasm (Merck 1977) *TNX - 102 SL is an investigational new drug and not approv

  6. Slide 6: TNX-102 SL: Sublingual Administration and Transmucosal Delivery

    6 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL: Sublingual Administration and Transmucosal Delivery Swallowed Oral Dose Sublingual Oral Dose □ Faster absorption provides pharmacokinetics that is designed for bedtime dosing □ Bypasses “first - pass” metabolism □ Reduced metab

  7. Slide 7: TNX-102 SL: Proprietary Eutectic Formulation

    7 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL: Proprietary Eutectic Formulation Proprietary Cyclobenzaprine HCl Eutectic Mixture Stabilizes Sublingual Tablet Formulation Base particle (K 2 HPO 4 ) Base particle (K 2 HPO 4 ) Base particle (K 2 HPO 4 ) C y cl o be n z a p r i

  8. Slide 8: Formulation with Base Increases Systemic Absorption of Sublingual Cyclobenzaprine

    8 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Formulation with Base Increases Systemic Absorption of Sublingual Cyclobenzaprine 1 Concentration gradient increases diffusion of free base across oral mucosa (Le Chatelier’s Principle) CBP - HCl Cyclobenzaprine free base Oral mucosa CBP - H

  9. Slide 9: Pharmacokinetic Study – Single Dose 2.8 mg

    9 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL Pharmacokinetic Study – Single Dose 2.8 mg Objectives • Single center, comparative, randomized, single - dose, open - label, parallel - design • Compare the rate and extent of absorption of 3 test formulations of TNX - 102 SL 2.

  10. Slide 10: Pharmacokinetics: Comparison with Oral IR

    10 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL Pharmacokinetics: Comparison with Oral IR 0 - 48 hr Parameter TNX - 102 SL 2.8 mg Oral IR CBP 5 mg C max (ng/mL) 3.4 4.3 AUC 0 - 48 ( ng•hr /mL) 57.4 69.5 T 1/2 ( hr ) 27.4 25.1 Tablet dose = 44% lower C max = 20% lower AUC 0 -

  11. Slide 11: TNX-102 SL Exhibits Rapid Systemic Exposure of Cyclobenzaprine

    11 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL Exhibits Rapid Systemic Exposure of Cyclobenzaprine Post SL Administration Absorption Time Lag ( T lag ) = 12 times faster AUC = 338% higher P<0.01 0 - 1 hr 0 - 48 hr

  12. Slide 12: TNX-102 SL Exhibits a Targeted Systemic Exposure Pattern During Sleep

    12 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO 0 - 48 hr TNX - 102 SL Exhibits a Targeted Systemic Exposure Pattern of Cyclobenzaprine During Sleep 0 - 8 hr AUC = 10% lower ~3hr

  13. Slide 13: TNX-102 SL Exhibits Higher Bioavailability Upon Dose Normalization

    13 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL Exhibits Higher Bioavailability Upon Dose Normalization of Oral IR 5 mg to 2.8 mg Relative Bioavailability = 154% of Oral IR 0 - 48 hr

  14. Slide 14: Multi-Compartment Pharmacokinetic Model for Cyclobenzaprine

    14 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Multi - Compartment Pharmacokinetic Model for Cyclobenzaprine 0 - 48 hr A B A) Distribution Phase ‒ Distribution from circulation into body tissues ‒ TNX - 102 SL rapid elimination half - life = 3.1 hr B) Elimination Phase ‒ Drug metabolism

  15. Slide 15: Norcyclobenzaprine is the Long-Lived Major Metabolite

    15 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL Pharmacokinetics: Norcyclobenzaprine is the Long - Lived Major Metabolite Parameter TNX - 102 SL 2.8 mg Oral IR CBP 5 mg C max (ng/mL) 0.81 1.71 AUC 0 - 48 ( ng•hr /mL) 30.5 58.6 T 1/2 ( hr ) 72.0 66.7 0 - 48 hr C max = 53% low

  16. Slide 16: Ratio of Cyclobenzaprine/Norcyclobenzaprine Exposure is Increased

    16 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Ratio of Cyclobenzaprine/ Norcyclobenzaprine Exposure is Increased with TNX - 102 SL AUC 0 - 48 (CBP/ nCBP ) = 59% higher TNX - 102 SL 2.8 mg Oral IR 5 mg AUC 0 - 48 CBP/ nCBP 1.88 1.18 0 - 48 hr

  17. Slide 17: TNX-102 SL: Single Dose PK Differentiation from Oral IR

    17 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL: Single Dose PK Differentiation from Oral IR CBP TNX - 102 SL 2.8 mg v. Oral IR CBP 5 mg: Single Dose Pharmacokinetics PK = pharmacokinetics IR = immediate release CBP = cyclobenzaprine C max = maximum concentration AUC = Area

  18. Slide 18: Multi-Functional Mechanism Involves Antagonism at Four Neuronal Receptors

    18 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Multi - Functional Mechanism Involves Antagonism at Four Neuronal Receptors Active ingredient, cyclobenzaprine, interacts with four receptors □ Antagonist at 5 - HT 2A receptors • Similar activity to Desyrel® ( t razodone ) and Nuplazid ® (

  19. Slide 19: Cyclobenzaprine Binding Affinities for Receptors and Transporters

    19 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Cyclobenzaprine Binding Affinities for Receptors and Transporters Antagonist Inhibitor CBP/ nCBP Activity H 1 5 - HT 2A a 1A M 1 a 1B D 1 SERT NET Cyclobenzaprine 1.3 5.2 5.6 7.9 9.1 12 29 35 Norcyclobenzaprine 5.6 13 34 30 11 57 91 2.6 Rec

  20. Slide 20: Receptor Occupancy Post Administration

    20 © 2024 Tonix Pharmaceuticals Holding Corp. Receptor Occupancy from 0 - 2 hr Post Administration TNX - 102 SL 2.8 mg vs Oral IR 5 mg 0 10 20 30 40 50 60 70 80 90 100 0 2 3 5 10 20 30 45 60 120 0 10 20 30 40 50 60 70 80 90 100 0 2 3 5 10 20 30 45 60 120 0 10 20 30 40 50 60 70 80 90 100 0 2 3 5 10 2

  21. Slide 21: Pharmacokinetic Study – Multiple Dose 5.6 mg

    21 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Objectives • Single center, comparative, randomized, multiple - dose, open - label, parallel - design • Compare the rate and extent of absorption of TNX - 102 SL tablets (2 x 2.8 mg) vs AMRIX ® 30 mg extended - release capsule once daily fo

  22. Slide 22: Pharmacokinetic Study by Treatment Day – Day 1 vs Day 20

    22 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Time, hours Plasma Cyclobenzaprine, pg /mL Parameter TNX - 102 SL 5.6 mg (N=26) AMRIX ® 30 mg (N=30) AUC 0 - t , ss (ng*h/mL) 174.7 ± 101.5 669.7 ± 204.5 C max , ss (ng/mL) 11.2 ± 5.7 39.6 ± 11.9 T max (h) 5.0 (2.0 - 9.0) 7.0 (5.0 - 9.0) T

  23. Slide 23: Concentration-Time Profiles for 5.6 mg vs. Simulated Oral IR Cyclobenzaprine

    23 © 2024 Tonix Pharmaceuticals Holding Corp. Concentration - Time Profiles for TNX - 102 SL 5.6 mg vs. Simulated Oral IR Cyclobenzaprine 5 and 10 mg – Day 20 Cyclo 5.6 mg Cyclo 10.0 mg Simulated Nor 5.6 mg Nor 10.0 Simulated Cyclo 5.6 mg Cyclo 5.0 mg Simulated Nor 5.6 mg Nor 5.0 Simulated □ Rapid s

  24. Slide 24: Pharmacokinetic Study - Dose Proportionality and Food Effect

    24 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL Pharmacokinetic Study - Dose Proportionality and Food Effect Objectives • Single center, comparative, randomized, single - dose, 3 - period, 6 - sequence crossover • Evaluate the dose proportionality of TNX - 102 SL 2.8 mg vs 5

  25. Slide 25: Pharmacokinetic Study - Dose Proportionality and Food Effect Results

    25 © 2024 Tonix Pharmaceuticals Holding Corp. TNX - 102 SL PHARMACOKINETIC STUDY - DOSE PROPORTIONALITY AND FOOD EFFECT Parameter 2.8 mg Fasted (N=15) 5.6 mg Fasted (N=16) 5.6 mg Fed (N=16) AUC 0 - t (ng*h/mL) 64.4 ± 14.1 128.1 ± 27.6 133.1 ± 27.6 C max (ng/mL) 2.5 ± 0.4 5.1 ± 1.0 4.5 ± 1.0 T max (h

  26. Slide 26: Fibromyalgia is a Large, Underserved and Dissatisfied Population

    26 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Fibromyalgia is a Large, Underserved and Dissatisfied Population • More than 10 million U.S. adults are affected – predominantly women 1,2 ‒ Debilitating and life altering condition ‒ Significant economic impact • Patients are dissatisfied,

  27. Slide 27: Chronic Overlapping Pain Conditions (COPC) Believed to Result from Shared Brain Processes

    27 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Chronic Overlapping Pain Conditions (COPC) Believed to Result from Shared Brain Processes • COPC is a set of disorders that coaggregate ; these disorders can include but are not limited to 1,2 : • Temporomandibular disorder • Fibromyalgia •

  28. Slide 28: The Third Primary Type of Pain: Nociplastic Pain

    28 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO The Third Primary Type of Pain: Nociplastic Pain 1 - 4 Nociplastic syndrome includes: (1) widespread pain (2) fatigue (3) sleep disturbances (4) cognitive dysfunction (“brain fog”) Nociplastic Pain Examples: Fibromyalgia ME/CFS Migraine Irr

  29. Slide 29: About Fibromyalgia

    29 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO About Fibromyalgia Fibromyalgia is considered a chronic overlapping pain condition (COPC) - the only COPC with any FDA - approved drugs 3 Fibromyalgia is the prototypic nociplastic syndrome Fibromyalgia is a chronic pain disorder resulting

  30. Slide 30: Fibromyalgia: Unrefreshing Sleep and Cyclobenzaprine Treatment

    30 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Fibromyalgia: Unrefreshing Sleep and Cyclobenzaprine Treatment 1 Moldofsky H et al. Psychosom Med. 1975. 37:341 - 51. 2 Moldofsky H and Scarisbrick P. Psychosom Med. 1976. 38:35 - 44. 3 Bennett RM, et al. Arthritis Rheum 1988 . 31 : 1535 –

  31. Slide 31: Cyclobenzaprine Long-Term Utilization

    31 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Cyclobenzaprine Long - Term Utilization • Flexeril® approved in 1977 by Merck for the treatment of muscle spasm • 10 mg T.I.D. for acute use (2 - 3 weeks) • Original NDA included “ 8 long term safety studies in which patients with various n

  32. Slide 32: Phase 3 RESILIENT Study Design

    32 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL: P hase 3 RESILIENT Study Design General s tudy c haracteristics: • Randomized, double - blind, multicenter, placebo - controlle d study in fibromyalgia • 33 U.S. sites enrolled 457 participants with fibromyalgia as defined by

  33. Slide 33: RESILIENT Primary Outcome Measure: Reduction in Widespread Pain

    33 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Weekly Average of Daily Diary NRS Ratings of Average Pain Over Prior 24 Hours RESILIENT Primary Outcome Measure Reduction in Widespread Pain **p<0.001; ***p<0.0001 Week 14 LS mean (SE) change from baseline for TNX - 102 SL - 1.82 (0.12) and

  34. Slide 34: RESILIENT Continuous Pain Responder Graph

    34 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Continuous Pain Responder Graph P e r c e n t o f S u b j e c t s 0 10 20 30 40 50 60 70 80 90 100 Percentage Redution in Pain ≥ 0 ≥ 10% ≥ 20% ≥ 30% ≥ 40% ≥ 50% ≥ 60% ≥ 70% ≥ 80% ≥ 90% ≥ 100% Placebo TNX-102 SL 30% Responders # (

  35. Slide 35: RESILIENT Safety

    35 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO RESILIENT Safety System Organ Class Preferred Term TNX - 102 SL N=231 Placebo N=226 Total* N=457 Systemic Adverse Events COVID - 19 10 (4.3%) 7 (3.1%) 17 (3.7%) Somnolence 7 (3.0%) 3 (1.3%) 10 (2.2%) Headache 7 (3.0%) 4 (1.8%) 11 (2.4%) Ora

  36. Slide 36: TNX-102 SL Showed Broad-Spectrum Activity and was Well Tolerated

    36 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL Showed Broad - Spectrum Activity and was Well Tolerated Lyrica ® Cymbalta ® Savella ® TNX - 102 SL Activity Pain + + + Sleep + - + Fatigue - + + Systemic Tolerability Issues Insomnia - + - Fatigue + - - Weight + - - Blood Press

  37. Slide 37: Conclusions

    37 © 2024 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 102 SL: A unique, sublingual formulation of cyclobenzaprine designed to optimize delivery and absorption □ Clinical Pharmacology of TNX - 102 SL • Rapid systemic exposure during the first 1 - 2 hr • Increased bioavailability during sl

  38. Slide 38: Thank You

    © 2023 Tonix Pharmaceuticals Holding Corp. THANK YOU

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