Slide 1: Controversies in Fibromyalgia - Brussels
Controversies in Fibromyalgia - Brussels Tonmya * (TNX-102 SL) in Development for the Management of Fibromyalgia March 7, 2024 NASDAQ: TNXP *Tonmya is conditionally accepted by FDA as the tradename for TNX-102 SL for the management of fibromyalgia Version P0535 March 7, 2024 (Doc 1389) © 2024 Tonix
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
Slide 3: About Fibromyalgia
About Fibromyalgia CNS PORTFOLIO Fibromyalgia is a chronic pain disorder resulting from amplified sensory and pain signaling within the CNS1 Fibromyalgia is a syndrome comprised of the symptoms: chronic widespread pain, nonrestorative sleep, and fatigue Fatigue Multisite Non-Restorative Sleep pain F
Slide 4: Fibromyalgia: Unrefreshing Sleep and Cyclobenzaprine Treatment
Fibromyalgia: Unrefreshing Sleep and Cyclobenzaprine Treatment CNS PORTFOLIO • Non-restorative sleep1,2 ‒ Harvey Moldofsky – recognition of unrefreshing/non-restorative sleep: Symptom Potential causative or potentiating factor • Cyclobenzaprine3,9 ‒ Potentially the earliest drug studied in fibro
Slide 5: Tonmya (TNX-102 SL, Cyclobenzaprine HCl Sublingual Tablets)
Tonmya (TNX-102 SL, Cyclobenzaprine HCl Sublingual Tablets)1 CNS PORTFOLIO • Non-opioid analgesic designed for long-term daily bedtime use in fibromyalgia patients ‒ Targets non-restorative sleep ‒ Potent binding and antagonist activities at the serotonin-5-HT2A, α1-adrenergic, histaminergic-H1, and
Slide 6: TNX-102 SL – Sublingual Administration and Transmucosal Delivery
TNX-102 SL – Sublingual Administration and Transmucosal Delivery CNS PORTFOLIO • Advantages of the sublingual route • Faster absorption provides PK that is ideal for bedtime dosing • Bypasses “first-pass” hepatic metabolism • Reduced metabolism of parent CBP to active metabolite norcyclobenzaprine (
Slide 7: Tonmya Fibromyalgia Program Status
Tonmya® Fibromyalgia Program Status CNS PORTFOLIO Tonmya (TNX-102 SL) Fibromyalgia Positive 2nd Phase 3 Topline Results Reported 4Q’23 Cyclobenzaprine Protectic® Sublingual Tablets 1) Positive Phase 3 study (RELIEF) reported – December 20201 2) Second Phase 3 study (RALLY) missed primary endpoint –
Slide 8: Tonmya (TNX-102 SL): Phase 3 RESILIENT Study Design
Tonmya (TNX-102 SL): Phase 3 RESILIENT Study Design CNS PORTFOLIO General study characteristics: • Randomized, double-blind, multicenter, placebo-controlled study in fibromyalgia • 33 U.S. sites enrolled 457 participants with fibromyalgia as defined by 2016 Revisions to the 2010/2011 FM Diagnostic C
Slide 9: RESILIENT Pre-Specified Primary Endpoint
RESILIENT Pre-Specified Primary Endpoint CNS PORTFOLIO Summary1 • Tonmya (TNX-102 SL) demonstrated statistically significant improvement in mean weekly pain scores over placebo at Week 14 • P-value of 0.00005 is highly statistically significant Additional Findings • Cohen’s d effect size 0.38 • All
Slide 10: RESILIENT Primary Outcome Measure: Reduction in Widespread Pain
RESILIENT Primary Outcome Measure Reduction in Widespread Pain CNS PORTFOLIO Weekly Average of Daily Diary NRS Ratings of Average Pain Over Prior 24 Hours 0 Placebo (N=225) TNX-102 SL (N=231) -0.2 LS Mean (SE) Change in NRS Pain Score -0.4 -0.6 -0.8 * -1 -1.2 *** -1.4 *** -1.6 *** -1.8 *** ** *** **
Slide 11: Summary of Key Secondary Endpoints
Summary of Key Secondary Endpoints CNS PORTFOLIO Endpoint1 P-value Effect Size2 Patient Global Impression of Change (PGIC) p = 0.00013 -- Fibromyalgia Impact Questionnaire – Symptoms Domain p = 0.000002 ES = 0.44 Fibromyalgia Impact Questionnaire – Function Domain p = 0.001 ES = 0.30 PROMIS Sleep Di
Slide 12: RESILIENT PROMIS Sleep Disturbance Inventory
RESILIENT PROMIS Sleep Disturbance Inventory Key Secondary Outcome Measure CNS PORTFOLIO PROMIS Sleep Disturbance 0 LS Mean (SE) Change in PROMIS SD T-score Placebo (N=225) TNX-102 SL (N=231) -1 -2 -3 -4 -5 -6 -7 -8 *** -9 *** * *** -10 Week 0 Week 2 Week 6 Week 10 Week 14 *p<0.001; ***p<0.00001 Wee
Slide 13: RESILIENT PROMIS Fatigue Inventory
RESILIENT PROMIS Fatigue Inventory Key Secondary Outcome Measure CNS PORTFOLIO PROMIS Fatigue 0 LS Mean (SE) Change in PROMIS Fatigue T-Score Placebo (N=225) TNX-102 SL (N=231) -1 -2 -3 -4 -5 -6 -7 *** -8 * *** *** -9 Week 0 Week 2 Week 6 Week 10 Week 14 *p<0.01; ***p<0.0001 Week 14 LS mean (SE) cha
Slide 14: RESILIENT – Cognitive Dysfunction or Brain Fog
RESILIENT – Cognitive Dysfunction or “Brain Fog” CNS PORTFOLIO Brain Fog assessed by the FIQ-R1 item on memory • Patients rated their level of memory problems • 11-pt scale going from “Good Memory” to “Very Poor Memory” • Prespecified endpoint, but not in the “waterfall” with the key secondary endpo
Slide 15: RESILIENT Summary of Efficacy
RESILIENT Summary of Efficacy CNS PORTFOLIO Fibromyalgia is a syndrome composed of symptoms • Widespread pain • Fatigue • Sleep disturbance Efficacy across symptoms of pain, fatigue and sleep • Pain: primary endpoint, daily pain diary: p-value of 0.00005 • Fatigue: PROMIS fatigue: p-value of 0.00009
Slide 16: Safety and Tolerability
Safety and Tolerability CNS PORTFOLIO • Completion Rate (safety population): TNX-102 SL 81.0% and Placebo 79.2% • No new safety signals observed • Only systemic adverse events (AEs) at rate ≥ 3.0% (TNX-102 SL v. Placebo) ‒ COVID-19 (4.3% v. 3.1%), somnolence (3.0% v. 1.3%), and headache (3.0% v. 1.8
Slide 17: RESILIENT Safety Summary
RESILIENT Safety Summary CNS PORTFOLIO Treatment-Emergent Adverse Events (TEAEs) at Rate of ≥ 3% in Either Treatment Group System Organ Class TNX-102 SL Placebo Total* Preferred Term N=231 N=226 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%
Slide 18: Tonmya Showed Broad-Spectrum Activity and was Well Tolerated
Tonmya Showed Broad-Spectrum Activity and was Well Tolerated No current product addresses pain, poor sleep and fatigue CNS PORTFOLIO Symptoms/Side Effects Pregabalin Duloxetine Tonmya Milnacipran Pain YES YES YES Activity Sleep YES - YES Fatigue - YES YES Sleep - YES - Fatigue YES - - Systemic Weigh
Slide 19: Poor Sleep and Pain have Bi-directional Reinforcing Effects
Poor Sleep and Pain have Bi-directional Reinforcing Effects1 CNS PORTFOLIO • Poor sleep and pain form a vicious cycle in driving fibromyalgia decompensation • Can’t sleep → worse pain / In pain → can’t sleep • Poor sleep and pain contribute to persistence, chronicity and severity • Syndrome includes
Slide 20: Key Clinical Programs
Key Clinical Programs NDA Molecule* Indication Phase 1 Phase 2 Phase 3 Submission Submission Fibromyalgia Positive Phase 3 Topline Results Reported 4Q’23 expected 2H’24 Tonmya TNX-102 SL Long COVID Phase 2 Topline Results Reported 3Q’23 Cyclobenzaprine HCl Protectic® Sublingual Tablets Phase 2** Stu
Slide 21: Additional Potential Indications for Tonmya (TNX-102 SL)
Additional Potential Indications for Tonmya (TNX-102 SL) CNS PORTFOLIO Fibromyalgia-Type Long COVID • Status: Phase 2 • Phase 2 study (PREVAIL) completed • Topline results reported 3Q 2023 Next Steps: Meet with FDA Acute Stress Reaction/ Acute Stress Disorder • Phase 2 ready investigator-initiated s
Slide 22: Thank You
THANK YOU © 2024 Tonix Pharmaceuticals Holding Corp.