TNX-102 SL
Fibromyalgia, Long COVID, and Acute Stress Disorder
NASDAQ: TNXP
Version P0577 July 15, 2024 (Doc 1474)
© 2024 Tonix Pharmaceuticals Holding Corp.
Tonmya (TNX-102 SL)*
Cyclobenzaprine HCl (Protectic®)
Non-opiate analgesic
A unique, sublingual formulation of cyclobenzaprine designed for bedtime dosing with sublingual delivery and transmucosal absorption, bypassing 1st pass metabolism
Potent binding and antagonist activities at the serotonergic-5-HT2A,adrenergic-α1,histaminergic-H1, and muscarinic-M1 cholinergic receptors to facilitate restorative sleep
Innovative and proprietary PROTECTIC® Rapid drug exposure following once nightly sublingual administration
Differentiators:
Relative to Oral Cyclobenzaprine
- Lower daytime exposure
- Avoids first-pass metabolism
- Reduces risk of pharmacological interference from major metabolite
Relative to Standard of Care
- Potential for better tolerability while maintaining efficacy
- Not scheduled, without recognized abuse potential
Patents Issued
Indications Most Recently Pursued
Fibromyalgia
Status: Two statistically significant Phase 3 studies completed
- First pivotal Phase 3 study (RELIEF) completed
- Second Phase 3 study (RALLY) missed primary endpoint
- Confirmatory pivotal Phase 3 study (RESILIENT) completed
Next Steps: pre-NDA meetings with FDA complete with alignment on requirements for filing and potential approval
Fibromyalgia-Type Long COVID
Status: Phase 2
- Phase 2 study (PREVAIL) completed
- Topline results reported 3Q 2023
Next Steps: Meeting with FDA regarding primary endpoint
Acute Stress Reaction/ Acute Stress Disorder
- Phase 2 ready investigator-initiated study
- Department of Defense funded/ UNC will perform study Next Steps: Expect to start Phase 2 in 3Q 2024
*TNX-102 SL has not been approved for any indication. | © 2024 Tonix Pharmaceuticals Holding Corp. |
About Fibromyalgia
Fibromyalgia is a chronic pain disorderresulting from amplified sensory and pain signaling within the CNS1
Fibromyalgia is a syndromecomprised of the symptoms: chronic widespread pain, nonrestorative sleep, and fatigue
Fatigue
Multisite | Non-Restorative Sleep |
pain | |
Fibromyalgia is considered a chronic overlapping pain condition (COPC)
- the only COPC with any FDA-approved drugs3
Fibromyalgia is the prototypic nociplastic syndrome
1American Chronic Pain Association (www.theacpa.org, 2019)
3CFS/ME = chronic fatigue syndrome/myalgic encephalomyelitis
3The three drugs with FDA approval for the treatment of fibromyalgia: Pregabalin (Lyrica®); Duloxetine (Cymbalta®); Milnacipran (Savella®)
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© 2024 Tonix Pharmaceuticals Holding Corp.
Fibromyalgia is a Large, Underserved and Dissatisfied Population
- ~10 million U.S. adults are affected - predominantly women1,2
- Debilitating and life altering condition
- Significant economic impact
- Patients are dissatisfied, despite three FDA approved drugs3,4
- 85% of patients fail first-line therapy5: efficacy variability, tolerability issues especially when used long-term and lack of broad-spectrum activity
- Typical for patients to rotate between drugs and be on multiple drugs at the same time; 79% of FM patients are on multiple therapies5
- ~2.7 million FM patients diagnosed and treated6
- >22 million prescriptions are issued for the treatment of fibromyalgia (on- and off-label usage) each year7,8
- No new Rx product since 2009
- The treatment objective is to restore functionality and quality of life by broadly improving symptoms while avoiding significant side effects
1American College of Rheumatology (www.ACRPatientInfo.org accessed May 7, 2019) - prevalence rate of 2-4% for U.S. adult population (~250 million)
2Vincent A, et al. Arthritis Care Res (Hoboken). 2013 65(5):786-92. doi: 10.1002; diagnosed prevalence rate was 1.1% of adult population or 50% of the prevalent population
3Robinson RL, et al. Pain Med. 2012 13(10):1366-76. doi: 10.1111; 85% received drug treatment
4The three drugs with FDA approval for the treatment of fibromyalgia: Pregabalin (Lyrica); Duloxetine (Cymbalta); Milnacipran (Savella)
5EVERSANA primary physician research, May 2024; commissioned by Tonix
6EVERSANA analysis of claims database, May 2024; commissioned by Tonix
7Productsales derived fromIMS MIDAS; IMS NDTI used to factorusage for fibromyalgia;data accessedApril 2015.
8Market research by Frost & Sullivan, commissioned by Tonix, 2011 | © 2024 Tonix Pharmaceuticals Holding Corp. |
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Poor Sleep and Pain have Bi-directional Reinforcing Effects1
- Poor sleep and pain form a vicious cyclein 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 symptoms of fatigue and brain fog
- Treating sleep disturbance in fibromyalgia has the potential to break the vicious cycle
- Potential to remove an obstacle to recovery
- Using the right medicine is important - some sedative/hypnotics don't work1,2
Fatigue PAIN
BAD | Brain Fog |
SLEEP |
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1Moldofsky H, et al. J Rheumatol. 1996;23:529-533. | 5 |
2Grönbald M, et al. Clin Rheumatol. 1993;12(2):186-191 | © 2024 Tonix Pharmaceuticals Holding Corp. |
Fibromyalgia: Unrefreshing Sleep and Cyclobenzaprine Treatment
- Non-restorativesleep1,2
- Harvey Moldofsky - recognition of unrefreshing/non-restorative sleep:
- Symptom
- Potential causative or potentiating factor
- Cyclobenzaprine3,9
- Potentially the earliest drug studied in fibromyalgia as an oral swallowed agent
- Studies showed equivocal effects and tolerability issues at "muscle spasm" doses
- Bedtime, low-dosecyclobenzaprine targeting non-restorativesleep10-11
- Recognition of unrefreshing sleep as a target of therapy
- Primitive oral, swallowed formulation - "flat" pharmacokinetics
- Bedtime, sublingual transmucosalcyclobenzaprine targeting non-restorative sleep12
- Dynamic pharmacokinetic profile, rapid absorption, decrease in major metabolite
- Two studies (Phase 2 and Phase 3) at 2.8 mg; three Phase 3 studies at 5.6 mg.
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1Moldofsky H et al. Psychosom Med. 1975. 37:341-51.
2Moldofsky H and Scarisbrick P. Psychosom Med. 1976. 38:35-44.3Bennett RM, et al. Arthritis Rheum 1988. 31:1535-42.
4Quimby LG, et al. J Rheumatol Suppl, 1989 Nov;19:140-3.
5Reynolds WJ, et al. J Rheumatol. 1991.18:452-4.
6Santandrea S, et al. J Int Med Res. 1993.21:74-80.
7Cantini F, et al. Minerva Med. 1994. 85:97-100.
8Carette S, et al. Arthritis Rheum. 1994. 37:32-40.
9Tofferi JK, et al. Arthritis Rheum. 2004. 51:9-13.1 10Iglehart IW. 2003; US Patent 6,541,523.
11Moldofsky et al. J Rheumatol. 2011. 38:2653-2663
12Lederman S et al. Arthritis Care Res. 2023. 75:2359-2368.
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© 2024 Tonix Pharmaceuticals Holding Corp.
Fibromyalgia Program Status
Tonmya
(TNX-102 SL) | Fibromyalgia | Statistically Significant 2nd Phase 3 Topline Results |
Cyclobenzaprine Protectic® | Reported 4Q'23 | |
Sublingual Tablets | ||
First pivotal Phase 3 study (RELIEF) reported - December 20201
Second Phase 3 study (RALLY) missed primary endpoint - July 2021
Confirmatory pivotal Phase 3 study (RESILIENT) reported - December 2023
Type B CMC and clinical pre-NDA meetings with FDA completed with alignment on requirements for filing and potential approval
Next Steps:
- NDA filing expected 2H'24
- FDA decision on NDA approval expected 2H'25
1Lederman S, et al. Arthritis Care Res (Hoboken). 2023 Nov;75(11):2359-2368. doi: 10.1002.
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© 2024 Tonix Pharmaceuticals Holding Corp.
Phase 3 RESILIENT Study Population
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© 2024 Tonix Pharmaceuticals Holding Corp.
Tonmya (TNX-102 SL): Phase 3 RESILIENT Study Design
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 Criteria1
Primary Endpoint:
- Change from baseline to Week 14 (TNX-102 SL vs. placebo) in weekly averages of daily diary average pain severity score
- Primary Endpoint, p-value = 0.00005
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TNX-102 SL once-daily at bedtime
5.6 mg (2 x 2.8 mg tablets)*
Placebo once-daily at bedtime
14 weeks
*Two-weekrun-in at 2.8 mg dose at bedtime
followed by 12 weeks at 5.6 mg dose
ClinicalTrials.gov Identifier: NCT05273749
Study Title: A Phase 3 Study to Evaluate the Efficacy and Safety of TNX-102 SL Taken Daily in Patients With Fibromyalgia (RESILIENT)
Trial ID: TNY-CY-F307 ('RESILIENT')
1Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RL, Mease PJ, Russell AS, Russell IJ, Walitt B. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016; 46(3):319-329.
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RESILIENT Demographics and Baseline Characteristics
TNX-102 SL | Placebo | |
(N=231) | (N=225) | |
Age (years) | 49.3 (10.45)* | 49.5 (11.35)* |
Female | 224 (97.0%)† | 211 (93.8%)† |
Hispanic or Latino | 36 (15.6%)† | 35 (15.6%)† |
White | 194 (84.0%)† | 192 (85.3%)† |
Black | 32 (13.9%)† | 26 (11.6%)† |
Pain Score (0-10 NRS) | 5.9 (1.05)* | 5.9 (1.08)* |
Employed Yes | 147 (63.6%)† | 150 (66.7%)† |
FM Duration (years) | 8.6 (8.44)* | 9.9 (9.53)* |
BMI (kg/m2) | 31.1 (6.34)* | 31.1 (6.32)* |
- Mean (standard deviation)
† N (%)
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© 2024 Tonix Pharmaceuticals Holding Corp.
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Tonix Pharmaceuticals Holding Corp. published this content on 15 July 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 15 July 2024 19:13:06 UTC.