Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP
Tonix Pharmaceuticals — Non-Opioid Pain Therapeutics Summit 2026
35 slides from Tonix Pharmaceuticals's conference presentation, Jan 29, 2026
Slide 1: TNX-102 SL: A Centrally Acting Non-Opioid Analgesic for Fibromyalgia
TNX-102 SL (SUBLINGUAL CYCLOBENZAPRINE HCL): A CENTRALLY ACTING NON-OPIOID ANALGESIC FOR THE TREATMENT OF FIBROMYALGIA Gregory Sullivan, MD Presented at the Non-Opioid Pain Therapeutics Summit, January 27-29, Boston, MA
Slide 2: Disclaimers
DISCLAIMERS • This presentation is being conducted as part of a non-promotional proactive scientific exchange. • These materials may include information that is not part of the FDA-approved labeling. • Please see the TONMYA (cyclobenzaprine HCl sublingual) full prescribing Information available at T
Slide 3: Overview
OVERVIEW • Background: Unmet needs in Fibromyalgia (FM) and rationale for new non- opioid options • TNX-102 SL (cyclobenzaprine HCl sublingual tablets): Mechanism of action and pharmacology • Clinical evidence in FM: RESILIENT Phase 3 Results (pain, sleep function; trial rigor) • Safety and tolerabi
Slide 4: Background
BACKGROUND
Slide 5: Definition of Fibromyalgia (FM)
DEFINITION OF FIBROMYALGIA (FM) • FM is a chronic pain disorder resulting from amplified sensory and pain signaling within the CNS—now recognized as nociplastic pain1-4 • FM is a syndrome marked by chronic widespread pain, nonrestorative sleep, and fatigue FM is considered a chronic overlapping pain
Slide 6: Fibromyalgia Epidemiology
FIBROMYALGIA EPIDEMIOLOGY Global Common prevalence 75 to 90%1 1.8%5 Comorbidities 2.6% EU5 Anxiety Depression 6–12 million adults affected2 2.4% US5 Disorders 54%7 2.8 million diagnosed3 1.6% Asia5 56%7 2.3 million treated currently4 Irritable Bowel Type 2 Syndrome4 Diabetes4,6 Diagnosed age 20-50 P
Slide 7: Unmet Needs in the Treatment of Fibromyalgia
UNMET NEEDS IN THE TREATMENT OF FIBROMYALGIA Treatment persistence Medication burden Therapeutic landscape • High rates of discontinuation, • Average of 2-3 medications • No new product approvals switching, and augmentation1 used simultaneously1 since 20094 • Currently approved medications • Typical
Slide 8: Substantial Opioid Use in Fibromyalgia
SUBSTANTIAL OPIOID USE IN FIBROMYALGIAa,b % Patients with FM (after indexb date) 50% 45% 40% 35% Off-Label Off-Label Off-Label 30% FDA Approved Opioid Opioid 25.50% 25% Off-Label Off-Label 22.62% 19.45% 20.47% 20% FDA Approved Opioid 17.58% Off-Label 15% Off-Label 12.96% 13.23% 11.74% 10% FDA Approv
Slide 9: Foundational Insight for TNX-102 SL
FOUNDATIONAL INSIGHT FOR TNX-102 SL
Slide 10: FM Is Driven by Central vs Peripheral Mechanisms
FM IS DRIVEN BY CENTRAL VS PERIPHERAL MECHANISMS • FM is characterized by nociplastic pain, reflecting altered nociceptive Central Sensitization processing in the CNS1,2 • Symptoms are typically out of proportion to identifiable tissue injury or inflammation3,4 • Central sensitization (amplified CNS
Slide 11: Cyclobenzaprine in the Treatment of Fibromyalgia
CYCLOBENZAPRINE IN THE TREATMENT OF FIBROMYALGIA • Non-restorative sleep1,2 ‒ Harvey Moldofsky (pictured) recognized non-restorative sleep in fibromyalgia in 1970s As a core symptom As a potential causative or potentiating factor • Oral, immediate-release (IR) cyclobenzaprine3-9 ‒ Potentially on
Slide 12: Sleep Disruption Is a Core Driver of FM Symptom Severity
SLEEP DISRUPTION IS A CORE DRIVER OF FIBROMYALGIA (FM) SYMPTOM SEVERITY • Non-restorative sleep is a common and well-recognized feature of FM1,2 • Non-restorative sleep amplifies pain sensitivity and symptom severity2 • Poor sleep contributes to fatigue and cognitive symptoms, not just pain2 • Impro
Slide 13: The Scientific Rationale for TNX-102 SL
THE SCIENTIFIC RATIONALE FOR TNX-102 SL
Slide 14: Why Cyclobenzaprine, Why Bedtime, Why Sublingual
WHY CYCLOBENZAPRINE, WHY BEDTIME, WHY SUBLINGUAL (TNX-102 SL) • Selected for sleep/arousal CNS effects and extensive clinical experience • Low-dose bedtime sublingual dosing pursued to optimize benefit and tolerability • Key point: Sublingual delivery results in a different parent–metabolite balance
Slide 15: Sublingual Delivery and Pharmacologic Benefits
SUBLINGUAL DELIVERY AND PHARMACOLOGIC BENEFITS
Slide 16: TNX-102 SL Bypasses First-Pass Metabolism
TNX-102 SL BYPASSES FIRST-PASS METABOLISM H3C N Free-base cyclobenzaprine Sublingual CH3 Sublingual vasculature Charged cyclobenzaprine administration + + Mannitol + + + + + + Sublingually administered + + TNX-102 SL is transmucosally + absorbed, leading to more rapid + + + CBP absorption, greater r
Slide 17: TNX-102 SL Multi-Dose Profile vs Oral IR Cyclobenzaprine
TNX-102 SL PRODUCES DISTINCT MULTI-DOSE PROFILE VS ORAL IR CYCLOBENZAPRINE Population PK simulated steady-state concentration-time profiles (median and 90% prediction intervals) for CBP and nCBP following once-daily dosing of TNX-102 SL 5.6 mg or oral IR CBP 5 mg Repeated oral CBP dosing leads to su
Slide 18: Different Pharmacology, Not Just a Reformulation
TNX-102 SL DIFFERENT PHARMACOLOGY, NOT JUST A REFORMULATION • Sublingual delivery reshapes parent–metabolite exposure1,2 ‒ Shifts effects toward the parent drug during sleep1 ‒ Limits daytime exposure to the longer-acting active metabolite1 ORAL CBP TNX-102 SL • Extensive first-pass metabolism • Lar
Slide 19: Clinical Development of TNX-102 SL
CLINICAL DEVELOPMENT OF TNX-102 SL
Slide 20: A Data-Driven Clinical Development Program
A DATA-DRIVEN CLINICAL DEVELOPMENT PROGRAM • Early studies with TNX-102 SL 2.8 mg demonstrated signal and informed treatment optimization1 • Iterative, data-driven refinement advanced to 5.6 mg in Phase 31,2 • Continuous FDA engagement guided trial design and program evolution • RALLY, RELIEF and co
Slide 21: Pivotal Clinical Trial Result Summary
TNX-102 SL (5.6 MG) IN FIBROMYALGIA PIVOTAL CLINICAL TRIAL RESULT SUMMARY RELIEF Statistically significant reduction in daily 12/2020 pain compared to placebo (p=.010) RALLY 7/2021 Stopped at interim analysis RESILIENT Statistically significant reduction in daily 12/2023 pain compared to placebo (p
Slide 22: Reducing Placebo Response in FM Trials
REDUCING PLACEBO RESPONSE IN FM TRIALS • High placebo response is a well-recognized challenge in fibromyalgia trials1,2 • RESILIENT trial participants were provided a standardized placebo response education strategy1 • Patient and site education focused on: ‒ Accurate pain reporting (0–10 NRS)1 ‒ Ne
Slide 23: Pivotal Phase 3 Study
PIVOTAL PHASE 3 STUDY
Slide 24: RESILIENT Phase 3 Study Design
RESILIENT PHASE 3 STUDY DESIGN Phase 3, randomized, multicenter (34 sites), parallel group, double-blind, placebo-controlled Study Design 16-week trial (NCT05273749) Study Objectives Evaluate the efficacy and safety of TNX-102 SL for treatment of adults with FM 457 participants with FM as defined by
Slide 25: RESILIENT: Summary of Primary and Key Secondary Outcomes
RESILIENT: SUMMARY OF PRIMARY AND KEY SECONDARY OUTCOMES Endpoint P-value Effect Size (ES)b Primary Endpoint Daily Diary Pain ratings p < 0.001 ES = 0.38 Key Secondary Endpointsa Patient Global Impression of Change (PGIC), responders p < 0.001 -- Fibromyalgia Impact Questionnaire – Symptoms domain p
Slide 26: RESILIENT Primary Outcome: Reduction in Widespread Pain
RESILIENT PRIMARY OUTCOME MEASURE: REDUCTION IN WIDESPREAD PAIN 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 * * * * * * * * -2 * ** -2.2 0 1
Slide 27: RESILIENT Secondary Outcomes: PROMIS Sleep Disturbance and Fatigue
RESILIENT SECONDARY OUTCOME MEASURES: PROMIS SLEEP DISTURBANCE AND FATIGUE SCORES PROMIS Sleep Disturbance PROMIS Fatigue LS Mean (SE) Change in PROMIS SD T-score LS Mean (SE) Change in PROMIS Fatigue T-Score 0 0 Placebo (N=225) TNX-102 SL (N=231) Placebo (N=225) TNX-102 SL (N=231) -1 -1 -2 -2 -3 -3
Slide 28: RESILIENT: Safety
RESILIENT: SAFETY Treatment-Emergent Adverse Events (TEAEs) at Rate of ≥3% in Any 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%) Headache 7 (3.0%) 4 (1.
Slide 29: RESILIENT: Conclusions
RESILIENT: CONCLUSIONS Efficacy: TNX-102 SL provides “broad spectrum, syndromal activity” in fibromyalgia • TNX-102 SL provides significant pain reduction in patients with fibromyalgia • TNX-102 SL improves core symptoms of fibromyalgia, including sleep disturbance and fatigue • Thus, broad-spectrum
Slide 30: Current FDA-Approved Fibromyalgia Drugs
CURRENT FDA-APPROVED FIBROMYALGIA DRUGS1 Improvement in fibromyalgia pain was primary endpoint for approval • No other current approved products address the triad of pain, poor sleep, and fatigue • Tolerability issues limit long-term use for many patients Duloxetine Drug Pregabalin Milnacipran Class
Slide 31: Conclusions
CONCLUSIONS • TONMYA (TNX-102 SL) is a newly approved, centrally-acting, non-opioid treatment designed to improve pain, sleep, and daytime fatigue and function Pathophysiology Design Clinical Outcomes • Bedtime sublingual dosing • Central hyperarousal and sensory sensitivity, e.g., pain • ↑ relative
Slide 32: Combined Safety from All 3 Phase 3 Trials
COMBINED SAFETY FROM ALL 3 PHASE 3 TRIALS Treatment-Emergent Adverse Events (TEAEs) at Rate of ≥ 2% in Either Treatment Group Cyclobenzaprine Placebo HCl Sublingual Adverse Reactions (N = 739) Tablets (N = 735) Oral hypoesthesiaa 0.7% 23% Oral discomfortb 0.7% 9% Abnormal product taste 0.7% 9% Somno
Slide 33: Cyclobenzaprine HCl Sublingual Tablets: Safety Profile
CYCLOBENZAPRINE HCL SUBLINGUAL TABLETS: SAFETY PROFILE Contraindications: • Hypersensitivity to cyclobenzaprine or any inactive ingredient in cyclobenzaprine HCl sublingual tablets • Concomitant use of monoamine oxidase inhibitors or within 14 days after their discontinuation • During acute recovery
Slide 34: Safety Profile (Continued)
CYCLOBENZAPRINE HCL SUBLINGUAL TABLETS: SAFETY PROFILE (CONTINUED) Drug Interactions: • Monoamine oxidase inhibitors: Life-threatening interactions may occur • Other serotonergic drugs: Serotonin syndrome has been reported • CNS depressants: CNS depressant effects of alcohol, barbiturates, and other
Slide 35: Questions?
QUESTIONS? © 2025 Tonix Medicines, Inc.
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