Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — Technical Presentation (May 2023)

20 slides from Tonix Pharmaceuticals's technical presentation, May 1, 2023

1. Slide 1: TNX-601 ER Major Depressive Disorder

   © 2023 Tonix Pharmaceuticals Holding Corp. TNX - 601 ER Major Depressive Disorder NASDAQ: TNXP Version P04 39 May 1, 2023 (Doc 11 98 )

2. Slide 2: Cautionary Note on Forward-Looking Statements

   2 © 2023 Tonix Pharmaceuticals Holding Corp. 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 Litigat

3. Slide 3: TNX-601 ER Profile and Development Program

   3 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO PROFILE DEVELOPMENT PROGRAM Patents Issued TNX - 601 E R*: Depression Tianeptine Hemioxalate Extended - Release Tablets (39.4 mg) CNS PORTFOLIO • A novel, oral, extended - release once - daily tablet • Treatment effect of tianeptine sodium i

4. Slide 4: Phase 2 UPLIFT Study Design

   © 2023 Tonix Pharmaceuticals Holding Corp. 4 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 601 ER - Phase 2 UPLIFT* Study Design General s tudy c haracteristics: • Randomized, double - blind, placebo - controlle d study in Major Depressive Disorder to evaluate monotherapy with TNX -

5. Slide 5: Major Depressive Disorder (MDD)

   © 2023 Tonix Pharmaceuticals Holding Corp. 5 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Major Depressive Disorder (MDD) • Major depressive disorder (MDD) is a leading cause of disability worldwide, with 21 million adults in the US alone experiencing a depressive episode in 2020 1 • L i

6. Slide 6: High Unmet Need for New Classes of Antidepressants

   © 2023 Tonix Pharmaceuticals Holding Corp. 6 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO • The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, regarded as the largest antidepressant trial ever conducted, indicated approximately 30% of depressed patients fail to ac

7. Slide 7: About TNX-601 ER: Targeted therapy for MDD

   © 2023 Tonix Pharmaceuticals Holding Corp. 7 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO About TNX - 601 ER CNS PORTFOLIO • Tianeptine sodium (amorphous) immediate release (IR) tablets have been available in Europe and many countries in Asia and Latin America for the treatment of MDD si

8. Slide 8: Clinical Trials of Tianeptine Sodium

   © 2023 Tonix Pharmaceuticals Holding Corp. 8 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Clinical Trials of Tianeptine Sodium • Antidepressant efficacy confirmed in multicenter double - blind, placebo - controlled, randomized trials 1,2 • Enriched enrollment randomized withdrawal design

9. Slide 9: Tianeptine Sodium

   © 2023 Tonix Pharmaceuticals Holding Corp. 9 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tianeptine Sodium • Tianeptine discovered and patented by French Society of Medical Research in 1960s • Tianeptine first marketed in 1989 for the treatment of major depression by French pharmaceutic

10. Slide 10: Structural Comparison: Tricyclic and TNX-102

    © 2023 Tonix Pharmaceuticals Holding Corp. 10 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Structural Comparison: Tricyclic and TNX - 601 Cyclobenzaprine and tianeptine share structural similarities with classic tricyclic antidepressants (TCAs) and to each other, but each has unique phar

11. Slide 11: Proposed Mechanism of Action (MOA)

    © 2023 Tonix Pharmaceuticals Holding Corp. 11 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Proposed Mechanism of Action (MOA) • The proposed MOA of TNX - 601 ER is distinct from traditional monoaminergic antidepressants in the U.S. − “It is now recognized that monoamine deficits are only

12. Slide 12: Proposed MOA of Tianeptine

    © 2023 Tonix Pharmaceuticals Holding Corp. 12 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO 1 Tartt et al., 2022. Molecular Psychiatry 27: 2689 – 2699. 2 Plaisant et al.,2003. Neuropharmacology 44: 801 – 809. 3 Slusarczyk et al., 2018. Int J Mol Sci 19: 1965. • In Table 1 (right), it is i

13. Slide 13: Observations Relating Tianeptine's Action to µ-Opioid Receptors

    © 2023 Tonix Pharmaceuticals Holding Corp. 13 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Observations that Relate Tianeptine’s Action to µ - Opioid Receptors • In 2014, tianeptine was reported to be a weak µ – opioid agonist by Javitch & Sames at Columbia 1 − K i = 383 nM and EC 50 = 1

14. Slide 14: Tianeptine's off-target activity

    © 2023 Tonix Pharmaceuticals Holding Corp. 14 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Tianeptine's off - target activity • Based on these µ – opioid data and interpretations, unregulated tianeptine entered the US ‒ As a research chemical - not for human use ‒ As an ingredient in foo

15. Slide 15: Prescription Tianeptine has Low Incidence of Abuse in France

    © 2023 Tonix Pharmaceuticals Holding Corp. 15 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Prescription Tianeptine has Low Incidence of Abuse in France • Tianeptine and its MC5 metabolite are weak mu - opioid (µ - opioid) receptor (MOR) agonists 1 that present a potential abuse liability

16. Slide 16: Drug product: abuse-deterrent properties

    © 2023 Tonix Pharmaceuticals Holding Corp. 16 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO TNX - 601 ER Drug product • The only abuse - deterrent properties approved for the labels of certain marketed opioids are extended - release formulations with physiochemical barriers +/ - aversive

17. Slide 17: Summary: TNX-601 ER vs. Other Antidepressants

    © 2023 Tonix Pharmaceuticals Holding Corp. 17 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Summary: TNX - 601 ER vs. Other Antidepressants • Given tianeptine’s unique metabolic pathway, which is independent of the hepatic P450 system, it is anticipated that, like tianeptine sodium, TNX -

18. Slide 18: About TNX-601 ER: Targeted therapy for MDD

    © 2023 Tonix Pharmaceuticals Holding Corp. 18 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO About TNX - 601 ER CNS PORTFOLIO • Tianeptine sodium (amorphous) immediate release (IR) tablets have been available in Europe and many countries in Asia and Latin America for the treatment of MDD s

19. Slide 19: Potential Indications for TNX-601 ER

    © 2023 Tonix Pharmaceuticals Holding Corp. 19 © 2023 Tonix Pharmaceuticals Holding Corp. CNS PORTFOLIO Potential Indications for TNX - 601 ER • Neurodegenerative disorders ‒ Parkinson’s (and associated conditions, e.g. depression and psychosis) 1 ‒ Alzheimer’s (and associated conditions, e.g. agitat

20. Slide 20: Thank You

    © 2023 Tonix Pharmaceuticals Holding Corp. © 2023 Tonix Pharmaceuticals Holding Corp. THANK YOU

Tonix Pharmaceuticals Holding — Technical Presentation (May 2023) on 6ix