Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Technical Presentation (August 2020)

14 slides from Tonix Pharmaceuticals's technical presentation, Aug 4, 2020

  1. Slide 1: Intranasal Oxytocin Relieves Pain and Depressive Behavior in a Rodent Model of Mild TBI

    Intranasal (IN) Oxytocin Relieves Pain and Depressive Behavior in a Rodent Model of Mild Traumatic Brain Injury (TBI) 1 July 2020 Shashidhar H Kori, MD, FAHS, David Yeomans, PhD, Michael Klukinov, PhD Version P0238 7-29-20 (Doc 0676) 1 © 2020 Tonix Pharmaceuticals Holding Corp.

  2. Slide 2: Disclosures

    DISCLOSURES 2 SHASHIDHAR H KORI: Full-time employee, Chief Medical Officer, Trigemina Inc. Consultant: Tonix Pharma, Exalys, Satsuma, NewBio DAVID YEOMANS: Full-time employee, Stanford University. Consultant: Trigemina Inc, Tonix, Exalys, NewBio, SiteOne, CereVu Michael Klukinov: Full-time employee,

  3. Slide 3: Consequences of TBI

    Consequences of TBI 3 • Post traumatic headaches (PTH) • Cognitive deficits in memory, attention, and concentration • Somatic complaints of fatigue, disordered sleep, dizziness • Affective complaints of irritability, anxiety, and depression • Post Traumatic Stress Disorder (PTSD) Hoffman et al 2020

  4. Slide 4: Post Traumatic Headache (PTH) is a Disabling Symptom of TBI

    Post Traumatic Headache (PTH) is a Disabling Symptom of TBI 4 • TBI is the most common brain disorder, the incidence of which exceeds that of dementia, epilepsy and stroke • 1.7 million TBIs are sustained each year in the United States, most of which are of mild initial severity • 5.3 million Americ

  5. Slide 5: CGRP and PACAP are Believed to Play a Critical Role in PTH

    CGRP and PACAP are Believed to Play a Critical Role in Post traumatic Headache (PTH) 5 • Most PTH are migraine like in character (Finkel 2012) • Some PTH have autonomic features (Finkel 2012) • CGRP (Friburg 1994) and PACAP (Amin 2014) are elevated in jugular blood during migraine attack • CGRP inje

  6. Slide 6: Intranasal Oxytocin (IN OT) as a Treatment for PTH

    Intranasal Oxytocin (IN OT) as a Treatment for PTH 6 • Natural hormone, deficiency of which is believed to lower pain threshold • Intranasal oxytocin is taken up by trigeminal (TG) system and believed to act in TG • Has multiple mechanism of action, suppresses trigeminal nociceptive transmission, bl

  7. Slide 7: Efficacy of IN OT Has Been Demonstrated in Other Headache Models

    Efficacy of IN OT Has Been Demonstrated in Other Headache Models 7 • Synergistic action between oxytocin and Mg demonstrated • Naso-cerebral pathway proved by radiolabeling studies • Decreased action potentials in TG cells demonstrated by elegant electrophysiological studies • Blockage of CGRP and P

  8. Slide 8: Efficacy of nasal OT was tested in a rat model of mild-moderate TBI

    Efficacy of nasal OT was tested in a rat model of mild-moderate traumatic brain injury (TBI)

  9. Slide 9: Elevated levels of OT in trigeminal ganglia and pons after nasal application

    Elevated levels of OT in trigeminal ganglia and pons after nasal application of OT vs vehicle control 1500 1000 Trigeminal Pons Concentration (pg/mL) 500 Spinal cord Olfactory Bulb 0 OxytocinControl OxytocinControl OxytocinControl OxytocinControl Trigeminal Pons Spinal cord Olfactory Bulb

  10. Slide 10: Nasal OT effects on post TBI pain

    Nasal OT effects on post TBI pain Mechanical sensitivity (von Frey) after mild The effect of nasal oxytocin on allodynia TBI or sham surgery after mild TBI. A. Left Hindpaw B. Right Hindpaw A. Left Hindpaw Mechanical Allodynia 50 40 B. Right Hind Paw Mechanical Sensitivity 40 Mild TBI * * Mild TBI O

  11. Slide 11: Nasal OT effects on post TBI pain

    Nasal OT effects on post TBI pain Anti-allodynic effect of nasal OT is blocked IV OT is ineffective in preventing post-TBI by the OT antagonist Atosiban allodynia A. Left hp I.V Oxytocin B. Right hp I.V Oxytocin A. Left Hind-paw Oxytocin +/- Atosiban B. Right Hind-paw Oxytocin +/- Atosiban 40 40 40

  12. Slide 12: Nasal OT effects on post TBI pain

    Nasal OT effects on post TBI pain Nasal OT has no effect on Conditioned Nasal OT is effective in some aspects of post-TBI Place Preference in control animals: Depression in the forced swim test analgesia without addictive potential Immobility Struggling 200 80 ________*________ * CPP 150 60 0.8 *p =

  13. Slide 13: IN OT for Core PTSD Symptom of Anxiety

    IN OT for Core PTSD Symptom of Anxiety • Proprietary Formulation of Nasal Oxytocin Plus Mg++ Provides Synergistic Improvement in Elevated Plus Maze test of Anxiety Elevated Plus Maze Test of 9 Anxiety 8.5 8 7.5 7 6.5 # of Open Arm Entries 6 5.5 5 Vehicle OT alone OT + Mg++ Mg++ alone

  14. Slide 14: Conclusions: IN Oxytocin in Post traumatic Headache (PTH)

    Conclusions: IN Oxytocin in Post traumatic Headache (PTH) 14 • After intranasal application, oxytocin concentrates in the trigeminal system • Intranasal, but not IV Oxytocin attenuates pain responses in a rat model of traumatic brain injury without addictive potential • These analgesic effects can b

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