Full Press Release Details
Tonix Pharmaceuticals Holding Corp. 8-K
Tonix Pharmaceuticals
Announces Publication of Paper in Pharmaceutics on the Enhancing Effect That Magnesium Contributes to in vivo Intranasal
Intranasal Oxytocin with Magnesium Demonstrated
Augmented Craniofacial Analgesia in an Animal Model
Enhanced Effect of Mg2+ is the
Core Patented Technology of TNX-1900 for Migraine
TNX-2900 Orphan Drug Designated Product for
Prader-Willi Syndrome Also Contains Mg2+
Issued Patents Expected to Provide Exclusivity
CHATHAM, N.J., June 21, 2022 - Tonix
Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company,
announced the publication of a paper, entitled "Impact of Magnesium on Oxytocin Receptor Function," in the journal Pharmaceutics,
that described results from a research team led by Professor David Yeomans1. The paper includes data showing the enhancing
effects of magnesium (Mg2+) on the activity of intranasal oxytocin in an animal model of craniofacial pain. The Mg2+
enhanced formulation of intranasal oxytocin is the basis for the Company's TNX-19002 drug candidate in development to
prevent migraine headaches in chronic migraineurs, and TNX-29002 which is in development to treat hyperphagia (over-eating)
in adolescent and young adult patients with Prader-Willi syndrome. Professor Yeomans was the scientific founder of Trigemina, Inc. from
which Tonix acquired rights to the Mg2+enhanced oxytocin technology. Professor Yeomans is a consultant to Tonix and the research
described in the paper was funded in part by Tonix.
"This new paper further evidences the
important role Mg2+ plays in the effect of oxytocin on pain reduction both in vitro and in vivo in an animal
model of head pain," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "Prior to this work, studies
of intranasal oxytocin on pain yielded inconsistent results because the analgesic effect of oxytocin decreased with higher doses, a phenomenon
called high dose inhibition' or colloquially, as an inverted U' shaped dose response. Professor Yeomans and
his team have shown that adding Mg2+ to intranasal oxytocin reduces or eliminates the high dose inhibition ,
such that analgesia increases with higher doses of oxytocin. Consequently, we expect that the Mg2+ enhanced formulation
of intranasal oxytocin in TNX-1900 and TNX-2900 may provide consistent effects to the extent that the Mg2+ component
of the formulation reduces or eliminates the high dose inhibition and may also allow for using higher oxytocin doses."
Professor Yeomans said, "Mg2+
levels modulate the affinity of oxytocin receptor for oxytocin in vitro. We have now confirmed that at above physiological concentrations
Mg2+ increases the activity of oxytocin for oxytocin receptor in vivo. Intranasal oxytocin with Mg2+ demonstrated
augmented craniofacial analgesia in animal models. Critically, we have also demonstrated that, under test conditions, oxytocin has an
inverted U' shaped dose response which Mg2+ can overcome, potentially allowing for the use of higher oxytocin
doses. The potential clinical significance of these observations is that the formulation of oxytocin
plus Mg2+ in Tonix's TNX-1900 and TNX-2900 has the potential to enhance
oxytocin efficacy for pain as well as for other uses."
is excited to develop Mg2+-enhanced
formulation of intranasal oxytocin as a non-addictive treatment for migraine and craniofacial pain
and for the treatment of Prader-Willi Syndrome," added Dr. Lederman. "TNX-1900 will enter Phase 2 for prophylaxis of
chronic migraine in the second half of 2022 and TNX-2900 is in development for treating hyperphagia in Prader Willi syndrome. The
preclinical data that we have seen to date are promising and show that oxytocin, a natural hormone, is capable of blocking the release
of the neurotransmitter calcitonin gene-related peptide (CGRP) in the brain coverings and trigeminal ganglia, thus potentially modulating
a key step in the causation of migraine. It has been shown that intranasally delivered oxytocin selectively reaches the trigeminal
ganglia with low systemic absorption. Overall, we believe that TNX-1900 has the potential to be a non-addicting, non-constipating
and easy to administer alternative to opioids to treat migraine and craniofacial pain. We believe targeted delivery of oxytocin
could translate into selective blockade of CGRP release 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 quickly reversible, in contrast to monthly or
quarterly dosing, giving physicians and their patients greater control."
About Intranasal Oxytocin
Oxytocin is a naturally
occurring human hormone that acts as a neurotransmitter in the brain. Oxytocin has no recognized addiction potential. Oxytocin is approved
by the U.S. Food and Drug Administration (FDA) as Pitocin 3, an intravenous infusion or intramuscular injection drug, for
use in pregnant women to induce labor. An intranasal form of oxytocin was marketed in the U.S. by Novartis to assist in the production
of breast milk as Syntocinon 4 (oxytocin nasal 40 units/ml), but the product was discontinued, and the New Drug Application
(NDA) has been withdrawn.
Migraine is a neurological
condition that manifests in throbbing headache, often on one side of the head, that lasts at least four hours. It can also be accompanied
by nausea, vomiting, visual disturbances, and sensitivity to bright light, strong smells, and loud noises5. Epidemiological
studies indicate that globally, approximately 1.2 billion individuals suffer from migraines annually.6 Approximately
39 million Americans suffer from migraines and among these individuals, approximately four million experience chronic migraines (15 or
more headache days per month).6
(intranasal potentiated oxytocin) is a proprietary formulation of oxytocin and Mg2+ in
development as a candidate for prophylaxis of chronic migraine and for the treatment of craniofacial pain, insulin resistance and related
conditions. In 2020, TNX-1900 was acquired from Trigemina, Inc. TNX-1900 is a drug-device combination product, based on an intranasal
actuator device that delivers oxytocin and Mg2+ into
the nose. It has been observed that low oxytocin levels in the body can lead to increase in migraine headache frequency, and that increased
oxytocin levels can relieve 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 nerve cells which, when activated, release of 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 system8 resulting in binding of oxytocin to receptors on neurons in
the trigeminal system, inhibiting transmission of pain signals and the release of CGRP.9 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 binding10 as well as its effects on trigeminal
neurons and craniofacial analgesic effects in animal models1. Intranasal oxytocin has been well tolerated in several clinical
trials in both adults and children11. 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 antibodies12. For
example, CGRP has roles in dilating blood vessels in response to ischemia, including in the heart. Tonix has licensed technology from
the University of Geneva to use TNX-1900 for the treatment of insulin resistance and related conditions.
About Prader Willi Syndrome
Prader-Willi syndrome is a rare genetic disorder
of failure to thrive in infancy and uncontrolled appetite and obesity in childhood and adulthood with no approved treatments available
that occurs in approximately one in 15,000 births. Prader-Willi syndrome results in physical, mental and behavioral problems. A key feature
of Prader-Willi syndrome in infants is a lack of suckling and poor muscle strength which leads to malnutrition and failure to thrive.
However, paradoxically in children and adults, the key feature of Prader-Willi syndrome is a constant sense of hunger (hyperphagia), which
leads to severe obesity. Intranasal oxytocin improves suckling in newborn animals but also suppresses feeding behaviors in adult animal
TNX-2900 (intranasal potentiated oxytocin)
is a proprietary formulation of oxytocin and Mg2+ in development as a candidate for treatment of hyperphagia in Prader-Willi
syndrome. TNX-2900 is a drug-device combination product, based on an intranasal actuator device that delivers oxytocin and Mg2
into the nose. Tonix licensed technology to treat Prader Willi Syndrome and non-organic failure to thrive disease from Inserm (the French
National Institute of Health and Medical Research). The licensing agreement was negotiated and signed by Inserm Transfert, the private
subsidiary of Inserm, on behalf of Inserm, Aix-Marseille Universit and Centre Hospitalier Universitaire of Toulouse. The co-exclusive
license allows Tonix to expand its intranasal potentiated oxytocin development program to the treatment of Prader-Willi syndrome. The
patents covering the technology are expected to provide market exclusivity for the co-licensees in the U.S. and Europe through 2031, which
exclusivity could be extended after marketing authorization by a Supplemental Protection Certificate in Europe or a Patent Term Extension
in the U.S., independent of other Tonix-held patents covering the formulation and oxytocin potentiation technologies for intranasal administration.
VN, et al., Pharmaceutics. 2022; 14(5):1105. https://doi.org/10.3390/pharmaceutics14051105
TNX-2900 are investigational new drugs and have not been approved for any indication.
a trademark of Par Pharmaceutical, Inc.
a trademark of BGP Products Operations GmbH.