Tonix Pharmaceuticals Initiates Enrollment in Phase 2 PREVENTION' Study of Potentiated Intranasal Oxytocin (TNX-1900) for the Prevention of Migraine Headaches in Chronic Migraineurs Results from Planned Interim Analysis

Tonix Pharmaceuticals Holding Corp. 8-K

Tonix Pharmaceuticals

Initiates Enrollment in Phase 2 PREVENTION' Study of Potentiated Intranasal Oxytocin (TNX-1900) for the Prevention of Migraine

Headaches in Chronic Migraineurs

Results from Planned

Interim Analysis Expected Fourth Quarter 2023

Million in U.S. Suffer from Chronic Migraine

Development of TNX-1900

Also Planned for Treatment of Episodic Migraine

CHATHAM, N.J., Feb. 6,

2023 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical

company, today announced that the first participant was enrolled in the Phase 2 PREVENTION' study of TNX-1900 (intranasal

potentiated oxytocin) for the prevention of migraine headache in chronic migraineurs.

The double-blind, placebo-controlled

study has a target enrollment of 300 participants at approximately 25 sites across the U.S. Results from a planned interim analysis are

expected to be released in the fourth quarter of 2023.

classes of migraine preventatives available, there remains an unmet need for novel approaches with an estimated four million individuals

in the United States suffering from chronic migraine, often a seriously disabling condition," said Seth Lederman, M.D., Chief Executive

Officer of Tonix Pharmaceuticals. "TNX-1900 has a unique, multimodal mechanism of action, that includes an ability to inhibit the

release of the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) in blood vessels within the brain, its lining and

the brainstem, and to suppress signaling in pain neurons. We believe that by engaging and activating oxytocin receptors in the trigeminal

ganglia, TNX-1900 has the potential to help those suffering from chronic migraine. TNX-1900 is a proprietary formulation of oxytocin that

contains magnesium, which Tonix has shown in animal models potentiates the action of oxytocin at oxytocin receptors and potentially improves

the consistency of treatment by reducing paradoxical high-dose inhibition."

Shashidar Kori, M.D.,

former Chief Medical Officer of Trigemina and consultant to Tonix added, "After a decade of development and optimization of our

proprietary oxytocin formulation, it is very gratifying and exciting to enter the next stage of testing required to make TNX-1900 available

to unfortunate chronic migraine sufferers who have few treatment options. This has the potential to improve the quality of life of people

suffering from chronic migraine."

About the Phase 2 PREVENTION Study

The Phase 2 PREVENTION

study is a double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-1900 taken prophylactically

on a daily basis to prevent chronic migraine. There are three arms: two treatment regimens of TNX-1900 and one placebo in a 1:1:1 ratio

in a total of 300 participants across approximately 25 U.S. sites. After a four-week Run-In phase to confirm meeting chronic migraine

criteria, there are 12-weeks of a double-blind Treatment phase with study drug, followed by a 2-week safety Follow-up phase. The primary

efficacy endpoint is mean change in the number of migraine headache days between the 28-day Run-In phase and the last 28-days of the

Treatment phase. Key secondary efficacy endpoints include proportion of patients experiencing a 50% reduction in the number of migraine

headache days, mean change in the number of days using migraine abortive medications, and mean change in a migraine-specific quality

of life measure. An interim analysis is expected to be completed after the first 50% of enrolled patients have completed the study for

the purpose of potential sample size re-estimation, currently anticipated in the fourth quarter of 2023.

For more information, see ClinicalTrials.gov

Identifier: NCT05679908

Migraine is a neurological condition that typically

manifests in a throbbing moderate to severe headache which lasts at least four hours, often on one side of the head and aggravated by

routine physical activity. It can also be accompanied by nausea, vomiting, visual disturbances, and sensitivity to bright light and loud

noises1. Epidemiological studies indicate that globally, approximately 1.2 billion individuals suffer from migraines annually.2 In

the U.S., approximately 39 million Americans suffer from migraines and among these individuals, approximately four million experience

chronic migraines (15 or more headache days per month, at least eight of which are migraines).2 The current FDA approved drugs

for migraine prevention in chronic migraine include Botox (onabotulinumtoxin),

and the anti-CGRP/CGRP-R monoclonal antibodies Aimovig (erenumab), Vyepti (eptinezumab), Ajovy (fremanezumab) and Emgality

TNX-1900 (intranasal potentiated oxytocin)

is a proprietary formulation of oxytocin in development as a candidate for prevention of chronic migraine and other conditions. In 2020,

TNX-1900 was acquired from Trigemina, Inc. who had licensed the technology underlying the composition and method from Stanford University.

TNX-1900 is a drug-device combination product, based on an intranasal actuator device that delivers oxytocin into the nasal cavity. Oxytocin

is a naturally occurring human peptide hormone that also acts as a neurotransmitter in the brain. Oxytocin has no recognized addiction

potential. It has been observed that low oxytocin levels in the body are associated with increases in migraine headache frequency, and

that increased oxytocin levels are associated with fewer migraine headaches. Certain other chronic pain conditions are also associated

with decreased oxytocin levels. Migraine attacks are caused, in part, by the activity of pain-sensing trigeminal neurons which, when activated,

release of calcitonin gene-related peptide (CGRP) which binds to receptors on other nerve cells and starts a cascade of events that is

believed to result in headache. Oxytocin when delivered via the nasal route, concentrates in the trigeminal system3 resulting

in binding of oxytocin to receptors on neurons in the trigeminal system, inhibiting the release of CGRP and transmission of pain signals

returning from the site of CGRP release.4 Blocking CGRP release is a distinct mechanism compared with CGRP antagonist

and anti-CGRP antibody drugs, which block the binding of CGRP to its receptor. With TNX-1900, the addition of magnesium to the oxytocin

formulation enhances oxytocin receptor binding5 as well as its inhibitory effects on trigeminal neurons and resultant

craniofacial analgesic effects, as demonstrated in animal models7. Intranasal oxytocin has been shown to be well tolerated

in several clinical trials in both adults and children6. Targeted nasal delivery results in low systemic exposure and lower

risk of non-nervous system, off-target effects, which could potentially occur with systemic CGRP antagonists such as anti-CGRP antibodies8.

For example, CGRP has roles in dilating blood vessels in response to ischemia, including in the heart. The Company believes nasally targeted

delivery of oxytocin could translate into selective blockade of CGRP release from neurons in the trigeminal ganglion and not throughout

the body, which could be a potential safety advantage over systemic CGRP inhibition. In addition, daily dosing is more rapidly reversible,

in contrast to monthly or quarterly dosing, as is the case with anti-CGRP antibodies, giving physicians and their patients greater control.

In addition to chronic migraine, TNX-1900 will be developed for treatment of episodic migraine, binge eating disorder, craniofacial pain

conditions, and insulin resistance. Tonix also has a license with the University of Geneva to use TNX-1900 for the treatment of insulin

resistance and related conditions.

TNX-2900 is another intranasal

potentiated oxytocin-based therapeutic candidate, being developed for the treatment of Prader-Willi syndrome, or PWS. The technology for

TNX-2900 was licensed from the French National Institute of Health and Medical Research. PWS, an orphan condition, is a rare genetic disorder

of failure to thrive in infancy, associated with uncontrolled appetite later in childhood.

1The International Classification

of Headache Disorders, 3rd Edition. Cephalalgia. 2018. 38(1):1-211.

2Burch et al., Migraine: Epidemiology, Burden, and Comorbidity, Neurol Clin 37 (2019):631-649.

3Yeomans DC, et al. Transl Psychiatry. 2021. 11(1):388.

4Tzabazis A, et al. Cephalalgia. 2016. 36(10):943-50.

5Antoni FA and Chadio SE. Biochem J. 1989. 257(2):611-4.

6Yeomans, DC et al. 2017. US patent US2017368095

7Cai Q, et al., Psychiatry Clin Neurosci. 2018. 72(3):140-151.

8MaassenVanDenBrink A, et al. Trends Pharmacol Sci. 2016. 37(9):779-788

About Tonix Pharmaceuticals Holding Corp.*

Tonix is a clinical-stage biopharmaceutical company focused on discovering,

licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix's portfolio is

composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix's CNS portfolio

includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix's lead CNS candidate,

TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase

3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed

to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022.

TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation

by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the second quarter of 2023. TNX-1900 (intranasal potentiated oxytocin),

a small molecule in development for chronic migraine, entered the clinic with a Phase 2 study in the first quarter of 2023 and interim

data are expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation

of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated