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.
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.
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.
TNX-4300 is a Dual PPAR-β/δ and PPAR-γAgonist,Free from µ-Opioid Receptor Activity
TNX-4300’s Mechanism of Restoring Neuroplasticity Supports Development as a First-in-Class Oral Therapy for Depression, Bipolar Disorder, Alzheimer’s Disease and Parkinson’s Disease
Restoring Atrophied Neuronal Connections in Psychiatric and Neurological Diseases Seen as Paramount to Achieving Better and More Durable Outcomes
CHATHAM, N.J., May 23, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced the isolation and functional characterization of the two mirror image isomers of racemic tianeptine, which is marketed outside the U.S. as a treatment for major depressive disorder (MDD). Tonix scientists discovered that the (S)-isomer of tianeptine activates PPAR-β/δ, restores neuroplasticity in neuronal tissue culture and is free of µ-opioid receptor activity. In contrast, (R)-tianeptine activates the µ-opioid receptor and lacks PPAR-β/δ activity. Based on these discoveries, Tonix has begun preclinical development of the (S)-isomer, TNX-4300 (estianeptine)*, as a treatment for MDD, bipolar disorder, Alzheimer’s disease, and Parkinson’s disease. Tonix is planning to submit data supporting tianeptine’s mechanism of action for presentation at upcoming scientific conferences and for publication in peer reviewed journals.
Tonix recently announced that tianeptine, a drug marketed outside the U.S. for more than 30 years, is a plastogen1 that acts on nuclear PPAR-β/δ and PPAR-γ in neurons and glia to restore neuronal connectivity in depression and has direct applicability in a number of neurodegenerative diseases in which neuronal connections are atrophying.2 The newly reported mechanism also provided clarity on why tianeptine does not cause sexual dysfunction, weight gain or several other treatment-limiting toxicities frequently associated with antidepressants.
“The tianeptine marketed outside the U.S. for treating depression is a 1:1 racemic mixture of two mirror image isomers,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “The discovery reported today is that the (S)-isomer is responsible for tianeptine’s activity on PPAR-β/δ and restoring neuroplasticity, and the (R)-isomer for its off-target activity on the µ-opioid receptor. Our team of scientists isolated and characterized the (S)-isomer, that is now TNX-4300 and under development for psychiatric and neurological diseases.”
Dr. Lederman continued, “Our ongoing work on racemic tianeptine in depression is expected to inform and potentially accelerate the development of TNX-4300. Although the dose of tianeptine for treating depression is well-established from racemic studies, the dose range for treating neurological diseases is not yet determined. Because TNX-4300 lacks the µ-opioid receptor activity, we believe such effects will not limit the dosing of the (S)-tianeptine for these other indications.”
Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals, said, “(S)-tianeptine mimics naturally occurring polyunsaturated fatty acid ligands in binding PPAR-β/δ and PPAR-γ. (S)-tianeptine’s activation of nuclear PPAR-β/δ and PPAR-γ receptors appears to be a more direct mechanism to achieve the goal of restoring neuronal connectivity than current therapies. Its proposed mechanism as a plastogen is consistent with its clinical effects in promoting cognition in Alzheimer’s disease and bipolar disorder2,3 in addition to posttraumatic stress disorder (PTSD) and corticosteroid-induced cognitive dysfunction. The PPAR-β/δ target is validated by prior work on agonists treating animal models of neurodegenerative and autoimmune diseases of the central nervous system4 and the concept that Alzheimer’s can be considered a form of diabetes that affects the CNS, or type-III diabetes.”5
Key experiments were performed by scientists at Tonix’s Research and Development Center (RDC) in Frederick, Maryland.
Racemic tianeptine sodium (amorphous) immediate release (dosed 3 times daily) was first marketed for depression in France in 1989 and has been available for decades in Europe, Russia, Asia, and Latin America for the treatment of depression. Tianeptine sodium has an established safety profile from decades of use in these jurisdictions. Currently no tianeptine-containing product is approved in the U.S. and no extended-release tianeptine product is approved in any jurisdiction. In animal models, tianeptine restores dendritic arborization of pyramidal neurons in the CA3 region of hippocampus and in the dentate gyrus region promotes new neuron formation and integration into hippocampal networks.1 Tianeptine’s enhancement of neuroplasticity in animal models of stress is believed to be mediated by activation of PPAR isoforms PPAR-β/δ and PPAR-γ, which makes its properties distinct from traditional monoaminergic antidepressants in the U.S. and contributes to its potential for clinical indications beyond MDD and stress disorders. Tianeptine and its MC5 metabolite are also weak mu-opioid receptor (MOR) agonists that present a potential abuse liability if illicitly misused in large quantities (typically abused at 8-80 times the therapeutic dose on a daily basis).2 In patients who were prescribed tianeptine for depression, the French Transparency Committee found an incidence of misuse of approximately 1 case per 1,000 patients treated3 suggesting low abuse liability when used at the antidepressant dose in patients prescribed tianeptine for depression. Clinical trials have shown that cessation of a therapeutic course of tianeptine does not appear to result in dependence or withdrawal symptoms following 6-weeks4-8, 3-months9, or 12-months10 of treatment. Tianeptine’s reported pro-cognitive and anxiolytic effects as well as its ability to attenuate the neuropathological effects of excessive stress responses suggest that it may also be used to treat posttraumatic stress disorder (PTSD), and neurocognitive dysfunction associated with corticosteroid use.
1 McEwen, B. S., et al. Mol. Psychiatry 2010, 15 (3), 237–249. 2 Lauhan, R., et al. Psychosomatics 2018, 59 (6), 547–53. 3 Haute Authorite de Sante; Transparency Committee Opinion. Stablon 12.5 Mg, Coated Tablet, Re- Assessment of Actual Benefit at the Request of the Transparency Committee. December 5, 2012. 4 Emsley, R., et al. J. Clin. Psychiatry 2018, 79 (4) 5 Bonierbale M, et al. Curr Med Res Opin 2003, 19(2):114-124. 6 Guelfi, J. D., et al. Neuropsychobiology 1989, 22 (1), 41–48. 7 Invernizzi, G. et al., Neuropsychobiology 1994, 30 (2–3), 85–93. 8 Lepine, J. P., et al. Hum. Psychopharmacol. 2001, 16 (3), 219–227. 9 Guelfi, J. D. et al., Neuropsychobiology 1992, 25 (3), 140–148. 10 Lôo, H. et al., Br. J. Psychiatry. Suppl. 1992, 15, 61–65.
Tonix Pharmaceuticals Holding Corp.*
Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’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 (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with topline data expected in the fourth quarter of 2023. 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-1900 (intranasal potentiated oxytocin), in development for chronic migraine, is currently enrolling with topline data expected in the fourth 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 interim 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 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 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, for which a Phase 1 study is expected to be initiated in the second half of 2023. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease portfolio also includes TNX-3900 and TNX-4000, classes of broad-spectrum small molecule oral antivirals.
*All of Tonix’s product candidates are investigational new drugs or biologics and have not been approved for any indication.
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; delays and uncertainties caused by the global COVID-19 pandemic; 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., March 27, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, today announced that Zeil Rosenberg, M.D., M.P.H., Executive Vice President, Medical and Farooq Nasar, Ph.D., Senior Principal Investigator, both of Tonix Pharmaceuticals, will deliver oral presentations at the World Vaccine Congress, which will be held in Washington D.C., April 3 – 6, 2023. Copies of the Company’s presentations will be available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com following the conference. Additional meeting information can be found on the World Vaccine Congress website here.
In addition, Sina Bavari, Ph.D., Executive Vice President, Infectious Disease Research and Development of Tonix Pharmaceuticals will be moderating a panel of key opinion leaders discussing Mpox and the challenges and opportunities in vaccine development.
A Live Attenuated Orthopoxvirus (Horsepox) Vaccine for Mpox and Smallpox
Location:
Walter E. Washington Convention Center, Washington D.C.
Date:
Wednesday April 5, 2023
Time:
12:25 p.m. ET
Oral Presentation Details
Presenter:
Farooq Nasar, Ph.D. (Tonix Pharmaceuticals)
Title:
The Development of Horsepox Virus as a Vaccine Platform: Evaluation of TNX-1800 as a SARS-CoV-2 Vaccine
Location:
Walter E. Washington Convention Center, Washington D.C.
Date:
Thursday April 6, 2023
Time:
10:10 a.m. ET
Panel Details
Title:
Mpox – Challenges and Opportunities in Vaccine Development
Panel:
Sina Bavari, Ph.D. (Tonix Pharmaceuticals); David Evans, Ph.D. (University of Alberta); Jose Esparza, M.D., Ph.D. (University of Maryland); Deborah Birx, M.D. (BGR Group); Michael Merchlinsky, Ph.D. (HHS/BARDA)
Location:
Walter E. Washington Convention Center, Washington D.C.
Date:
Thursday April 6, 2023
Time:
11:30 a.m. ET
Tonix Pharmaceuticals Holding Corp.*
Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’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 (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition, for which a Phase 2 study was initiated in the third quarter of 2022. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is currently enrolling with interim data expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation of tianeptine being developed as a treatment for major depressive disorder (MDD), is also currently enrolling with interim 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 second quarter of 2023. Tonix’s rare disease 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 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 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 quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox, for which a Phase 1 study is expected to be initiated in the second half of 2023. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease portfolio also includes TNX-3900, a class of broad-spectrum small molecule oral antivirals.
*All of Tonix’s product candidates are investigational new drugs or biologics and have not been approved for any indication.
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; delays and uncertainties caused by the global COVID-19 pandemic; 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.
The Acquired Portfolio of Infectious Disease Assets Includes a Class of Potential Broad Spectrum Oral Antiviral Agents, TNX-3900 with a Host-Directed Mechanism
Tonix Plans to Develop the TNX-3900 Series of Molecules as Oral Antivirals Either as Monotherapy or in Combination with Other Antivirals
The TNX-3900 Class of Antivirals Has a Novel Mechanism of Action Based on Inhibition of Certain Cathepsin Proteases which are Required for Cell Infection by Many Viruses like SARS-CoV-2
Sina Bavari, Ph.D., Tonix EVP of Infectious Disease R&D and Director of the Frederick, MD Research and Development Center (RDC) was a Scientific Founder of Healion Bio, Inc.
CHATHAM, N.J., Feb. 02, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced an agreement whereby Tonix has acquired all of the assets of Healion Bio, Inc. (Healion) including its entire portfolio of next-generation antiviral technology assets. Healion’s drug portfolio includes a class of broad-spectrum small molecule oral antiviral drug candidates with a novel host-directed mechanism of action. Host-directed antivirals modulate human cells and tissues and are different from direct-acting antivirals which inhibit virus proteins and processes. Tonix’s TNX-3900, formerly known as HB-121, are cathepsin protease inhibitors, some of which have strong activity in vitro against SARS-CoV-2.
“We are excited to develop Healion’s drug programs that include TNX-3900, which is a class of drugs with potential broad spectrum anti-viral activity, either as monotherapies or in combination with other antivirals”, said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Broad-spectrum antiviral agents have the potential to reduce viral load and allow the adaptive immune system to alert the other arms of the immune system to mount a protective response. Examples of other classes of host-directed antivirals that have been approved by the U.S. Food and Drug Administration (FDA) include alpha interferon like Pegasys® (peginterferon alfa-2a) for viral hepatitis, the CCR5 antagonist Selzentry® (maraviroc) for HIV, and the anti-IL-6 receptor antagonist monoclonal antibody Actemra® (tocilizumab) for COVID-19.”
Sina Bavari, Ph.D., Executive Vice President for Infectious Disease Research at Tonix said, “I am pleased to be reunited with the infectious disease assets of Healion, since I was the scientific founder of Healion after I retired from my position as Chief of R&D at the United States Army Medical Research Institute of Infectious Disease (USAMRIID). While Healion made some progress developing these advanced technologies, Tonix’s state-of-the art facilities and depth of drug development expertise have the potential to advance the TNX-3900 class of drugs into clinical trials. On behalf of the talented scientific team that I direct at our 48,000 square-foot cutting-edge infectious disease research facility in Frederick, Md., I am pleased to add this technology to the therapeutic development programs underway.”
About TNX-3900
TNX-3900 is the term for a series of molecules that inhibit essential cathepsins which are required by viruses such as coronaviruses and filoviruses to infect cells. Because of the unique antiviral mechanism of these compounds, the Company believes they can potentiate the activity of other antivirals with differing mechanisms. The Company believes this makes cathepsin inhibitors suitable for combination therapy.
Tonix Pharmaceuticals Holding Corp.*
Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’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 (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022. 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 second quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is expected to enter the clinic with a Phase 2 study in the first quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease 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 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 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 quarter of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801, a next-generation vaccine to prevent COVID-19, TNX-1850, a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600, and humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800, recently licensed from Curia. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in Kenya in the second half of 2023.
*All of Tonix’s product candidates are investigational new drugs or biologics and have not been approved for any indication.
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; delays and uncertainties caused by the global COVID-19 pandemic; 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, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, 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.
Research Study to Assess the Role of TNX-1500 in the Prevention of Heart Xenograft Rejection
Preclinical Xenotransplantation Studies are Expected to Support Regulatory Filings for TNX-1500
CHATHAM, N.J., Feb. 01, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that it has entered into a sponsored research agreement with the University of Maryland, Baltimore (UMB), for the prevention of rejection in heart xenograft transplantation in animals utilizing TNX-15001, an Fc-modified humanized monoclonal antibody directed against CD40-ligand. UMB’s preclinical studies will utilize genetically-modified porcine hearts supplied by Revivicor, Inc., a subsidiary of United Therapeutics Corporation. The principal investigator is Muhammad M. Mohiuddin, M.D., MBBS, Professor of Surgery, and Director, Cardiac Xenotransplantation Program, University of Maryland School of Medicine.
“We are excited to collaborate with the University of Maryland and Dr. Mohiuddin on the development of TNX-1500 for the prevention of rejection in xenograft transplantation,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “TNX-1500 is a third generation anti-CD40L monoclonal antibody that has been designed by protein engineering to decrease FcγRII binding and to reduce the potential for thrombosis. Previous preclinical studies in non-human primates demonstrated that TNX-1500 showed activity in preventing allograft and xenograft organ rejection and was well tolerated. A positive result from this study would potentially help support an Investigational New Drug (IND) application and human clinical studies.”
“Despite exciting advancements in the field of xenotransplantation, better therapeutics are needed to prevent xenograft organ rejection,” said Dr. Mohiuddin. “Several lines of research indicate that anti-CD40L is required for long term xenograft acceptance. We are excited to collaborate in support of developing an effective immunosuppression regimen for patients requiring xenograft transplantation.”
The primary objective of the preclinical research study is to study the activity of TNX-1500 in preventing cardiac xenograft rejection in animals to support an IND application for human studies.
About TNX-1500
TNX-1500 (Fc-modified 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 is expected to be initiated in the second quarter of 2023. TNX-1500 is a third generation anti-CD40L mAb that has been designed by protein engineering to decrease FcγRII binding and to reduce the potential for thrombosis. In June 2022, Tonix announced data from three oral presentations at the 2022 American Transplant Congress of animal studies found that TNX-1500 showed activity in preventing organ rejection and was well tolerated in non-human primates. In those studies, blockade of CD40L with TNX-1500 monotherapy consistently and safely prevented pathologic alloimmunity in non-human primate models of cardiac and kidney allograft transplantation without clinical thrombosis. Copies of the presentations are available under Scientific Presentations on the Tonix Pharmaceuticals corporate website at www.tonixpharma.com.
1TNX-1500 is a biologic at the pre-IND stage of development and has not been approved for any indication
Tonix Pharmaceuticals Holding Corp.*
Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’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 (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022. 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 second quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is expected to enter the clinic with a Phase 2 study in the first quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease 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 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 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 quarter of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801, a next-generation vaccine to prevent COVID-19, TNX-1850, a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600, and humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800, recently licensed from Curia. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in Kenya in the second half of 2023.
*All of Tonix’s product candidates are investigational new drugs or biologics and have not been approved for any indication.
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; delays and uncertainties caused by the global COVID-19 pandemic; 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, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, 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.
Results from Planned Interim Analysis of First 50 Percent of Participants Expected Second Quarter 2023
Topline Results Expected Fourth Quarter 2023
Positive Outcome in RESILIENT, Together with Results from Previous Positive Phase 3 RELIEF Study, Would Support Submission of an NDA
CHATHAM, N.J., Dec. 19, 2022 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that the first 50% of participants have been randomized in the Phase 3 RESILIENT study of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) 5.6 mg for the management of fibromyalgia. An interim analysis by an Independent Data Monitoring Committee (IDMC) of the first 50% of randomized participants for a potential sample size adjustment or early stop for futility is expected in the second quarter of 2023.
TNX-102 SL is in mid-Phase 3 development for the management of fibromyalgia, a chronic pain disorder that afflicts between 6 and 12 million adults in the U.S., of which 90 percent are women. Despite dissatisfaction with currently marketed products, no new treatment for fibromyalgia has been approved by the FDA since 2009.
In December 2020, Tonix reported positive results from the first Phase 3 study (RELIEF) of TNX-102 SL 5.6 mg for the management of fibromyalgia (primary endpoint, p=0.010). Several secondary measures in RELIEF highlighted the broad effects of TNX-102 SL across several cardinal symptoms of fibromyalgia beyond pain. In March 2022, Tonix reported results of a subsequent Phase 3 study (RALLY) in which TNX-102 SL did not achieve statistical significance on the primary endpoint (p=0.115). Relative to the previous positive Phase 3 study (RELIEF), RALLY had an unexpected increase in study participant adverse event-related discontinuations in both the drug and placebo groups. TNX-102 SL was generally well tolerated in both studies with an adverse event profile comparable to prior studies, and no new safety signals observed.
“We are pleased to have reached this important milestone in our ongoing development of TNX-102 SL for fibromyalgia. RESILIENT is a potentially pivotal and confirmatory Phase 3 study, and we look forward to the IDMC’s assessment of interim results in the second quarter of 2023,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Fibromyalgia is a complex syndrome in which many patients remain unsatisfied by existing treatment options. Approximately one-fourth of people with fibromyalgia resort to prescription opioids for analgesia1. TNX-102 SL is a centrally acting analgesic that has the potential to be a new non-addictive, non-opioid bedtime medication for the management of fibromyalgia with broad spectrum symptom coverage.”
1Sarmento, CVM, et al. (2019) “Opioid prescription patterns among patients with fibromyalgia.” J Opioid Manag. 15(6):469-477. doi: 10.5055/jom.2019.0537. PMID: 31850508
About the Phase 3 RESILIENT Study
The RESILIENT study is a double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) in the management of fibromyalgia. The two-arm trial is expected to enroll approximately 470 participants in the U.S. The first two weeks of treatment consist of a run-in period in which participants start on TNX-102 SL 2.8 mg (1 tablet) or placebo. Thereafter, all participants increase their dose to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks. The primary endpoint is the daily diary pain severity score change (TNX-102 SL 5.6 mg vs. placebo) from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation. An interim analysis by an Independent Data Monitoring Committee will be conducted on the primary endpoint based on the first 50% of enrolled participants for a potential sample size adjustment or early stop for futility.
Fibromyalgia is a chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system. Fibromyalgia afflicts an estimated 6-12 million adults in the U.S., approximately 90% of whom are women. Symptoms of fibromyalgia include chronic widespread pain, nonrestorative sleep, fatigue, and morning stiffness. Other associated symptoms include cognitive dysfunction and mood disturbances, including anxiety and depression. Individuals suffering from fibromyalgia struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products.
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, PTSD, 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 clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’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 (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022 and expects interim data in the third 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 first quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is expected to enter the clinic with a Phase 2 study in the first quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease 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 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 and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the first half of 2023. Tonix’s infectious disease pipeline consists of a vaccine in development to prevent smallpox and monkeypox, next-generation vaccines to prevent COVID-19, and a platform to make fully human monoclonal antibodies to treat COVID-19. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in Kenya in the second half of 2023. Tonix’s lead vaccine candidate for COVID-19 is TNX-1850, a live virus vaccines based on Tonix’s recombinant pox live virus vector vaccine platform.
*All of Tonix’s product candidates are investigational new drugs or biologics and have not been approved for any indication.
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; delays and uncertainties caused by the global COVID-19 pandemic; 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, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, 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.
Hematopoietic Stem Cell Transplantation (HCT) from Unrelated Donors is a Component of the Treatment Protocol for Several Hematologic Malignancies
GvHD Complicates Treatment and Limits the Success of Engraftment after HCT
In addition to GvHD, Tonix is Developing TNX-1500 for Prophylaxis of Organ Transplant Rejection and Treatment of Autoimmune Disorders
Phase 1 Study of TNX-1500 is Expected to Start in First Half 2023
CHATHAM, N.J., Dec. 05, 2022 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that it has entered into a sponsored research agreement with Boston Children’s Hospital to study TNX-15001 (Fc-modified anti-CD40L mAb) for the prevention of graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation (HCT) in animals. The principal investigator is Leslie S. Kean M.D., Ph.D., Director, Stem Cell Transplantation Program, Division of Hematology/Oncology, Boston Children’s Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute and Robert A. Stranahan Professor of Pediatrics, Harvard Medical School. The primary objective of the preclinical research study is to study the activity of TNX-1500 administered prophylactically to modify GvHD progression in animals after HCT to support an Investigational New Drug (IND) application for human studies. A Phase 1 study of TNX-1500 to assess pharmacokinetics and tolerability is expected to start in the first half of 2023.
“We are excited to work with Leslie Kean on studying the potential of TNX-1500 for preventing GvHD after HCT,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Stem cell transplantation is an essential component of the treatment of several blood cell or hematologic cancers, but GvHD remains the most deadly complication, and limits the success of this otherwise life-saving treatment. To date, there has not been a humanized anti-CD40L antibody that can effectively prevent transplant rejection or GvHD with acceptable levels of tolerability. TNX-1500 is a third generation anti-CD40L monoclonal antibody that has been designed by protein engineering to decrease FcγRII binding and to reduce the potential for thrombosis. We are excited to sponsor this study of testing anti-CD40L in HCT to potentially replace cyclophosphamide in the post-transplant setting. A positive result would potentially support an IND and human studies.”
Dr. Kean, the principal investigator of the sponsored research said, “GvHD remains one of the most severe complications associated with HCT. For myeloablative MHC-haploidentical HCT, the risk of GvHD is substantial, and with the most severe form of acute GvHD, as many as half of patients can die from this disease. For these high-risk transplants, there is no fully effective GvHD prevention strategy. I have studied first generation anti-CD40L antibodies previously and I’m excited to test the effects of Tonix’s Fc-modified anti-CD40L.”
Dr. Lederman continued, “The application that we envision is for post-HCT, when the GvHD-causing alloreactive T cells are at peak activation. This is the timing for post-transplant cyclophosphamide that has been shown to decrease chronic GvHD, allow for haplo-identical transplants and shorten the period of profound immunosuppression. In post-transplant cyclophosphamide therapy, the effect is targeted to the appropriate cells by the cell cycle of activated T cells. In CD40L therapy, we believe appropriate T cells may be targeted by the transient expression of CD40L. To be successful, the post-HCT indication requires prolonged engraftment. Anti-CD40L is already used in solid organ transplant tolerance models (and therapy) that only require transient chimerism.”
About TNX-1500
TNX-15001 (Fc-modified anti-CD40L mAb) is a humanized monoclonal antibody that interacts with the CD40-ligand (CD40L), which is also known as CD154. TNX-1500is 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 is expected to be initiated in the first half of 2023. TNX-1500 is a third generation anti-CD40L mAb that has been designed by protein engineering to decrease FcγRII binding and to reduce the potential for thrombosis. In June 2022, Tonix announced data from three oral presentations at the 2022 American Transplant Congress by faculty at the Center for Transplantation Sciences, Massachusetts General Hospital. The data involved studies of TNX-1500 in development for the prevention of organ transplant rejection. The animal studies found that TNX-1500 showed activity in preventing organ rejection and was well tolerated in non-human primates. Blockade of CD40L with TNX-1500 monotherapy consistently and safely prevented pathologic alloimmunity in non-human primate models of cardiac and kidney allograft transplantation without clinical thrombosis. Copies of the presentations are available under Scientific Presentations on the Tonix Pharmaceuticals corporate website at www.tonixpharma.com.
1TNX-1500 is a biologic at the pre-IND stage of development and has not been approved for any indication
Tonix Pharmaceuticals Holding Corp.*
Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’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 (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022 and expects interim data in the second 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 first quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is expected to enter the clinic with a Phase 2 study in the first quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease 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 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 and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the first half of 2023. Tonix’s infectious disease pipeline consists of a vaccine in development to prevent smallpox and monkeypox, next-generation vaccines to prevent COVID-19, and a platform to make fully human monoclonal antibodies to treat COVID-19. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in Kenya in the first half of 2023. Tonix’s lead vaccine candidate for COVID-19 is TNX-1850, a live virus vaccines based on Tonix’s recombinant pox live virus vector vaccine platform.
*All of Tonix’s product candidates are investigational new drugs or biologics and have not been approved for any indication.
This press release and further information about Tonix can be found at www.tonixpharma.com.
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