Tonix Pharmaceuticals Holding Corp. (TNXP)

TNX-102 SL for AAD

Agitation in Alzheimer's Disease (AAD)

Agitation is a common behavioral symptom experienced by a majority of patients with Alzheimer's Disease. It includes emotional lability, restlessness, irritability, and aggression1 and is one of the most distressing and debilitating of the behavioral complications of Alzheimer's disease. Both sleep disturbances and agitation are common and co-morbid features of Alzheimer's disease.1,2,3

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TNX-102 SL: Development For AAD

The improved sleep quality seen in earlier clinical trials of TNX-102 SL for other disorders suggests TNX-102 SL could potentially be an effective treatment for agitation in Alzheimer's disease. Currently, there are no FDA-approved treatments for AAD, despite a high disease burden and a need for an effective therapy. TNX-102 SL for the treatment of AAD has been designated by the FDA a Fast Track development program, designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. It is anticipated that there will be more frequent meetings and written communication with the FDA regarding the development plan and trial design throughout the entire drug development and review process with the goal to have earlier drug approval and access by patients.

What makes TNX-102 SL unique?

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Scientific Rationale for TNX-102 SL* for the treatment of AAD

Both sleep disturbances and agitation are common and co-morbid features of Alzheimer's disease.3 TNX-102 SL's mechanism of improving sleep quality may be relevant as sleep disturbance is a significant and common symptom in AAD.

  • TNX-102 is a multifunctional agent including antagonism of 5-HT2A, α1-adrenergic and histamine H1 receptors4
  • Certain 5-HT2A antagonists have shown clinical efficacy against agitation in dementia including trazodone5,6 and mirtazapine7
  • The α1-drenergic antagonist prazosin has shown efficacy in the treatment of agitation in dementia8
  • The histamine H1 antagonist hydroxyzine has historical use in treating agitation in dementia9

Development Status

A separate TNX-102 SL IND for AAD has been cleared and has sufficient data to support a Phase 2 study in patients with AAD. Tonix plans to include genomic DNA analysis to identify biomarkers that may be associated with treatment response in the Phase 2 potential pivotal efficacy study in Alzheimer’s disease patients with agitation. A final Phase 2 protocol has been submitted to the FDA for final review and acceptance.

Basis for Exclusivity

Tonix has filed a patent for the use of TNX-102 SL for agitation, psychosis, and cognitive decline in dementia and neurodegenerative diseases (which includes Alzheimer's Disease). TNX-102 SL is also covered by a number of issued and pending worldwide patents which cover the eutectic composition of matter as well as the pharmacokinetic profile. These patents are owned outright by Tonix Pharmaceuticals and no obligations are owed to another party.

*TNX-102-SL (cyclobenzaprine HCl sublingual tablets) is an investigational new drug and has not been approved for any indication.

  1. Canevelli M, Valletta M, Trebbastoni A, Sarli G, D'Antonio F, Tariciotti L, de Lena C, Bruno G. Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches. Front Med (Lausanne). 2016;3:73.
  2. Rose K, Specht J, Forch W. Correlates among nocturnal agitation, sleep, and urinary incontinence in dementia. Am J Alzheimers Dis Other Demen. 2015;30(1):78-84.
  3. Shih YH, Pai MC, Huang YC, Wang JJ. Sundown Syndrome, Sleep Quality, and Walking Among Community-Dwelling People With Alzheimer Disease. J Am Med Dir Assoc. 2017;18(5):396-401.
  4. Daugherty B, Sullivan G, Gershell L, Lederman S. Serotonin receptor profiles of bedtime pharmacotherapies targeting posttraumatic stress disorder (PTSD) [abstract 728]. Biological Psychiatry. 2015;77(Supplement):271S-272S.
  5. Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dement Geriatr Cogn Disord. 2004;17(4):355-359.
  6. Sultzer DL, Gray KF, Gunay I, Berisford MA, Mahler ME. A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia. Am J Geriatr Psychiatry. 1997;5(1):60-69.
  7. Cakir S, Kulaksizoglu IB. The efficacy of mirtazapine in agitated patients with Alzheimer's disease: A 12-week open-label pilot study. Neuropsychiatr Dis Treat. 2008;4(5):963-966.
  8. Wang LY, Shofer JB, Rohde K, Hart KL, Hoff DJ, McFall YH, Raskind MA, Peskind ER. Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression. Am J Geriatr Psychiatry. 2009;17(9):744-751.
  9. Settel E. Clinical observations on the use of hydroxyzine in anxiety-tension states and senile agitation. Am Pract Dig Treat. 1957;8(10):1584-1588.