Tag: TNXP

Research News and Market Data on TNXP

June 26, 2023 7:00am EDTDownload as PDF

Zembrace® SymTouch® (sumatriptan injection) and Tosymra® (sumatriptan nasal spray) are Indicated for the Treatment of Acute Migraine in Adults

Strategic Acquisition Helps Build Tonix’s Commercial Capabilities and Infrastructure Ahead of Potential Launch of TNX-102 SL for the Treatment of Fibromyalgia

Acute Migraine Products Complement Tonix’s Current Intranasal Clinical Development Program of TNX-1900 for Migraine Prevention

Injection and Nasal Spray Products that Bypass the Gastrointestinal Tract Have the Potential to Provide Treatment Options for Migraine Associated with Nausea

CHATHAM, N.J., June 26, 2023 (GLOBE NEWSWIRE) —  Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix Pharmaceuticals or Tonix) and its wholly-owned subsidiary Tonix Medicines, Inc. (Tonix Medicines), a clinical-stage biopharmaceutical company, today announced that they have entered into an agreement to acquire two currently-marketed products from Upsher-Smith Laboratories, LLC (Upsher-Smith): Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are both indicated for the treatment of acute migraine with or without aura in adults. Zembrace SymTouch is the only branded sumatriptan autoinjector professionally promoted in the United States and is designed for ease of use and favorable tolerability with a low 3 mg dose.^1,3 Tosymra is a novel intranasal sumatriptan product formulated with a permeation enhancer that provides rapid and efficient absorption of sumatriptan.^4,5 Collectively, these products generated product sales of approximately $23 million for the full year 2022.⁶ Zembrace SymTouch and Tosymra each may provide onset of migraine pain relief in as few as 10 minutes for some patients and currently have patent protection to 2036 and 2031, respectively.^1,4

Under the terms of the agreement with Upsher-Smith:

• Tonix Medicines will make an upfront payment of $12 million in cash to Upsher-Smith at closing and an additional $3 million in March 2024, or upon earlier conclusion of the transition services period.
• In addition, Tonix Medicines will pay approximately $10 million in cash to Upsher-Smith at closing to acquire certain product-related inventories.
• To support the transition of the products, Upsher-Smith has agreed to provide certain commercial operations, regulatory and other transition services to Tonix Medicines for up to nine months after closing, in exchange for agreed upon service fees.
• The assets to be acquired include New Drug Applications issued by the U.S. Food & Drug Administration for the products, as well as patents and trademarks related to the products in the United States and in certain countries outside the United States.
• The closing is expected to take place on June 30, 2023.

“Approximately 16% of Americans suffer from migraines, which represents about 40 million patients in the U.S.⁷,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Sumatriptan remains the acute migraine ‘gold standard’ treatment for many patients and continues to represent the largest segment of the market in terms of unit sales.⁸ With migraine pain relief possible in as few as ten minutes for some patients and convenient administration, we believe both Zembrace SymTouch and Tosymra are well-suited to address the unmet needs of patients using traditional or emerging oral acute migraine medications, particularly for rapid-onset treatment.”

“Despite increasing options for prevention and treatment of migraine, migraine headaches and breakthrough migraine headaches remain significant unmet needs, and can lead to emergency room visits,” said Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals. “For adults needing acute treatment of migraine, Zembrace SymTouch and Tosymra have the potential to be first-line treatments or ‘rescue’ medications for breakthrough migraines, due to their fast onset of action and high pain-relief rates. For certain patients who present to ERs, Zembrace SymTouch and Tosymra also provide ER staff a straightforward acute treatment option. Additionally, because both of these products bypass the gastrointestinal tract, they have the potential to provide a treatment option for migraines complicated by severe nausea and vomiting.”

“These two products are a strategic fit for our company, and we look forward to working with Upsher-Smith to ensure a smooth product transition. To that end, this transaction includes established manufacturing and supplier relationships that allow for a seamless transition of manufacturing and supply chain responsibilities. The franchise today is supported by managed care contracts covering approximately 200 million lives. During the transition, we expect to secure our own contracts,” said James Hunter, Executive Vice President of Commercial Operations at Tonix Pharmaceuticals and President of Tonix Medicines.

Dr. Lederman concluded, “In addition to the potential growth that these two on-market products represent over time, the acquisition helps build Tonix’s commercial capabilities ahead of the potential launch of our TNX-102 SL product candidate for the treatment of fibromyalgia. In addition, these products align strongly with our TNX-1900 (intranasal potentiated oxytocin) product candidate, in clinical development for the prevention of chronic migraine. This is an important step in the evolution of Tonix into a fully integrated pharmaceutical company.”

Zembrace SymTouch (sumatriptan injection) 3 mg is the only actively promoted brand of sumatriptan autoinjector in the United States (other sumatriptan autoinjector products on the market are Imitrex® and generics to Imitrex®). It has a unique low dose and has demonstrated onset of migraine pain relief in as few as 10 minutes (17% of patients vs. 5% for placebo).⁹ Zembrace SymTouch also demonstrated migraine pain freedom for 46% of patients (vs 27% for placebo) at 2 hours in a single-attack, double-blind study (N=230).² Zembrace SymTouch currently has patent protection to 2036. Tosymra (sumatriptan nasal spray) 10 mg employs Intravail® permeation enhancer technology and is pharmacokinetically equivalent to 4 mg subcutaneous sumatriptan.^3,4 Tosymra delivers migraine pain relief in as little as 10 minutes with just one spray for some patients (13% vs. 5% for placebo).^4,9,10 Tosymra currently has patent protection to 2031.

About Migraine

Nearly 40 million people in the United States suffer from migraine⁶ and it has been recognized as the second leading cause of disability in the world.¹¹ 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).¹²

References:

1. Zembrace SymTouch [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, LLC: February 2021.
2. Landy, S. et al. Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: a multicenter, randomized, double-blind, placebo-controlled study. J Headache Pain. 19, 69 (2018).
3. Brand-Schieber E, Munjal S, Kumar R, et al. Human factors validation study of 3 mg sumatriptan autoinjector, for migraine patients. Med Devices (Auckl). 2016;9:131-137.
4. Tosymra [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, LLC: Feb 2021.
5. Maggio ET. Intravail®: highly effective intranasal delivery of peptide and protein drugs. Expert Opinion Drug Delivery. 2006;3(4):529-539.
6. IQVIA 2022 retail sales from the National Sales Perspectives (NSP) audit within the SMART database estimates Zembrace sales of ~$19.6 M and Tosymra sales of ~$3.5 M
7. Buse et al. Burden of Illness Among People with Migraine and ≥ 4 Monthly Headache Days While Using Acute and/or Preventive Prescription Medications for Migraine. Journal of Managed Care & Specialty Pharmacy. 2020;26(10):1334-1343.
8. Upsher-Smith Laboratories; Data on File; 2023
9. Mathew NT, et al. Dose ranging efficacy and safety of subcutaneous sumatriptan in the acute treatment of migraine. US Sumatriptan Research Group. Arch Neurol. 1992;49(12):1271-1276.
10. Wendt J, et al. A randomized, double-blind, placebo-controlled trial of the efficacy and tolerability of a 4-mg dose of subcutaneous sumatriptan for the treatment of acute migraine attacks in adults. Clinical Therapeutics. 2006;28(4):517-526.
11. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018;17(11):954-976.
12. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211.

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.

Tosymra® (sumatriptan nasal spray): IMPORTANT SAFETY INFORMATION

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.

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 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-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 first quarter of 2024. 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.

Investor Contact

Jessica Morris
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 904-8182

Peter Vozzo
ICR Westwicke
peter.vozzo@westwicke.com
(443) 213-0505

Media Contact

Ben Shannon
ICR Westwicke
ben.shannon@westwicke.com
(919) 360-3039

Zembrace, SymTouch and Tosymra are registered trademarks of Upsher-Smith Laboratories, LLC. Intravail is a registered trademark of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis, Inc. All other marks are the property of their respective owners.

Research News and Market Data on TNXP

June 15, 2023 7:00am EDT

Previously Disclosed Data Demonstrated that TNX-102 SL Achieved Statistically Significant Pain Reduction Over Placebo at Week 14 (Primary Endpoint, p=0.01) and Was Generally Safe and Well Tolerated

Topline Data from RESILIENT, a Potentially Confirmatory Registration-Enabling Phase 3 Fibromyalgia Trial of TNX-102 SL, Expected Fourth Quarter 2023

CHATHAM, N.J., June 15, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, today announced that previously disclosed results from the Phase 3 RELIEF study of TNX-102 SL for the management of fibromyalgia have been published in the peer-reviewed journal Arthritis Care & Research, an official journal of the American College of Rheumatology. In RELIEF, treatment with TNX-102 SL was associated with significant reductions in daily pain and was generally safe and well tolerated in patients with fibromyalgia. Secondary results also suggest that treatment with TNX-102 SL can improve sleep and reduce fatigue, which together with pain are recognized as core fibromyalgia symptoms. TNX-102 SL is a novel, non-opioid, centrally-acting analgesic, intended to be taken once daily at bedtime. The paper can be accessed online at https://pubmed.ncbi.nlm.nih.gov/37165930/.

“There continues to be a pressing need for novel, safe and more tolerable drugs to treat patients with fibromyalgia, a debilitating chronic disease that afflicts an estimated 6 to 12 million adults in the United States, with symptoms including multisite pain and disturbed sleep,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Current fibromyalgia therapies have limited efficacy in alleviating symptoms of sleep disturbance and fatigue. These Phase 3 RELIEF data suggest that treatment with TNX-102 SL may improve sleep quality and fatigue in patients with fibromyalgia, in addition to reducing pain.”

The paper, titled, “Efficacy and Safety of TNX-102 SL (Sublingual Cyclobenzaprine) for the Treatment of Fibromyalgia: Results From the Randomized, Placebo Controlled RELIEF Trial,” includes data demonstrating that TNX-102 SL met its pre-specified primary endpoint in the Phase 3 RELIEF trial, significantly reducing daily pain compared to placebo (p=0.01) in participants with fibromyalgia. Also, in an exploratory analysis, when the primary endpoint was analyzed as a ≥30% pain responder analysis, there was a higher rate of responders to TNX-102 SL (47%) than to placebo (35%; p=0.006). TNX-102 SL at 5.6 mg also showed activity in key secondary endpoints demonstrating improvements in sleep quality, mitigation of fatigue and fibromyalgia-specific global symptomatic and functional recovery.

Early discontinuation rates were similar for TNX-102 SL and placebo (17.7% and 16.5%, respectively). In addition, TNX-102 SL was well tolerated with the most common adverse event from active treatment being oral numbness or hypoaesthesia, an administration site reaction that is typically transient, was never rated as severe, and lead to only one discontinuation.

Tonix is currently enrolling in a potentially confirmatory, registration-enabling Phase 3 study (RESILIENT). Topline results are expected in the fourth quarter of this year.

About Fibromyalgia

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, 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.

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.

For more information, see ClinicalTrials.gov Identifier: NCT05273749.

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-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. 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 first quarter of 2024. 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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 904-8182

Maddie Stabinski (media)
Russo Partners
madeline.stabinski@russopartnersllc.com
(212) 845-4273

Peter Vozzo (investors)
ICR Westwicke
peter.vozzo@westwicke.com
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Released June 15, 2023

Research News and Market Data on TNXP

June 07, 2023 7:00am EDT

Research Directed by Faculty of the Center for Transplantation Sciences, Massachusetts General Hospital

TNX-1500 is Expected to Enter Phase 1 Clinical Development in Third Quarter 2023

CHATHAM, N.J, June 07, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced data from two oral presentations and one poster presentation at the 2023 American Transplant Congress (ATC) by faculty at the Center for Transplantation Sciences, Massachusetts General Hospital. The data involve studies of Tonix’s TNX-1500 (Fc-modified anti-CD40L monoclonal antibody) in development for the prevention of organ transplant rejection. The molecular target of TNX-1500 is CD40-ligand (CD40L), which is also known as CD154. Copies of the presentations are available on the Tonix Pharmaceuticals website at www.tonixpharma.com.

The oral presentations titled, “Fc-Modified anti-CD154 Mab Induced Long Term Renal Allograft Survival without Thromboembolic Complications” by Dr. Ryo Otsuka et al. and “Efficacy of CD154 Blockade with TNX-1500 to prevent heart allograft immune injury” by Dr. Ikechukwu Ileka et al., and the poster presentation titled “anti-CD154 mAb (TNX-1500) Alone, or in Combination with Rapamycin, MMF, or anti-CD28 mAb (VEL-101) Prolongs Cynomolgus Cardiac Allograft Survival” by Dr. Kohei Kinoshita et al. include data demonstrating 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 prevented pathologic alloimmunity in non-human primate kidney and cardiac allograft models without clinical thrombosis. Dr. Kinoshita was recognized with “Poster of Distinction” for his poster presentation.

“The animal studies found that TNX-1500 retains activity to prevent rejection and preserve graft function, which we believe provides strong rationale for us to pursue development of TNX-1500 to prevent rejection in human transplant,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “We expect to begin a Phase 1 trial with TNX-1500 in the third quarter of 2023. There remains a significant need for new treatments with improved activity and tolerability to prevent organ transplant rejection. 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. We believe TNX-1500 has the potential for treating and preventing organ transplant rejection. Beyond transplantation, we believe TNX-1500 has potential for treating autoimmune conditions including systemic lupus erythematosus, Sjögren’s syndrome and multiple sclerosis.”

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-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. 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 first quarter of 2024. 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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 904-8182

Maddie Stabinski (media)
Russo Partners
Madeline.Stabinski@russopartnersllc.com
(212) 845-4273

Peter Vozzo (investors)
Westwicke/ICR
peter.vozzo@westwicke.com
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Released June 7, 2023

Research News and Market Data on TNXP

June 05, 2023 7:00am EDT

Tianeptine’s Mechanism of Restoring Neuroplasticity and Neurogenesis by Dual PPAR-β/δ and PPAR-γ Agonism Supports Development as a First-in-Class Oral Therapy for Psychiatric and Neurodegenerative Diseases

Racemic Tianeptine, or TNX-601 ER, is Enrolling in a Potentially Pivotal Phase 2 Study for the Treatment of Major Depressive Disorder; Results from Interim Analysis Expected Fourth Quarter 2023

Single (S)-Isomer of Tianeptine, or TNX-4300, is Free from µ-Opioid Receptor Activity Associated with the (R)-Isomer

TNX-4300 is in Preclinical Development for Depression, Bipolar Disorder, Alzheimer’s Disease and Parkinson’s Disease

CHATHAM, N.J., June 05, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced the presentation of data detailing the mechanism of action and pharmacokinetics of TNX-601 ER (tianeptine hemioxalate extended release) and TNX-4300 (estianeptine) at the American Society of Clinical Psychopharmacology (ASCP) meeting in Miami, Fla. TNX-601 ER is being tested in a potentially pivotal Phase 2 trial for the treatment of major depressive disorder (MDD) for which results of a preplanned interim analysis are expected in the fourth quarter of 2023. TNX-4300 is in preclinical development for mood disorders, Alzheimer’s disease and Parkinson’s disease. The active ingredient of both products is the (S)-isomer of tianeptine.¹ The (S)-isomer of tianeptine activates PPAR-β/δ, restores neuroplasticity in neuronal tissue culture and lacks µ-opioid liability. In contrast, the (R)-isomer of tianeptine lacks PPAR-β/δ activity and is an agonist at the µ-opioid receptor. The poster presentation is available on Tonix’s website: www.tonixpharma.com.

Tonix recently announced that the plastogen anti-depressant tianeptine, a drug marketed outside the U.S. for more than 30 years, acts on nuclear PPAR-β/δ and PPAR-γ in neurons and glia to restore neuronal connectivity in depression.² The understanding that tianeptine bypasses the synapse and acts on the nucleus to exert its effects on restoring neuroplasticity and neurogenesis has direct applicability in a number of neurodegenerative diseases in which neuronal connections are atrophying.² The newly reported mechanism also provides clarity on why tianeptine is not associated with sexual dysfunction, weight gain or several other treatment-limiting toxicities, which are associated with the antidepressants currently marketed in the U.S. for long-term use.

“Restoring atrophied neuronal connections in psychiatric and neurodegenerative diseases has the potential to achieve better and more durable outcomes,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “The tianeptine marketed outside the U.S. for treating depression is a 1:1 racemic mixture of two mirror image isomers. Our team of scientists isolated and characterized the (S)-isomer of tianeptine, which is free from µ-opioid receptor activity and is now under development as TNX-4300 for treating psychiatric and neurodegenerative diseases. The (S)-isomer of tianeptine is responsible for tianeptine’s activity on PPAR-β/δ and restoring neuroplasticity and neurogenesis, while the (R)-isomer is responsible for any off-target activity on the µ-opioid receptor.”

The findings reported at the meeting show how the pharmacokinetics of oral TNX-601 ER in humans differ from intraperitoneal (i.p.) tianeptine in mice. In humans, after an oral dose of TNX-601 ER the half-life of tianeptine in the blood is approximately 5-7 hours. In contrast, in mice after an i.p. dose of tianeptine the half-life of tianeptine in the blood has been reported to be less than approximately 30 minutes and the behavioral effects appear dominated by the longer-lasting MC5 metabolite, which maintains µ-opioid receptor activity.³ The data Tonix presented also show that the (R)-isomer of tianeptine is responsible for the decrease in immobility in the mouse forced swim test after i.p. administration, which is consistent with previous reports that the effect of tianeptine on the forced swim test is a µ-opioid receptor-dependent phenomenon.³

Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals, said, “From our clinical studies on volunteers, after oral dosing with TNX-601 ER, the extended pharmacokinetics of parent tianeptine is consistent with tianeptine exerting activity on PPAR-β/δ and resulting in neurorestorative effects. In contrast, after i.p. dosing of tianeptine in mice, the exposure of tianeptine is brief and the behavioral effects appear dominated by the MC5 metabolite.³ While tianeptine’s MC5 metabolite has been reported to maintain µ-opioid receptor activity³, we found that MC5 metabolite lacks activity on either PPAR-β/δ or PPAR-γ in culture. Together, we believe these findings support the interpretation that the parent tianeptine and specifically, the (S)-isomer of tianeptine exert antidepressant effects in humans by interacting with PPAR-β/δ and PPAR-γ.”

Dr. Sullivan continued, “Our ongoing work on racemic tianeptine in depression is expected to inform and potentially accelerate the development of TNX-4300. The dose of tianeptine for treating depression is well-established from racemic studies, so we plan to test single isomer TNX-4300 at a dose equivalent to 50% of the racemic dose, which is expected to provide equivalent exposure of (S)-tianeptine as racemic tianeptine. Subsequently, we plan to test higher doses of (S)-tianeptine, because TNX-4300 lacks µ-opioid receptor activity, but such studies will require additional non-clinical studies.”

Key experiments were performed by scientists at Tonix’s Research and Development Center (RDC) in Frederick, Maryland.

^* TNX-601 and TNX-4300 are investigational new drugs and are not approved for any indication
¹Tonix press release, May 23, 2023 https:// ir.tonixpharma.com/news-events/press-releases/detail/1392/tonix-pharmaceuticals-announces-the-isolation-and
²Tonix press release, May 17, 2023 https://ir.tonixpharma.com/news-events/press-releases/detail/1389/tonix-pharmaceuticals-announces-pharmacology-and-medicinal
³ Samuels et al., Neuropsychopharmacology. 2017, 42(10):2052-2063

About Tianeptine

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-weeks^4-8, 3-months⁹, or 12-months¹⁰ of treatment. (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 disorder^11,12 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 system¹³ and the concept that Alzheimer’s can be considered a form of diabetes that affects the CNS, or type-III diabetes.”¹⁴ 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.
¹¹ García-Alberca JM, et al. J Alzheimer’s Dis 2022, 88 (2), 707-720.
¹² Kauer-Sant’Anna M, et al. J Psychopharmacol 2019, 33 (4), 502-510.
¹³ Kahremany S et al. Br J Pharmacol 2015, 172(3):754-70
¹⁴ Nguyen et al., Int J Mol Sci. 2010, 21(9):3165

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-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. 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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 904-8182

Maddie Stabinski (media)
Russo Partners
Madeline.Stabinski@russopartnersllc.com
(212) 845-4273

Peter Vozzo (investors)
Westwicke/ICR
peter.vozzo@westwicke.com
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Released June 5, 2023

Research News and Market Data on TNXP

May 31, 2023 7:00am EDT

Research Directed by Faculty of the Center for Transplantation Sciences, Massachusetts General Hospital

CHATHAM, N.J., May 31, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced an upcoming oral presentation by Ryo Otsuka, Ph.D., and poster presentation by Kohei Kinoshita, M.D at the 2023 American Transplant Congress (ATC). Both presenters are faculty members at the Center for Transplantation Sciences, Massachusetts General Hospital, and collaborators of Tonix. The Congress is being held June 3-7, 2023, in San Diego, Calif. The research involves studies of Tonix’s TNX-1500 (Fc-modified anti-CD40L monoclonal antibody) for the prevention of renal and cardiac allograft rejection.   A copy of the presentation and poster will be made available on the Scientific Presentations page of the Tonix website at www.tonixpharma.com following the congress.

Oral Presentation Details
Title:		Fc-Modified Anti-Cd154 Mab Induced Long Term Renal Allograft Survival without Thromboembolic Complications
Authors:		R. Otsuka, G. Lassiter, T. Hirose, A. Karadagi, T. Tomosugi, I. Rosales, T. Kawai
Date:		Tuesday, June 6, 2023
Time:		6:00 p.m. PT
Location:		Ballroom 6E Upper Level, San Diego Convention Center, San Diego, Calif.
Number:		Presentation 544
Poster Presentation Details
Title:		aCD154mAb (TNX-1500) Alone, or in Combination with Rapamycin, MMF, or aCD28mAb (VEL-101) Prolongs Cynomolgus Cardiac Allograft Survival
Authors:		K. Kinoshita, A. Maenaka, Z. Habibabady, G. McGrath, R. Chaban, I. Ileka, M. Ma, V. Diaz, I. Rosales, S. Fogarty, P. Maguire, B. Daugherty, S. Lederman, R. Pierson III
Date:		Saturday, June 3, 2023
Time:		5:30 – 7:30 p.m. PT
Location:		Exhibit Halls A & B1, San Diego Convention Center, San Diego, Calif.
Number:		Poster Board A030

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-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. 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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 904-8182

Maddie Stabinski (media)
Russo Partners
madeline.stabinski@russopartnersllc.com
(212) 845-4273

Peter Vozzo (investors)
ICR Westwicke
peter.vozzo@westwicke.com
(443) 213-0505

Research, News and Market Data on TNXP

May 25, 2023 4:05pm EDT

CHATHAM, N.J., May 25, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that it has regained compliance with the minimum bid price requirement for continued listing on The Nasdaq Capital Market. On May 24, 2023, Tonix received a letter from The Nasdaq Stock Market LLC stating that because Tonix’s shares had a closing bid price at or above $1.00 per share for a minimum of 10 consecutive business days, Tonix’s stock had regained compliance with the minimum bid price requirement of $1.00 per share for continued listing on The Nasdaq Capital Market, as set forth in Nasdaq Listing Rule 5550(a)(2), and the matter is now closed.

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-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. 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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 904-8182

Maddie Stabinski (media)
Russo Partners
madeline.stabinski@russopartnersllc.com
(212) 845-4273

Peter Vozzo (investors)
ICR Westwicke
peter.vozzo@westwicke.com
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Released May 25, 2023

Research News and Market Data on TNXP

May 25, 2023 7:00am EDT

CHATHAM, N.J., May 25, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, today announced that Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals, will present a poster at the 2023 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting being held May 30 – June 2, 2023, at the Loews Miami Beach Hotel in Miami Beach, Florida. The poster will provide an update on the status of the Phase 2 UPLIFT study of TNX-601 ER* (tianeptine hemioxalate extended-release tablets) for the treatment of major depressive disorder (MDD). The poster will also highlight advances in the understanding of tianeptine’s mechanism of action and provide new details regarding the preclinical development of the (S)-isomer of tianeptine, TNX-4300* (estianeptine) for MDD, Alzheimer’s disease, and Parkinson’s disease.

A copy of the Company’s poster will be available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com following the conference.

Poster Presentation Details

Title:	A Randomized Placebo-Controlled Multicenter Trial of Monotherapy with TNX-601 ER* (Tianeptine Hemioxalate Extended-Release Tablets) for Treatment of Major Depressive Disorder (MDD)
Location:	Loews Miami Beach Hotel, Miami Beach, Florida
Salon No.:	Salon 4
Date:	Thursday, June 1, 2023
Time:	12:30 p.m. – 2:15 p.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 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-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. 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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 904-8182

Maddie Stabinski (media)
Russo Partners
madeline.stabinski@russopartnersllc.com
(212) 845-4273

Peter Vozzo (investors)
ICR Westwicke
peter.vozzo@westwicke.com
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Released May 25, 2023

Research News and Market Data on TNXP

May 24, 2023 7:00am EDT

CHATHAM, N.J., May 24, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, announced today that Jessica Morris, Chief Operating Officer of Tonix Pharmaceuticals, will present at the June 1^st Virtual Investor Summit on Thursday, June 1, 2023, at 10:30 a.m. ET.

Investors interested in arranging a meeting with the Company’s management during the conference should contact the Investor Summit conference coordinator. A webcast of the presentation can be found here and will be available under the IR Events tab of the Tonix website at www.tonixpharma.com.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a 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-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. 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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 904-8182

Maddie Stabinski (media)
Russo Partners
madeline.stabinski@russopartnersllc.com
(212) 845-4273

Peter Vozzo (investors)
ICR Westwicke
peter.vozzo@westwicke.com
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Released May 24, 2023

Research News and Market Data on TNXP

May 22, 2023 7:00am EDT

Intranasal Oxytocin Blocks the Release of CGRP in Animal Models

Intranasal Oxytocin is the Core Technology of TNX-1900 for Migraine

Oxytocin Treatment Affects a Pathway that is Distinct from the Recently Available CGRP Migraine Treatment Drug Class

CHATHAM, N.J., May 22, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, today announced that it has entered into a research collaboration agreement to evaluate the effect of TNX-1900 (intranasal potentiated oxytocin) on capsaicin- or electrical stimulation-induced forehead dermal blood flow in healthy female human volunteers. Dr. Antoinette Maassen van den Brink, Professor of Neurovascular Pharmacology, Erasmus University Medical Center, will serve as principal investigator for the study.

“Collaborating with Professor Maassen van den Brink is an exciting opportunity to learn about the potential for TNX-1900 for treating migraine, facial pain and other related conditions,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “In animal studies, intranasal oxytocin blocks the release of calcitonin gene-related peptide (CGRP) release from trigeminal neurons.¹ CGRP is released from trigeminal neurons during a migraine attack and several CGRP inhibitors are approved for the treatment of migraine. Both a CGRP inhibitor and a triptan have been successfully tested in the model and have been found to inhibit the forehead dermal blood flow response to capsaicin in migraineurs and healthy volunteers, respectively.^2,3 We look forward to learning the results of TNX-1900 in this proof-of-concept study. Together with other studies, the results will guide future development of this potential non-addictive treatment for migraine and other painful conditions.”

Dr. Maassen van den Brink, the principal investigator of the study said, “The signaling pathways that mediate migraine and facial pain are becoming understood. Oxytocin represents a potential new therapeutic option, targeting a pathway in migraine that is distinct from the recently available CGRP inhibitor migraine treatment drug class.”

In February 2023, Tonix initiated enrollment in its Phase 2 PREVENTION study of TNX-1900 for chronic migraine. The Company expects topline results in the fourth quarter of this year.

About Migraine

Migraine is a neurovascular condition that typically manifests in a throbbing moderate to severe headache which lasts at least four hours, often on one side of the head and aggravated by routine physical activity. It can also be accompanied by nausea, vomiting, visual disturbances, and sensitivity to bright light and loud noises.⁴ Epidemiological studies indicate that globally, approximately 1.2 billion individuals suffer from migraines annually.⁵ In the U.S., approximately 39 million Americans suffer from migraines and among these individuals, approximately four million experience chronic migraines (15 or more headache days per month, at least eight of which are migraines).⁵ The current FDA approved drugs for migraine prevention in chronic migraine include Botox^® (onabotulinumtoxin), and the anti-CGRP/CGRP-receptor monoclonal antibodies Aimovig^® (erenumab), Vyepti^® (eptinezumab), Ajovy^® (fremanezumab) and Emgality^® (galcanezumab).

About TNX-1900

TNX-1900 (intranasal potentiated oxytocin) is a proprietary formulation of oxytocin in development as a candidate for prevention of chronic migraine and other conditions. In 2020, TNX-1900 was acquired from Trigemina, Inc. who had licensed the technology underlying the composition and method from Stanford University. TNX-1900 is a drug-device combination product, based on an intranasal actuator device that delivers oxytocin into the nasal cavity. Oxytocin is a naturally occurring human peptide hormone that also acts as a neurotransmitter in the brain. Oxytocin has no recognized addiction potential. It has been observed that low oxytocin levels in the body are associated with increases in migraine headache frequency, and that increased oxytocin levels are associated with fewer migraine headaches. Certain other chronic pain conditions are also associated with decreased oxytocin levels. Migraine attacks are caused, in part, by the activity of pain-sensing trigeminal neurons which, when activated, release calcitonin gene-related peptide (CGRP) which binds to receptors on other nerve cells and starts a cascade of events that is believed to result in migraine. Oxytocin when delivered via the nasal route, concentrates in the trigeminal system⁶ resulting in binding of oxytocin to receptors on neurons in the trigeminal system, inhibiting the release of CGRP and transmission of pain signals returning from the site of CGRP release.¹ Blocking CGRP release is a distinct mechanism compared with CGRP receptor antagonist and anti-CGRP antibody drugs, which block the binding of CGRP to its receptor, or bind to the peptide CGRP. With TNX-1900, the addition of magnesium to the oxytocin formulation enhances oxytocin receptor binding⁷ as well as its inhibitory effects on trigeminal neurons and resultant craniofacial analgesic effects, as demonstrated in animal models.⁸ Intranasal oxytocin has been shown to be well tolerated in several clinical trials in both adults and children⁹. Targeted nasal delivery results in low systemic exposure and lower risk of non-nervous system, off-target effects, which could potentially occur with systemic CGRP receptor antagonists and anti-CGRP (receptor) antibodies¹⁰. For example, CGRP has roles in dilating blood vessels in response to ischemia, including in the heart. The Company believes nasally targeted delivery of oxytocin could translate into selective blockade of CGRP release from neurons in the trigeminal ganglion and not throughout the body, which could be a potential safety advantage over systemic CGRP inhibition. In addition, daily dosing is more rapidly reversible, in contrast to monthly or quarterly dosing, as is the case with anti-CGRP antibodies, giving physicians and their patients greater control. In addition to chronic migraine, TNX-1900 will be developed for treatment of episodic migraine, craniofacial pain conditions, binge eating disorder, and insulin resistance. Tonix also has a license with the University of Geneva to use TNX-1900 for the treatment of insulin resistance and related conditions.

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.
¹Tzabazis A, et al. Cephalalgia. 2016. 36(10):943-50.
²de Vries Lentsch S, et al. CGRP-mediated trigeminovascular reactivity in migraine patients treated with
erenumab. J Neurol Neurosurg Psychiatry. 2022 Aug;93(8):911-912.
³Ibrahimi K, et al. A human trigeminovascular biomarker for antimigraine drugs: A randomized double-blind, placebo-controlled, crossover trial with sumatriptan. Cephalalgia. 2017 Jan;37(1):94-98.
⁴The International Classification of Headache Disorders, 3^rd Edition. Cephalalgia. 2018. 38(1):1-211
⁵Burch et al., Migraine: Epidemiology, Burden, and Comorbidity, Neurol Clin 37 (2019):631–649
⁶Yeomans DC, et al. Transl Psychiatry. 2021. 11(1):388.
⁷Antoni FA and Chadio SE. Biochem J. 1989. 257(2):611-4.
⁸Cai Q, et al., Psychiatry Clin Neurosci. 2018. 72(3):140-151.
⁹Yeomans, DC et al. 2017. US patent US2017368095
¹⁰MaassenVanDenBrink A, et al. Trends Pharmacol Sci. 2016. 37(9):779-788

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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 904-8182

Maddie Stabinski (media)
Russo Partners
madeline.stabinski@russopartnersllc.com
(212) 845-4273

Peter Vozzo (investors)
ICR Westwicke
peter.vozzo@westwicke.com
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Released May 22, 2023

Research News and Market Data on TNXP

May 18, 2023 7:00am EDTDownload as PDF

CHATHAM, N.J., May 18, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, announced today that management will participate in the A.G.P. Virtual Healthcare Conference and host investor meetings. The conference is being held May 23-24, 2023.

In addition, Seth Lederman, M.D., Chief Executive Officer of Tonix, will participate in a panel discussion titled, “New Approaches to Depression,” scheduled from 12:00 p.m. – 1:00 p.m. ET, Tuesday, May 23, 2023.

Investors interested in arranging a meeting with the Company’s management during the conference should contact the conference coordinator or Ian Frost at ian.frost@westwicke.com.

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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 904-8182

Maddie Stabinski (media)
Russo Partners
madeline.stabinski@russopartnersllc.com
(212) 845-4273

Peter Vozzo (investors)
ICR Westwicke
peter.vozzo@westwicke.com
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Released May 18, 2023