Tonix Pharmaceuticals : TNX-102 SL for Fibromyalgia and Long COVID

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®)

CNS PORTFOLIO

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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

CNS PORTFOLIO

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.

CNS PORTFOLIO

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

CNS PORTFOLIO

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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© 2024 Tonix Pharmaceuticals Holding Corp.

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.