Proof of concept data from Phase 2 study for prevention of migraine headache expected in early December 2023
CHATHAM, N.J., Oct. 04, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, announced today that the European Patent Office (EPO) issued European Patent No. 3242676 to the Company on October 4, 2023. The patent, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use”, claims methods and compositions for treating pain, including migraine headaches, using intranasal magnesium-containing oxytocin formulations. This patent, excluding possible patent term extensions, is expected to provide Tonix with market exclusivity in the member states of the European Patent Office until 2036. The U.S. Patent and Trademark Office (USPTO) has previously issued U.S. Patents No. 9,629,894 and 11,389,473 which are expected to provide market exclusivity in the U.S. until 2036.
In August 2023, Tonix announced it completed enrollment in its proof-of-concept Phase 2 PREVENTION study of TNX-1900 (intranasal potentiated oxytocin) for the prevention of migraine headache in chronic migraineurs with a total of 88 patients enrolled. The Company expects topline results from this trial in early December 2023.
“We believe this European patent combined with the U.S. issuance provides a strong patent position for TNX-1900 as we move forward in clinical development for the treatment of chronic migraine,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “With a differentiated formulation including magnesium, which Tonix has shown to potentiate the action of oxytocin at oxytocin receptors in animal models, we believe TNX-1900 has the potential to help those chronic migraine sufferers by engaging and stimulating oxytocin receptors in the trigeminal ganglia. By expanding our patent coverage in Europe, we are ensuring the IP protection of this unique approach.”
In addition to Tonix’s patents that protect certain uses including treating migraine, Tonix has licensed patents from INSERM, the French national health and medical research institute, that claim methods of treating feeding disorders with onset during neonatal development, specifically Prader Willi syndrome and non-organic failure to thrive (NOFTT), using oxytocin (EP 2575853, US8853158 and US9125862) and licensed patents from University of Geneva that claim methods of treating insulin resistance using oxytocin (US9101569 and EP2571511).
About Migraine
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 noises.1 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).2
About TNX-1900
TNX-1900 (intranasal potentiated oxytocin) is a proprietary formulation of oxytocin 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. 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 nose. Oxytocin is a naturally occurring human hormone that acts as a neurotransmitter in the brain. Oxytocin has no recognized addiction potential. It has been observed that low oxytocin levels in the body can lead to an 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 the 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 transmission of pain signals and releasing of the CGRP.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 formula enhances oxytocin receptor binding5, its effects on trigeminal neurons, and its craniofacial analgesic effects in animal models.7 Intranasal oxytocin has been shown to be well tolerated in several clinical trials in both adults and children.6 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 antibodies.8 For example, CGRP has roles in dilating blood vessels in response to ischemia, including in the heart. We believe nasally 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, as is the case with anti-CGRP antibodies, giving physicians and their patients greater control.
Burch et al., Migraine: Epidemiology, Burden, and Comorbidity, Neurol Clin 37 (2019) 631–649.
Yeomans DC, et al. Transl Psychiatry. 2021. 11(1):388.
Tzabazis A, et al. Cephalalgia. 2016. 36(10):943-50.
Antoni FA and Chadio SE. Biochem J. 1989. 257(2):611-4.
Yeomans, DC et al. 2017. US patent US2017368095
Cai Q, et al., Psychiatry Clin Neurosci. 2018. Mar;72(3):140-151.
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. 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 early November 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 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. 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. 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.
CHATHAM, N.J., Sept. 28, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (“Tonix” or the “Company”), a biopharmaceutical company, today announced it has entered into securities purchase agreements with healthcare focused institutional investors for the purchase and sale of 9,000,000 shares of its common stock (or common stock equivalents in lieu thereof) together with Series A warrants to purchase up to an aggregate of 9,000,000 shares of common stock and Series B warrants to purchase up to an aggregate of 9,000,000 shares of common stock in a public offering at a combined offering price of $0.50 per share (or common stock equivalents in lieu thereof) and accompanying Series A and Series B warrant. The Series A and Series B warrants will have an exercise price of $0.50 per share, will be exercisable immediately, and will expire in five years and one year, respectively. The closing of the public offering is expected to take place on or about October 3, 2023, subject to the satisfaction of customary closing conditions.
The gross proceeds of the offering will be approximately $4.5 million before deducting placement agent fees and other estimated offering expenses payable by the Company. The Company intends to use the net proceeds from the offering for working capital and general corporate purposes, the build out of the Company’s manufacturing and research and development facilities, and the acquisition or licensing of approved products and products in development.
A.G.P./Alliance Global Partners is acting as lead placement agent for the offering.
Brookline Capital Markets, a division of Arcadia Securities, LLC is acting as co-placement agent for the offering.
This offering is being made pursuant to an effective shelf registration statement on Form S-3 (File No. 333-254975) previously filed with the U.S. Securities and Exchange Commission (the “SEC”). The offering will be made only by means of a prospectus supplement and accompanying base prospectus, as may be further supplemented by any free writing prospectus and/or pricing supplement that Tonix may file with the SEC. A preliminary prospectus supplement and accompanying prospectus describing the terms of the proposed offering have been filed with the SEC and are available on the SEC’s website located at http://www.sec.gov. Electronic copies of the final prospectus supplement may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at prospectus@allianceg.com. Before investing in this offering, interested parties should read in their entirety the prospectus supplement and the accompanying prospectus and the other documents that Tonix has filed with the SEC that are incorporated by reference in such prospectus supplement and the accompanying prospectus, which provide more information about Tonix and such offering.
This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.
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 markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg. 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 CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with topline data expected in the first quarter of 2024. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 study has been completed, and topline results are expected in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation being developed as a treatment for major depressive disorder (MDD), is also currently enrolling with topline results expected in the first quarter of 2024. TNX-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. TNX-1900 (intranasal potentiated oxytocin), in development for chronic migraine, is currently enrolling with topline data expected in the fourth quarter of 2023. 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 third 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 is expected to be 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, 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.
Tonix Medicines has contracted to acquire the Zembrace SymTouch and Tosymra registered trademarks. Intravail is a registered trademark of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis, Inc.
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 those relating to the completion of the public offering, the satisfaction of customary closing conditions, the intended use of proceeds from the public offering and other statement 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.
CHATHAM, N.J., Sept. 28, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (“Tonix” or the “Company”), a biopharmaceutical company, today announced that it intends to offer and sell shares of its common stock (or common stock equivalents in lieu thereof) and warrants to purchase shares of common stock in a public offering. All of the securities to be sold in the offering are to be offered by Tonix. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.
The Company intends to use the net proceeds from the offering for working capital and general corporate purposes, the build out of the Company’s manufacturing and research and development facilities, and the acquisition or licensing of approved products and products in development.
A.G.P./Alliance Global Partners is acting as lead placement agent for the offering. Brookline Capital Markets, a division of Arcadia Securities, LLC is acting as co-placement agent for the offering.
This offering is being made pursuant to an effective shelf registration statement on Form S-3 (File No. 333-254975) previously filed with the U.S. Securities and Exchange Commission (the “SEC”). The offering will be made only by means of a prospectus supplement and accompanying prospectus. The preliminary prospectus supplement and accompanying prospectus describing the terms of the proposed offering will be filed with the SEC and will be available on the SEC’s website located at http://www.sec.gov. Electronic copies of the preliminary prospectus supplement may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at prospectus@allianceg.com. Before investing in this offering, interested parties should read in their entirety the prospectus supplement and the accompanying prospectus and the other documents that Tonix has filed with the SEC that are incorporated by reference in such prospectus supplement and the accompanying prospectus, which provide more information about Tonix and such offering.
This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.
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.
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.
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 those relating to the completion of the public offering, the timing and size of the public offering, the intended use of proceeds from the public offering and other statement 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.
$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 disorder (PTSD)
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., Sept. 27, 2023 (GLOBE NEWSWIRE) — 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
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.
mTNX-1700 (mTFF2-MSA) suppresses tumor growth and increases survival rates in preclinical colorectal cancer models
mTNX-1700 shows single agent activity and additive effects in combination with anti-PD-1
mTNX-1700 targets myeloid-derived suppressor cells (MDSCs) in a novel mechanism to treat cancer
CHATHAM, N.J., Sept. 21, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced a poster presentation showing research results for mTNX-1700 (murine trefoil factor family member 2- murine serum albumin, or mTFF2-MSA) at the Seventh International Cancer Immunotherapy Conference 2023 (CICON23): Translating Science into Survival, being held September 20-23, 2023, in Milan, Italy. The poster is available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com.
The poster presentation, titled, “mTFF2-MSA (mTNX-1700) Suppresses Tumor Growth and Increases Survival in Anti-PD-1 Treated CT26.WT Subcutaneous and CT26-Luciferase Orthotopic Syngeneic Colorectal Cancer Models by Targeting MDSCs in BALB/C Mice,” includes data demonstrating that the novel fusion protein, mTNX-1700 has single agent activity and can improve on the therapeutic effects of anti-PD-1 in treating syngeneic mouse models of advanced colorectal cancer. In two models, mTNX-1700 increases survival rates and suppresses tumor growth. Additive tumor growth suppression effects were observed when mTNX-1700 and anti-PD-1 were used in combination.
“mTNX-1700 is a novel fusion protein that has single agent activity and augments PD-1 blockade therapy in combination therapy in advanced and metastatic syngeneic mouse models of colorectal and gastric cancer,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Certain cancers are unresponsive to anti-PD-1 therapy. Despite the significance of PD-1 checkpoint blockade in treating many types of cancer, there’s a need to better understand why some cancers don’t respond and how to make them responsive. We believe these data show the potential of TNX-1700 in treating cancer both as a single agent and in combination with other immuno-oncology drugs, particularly anti-PD-1, and highlight how mTNX-1700 targets MDSCs as a novel mechanism to treat cancer.”
About Trefoil Factor Family Member 2 (TFF2)
Human TFF2 is a secreted protein, encoded by the TFF2 gene in humans, that is expressed in gastrointestinal mucosa where it functions to protect and repair mucosa. TFF2 is also expressed at low levels in splenic immune cells and is now appreciated to have intravascular roles in the spleen and in the tumor microenvironment. In gastric cancer, TFF2 is epigenetically silenced, and TFF2 is suggested to be protective against cancer development through several mechanisms. Tonix is developing TNX-1700 (rTFF2-HSA) for the treatment of gastric and colon cancers under a license from Columbia University. The inventor of the core technology at Columbia is Dr. Timothy Wang, who is an expert in the molecular mechanisms of carcinogenesis whose research has focused on the carcinogenic role of inflammation in modulating stem cell functions. Dr. Wang demonstrated that knocking out the mTFF2 gene in mice leads to faster tumor growth and that overexpression of TFF2 markedly suppresses tumor growth by curtailing the homing, differentiation, and expansion of MDSCs to allow activation of cancer-killing CD8+ T cells.1 He went on to show that a novel engineered form of recombinant murine TFF2 (mTFF2-CTP) had an extended half-life in vivo and was able to suppress MDSCs and tumor growth in an animal model of colorectal cancer. Later, he showed in gastric cancer models that suppressing MDSCs using chemotherapy enhances the effectiveness of anti-PD1 therapy and significantly reduces tumor growth.2 Dr. Wang proposed the concept of employing rTFF2 in combination with other therapies in cancer prevention and early treatment. Dr. Wang presented data at the American Association for Cancer Research (AACR) conference as a collaboration between Tonix and Columbia University in 2020 that includes data from a preclinical study which investigated the role of PD-L1 in colorectal tumorigenesis and evaluated the utility of targeting myeloid-derived suppressor cells (MDSCs) in combination with PD-1 blockade in mouse models of colorectal cancer. The data show that anti-PD-1 monotherapy was unable to evoke anti-tumor immunity in this model of colorectal cancer, but mTFF2-CTP augmented the efficacy of anti-PD-1 therapy. Anti-PD-1 in combination with TFF2-CTP showed greater anti-tumor activity in PD-L1-overexpressing mice.
1Dubeykovskaya ZA et al, Nat Commun 2016 2Kim W et al, Gastroenterology 2021
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 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 fourthquarter 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.
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.
Oxytocin receptors and CGRP are co-expressed on human trigeminal ganglia neurons and their expression is increased in inflammation
Human tissue data support the proposed mechanism of action of TNX-1900 in treating headache: oxytocin treatment blocks the release of CGRP
CHATHAM, N.J., Sept. 18, 2023 (GLOBE NEWSWIRE) — 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 David C. Yeomans, Ph.D. presented data relevant to the proposed mechanism of TNX-1900 (intranasal potentiated oxytocin) in treating chronic migraine in a poster and an oral presentation at the 2023 International Headache Congress (IHC), being held September 14-17, 2023, in Seoul, South Korea. The poster and oral presentation titled, “Human trigeminal ganglia possess oxytocin receptors on CGRP positive neurons: expression increased by inflammation,” include research sponsored by and licensed to Tonix Pharmaceuticals. Professor Yeomans was a founder of Trigemina, which Tonix acquired, and he remains a consultant to Tonix. A copy of the poster is available under the Scientific Presentations tab of the Tonix Pharmaceuticals corporate website at www.tonixpharma.com.
The presentations show that oxytocin receptors are co-expressed with calcitonin gene-related peptide (CGRP) on human trigeminal ganglia neurons, which is similar to Professor Yeomans’ previous findings in animal trigeminal ganglia. The inflammatory cytokine IL-6 upregulated expression of oxytocin receptors on human trigeminal neurons, consistent with the previously observed impact of inflammation on the potency of oxytocin. In animals, oxytocin has been shown to functionally inhibit the excitability of trigeminal neurons, which is consistent with oxytocin inhibiting the release of CGRP at trigeminal nerve terminals.1
“In animal studies, oxytocin has been shown to inhibit trigeminal neurons which we believe relates to its mechanism in preventing migraines,”1 said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “The data presented at 2023 IHC by Professor Yeomans shows that oxytocin receptors are present on human trigeminal ganglia neurons, and that these same neurons express CGRP, a key peptide in the pathogenesis of migraine. These data support the proposed mechanism of TNX-1900, which we believe inhibits the release of CGRP from trigeminal neurons that otherwise would trigger a cascade leading to migraine.”
“Similar to animals, human trigeminal ganglia neurons express oxytocin receptors and also co-express CGRP,” said Professor Yeomans. “In addition, the inflammatory mediator IL-6 induces robust upregulation of oxytocin receptors on human trigeminal ganglia neurons. In the presence of inflammation, which is persistently present in chronic migraine, there is a robust increase in the expression of both oxytocin receptors and CGRP in human trigeminal neurons.”
In February 2023, Tonix initiated enrollment in the Phase 2 ‘PREVENTION’ study of TNX-1900 for the prevention of migraine headache in chronic migraineurs. Topline results from the study are expected in the fourth quarter of 2023. In addition, TNX-1900 is also being evaluated in investigator-initiated Phase 2 trials in adolescent obesity (initiated July 2023), binge eating disorder and social anxiety disorder.
Tzabazis A, et al. Cephalalgia. 2016. 36(10):943-50.
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 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. Topline results from a proof-of-concept Phase 2 study 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, a 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.
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.
CHATHAM, N.J., Sept. 14, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced a poster presentation at the Seventh International Cancer Immunotherapy Conference 2023 (CICON23): Translating Science into Survival. The Conference is being held September 20-23, 2023, in Milan, Italy. A copy of the poster will be made available on the Tonix Pharmaceuticals website following the presentation at www.tonixpharma.com.
Poster Presentation Details
Title:
mTFF2-MSA (mTNX-1700) Suppresses Tumor Growth and Increases Survival in Anti-PD-1 Treated CT26.WT Subcutaneous and CT26-Luciferase Orthotopic Syngeneic Colorectal Cancer Models by Targeting MDSCs in BALB/C Mice
Authors:
Bruce L. Daugherty, Rebecca J. Boohaker, Rebecca Johnstone, Karr Stinson, Grace Zhao, Mingfa Zang, Jin Qian, Timothy C. Wan, Seth Lederman
Session Date:
September 21, 2023
Session Time:
12:30 p.m. – 2:00 p.m
Poster Number:
P220
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 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 third 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.
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.
Tosymra Nasal Spray 10 mg is a Proprietary Acute Migraine Treatment Approved Under the 505(b)2 Pathway Based on Bioequivalence to Imitrex (sumatriptan) Injection 4 mg
GlaxoSmithKline Recently Notified FDA that it will Discontinue Imitrex Nasal Spray 5 mg and 20 mg Products after January 2024
CHATHAM, N.J., Sept. 06, 2023 (GLOBE NEWSWIRE) — 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 it is committed to meeting potential increased demand for Tosymra® (sumatriptan) nasal spray 10 mg after GlaxoSmithKline’s (GSK) planned discontinuation of Imitrex (sumatriptan) nasal spray 5 mg and 20 mg products after January, 2024.
On August 8, 2023, GSK informed the U.S. Food and Drug Administration (FDA) of its plan to discontinue Imitrex nasal spray 5 mg and 20 mg doses after January 31, 2024. The notification is posted on the FDA Drug Shortages website.1 Tonix is preparing for potential increased demand for Tosymra (sumatriptan nasal spray) 10 mg to help avoid possible drug shortages for patients who suffer from migraines. Tosymra nasal spray is approved on the basis of bioequivalence to Imitrex injection 4 mg.
Drug shortages have presented an ongoing challenge for the U.S. healthcare system, reaching near-record levels2 in recent months, causing treatment delays and rationing. Tonix is ready to step in to alleviate potential shortages in sumatriptan, a widely used treatment option for acute migraine.
“In response to FDA outreach, we have confirmed our commitment to meet potential increased demand for sumatriptan nasal spray from patients who suffer from migraines,” said Seth Lederman, M.D., President and Chief Executive Officer of Tonix. “While Tosymra nasal spray and Imitrex nasal spray are not substitutable at the pharmacy, we plan to alert providers to the possibility of prescribing Tosymra for patients who may benefit from a nasal spray formulation of sumatriptan.”
The American Headache Society Consensus Statement on migraine treatments recommends that “a non-oral formulation should be used in patients whose attacks are associated with severe nausea or vomiting, who do not respond well to traditional oral treatments, or who have trouble swallowing orally administered medications.”3 Approximately 73% of migraine patients have been reported to experience nausea with or without vomiting during their attacks.4
“Intranasal sumatriptan is an important therapy for those who suffer from migraines. We believe Tosymra is differentiated from other intranasal formulations of sumatriptan, which are generic equivalents to Imitrex nasal spray because of its proprietary Intravail® absorption enhancer technology,” said James Hunter, Executive Vice President of Commercial Operations at Tonix Pharmaceuticals and President of Tonix Medicines. “Intravail technology helps the medication absorb into the bloodstream so it can work quickly, providing migraine pain relief in as little as 10 minutes for some patients.”5,6,7
About Migraine
Nearly 40 million people in the United States suffer from migraine8 and it has been recognized as the second leading cause of disability in the world.9 Migraine is characterized by debilitating attacks lasting four to 72 hours with multiple symptoms, including pulsating headaches of moderate to severe pain intensity often associated with nausea or vomiting, and/or sensitivity to sound (phonophobia) and sensitivity to light (photophobia).
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 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 third 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.
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.
Tosymra can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop Tosymra and get emergency medical help if you have any signs of heart attack:
discomfort in the center of your chest that lasts for more than a few minutes or goes away and comes back
severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
pain or discomfort in your arms, back, neck, jaw, or stomach
shortness of breath with or without chest discomfort
breaking out in a cold sweat
nausea or vomiting
feeling lightheaded
Tosymra is not for people with risk factors for heart disease (high blood pressure or cholesterol, smoking, overweight, diabetes, family history of heart disease) unless a heart exam is done and shows no problem.
Do not use Tosymra if you have:
history of heart problems
narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease)
uncontrolled high blood pressure
severe liver problems
hemiplegic or basilar migraines. If you are not sure if you have these, ask your healthcare provider.
had a stroke, transient ischemic attacks (TIAs), or problems with blood circulation
taken any of the following medicines in the last 24 hours: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, ergotamines, or dihydroergotamine. Ask your provider if you are not sure if your medicine is listed above.
are taking certain antidepressants, known as monoamine oxidase (MAO)-A inhibitors or it has been 2 weeks or less since you stopped taking a MAO-A inhibitor. Ask your provider for a list of these medicines if you are not sure.
an allergy to sumatriptan or any ingredient in Tosymra
Tell your provider about all of your medical conditions and medicines you take, including vitamins and supplements.
Tosymra can cause dizziness, weakness, or drowsiness. If so, do not drive a car, use machinery, or do anything where you need to be alert.
Tosymra may cause serious side effects including:
changes in color or sensation in your fingers and toes
sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrhea, fever
cramping and pain in your legs or hips, feeling of heaviness or tightness in your leg muscles, burning or aching pain in your feet or toes while resting, numbness, tingling, or weakness in your legs, cold feeling or color changes in one or both legs or feet
increased blood pressure including a sudden severe increase even if you have no history of high blood pressure
medication overuse headaches from using migraine medicine for 10 or more days each month. If your headaches get worse, call your provider.
serotonin syndrome, a rare but serious problem that can happen in people using Tosymra, especially when used with anti-depressant medicines called SSRIs or SNRIs. Call your provider right away if you have: mental changes such as seeing things that are not there (hallucinations), agitation, or coma; fast heartbeat; changes in blood pressure; high body temperature; tight muscles; or trouble walking.
hives (itchy bumps); swelling of your tongue, mouth, or throat
seizures even in people who have never had seizures before
The most common side effects of Tosymra include: tingling, dizziness, feeling warm or hot, burning feeling, feeling of heaviness, feeling of pressure, flushing, feeling of tightness, numbness, application site (nasal) reactions, abnormal taste, and throat irritation.
Tell your provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of Tosymra. For more information, ask your provider.
This is the most important information to know about Tosymra but is not comprehensive. For more information, talk to your provider and read the Patient Information and Instructions for Use. You can also visit www.upsher-smith.com or call 1-888-650-3789.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
INDICATION AND USAGE Tosymra is a prescription medicine used to treat acute migraine headaches with or without aura in adults.
Tosymra is not used to treat other types of headaches such as hemiplegic or basilar migraines or cluster headaches.
Tosymra is not used to prevent migraines. It is not known if Tosymra is safe and effective in children under 18 years of age.
Zembrace® SymTouch® (sumatriptan Injection): IMPORTANT SAFETY INFORMATION
Zembrace SymTouch (Zembrace) can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop use and get emergency help if you have any signs of a heart attack:
discomfort in the center of your chest that lasts for more than a few minutes or goes away and comes back
severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
pain or discomfort in your arms, back, neck, jaw or stomach
shortness of breath with or without chest discomfort
breaking out in a cold sweat
nausea or vomiting
feeling lightheaded
Zembrace is not for people with risk factors for heart disease (high blood pressure or cholesterol, smoking, overweight, diabetes, family history of heart disease) unless a heart exam shows no problem.
Do not use Zembrace if you have:
history of heart problems
narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease)
uncontrolled high blood pressure
hemiplegic or basilar migraines. If you are not sure if you have these, ask your provider.
had a stroke, transient ischemic attacks (TIAs), or problems with blood circulation
severe liver problems
taken any of the following medicines in the last 24 hours: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, ergotamines, dihydroergotamine.
are taking certain antidepressants, known as monoamine oxidase (MAO)-A inhibitors or it has been 2 weeks or less since you stopped taking a MAO-A inhibitor. Ask your provider for a list of these medicines if you are not sure.
an allergy to sumatriptan or any of the components of Zembrace
Tell your provider about all of your medical conditions and medicines you take, including vitamins and supplements.
Zembrace can cause dizziness, weakness, or drowsiness. If so, do not drive a car, use machinery, or do anything where you need to be alert.
Zembrace may cause serious side effects including:
changes in color or sensation in your fingers and toes
sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrhea, fever
cramping and pain in your legs or hips; feeling of heaviness or tightness in your leg muscles; burning or aching pain in your feet or toes while resting; numbness, tingling, or weakness in your legs; cold feeling or color changes in one or both legs or feet
increased blood pressure including a sudden severe increase even if you have no history of high blood pressure
medication overuse headaches from using migraine medicine for 10 or more days each month. If your headaches get worse, call your provider.
serotonin syndrome, a rare but serious problem that can happen in people using Zembrace, especially when used with anti-depressant medicines called SSRIs or SNRIs. Call your provider right away if you have: mental changes such as seeing things that are not there (hallucinations), agitation, or coma; fast heartbeat; changes in blood pressure; high body temperature; tight muscles; or trouble walking.
hives (itchy bumps); swelling of your tongue, mouth, or throat
seizures even in people who have never had seizures before
The most common side effects of Zembrace include: pain and redness at injection site; tingling or numbness in your fingers or toes; dizziness; warm, hot, burning feeling to your face (flushing); discomfort or stiffness in your neck; feeling weak, drowsy, or tired.
Tell your provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of Zembrace. For more information, ask your provider.
This is the most important information to know about Zembrace but is not comprehensive. For more information, talk to your provider and read the Patient Information and Instructions for Use. You can also visit www.upsher-smith.com or call 1-888-650-3789.
You are encouraged to report adverse effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
INDICATION AND USAGE
Zembrace is a prescription medicine used to treat acute migraine headaches with or without aura in adults who have been diagnosed with migraine.
Zembrace is not used to prevent migraines. It is not known if it is safe and effective in children under 18 years of age.
Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics and diagnostics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of immunology, rare disease, infectious disease, and central nervous system (CNS) product candidates. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-15001 which is a humanized monoclonal antibody targeting CD40-ligand being developed for the prevention of allograft and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the second half of 2022. Tonix’s rare disease portfolio includes TNX-29002 for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan-Drug Designation by the FDA. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox called TNX-8013, next-generation vaccines to prevent COVID-19, and an antiviral to treat COVID-19. Tonix’s lead vaccine candidates for COVID-19 are TNX-1840 and TNX-18504, which are live virus vaccines based on Tonix’s recombinant pox vaccine (RPV) platform. TNX-35005 (sangivamycin, i.v. solution) is a small molecule antiviral drug to treat acute COVID-19 and is in the pre-IND stage of development. TNX-102 SL6, (cyclobenzaprine HCl sublingual tablets), is a small molecule drug being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix expects to initiate a Phase 2 study in Long COVID in the second quarter of 2022. The Company’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, is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022. Finally, TNX-13007 is a biologic designed to treat cocaine intoxication that is expected to start a Phase 2 trial in the second quarter of 2022. TNX-1300 has been granted Breakthrough Therapy Designation by the FDA.
Robert LeBoyer, Senior Vice President, Equity Research Analyst, Biotechnology, Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
Phase 2 PREVAIL Study Announces Mixed Results. Tonix announced that the Phase 2 PREVAIL study testing TNX-102 SL in Long COVID did not meet its primary endpoint of multi-site pain reduction at week 14. The study was able to improve several important symptoms of Long COVID that could become acceptable endpoints in a Phase 3 trial.
Several Measures Showed Benefits In The Trial. PREVAIL was a blinded placebo-controlled study with an enrollment of 63 patients. Several secondary endpoints showed consistent benefits over the course of the study. These include fatigue, sleep quality, cognitive function, disability, and the Patient Global Impression of Change (PGIC). We believe these data show the drug can reduce several important symptoms of Long COVID.
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*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.
TNX-102 SL showed a robust effect size of 0.5 in improving fatigue and showed consistent activity across secondary measures of sleep quality, cognitive function, disability and Patient Global Impression of Change, but did not meet the primary endpoint of multi-site pain reduction at week 14
Findings fulfill the objectives of this proof-of-concept study, supporting the decision to advance the program based on a proposed primary endpoint using the PROMIS Fatigue scale
Tonix plans to meet with FDA to discuss a path to registration; fatigue is the signature symptom of Long COVID and the principal symptom overlapping with CFS/ME and fibromyalgia syndromes
CHATHAM, N.J., Sept. 05, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced topline results from the Phase 2 proof-of-concept PREVAIL study of TNX-102 SL 5.6 mg for the management of fibromyalgia-type Long COVID. TNX-102 SL treatment showed a robust effect size (ES) in improving fatigue and showed consistent activity trending to improvements across the secondary endpoints of sleep quality, cognitive function, disability and patient global impression of change (PGIC). TNX-102 SL trended towards improvement but did not achieve the pre-specified primary endpoint of improving Long COVID pain intensity scores at Week 14. The proposed mechanism of TNX-102 SL is improving sleep quality, which NIH recently announced is a target of future RECOVER clinical trials in Long COVID, a National Institute of Health (NIH) research program designed to understand, treat, and prevent long COVID.1,2 There is currently no approved drug for the treatment of Long COVID.
PREVAIL was a randomized, double-blind, placebo-controlled, multi-site proof-of-concept study of 63 patients with laboratory-documented COVID-19 illness preceding Long COVID. PREVAIL was designed and conducted to guide the design of registrational studies of TNX-102 SL in fibromyalgia-type Long COVID. TNX-102 SL was generally well tolerated with an adverse event (AE) profile comparable to prior studies with TNX-102 SL. AE-related discontinuations were similar in drug and placebo arms. No new safety signals were observed.
“The robust activity of TNX-102 SL on the PROMIS Fatigue scale3-5 (ES=0.5, Figure 4) is important because patients and experts view fatigue as the signature symptom of Long COVID and it has been identified as the dominant symptom contributing to disability,”6 said Dr. Seth Lederman, President and CEO of Tonix Pharmaceuticals. “In addition, TNX-102 SL showed consistent trends toward improvement in sleep quality, cognitive function, disability and the PGIC responder rate for TNX-102 SL compared to placebo (Figure 5) at week 14 (34.4% vs. 16.1%, difference=18.2%). Together, these findings fulfill the objectives of this proof-of-concept study in supporting the decision to advance the program based on a proposed primary endpoint using the PROMIS Fatigue scale.”
The Company intends to request an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) to discuss a potential Phase 3 program based on a proposed primary outcome measure using the PROMIS Fatigue scale. The meeting is expected to take place in the first quarter of 2024. Fatigue is the symptom of Long COVID that principally overlaps with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and fibromyalgia. In the NIH funded RECOVER study analysis, fatigue was the top featured symptom and is common in each of the four clusters.7
“The data from PREVAIL reinforce our belief in TNX-102 SL as a potential bedtime medicine for the management of fibromyalgia-type Long COVID,” said Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals. “We believe the PREVAIL trial results will help guide the next phase of development for TNX-102 SL, supporting the design of a potential registrational trial for fibromyalgia-type Long COVID based on PROMIS fatigue as a primary endpoint, pending review and feedback from the FDA. In both of our prior Phase 3 studies of TNX-102 SL 5.6 mg in fibromyalgia, we observed numerical improvement in the PROMIS fatigue score (in RELIEF p=0.007 MMRM8 and in RALLY p=0.007 MMRM9).”
Dr. Sullivan continued, “Although the validity of PROMIS Fatigue is not yet established in Long COVID, we believe the results of PREVAIL, together with extensive data from studies in other chronic conditions3-5 – including Tonix’s studies in fibromyalgia – make PROMIS Fatigue a solid candidate for the primary endpoint of future Long COVID registrational studies. We look forward to an anticipated End-of-Phase 2 meeting with the FDA to discuss these data and expect to present full data from PREVAIL in a peer-reviewed format and at upcoming medical conferences. Together, we believe these findings support the recognition of fibromyalgia-type Long COVID as a clinically meaningful subgroup of Long COVID patients and underscore the potential of TNX-102 SL as a once daily, oral therapy for this debilitating condition. We are grateful to the patients and their families and supporters, who participated in this study.”
Key Phase 2 PREVAIL Study Results
In the study, 63 subjects were enrolled and randomized 1:1 across approximately 30 U.S. sites to receive either TNX-102 SL or placebo daily at bedtime for 14 weeks. Subjects started with TNX-102 SL 2.8 mg tablet or one placebo tablet for the first 2 weeks and then increased to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks of the treatment period. The percentage of subjects completing the study was 81.3% in the TNX-102 SL group and 80.6% in the placebo group. Demographics and baseline characteristics are shown in Table 1.
Table 1: Demographics and Baseline Characteristics
Variable
Placebo
TNX-102 SL
Total
N=31
N=32
N=63
Age, mean years (SD)
51.4 (10.01)
48.6 (8.80)
50.0 (9.45)
Female, number (%)
25 (80.6%)
21 (65.6%)
46 (73.0%)
Male, number (%)
6 (19.4%)
11 (34.4%)
17 (27.0%)
Ethnicity
Hispanic or Latino
3 (9.7%)
2 (6.3%)
5 (7.9%)
Not Hispanic or Latino
28 (80.6%)
30 (93.8%)
58 (92.1%)
Race
American Indian or AN, number (%)
1 (3.2%)
0 (0.0%)
1 (1.6%)
Asian, number (%)
0 (0.0%)
1 (3.1%)
1 (1.6%)
Black or African American, number (%)
5 (16.1%)
7 (21.9%)
12 (19.0%)
Native Hawaiian or PI, number (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
White or Caucasian, number (%)
24 (77.4%)
21 (65.6%)
45 (71.4%)
Multiple Races, number (%)
1 (3.2%)
3 (9.4%)
4 (6.3%)
BMI, mean kg/m2 (SD)
29.5 (4.44)
29.8 (4.07)
29.6 (4.22)
Employed, number (%)
26 (83.9%)
25 (78.1%)
51 (81.0%)
Abbreviations: AN, Alaskan Native; BMI, body mass index; PI, Pacific Islander; SD, standard deviation
Primary endpoint
Given the lack of Long COVID treatments and the size of the current proof-of-concept study, an ES ≥ 0.2 was the pre-specified threshold for declaring the primary endpoint positive. The study trended towards a benefit but did not achieve statistical significance on the primary efficacy endpoint of change from baseline in the diary numerical rating scale (NRS) weekly average of daily self-reported worst Long COVID pain intensity scores for TNX-102 SL at the Week 14 endpoint versus placebo (effect size (ES) = 0.08, Figure 1.)
Secondary endpoints
The change from baseline to the Week 14 endpoint for the daily sleep quality diary, PROMIS Sleep Disturbance, PROMIS Fatigue, PROMIS Cognitive function, the Insomnia Severity Index (ISI) and Sheehan Disability Scale showed numerical improvements (MMRM, ES ≥ 0.2): sleep diary (MMRM, ES =0.23, Figure 2.), PROMIS sleep Disturbance (MMRM, ES=0.32, Figure 3.), PROMIS fatigue (MMRM, ES=0.50, Figure 4.), PROMIS Cognitive Function – Abilities, (MMRM, ES=0.21), the ISI (ANCOVA, ES=0.24) and the Sheehan Disability Scale (ANCOVA, ES=0.26). Moreover, robust activity was observed in the PGIC responder (very much improved or much improved) rate for TNX-102 SL compared to placebo (Figure 5): week 6 (31.3% vs. 9.7%, difference=21.6%), week 10 (28.1% vs. 12.9%, difference=15.2%), week 14 (34.4% vs. 16.1%, difference=18.2%).
Safety profile
TNX-102 SL demonstrated a favorable safety and tolerability profile over 14 weeks of treatment with no new safety signals. The most common adverse events are shown in Table 2. Participants with at least one treatment-emergent adverse event (TEAE) were at a rate of 56.3% on TNX-102 SL and 38.7% on placebo. In the TNX-102 SL group, 6.3% discontinued due to TEAE compared to 9.7% on placebo. Only one TEAE in the study was rated as severe, gastritis in a participant in the TNX-102 SL group. There were no serious adverse events (SAEs) in the study.
Table 2: Adverse Events Occurring in ≥ 2 Participants in Either Treatment Group
Placebo
TNX-102 SL
Total
N=31
N=32
N=63
Administration Site Reactions
Hypoaesthesia oral
0
6
6
Product taste abnormal
0
3
3
Glossodynia
0
2
2
Oral pain
0
2
2
Paraesthesia oral
0
2
2
Systemic Adverse Events
Influenza like illness
2
0
2
Abbreviations: LS, least squares; SE, standard error
Abbreviations: LS, least squares; SE, standard error
Abbreviations: LS, least squares; SE, standard error; SD, sleep disturbance
Abbreviations: LS, least squares; SE, standard error
*p=0.034, #p=0.096
About the Phase 2 PREVAIL Study The Phase 2 PREVAIL proof-of-concept study was a 14-week double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-102 SL taken daily at bedtime in patients with multi-site pain associated with laboratory-documented post-acute sequelae of SARS-CoV-2 infection (PASC). The trial was conducted at approximately 30 sites in the U.S. The primary efficacy endpoint is the change from baseline in the weekly average of daily self-reported worst pain intensity scores at the Week 14 endpoint. Key secondary efficacy endpoints include change from baseline in self-reported scores for sleep disturbance, fatigue, and cognitive function.
For more information, see ClinicalTrials.gov Identifier: NCT05472090.
About Long COVID or Post-Acute Sequelae of COVID-19 (PASC)
Post-acute sequelae of COVID-19, or PASC is the formal name for a condition now widely known as Long COVID. The U.S. Department of Health and Human Services (HHS) recently estimated that 7.7 million to 23 million Americans have developed Long COVID and announced the formation of the “Office of Long COVID Research and Practice” to lead the Long COVID response and coordinate efforts across the federal government. 10 Although most people recover from COVID-19 within weeks of the acute illness, a substantial portion develops a chronic syndrome called Long COVID.11 These individuals experience a constellation of disabling symptoms long past the time of recovery from acute COVID-19. Most Long COVID patients who have been studied appear to have cleared the SARS-CoV-2 infection from their systems. The symptoms of Long COVID can include fatigue, sleep disorders, multi-site pain, fevers, shortness of breath, cognitive impairment described as “brain fog” or memory disturbance, gastrointestinal symptoms, anxiety, and depression. According to the Centers for Disease Control and Prevention (CDC), 1 in 13 adults in the U.S. (7.5%) have Long COVID symptoms.11 Long COVID is typically associated with moderate or severe COVID-19 but can occur after mild COVID-19 or even after asymptomatic SARS-CoV-2 infection. More than 40% of adults in the United States reported having COVID-19 in the past, and nearly one in five of those (19%) are currently still having symptoms of Long COVID.11 Long COVID is a chronic disabling condition that is expected to result in a significant global health and economic burden.12-15 In response to the urgent need for therapies that address Long COVID, Congress awarded $1.15 billion to the National Institutes of Health to study Long COVID in December 2020.16 The U.S. Department of Health and Human Services National Research Action Plan on Long COVID17, released in August 2022, addresses the overlap of Long COVID with CFS/ME, which, like fibromyalgia, is one of the overlapping chronic pain syndromes with central and peripheral sensitization.18 A published survey19 found comparable pain, fatigue, and functional impairment between Long COVID, fibromyalgia, and CFS/ME. This symptom overlap between these conditions has suggested that altered neurologic function is one of the leading hypotheses to explain them.20 While the vaccines available in the U.S., through either FDA approval or under Emergency Use Authorization, have been shown to prevent acute COVID, their ability to prevent Long COVID is unknown. There is currently no approved drug for the treatment of Long COVID.
About Fibromyalgia-Type Long COVID
Common symptoms of Long COVID, including multi-site pain, fatigue, unrefreshing sleep, and cognitive dysfunction, or ‘brain fog,’ are hallmarks of conditions like fibromyalgia and CFS/ME. Defining subgroups of Long COVID patients that overlap with fibromyalgia and CFS/ME is expected to facilitate the development of new treatments.20 We are studying TNX-102 SL in the subgroup of Long COVID patients whose symptoms overlap with fibromyalgia, which we have termed ‘Fibromyalgia-type Long COVID.’ TNX-102 SL is in phase 3 development for the management of fibromyalgia.8,21 Fibromyalgia has been recognized by the U.S. Food and Drug Administration (FDA) with three approved medicines. The recent identification of Long COVID subgroups in the National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored RECOVER study7 was an important step. In their recent publication7 cluster analysis of the symptom frequencies in the RECOVER study (Researching COVID to Enhance Recovery (RECOVER) research program) identified four subgroups of Long COVID patients. Cluster #4 represented approximately one quarter of the population (28%) and reported the highest frequencies of pain (back pain (58%), joint pain (64%) or muscle pain (60%)), high frequencies of fatigue (94%) and ’Brain Fog,’ (94%) and a high level of impairment of Quality of Life. We believe Cluster #4 is a subgroup of Long COVID that overlaps with fibromyalgia. We also believe that Cluster #3, representing another approximately 29% of the RECOVER cohort, includes many patients with Fibromyalgia-type Long COVID because 100% of that group suffer from ‘Brain Fog’, 94% experience fatigue and approximately one third experience pain (back pain (32%), joint pain (36%) or muscle pain (34%)). Fibromyalgia can result from a variety of different stressors, in addition to infectious illnesses, including hormonal, metabolic, and psychological stressors.23,24 It can be challenging to distinguish fibromyalgia and CFS/ME clinically, given the high level of symptom overlap between them. Each of these conditions is defined by a constellation of symptoms, and there is no widely recognized diagnostic laboratory test that distinguishes them. We presented an analysis of a Fibromyalgia-type Long COVID subgroup from the TriNetX claims database at the BIO-sponsored Long COVID meeting in February 2023.21 That study provided real-world evidence that the majority of Long COVID patients present with a constellation of symptoms that overlap with fibromyalgia and CFS/ME. These symptoms include fatigue, cognitive symptoms, and multi-site pain. Fibromyalgia-type Long COVID, like fibromyalgia and CFS/ME, appears to be both a subgroup of Long COVID and one of several chronic overlapping pain conditions that have in common the neurological process called central and peripheral sensitization, which is increasingly known by the term nociplastic pain.
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.
*TNX-102 SL is an investigational new drug and is not approved for any indication
Briggs, A, and Vassall, A. Nature. 2021. 593(7860): 502-505
Nittas V, et al. Public Health Rev. 2022. 43:1604501
Davis, HE., et al. EClinicalMedicine. 2021. 38:101019
Martin C, et al. PLoS One. 2021. 16(12):e0260843
The NIH provision of Title III Health and Human Services, Division M–Coronavirus Response and Relief Supplemental Appropriations Act, 2021, of H.R. 133, The Consolidated Appropriations Act of 2021. The bill was enacted into law on 27 December 2020, becoming Public Law 116-260.
Moldofsky H, et al. J Rheumatol. 2011. 38(12):2653-63
Clauw DJ, and Calabrese L. Ann Rheum Dis. 2023
Clauw DJ, et al. Pain. 2020. 161(8):1694-1697
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 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. Topline results from a proof-of-concept Phase 2 study 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 third 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.
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.
Phase 1/2 Clinical Trial of TNX-801 for the Prevention of Mpox and Smallpox to Commence Following Submission of an IND
TNX-801 is Based on a Proprietary Live Virus Vaccine Platform Designed to Stimulate Durable T-Cell Immunity
TNX-801 Vaccination Protected Animals from a Lethal Challenge with Monkeypox in Preclinical Testing
CHATHAM, N.J., Aug. 21, 2023 (GLOBE NEWSWIRE) — 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 it received the official written response from a Type B pre-Investigational New Drug Application (IND) meeting with the U.S. Food and Drug Administration (FDA) to develop TNX-8011 (recombinant horsepox virus, live vaccine) as a potential vaccine to protect against mpox disease (formerly known as monkeypox) and smallpox. Tonix believes the FDA feedback provides a path to agreement on the design of a Phase 1/2 study and the overall clinical development plan. The Phase 1/2 clinical trial will assess the safety, tolerability, and immunogenicity of TNX-801, following the submission and clearance of an IND.
“The FDA’s response to the pre-IND meeting marks an important milestone in the development of TNX-801 since we have FDA concurrence on the proposed manufacturing, toxicology studies, and the Phase 1/2 clinical design,” said Seth Lederman, M.D., President and Chief Executive Officer of Tonix. “TNX-801 is believed to be closely related to Edward Jenner’s original smallpox vaccine.2-10 Jenner’s live virus smallpox vaccine – the first vaccine – remains one of the most effective vaccines in history, since it typically provided lifetime immunity with a single dose, prevented forward transmission of the smallpox virus, and ultimately eradicated the disease. TNX-801 has an attenuated phenotype relative to modern vaccinia viruses, which comprise a group of vaccine viruses that evolved from Jenner’s vaccine during passage in man and animals for over 100 years. When live virus vaccinia vaccination was routinely practiced in Africa, mpox was kept out of the human population.”2,11
TNX-801 is a live replicating attenuated vaccine based on horsepox that is believed to protect against smallpox and mpox, primarily by eliciting a T-cell response evidenced by the “take”. The “take” is a functional measure of protective T-cell immunity validated by the eradication of smallpox. TNX-801 is administered with a single dose, can be readily scaled up for manufacturing using proven technology and can be distributed and stored without requiring a costly and cumbersome ultra-cold supply chain. Live replicating vaccines have the potential to induce durable T-cell immunity, prevent serious illness after infection and block forward transmission. Tonix reported positive preclinical efficacy data, demonstrating that TNX-801 vaccination protected non-human primates against lethal challenge with mpox.12
“More than 30,000 people have contracted mpox in the U.S. so far during the 2022-23 epidemic,”13 said Dr. Zeil Rosenberg, Executive Vice President, Medical at Tonix. “The recent cluster of mpox in Chicago revealed breakthrough cases of mpox in individuals who had been vaccinated with the currently authorized non-replicating vaccine, which is administered in two doses.14 In contrast, TNX-801 is delivered intradermally with only one dose and therefore may achieve higher rates of community protection by eliminating drop-out between doses and limiting forward transmission. Moreover, relying on only one approved mpox vaccine at present is a risk for the global supply chain that has already led to insufficient availability of vaccine to meet global health needs, especially in Africa.”
Dr. Rosenberg added, “We believe TNX-801 could make a global impact on mpox and the risk of smallpox because of its potential durable T-cell immune response, the ability to manufacture at scale, to use a lower dose than non-replicating vaccines. The current formulation is a frozen liquid, but we believe that future lyophilized versions can be stored and shipped at standard refrigeration. Moreover, we believe the low dose of TNX-801 makes this technology amenable for future implementation in microneedle delivery systems.”
Dr. Lederman concluded, “In addition to its potential use as a vaccine, TNX-801 also has the potential as a viral vector platform, for which versions can be developed to protect against a host of infectious diseases beyond smallpox and mpox, including COVID-19. In light of the recent resurgence in COVID cases across the country with the new EG.5 “Eris” variant, we believe that the horsepox recombinant pox virus platform may provide next generation vaccines to prevent future outbreaks.”
About TNX-801* TNX-801 is a live virus vaccine based on horsepox2,11. Horsepox and vaccinia are closely related orthopoxviruses that are believed to share a common ancestor. TNX-801 is believed to be more closely related to Jenner’s vaccinia vaccine than modern vaccinia vaccines, which appear to have evolved by deletions and mutations to a phenotype of larger plaque size in tissue culture and greater virulence in mice. Molecular analysis shows that horsepox is closer than modern vaccinia vaccines in DNA sequence to the vaccine discovered and disseminated by Dr. Edward Jenner.2-10 Vaccine genome researchers have recently shown the contemporaneous use of horsepox and horsepox-related viruses in the United States as smallpox vaccines in the 1860’s9,10. Additionally they found a remarkable degree of identity with the circa 1860 U.S. smallpox vaccine VK05 and the 1976 Mongolian horsepox isolate called MNR-76, upon which Tonix’s TNX-801 is based.3,5 These recent discoveries are further steps in establishing that what is called ’horsepox‘ today was used to vaccinate against smallpox in the 19th century. Dr. Edward Jenner invented vaccination in 1798 and the procedure was called “vaccination” because the inoculum material was initially obtained from lesions on the udders of cows affected by a mild disease known as cowpox2. ‘Cow’ is ‘vacca’ in Latin. However, Dr. Jenner suspected that cowpox originated from horsepox.2 Subsequently, Dr. Jenner and others immunized against smallpox using material directly obtained from horses. The use of vaccines from horses was sometimes called ‘equination’ from the Latin ‘equus’ which means ‘horse’. Equination and vaccination were practiced side-by-side in Europe6. The small plaque size in culture of TNX-801 appears identical to the U.S. Centers for Disease Control publication of the natural isolate12. Relative to vaccinia, horsepox has substantially decreased virulence in mice3. Tonix’s TNX-801 vaccine candidate is administered intradermally. The major cutaneous reaction or “take” to vaccinia vaccine was described by Dr. Edward Jenner in 1796 and has been used since then as a biomarker for protective immunity to smallpox, including in the World Health Organization’s (WHO) accelerated smallpox eradication program that successfully eradicated smallpox in the 1960’s.
TNX-801 is in the pre-IND stage and has not been approved for any indication.
Jenner E. “An Inquiry Into the Causes and Effects of the Variole Vaccinae, a Disease Discovered in Some of the Western Counties of England, Particularly Gloucestershire and Known by the Name of the cow‐pox.” London: Sampson Low, 1798.
Noyce RS, et al. (2018) PLoS One. 13(1):e0188453
Schrick L, et al. (2017) N Engl J Med 377:1491-1492
Tulman ER, et al. (2006) J Virol. 80(18):9244-58.
Esparza J, et al. (2017) Vaccine. 35(52):7222-7230.
Esparza J, et al. (2020) Vaccine. 38(30):4773-4779.
Qin L, et al. (2015) J Virol. 89(3):1809-24.
Brinkmann A, et al, (2020) Genome Biology 21:286
Duggan A, et al. (2020) Genome Biology 21:175 https://doi.org/10.1186/s13059-020-02079-z
Noyce RS, et al., (2023) Viruses. 15(2):356.
Trindade GS, et al. (2016) Viruses. 8(12):328.
McQuiston JH, et al. (2023) The CDC Domestic Mpox Response — United States, 2022–2023. MMWR Morb Mortal Wkly Rep. 72(20):547–552
Faherty EAG, et al.(2023) Emergence of an mpox cluster primarily affecting persons previously vaccinated against mpox-Chicago, Illinois, March 18-June 12, 2023. MMWR Morb Mortal Wkly Rep. , 72(25);696-698.
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 are expected 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 third 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.
Tonix Medicines has contracted to acquire the Zembrace SymTouch and Tosymra registered trademarks. Intravail is a registered trademark of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis, Inc.
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.
CHATHAM, N.J., Aug. 17, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates, announced today that Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals, will present at the August 2023 Virtual Investor Summit on Thursday, August 24, 2023, at 10:00 a.m. ET.
Investors interested in arranging a meeting with the Company’s management during the conference should contact the Investor Summit conference coordinator. A webcast of the presentation can be found here and will be available under the IR Events tab of the Tonix website at www.tonixpharma.com.
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 are expected 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 third 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.
Tonix Medicines has contracted to acquire the Zembrace SymTouch and Tosymra registered trademarks. Intravail is a registered trademark of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis, Inc.
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.
Single Ascending Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TNX-1500
Study Designed to Support Planned Phase 2 Trial in Prevention of Kidney Transplant Rejection
Multiple Possible Indications, Including Bone Marrow Transplantation and Autoimmune Diseases: Potential Pipeline in a Product
TNX-1500 is the First of Tonix’s Internally-Developed Biologic Candidates to Reach the Clinic
CHATHAM, N.J., Aug. 16, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced the initiation of a Phase 1 single ascending dose escalation study of TNX-1500 (Fc-modified humanized anti-CD40L monoclonal antibody or mAb) in healthy volunteers. The primary objectives of the study are to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous (IV) TNX-1500.
TNX-1500 is in development for the prevention of kidney transplant rejection and other potential transplant and autoimmune disorder indications. Recent animal studies indicate that TNX-1500 prevents organ rejection and preserves graft function either as a single agent or in combination with other drugs.1,2 Eligible participants enrolled in the Phase 1 study will be evaluated regularly over a 120-day period after dosing. Target enrollment is 36 participants. Initiation of this first-in-human study is intended to support dosing in a planned Phase 2 trial in kidney transplant recipients.
“Despite advancements in the field of solid organ transplantation, there remains a significant need for new treatments with improved activity and tolerability,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “TNX-1500 has demonstrated single agent activity for long-term organ acceptance and induction of tolerance in animals.1,2 Potentially related to its activity, in preclinical studies, TNX-1500 preserves T regulatory cells, or Tregs, which are key to maintaining tolerance to grafts as well as to self-antigens. We believe TNX-1500 has the potential to prevent organ transplant rejection and improve long-term graft survival with reduced long-term toxicity burden compared to current immunosuppressive regimens. In addition, TNX-1500 has the potential to address multiple indications, including a number of autoimmune diseases. The range of potential indications suggests ‘pipeline in a product’ potential.”
“We are excited to advance TNX-1500 into the clinic by initiating this Phase 1 trial,” said Dr. Greg Sullivan, Chief Medical Officer of Tonix. “TNX-1500 is a third generation anti-CD40L mAb that has been designed by protein engineering to decrease FcγRIIA binding. Preclinical studies in non-human primates demonstrated that TNX-1500 is active in preventing allograft organ rejection and is well tolerated. Specifically, thrombotic complications associated with first generation anti-CD40L mAbs, were not observed, suggesting that the protein engineering underlying TNX-1500 has achieved its design goals.”
Dr. Lederman continued, “Recently, positive clinical data with other CD40L blockers have been reported by Sanofi, with its Fc-modified humanized anti-CD40L mAb frexalimab in treating relapsing multiple sclerosis,3 and from Horizon Therapeutics plc with its tn03 fusion protein dazodalibep in treating Sjögren’s syndrome.4,5 UCB is in Phase 3 development with its anti-CD40L pegylated Fab, dapirolizumab pegol, for the treatment of systemic lupus erythematosus.6 Based on results from animals, we consider Fc-modified humanized TNX-1500 to be a potential best-in-class therapeutic in the CD40L blocker space.”
CD40L is a member of the TNF-α superfamily, which includes TNF-α and RANKL. TNF-α is the target for several established drugs, including Humira® (adalimumab), Remicade® (infliximab), Enbrel® (etanercept), and Cimzia® (certolizumab). RANKL is targeted by Prolia® and Xgeva® (denosumab). Emerging TNF-α superfamily targets for therapeutics include TL1A, CD30L, Ox40L, and 41BBL. Merck acquired Prometheus Biosciences for its anti-TL1A and anti-CD30L programs.
Dr. Lederman concluded, “TNX-1500 is the first of Tonix’s internally-developed biologic candidates to reach the clinic. Tonix owns worldwide rights to TNX-1500, which are unencumbered by royalties. Our ability to develop and advance protein therapeutics is facilitated by our Research and Development Center (RDC) in Frederick, Md. and our Advanced Development Center (ADC) in Dartmouth, Mass.”
About TNX-1500
TNX-1500 (Fc-modified humanized anti-CD40L mAb) is a humanized monoclonal antibody that interacts with the CD40-ligand (CD40L), which is also known as CD154. TNX-1500 is being developed for the prevention of allograft and xenograft rejection, for the treatment of autoimmune diseases and for the prevention of graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation (HCT). A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Two articles have recently published in the American Journal of Transplantation that demonstrate TNX-1500 prolongs non-human primate renal and heart allograft survival1,2.
Lassiter, G., et al. (2023). TNX-1500, a crystallizable fragment–modified anti-CD154 antibody, prolongs non-human primate renal allograft survival. American Journal of Transplantation. April 3, 2023. https://doi.org/10.1016/j.ajt.2023.03.022
Miura, S., et al. (2023) TNX-1500, a crystallizable fragment–modified anti-CD154 antibody, prolongs non-human primate cardiac allograft survival. American Journal of Transplantation. April 6, 2023. https://doi.org/10.1016/j.ajt.2023.03.025
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 are expected 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 third 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.
Tonix Medicines has contracted to acquire the Zembrace SymTouch and Tosymra registered trademarks. Intravail is a registered trademark of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis, Inc.
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.
