Tonix Pharmaceuticals Announces Department of Defense Grant to Support the University of North Carolina's Proposed Investigator Sponsored OASIS Trial of TNX-102 SL for Treatment of Acute Stress Reaction, Acute Stress Dis

Tonix Pharmaceuticals Holding Corp. 8-K

Tonix Pharmaceuticals Announces Department

of Defense Grant to Support the University of North Carolina's Proposed Investigator Sponsored OASIS Trial of TNX-102 SL for Treatment

of Acute Stress Reaction, Acute Stress Disorder, and Posttraumatic Stress Disorder

$3 million awarded by DoD to University of North

Carolina Institute of Trauma Recovery to support a proposed 180-patient, randomized, placebo-controlled trial in acute trauma patients

Investigator sponsored trial to evaluate the potential

for TNX-102 SL1 to reduce the frequency and severity of acute stress reaction, acute stress disorder, and post-traumatic stress

Acute stress disorder is identified in 13-21% of

motor vehicle accidents;2,3 Individuals with acute stress disorder have an increased risk of developing PTSD; U.S. lifetime

PTSD prevalence is approximately 6%4-7

CHATHAM, N.J., September

27, 2023 - Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company, today announced

that the University of North Carolina (UNC) Institute for Trauma Recovery has been awarded a $3 million grant from the Department of Defense

(DoD) to investigate the potential of Tonix's TNX-102 SL (cyclobenzaprine HCl sublingual tablets) to reduce the frequency and severity

of adverse effects of acute trauma. Such adverse effects include acute stress reaction (ASR), acute stress disorder (ASD), and posttraumatic

stress disorder (PTSD). ASR refers to the body's immediate response to trauma, whereas ASD represents the short-term effects of

trauma, and PTSD represents the long-term effects of trauma.

"In addition to emergency care to treat

and help patients recover from physical wounds, whether in the emergency room or on the battlefield, we must also address the unmet need

for treatment options to address invisible wounds' that survivors may experience following a traumatic event," said

Samuel McLean, M.D., Professor of Psychiatry and Emergency Medicine at the UNC School of Medicine at UNC, School of Medicine, and lead

principal investigator of the proposed study. "To address these needs, we are investigating TNX-102 SL as a potential treatment

for patients who experience trauma and traumatic stress."

The proposed Optimizing Acute Stress

reaction Interventions with TNX-102 SL (OASIS) trial will examine the safety and efficacy of TNX-102 SL to reduce adverse

posttraumatic neuropsychiatric sequelae among patients presenting to the emergency department after a motor vehicle collision. The trial

will enroll approximately 180 trauma survivors at study sites around the U.S. Participants will be randomized in the emergency department

to receive a two-week course of either TNX-102 SL or placebo.

Initiation of patient enrollment in the proposed investigator

sponsored OASIS trial is anticipated in the beginning of 2024, subject to Investigational New Drug (IND) application submission and U.S.

Food and Drug Administration (FDA) clearance.

The OASIS trial will build upon a foundation of knowledge

and infrastructure developed through the UNC-led, $40 million AURORA initiative. The AURORA study is a major national research initiative

to improve the understanding, prevention, and recovery of individuals who have experienced a traumatic event. AURORA is supported by funding

from the National Institutes of Health (NIH), leading brain health nonprofit One Mind, private foundations, and partnerships with leading

tech companies such as Mindstrong Health and Verily Life Sciences, the health care arm of Google's parent company Alphabet.

are currently available at or near the point of care to treat patients suffering from traumatic events and support long-term health, whether

U.S. military exposed to life-threatening events or civilians experiencing traumatic events such as motor vehicle collisions," said

Seth Lederman, M.D., Chief Executive Officer of Tonix. "Acute stress reaction and posttraumatic stress symptoms are common among

civilian motor vehicle collision survivors. The AURORA study, which has collected thousands of data points from motor vehicle collisions,

will allow us to better investigate the correlation between motor vehicle collisions and the emergence of acute stress disorder or PTSD

symptoms. And leveraging support from the AURORA study and utilizing the DoD's non-dilutive capital to primarily fund OASIS allows

Tonix and UNC to streamline trial efficiency, reduce costs and increase trial power through enriching the target patient population."

Added Brandon Staglin, President of One Mind, "For

individuals who experience trauma and traumatic stress, the need for effective treatments is an urgent one. The OASIS trial's focus

on evaluating a promising potential treatment option exemplifies the kind of evidence-based outcomes One Mind and our partners hoped to

achieve as part of the AURORA initiative's broader efforts to improve the lives of trauma survivors."

Acute and chronic stress disorders can affect both

civilian and military populations. According to the National Center for PTSD, in the U.S. about 60% of men and 50% of women experience

at least one trauma in their lives.5 In the U.S. alone, one-third of emergency department visits (40-50 million patients

per year) involve evaluation after trauma exposures, and in a 2014 study involving 3,157 US veterans, 87% reported exposure to at least

one potentially traumatic event during their service.8 Moreover, as many as 500,000 U.S. troops who served in wars between

2001 and 2015 were diagnosed with PTSD.9

About TNX-102 SL in Post-Traumatic Stress Disorder

Sleep disturbances in PTSD are a potential target for pharmacotherapy. TNX-102 SL is a sublingual formulation of cyclobenzaprine designed

for once-daily bedtime dosing and rapid transmucosal absorption such that cyclobenzaprine plasma levels rapidly rise during the onset

of sleep and first four hours of sleep, then rapidly fall through the second half of sleep through awakening. Cyclobenzaprine has potent

binding and antagonist activity at 5-HT2A, 1-adrenergic, H1-histaminergic, and M1 muscarinic

receptors, each of which play roles in the pharmacological management of insomnia. The sublingual transmucosal formulation of cyclobenzaprine

is designed to bypass first-pass hepatic metabolism, increasing the ratio in plasma of the parent

cyclobenzaprine to the long-lived active metabolite, norcyclobenzaprine, which has a longer half-life and consequently less circadian

variation with once-daily dosing. The use of TNX-102 SL 5.6 mg administered daily at bedtime to reduce PTSD symptoms and improve

sleep quality in patients with PTSD is supported by the results of a Phase 2 trial (AtEase NCT02277704 in military-related PTSD) and

two Phase 3 trials (HONOR or NCT03062540 in military-related PTSD and RECOVERY

or NCT03841773 in PTSD). 10-12 In each of these studies, early

improvements in sleep were associated with TNX-102 SL treatment as measured by the PROMIS sleep disturbance (SD) scale. Moreover, in

AtEase and HONOR, early and sustained improvement in sleep were associated with TNX-102 SL treatment by the Clinician Administered PTSD

Scale (CAPS-5)13 "sleep disturbance" item. Primary analyses comparing change from baseline CAPS-5 total severity

between TNX-102 SL 5.6 mg and placebo at week 12 were not significant in AtEase, HONOR or RECOVERY. However, in HONOR and RECOVERY at

week 4, TNX-102 SL treatment was associated with an improvement in CAPS-5 total severity as compared to placebo. Moreover, secondary

analyses in all three studies showed TNX-102 SL treatment was associated with benefits on the patient global impression of change (PGIC),

indicating that across studies TNX-102 SL treated patients self-reported greater symptom improvement than those treated with placebo.

The most common side-effects were administration site reactions described as tongue numbness or abnormal taste and reported by approximately

30% of participants. There were no unexpected safety findings. Together these studies, with approximately 650 trauma-exposed patients

(included 254 patients treated with TNX-102 SL 5.6 mg), provide preliminary evidence that TNX-102 SL is well-tolerated and may promote

recovery from PTSD via a pharmacodynamic mechanism of sleep-dependent emotional memory processing.

TNX-102 SL is a patented sublingual tablet formulation

of cyclobenzaprine hydrochloride which provides rapid transmucosal absorption and reduced production of a long half-life active metabolite,

norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities

at the 5-HT2A-serotonergic, 1-adrenergic, H1-histaminergic, and M1-muscarinic receptors, TNX-102 SL is in development as a daily

bedtime treatment for fibromyalgia, Long COVID (formally known as post-acute sequelae of COVID-19 [PASC]), alcohol use disorder and agitation

in Alzheimer's disease. The United States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408 in May 2017,

Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No. 10736859 in August

2020. The Protectic protective eutectic and Angstro-Technology formulation claimed in the patent are important elements

of Tonix's proprietary TNX-102 SL composition. These patents are expected to provide TNX-102 SL, upon NDA approval, with U.S. market

exclusivity until 2034/2035.

Tonix Pharmaceuticals Holding Corp.*

Tonix is a biopharmaceutical company focused on commercializing,

developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial

subsidiary markets Zembrace SymTouch (sumatriptan injection) 3 mg and Tosymra (sumatriptan nasal spray)

10 mg under a transition services agreement with Upsher-Smith Laboratories from whom the products were acquired on June 30, 2023. Zembrace

SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix's development

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

CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions.

Tonix's lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the

management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with

topline data expected in the fourth quarter of 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic

post-acute COVID-19 condition. Enrollment in a Phase 2 proof-of-concept study has been completed, and topline results were reported in

the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily oral formulation being developed