Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the
Company), a biopharmaceutical company with marketed products and a
pipeline of development candidates, today announced that the first
participant was enrolled in an investigator-initiated Phase 2 study
of TNX-1900 (intranasal potentiated oxytocin) for improving bone
health in children with autism spectrum disorder (ASD), named the
BOX study, at Massachusetts General Hospital (MGH). The aim of this
Department of Defense-funded study is to investigate the efficacy
and safety of TNX-1900 as a novel therapeutic agent to increase
bone density and improve bone structure and strength in children
with ASD. Tonix is providing active drug and placebo for the BOX
study as part of a drug donation agreement with MGH. MGH is the
sponsor of the trial, which is being conducted under an
investigator-initiated investigational new drug (IND) application.
“Low bone density in ASD is a serious problem,”
said Seth Lederman, M.D., Chief Executive Officer of Tonix
Pharmaceuticals. “Intranasal potentiated oxytocin is a potential
treatment option that addresses the biology of bone loss specific
to ASD which is different from osteoporosis in post-menopausal
women. Intranasal oxytocin has a long history of being tested for
the treatment of ASD, but results have been inconsistent. Tonix’s
magnesium-potentiated intranasal oxytocin is designed to improve
consistency in clinical effects, because it reduces the ‘high-dose’
inhibition seen in the ‘inverted U’ dose response in animals.”2
Madhusmita Misra, M.D., MPH, Chief, Division of
Pediatric Endocrinology, Department of Pediatrics, Mass General for
Children, and principal investigator of the study said, “The
childhood and adolescent years are critical for bone mass accrual
towards achievement of peak bone mass, a key determinant of future
bone health and fracture risk. Preliminary data show that over a
four-year period, children with ASD fail to catch-up with typically
developing children for bone health measures despite optimizing
calcium and vitamin D intake3. The difference between these groups
often becomes more drastic over time.”
Elizabeth A. Lawson, M.D., M.M.Sc., Director,
Interdisciplinary Oxytocin Research Program in the Neuroendocrine
Unit, Department of Medicine, MGH, who is a co-investigator on the
study continued, “Preclinical studies indicate that, in addition to
its known central prosocial effects,4 oxytocin is an important
mediator of bone homeostasis, promoting bone formation over
resorption.5-7 Pilot data indicate strong associations between low
levels of oxytocin and worse bone health in both sexes and across
clinical populations, supporting the critical role of oxytocin in
bone metabolism.”8-11
“Preclinical studies and some clinical trials
have shown prosocial effects of oxytocin in individuals with
autism,” reported Ann Neumeyer, M.D., Medical Director of Lurie
Center for Autism, Department of Pediatrics and Neurology, Mass
General for Children and also a co-investigator. “This research
study will further investigate effects of oxytocin on social
impairment associated with autism as a secondary
outcome.”12
Dr. Lederman continued, “Given the increasing
prevalence of ASD in children and its association with impaired
bone health, lower oxytocin levels in those with ASD than
neurotypical controls, and preclinical data showing that oxytocin
can favorably impact bone health, a study examining the role of
oxytocin in improving bone health in children with ASD is both
timely and essential.”
The Phase 2 investigator-initiated BOX study is
a randomized, placebo-controlled study to evaluate the effects of
twice daily administration of TNX-1900 on bone measures in children
with ASD. Study subjects, ages six to 18 years old, will be
randomized 1:1 to receive TNX-1900 twice per day or placebo for 12
months in the double-blind phase, followed by a six-month open
label phase during which all study subjects will receive TNX-1900
twice daily. The primary endpoint is the difference between
TNX-1900 compared to placebo groups in 12-month change in whole
body less head bone mineral density Z-scores. A Z-score compares
one’s bone density to the average bone density of age and gender
matched controls.
- John S and Jaeggi,
AV. Autism. 2021. 25:2152-2161.
- Bharadwaj VN, et
al. Pharmaceutics. 2022. 14(5):1105.
- Neumeyer AM, et al.
J Pediatr. 2017. 181:195-201 e196.5274559
- Marsh N, et al.
Neuroscientist. 2021. 27(6):604-619.
- Tamma R, et al.
Proc Natl Acad Sci U S A. 2009. 106:7149-7154.
- Colucci S, et al.
Biochem Biophys Res Commun. 2002. 297:442-445.
- Copland JA, et al.
Endocrinology. 1999. 140:4371-4374.
- Fazeli PK, et al. J
Clin Psychiatry. 2018. 79:17m11585.
- Lawson EA, et al. J
Clin Psychiatry. 2011. 72:1546-1551.
- Aulinas A, et al.
Neuroendocrinology. 2021. 111:87-98.
- Bachrach LK. Trends
Endocrinol Metab. 2001. 12:22-28.
- Hu L, et al. Eur J Clin Pharmacol. 2023. doi:
10.1007/s00228-023-03545-w. Epub ahead of print. PMID:
37540265.
About TNX-1900
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 within the central nervous
system (CNS). 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 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
system1 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.2 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
binding3 as well as oxytocin’s inhibitory effects on trigeminal
neurons and resultant craniofacial analgesic effects, as
demonstrated in animal models4. Intranasal oxytocin has been shown
to be well tolerated in several clinical trials in both adults and
children5. Targeted nasal delivery results in low systemic exposure
and lower risk of non-CNS, off-target effects, which could
potentially occur with systemic CGRP antagonists such as anti-CGRP
antibodies6. 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 patients greater control. In addition to chronic
migraine, TNX-1900 will be developed for treatment of episodic
migraine, binge eating disorder, and craniofacial pain conditions.
Tonix also has a license with the University of Geneva for the use
of TNX-1900 in the treatment of insulin resistance and related
conditions.
About TNX-2900
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.
1. Yeomans DC, et al. Transl Psychiatry. 2021.
11(1):388.2. Tzabazis A, et al. Cephalalgia. 2016. 36(10):943-50.3.
Antoni FA and Chadio SE. Biochem J. 1989. 257(2):611-4.4. Cai Q, et
al., Psychiatry Clin Neurosci. 2018. 72(3):140-151.5. Yeomans, DC
et al. 2017. US patent US20173680956. MaassenVanDenBrink A, et al.
Trends Pharmacol Sci. 2016. 37(9):779-788
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, LLC 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 late December 2023.
TNX-102 SL is also being developed to treat fibromyalgia-type Long
COVID, a chronic post-acute COVID-19 condition, and topline results
were reported in the third quarter of 2023. TNX-1900 (intranasal
potentiated oxytocin), is in development as a preventive treatment
in chronic migraine, and enrollment has completed in a Phase 2
proof-of-concept study with topline data expected in early December
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, including TNX-1800, in development as a vaccine to
protect against COVID-19. During the fourth quarter of 2023,
TNX-1800 was selected by the U.S. National Institutes of Health
(NIH), National Institute of Allergy and Infectious Diseases
(NIAID) Project NextGen for inclusion in Phase 1 clinical trials.
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.
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, including the intended use of
proceeds from the public offering and other statements that are
predictive in nature. 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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