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.
“No medications 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, α1-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.
About TNX-102 SL
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,
α1-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 as a treatment for major
depressive disorder (MDD), that completed enrollment in a Phase 2
proof-of-concept study in the third quarter of 2023, with topline
results expected in the fourth quarter of 2023. TNX-4300
(estianeptine) is a single isomer version of TNX-601, small
molecule oral therapeutic in preclinical development to treat MDD,
Alzheimer’s disease and Parkinson’s disease. Relative to
tianeptine, estianeptine lacks activity on the µ-opioid receptor
while maintaining activity in the rat Novel Object Recognition test
in vivo and the ability to activate PPAR-β/δ and neuroplasticity in
tissue culture. TNX-1900 (intranasal potentiated oxytocin), is in
development for preventing headaches in chronic migraine, and has
completed enrollment in a Phase 2 proof-of-concept study with
topline data expected in the fourth quarter of 2023. TNX-1900 is
also being studied in binge eating disorder, pediatric obesity and
social anxiety disorder by academic collaborators under
investigator-initiated INDs. 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 fourth quarter
of 2023. Tonix’s rare disease development portfolio includes
TNX-2900 (intranasal potentiated oxytocin) for the treatment of
Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug
designation by the FDA. Tonix’s immunology development portfolio
includes biologics to address organ transplant rejection,
autoimmunity and cancer, including TNX-1500, which is a humanized
monoclonal antibody targeting CD40-ligand (CD40L or CD154) being
developed for the prevention of allograft rejection and for the
treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was
initiated in the third quarter of 2023. Tonix’s infectious disease
pipeline includes TNX-801, a vaccine in development to prevent
smallpox and mpox. TNX-801 also serves as the live virus vaccine
platform or recombinant pox vaccine platform for other infectious
diseases. The infectious disease development portfolio also
includes TNX-3900 and TNX-4000, which are classes of broad-spectrum
small molecule oral antivirals.
*Tonix’s product development candidates are
investigational new drugs or biologics and have not been approved
for any indication.
- TNX-102 SL has not been approved
for any indication
- Diagnostic and statistical manual
of mental disorders (5th ed.). American Psychiatric Association. Pg
284
- Dai W, et al. BMC Psychiatry.
2018. 18, 188
- U.S. Department of Veterans
Affairs. Epidemiology and Impact of PTSD.
www.ptsd.va.gov/professional/treat/essentials/epidemiology.asp#one
- Goldstein RB, et al. Soc Psychiatry
Psychiatr Epidemiol. 2016. 51(8):1137-48
- Kessler RC, et al. Arch Gen
Psychiatry. 2005. 62(6):593-602
- U.S. Department of Veteran Affairs.
How Common is PTSD in Adults?
www.ptsd.va.gov/understand/common/common_adults.asp
- Wisco BE, et al. J Clin Psychiatry.
2014. 75(12):1338-46
- Thompson M. Time.
2015;185(12):40-3
- Sullivan GM, et al. Psychiatry Res.
2021. 301:113974
- Rauch SAM, et al. J Clin
Psychiatry. 2021. 82(4)
- Ivanova A, et al. J Biopharm Stat.
2022. 32(3):441-449
- U.S. Department of Veterans
Affairs. PTSD Checklist for DSM-5 (PCL-5).
https://www.ptsd.va.gov/professional/assessment/adult-sr/ptsd-checklist.asp#obtain
Zembrace SymTouch and Tosymra are registered
trademarks of Tonix Medicines. Intravail is a registered trademark
of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis,
Inc. All other marks are property of their respective owners.
This press release and further information about
Tonix can be found at www.tonixpharma.com.
Forward-Looking Statements
Certain statements in this press release are
forward-looking within the meaning of the Private Securities
Litigation Reform Act of 1995. These statements may be identified
by the use of forward-looking words such as “anticipate,”
“believe,” “forecast,” “estimate,” “expect,” and “intend,” among
others. These forward-looking statements are based on Tonix's
current expectations and actual results could differ materially.
There are a number of factors that could cause actual events to
differ materially from those indicated by such forward-looking
statements. These factors include, but are not limited to, risks
related to the failure to obtain FDA clearances or approvals and
noncompliance with FDA regulations; risks related to the failure to
successfully market any of our products; risks related to the
timing and progress of clinical development of our product
candidates; our need for additional financing; uncertainties of
patent protection and litigation; uncertainties of government or
third party payor reimbursement; limited research and development
efforts and dependence upon third parties; and substantial
competition. As with any pharmaceutical under development, there
are significant risks in the development, regulatory approval and
commercialization of new products. Tonix does not undertake an
obligation to update or revise any forward-looking statement.
Investors should read the risk factors set forth in the Annual
Report on Form 10-K for the year ended December 31, 2022, as filed
with the Securities and Exchange Commission (the “SEC”) on March
13, 2023, and periodic reports filed with the SEC on or after the
date thereof. All of Tonix's forward-looking statements are
expressly qualified by all such risk factors and other cautionary
statements. The information set forth herein speaks only as of the
date thereof.
Investor Contact
Jessica MorrisTonix
Pharmaceuticalsinvestor.relations@tonixpharma.com (862)
904-8182
Peter VozzoICR
Westwickepeter.vozzo@westwicke.com (443) 213-0505
Media Contact
Ben ShannonICR
Westwickeben.shannon@westwicke.com(919) 360-3039
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