Tag: TNXP

Research News and Market Data on TNXP

November 09, 2023 4:15pm EST

Topline Results from Phase 3 Potentially NDA-Enabling Study of TNX-102 SL in Fibromyalgia Expected Late December 2023: Centrally-Acting Non-Opioid Analgesic

Topline Results from Phase 2 Proof-of-Concept Study of TNX-1900 in Chronic Migraine Expected Early December 2023: Intranasal Potentiated Oxytocin

Meaningful Progress Made in Obtaining External Support for Clinical Trials from U.S. Government Agencies and Other Institutions

Revenue from Marketed Acute Migraine Products: Zembrace^® SymTouch^® (sumatriptan injection) and Tosymra^® (sumatriptan nasal spray) Included in Third Quarter Financial Statements

CHATHAM, N.J., Nov. 09, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced financial results for the third quarter ended September 30, 2023, and provided an overview of recent operational highlights.

“Tonix expects topline results from its Phase 3 fibromyalgia study and Phase 2 chronic migraine study before year end,” said Seth Lederman, M.D., Chief Executive Officer of Tonix. “The Phase 3 RESILIENT trial in fibromyalgia, if successful, is expected to be the final efficacy trial required for submitting a New Drug Application (NDA) for approval by the U.S. Food and Drug Administration (FDA) for TNX-102 SL (cyclobenzaprine HCl sublingual tablets). In the Phase 2 proof-of-concept PREVENTION study in chronic migraine of TNX-1900 (intranasal potentiated oxytocin), all patients have completed their final visit and topline results are expected in early December 2023.”

Dr. Lederman continued, “We are continuing to shift the expense of clinical trials from our operating budget to U.S. government agencies and other institutions through partnerships. The U.S. Department of Defense (DoD) is supporting the upcoming Phase 2 study of TNX-102 SL in acute stress disorder, being conducted and sponsored by University of North Carolina (UNC). The U.S. National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID), through its Project NextGen, will conduct the Phase 1 study of our vaccine candidate TNX-1800 (modified recombinant horsepox virus, live vaccine). The National Institute of Drug Abuse (NIDA) is supporting our Phase 2 study of TNX-1300 (recombinant double mutant cocaine esterase) for cocaine intoxication. Massachusetts General Hospital (MGH) is conducting Phase 2 studies of TNX-1900 in binge eating disorder and pediatric obesity, and the University of Washington is conducting a Phase 2 study of TNX-1900 in social anxiety disorder. Finally, we continue to collaborate with MGH on several preclinical non-human primate studies for TNX-1500 (anti-CD40L Fc-modified humanized monoclonal antibody), currently in a Phase 1 study being conducted by Tonix. These outside collaborations leverage our internal resources and allow us to progress our clinical programs in a capital efficient manner.”

Partnerships with External Funding – Recent Highlights

• NIH/NIAID selected Tonix’s vaccine candidate, TNX-1800, as part of Project NextGen; a Phase 1 study is expected to start in the second half of 2024. NIH/NIAID will cover the full cost of the clinical trial, while Tonix will supply the vaccine candidate.
• NIDA is supporting a Phase 2 study on TNX-1300 for cocaine Intoxication; expected to start enrolling patients in the fourth quarter of 2023.
• DoD is supporting a Phase 2 investigator-initiated study of TNX-102 SL for acute stress disorder at UNC for motor vehicle accident victims; expected to start enrolling patients in 2024.
• MGH/Harvard Medical School is conducting Phase 2 investigator-initiated studies of TNX-1900 in binge eating disorder and adolescent obesity.
• The University of Washington is conducting a Phase 2 investigator-initiated study of TNX-1900 in social anxiety disorder.
  
  

Marketed Products – Recent Highlights

• In September 2023, Tonix announced that it is committed to meeting potential increased demand for Tosymra^® (sumatriptan nasal spray) 10 mg after GlaxoSmithKline’s planned discontinuation of Imitrex^® (sumatriptan) nasal spray 5 mg and 20 mg products after January 2024. Tonix is preparing for potential increased demand for Tosymra to help avoid possible drug shortages for patients who suffer from migraines. Tosymra nasal spray is approved on the basis of bioequivalence to Imitrex injection 4 mg.
• Tonix completed the acquisition of Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra from Upsher-Smith Laboratories, LLC in June 2023. Both products are indicated for the treatment of acute migraine with or without aura in adults.
  
  

Key Product Candidates* — Recent Highlights

Central Nervous System (CNS) Pipeline

TNX-102 SL (cyclobenzaprine HCl sublingual tablets): once-daily at bedtime small molecule for the management of fibromyalgia (FM) – a centrally-acting, non-opioid analgesic.

• The Company announced in August 2023 that it completed enrollment of its potentially confirmatory Phase 3 RESILIENT trial of TNX-102 SL 5.6 mg in FM. 457 participants were randomized in the trial, which, if successful, is expected to serve as the final, well-controlled efficacy trial required for submission of NDA for approval by the FDA. RESILIENT is a registration-quality, double-blind, placebo-controlled study. Topline results from the RESILIENT trial are expected in late December of 2023.

TNX-102 SL for the treatment of acute stress reaction (ARS) and acute stress disorder (ASD), and prophylaxis against development of posttraumatic stress disorder (PTSD)

• In September 2023, the Company announced that the UNC Institute for Trauma Recovery has been awarded a $3 million grant from the DoD to investigate the potential of Tonix’s TNX-102 SL to reduce the frequency and severity of adverse effects of acute trauma, which include ASR and ASD, and development of PTSD. The proposed Phase 2, Optimizing Acute Stress Reaction Interventions with TNX-102 SL (OASIS) study will examine the safety and efficacy of TNX-102 SL to reduce adverse posttraumatic neuropsychiatric sequelae among patients presenting to the emergency department (ED) after a motor vehicle collision (MVC). The study will enroll approximately 180 MVC trauma survivors at ED study sites in the U.S. Participants will be randomized in the ED to receive a two-week course of either TNX-102 SL or placebo.
• Initiation of patient enrollment in the proposed investigator-sponsored OASIS study is anticipated in the beginning of 2024, subject to clearance by the FDA of an investigator-initiated Investigational New Drug (IND) application.

TNX-102 SL for the treatment of Fibromyalgia-Type Long COVID, also known as Post-Acute Sequelae of COVID-19 (PASC)

• In September 2023, the Company announced topline results from its Phase 2 PREVAIL proof-of-concept study of TNX-102 SL for fibromyalgia-type Long COVID. TNX-102 SL showed a robust Cohen’s d effect size of 0.5 in improving fatigue relative to placebo; and it showed consistent activity across secondary measures of sleep quality, cognitive function, disability and Patient Global Impression of Change, but did not meet the primary endpoint of multi-site pain reduction at week 14. TNX-102 SL was generally well tolerated and no new safety signals were observed.
• The Company intends to request an End-of-Phase 2 meeting with the FDA to discuss a potential Phase 3 program based on a proposed primary outcome measure using the PROMIS Fatigue scale. The meeting is expected to take place in the first quarter of 2024.

TNX-1900 (intranasal potentiated oxytocin): small peptide for migraine, craniofacial pain, social anxiety disorder (SAD), insulin resistance and related disorders, and adolescent obesity and binge eating disorder

• In October 2023, the Company announced it completed the clinical phase of the PREVENTION study, a Phase 2 proof-of-concept study of TNX-1900 for the prevention of migraine headaches in chronic migraineurs, as the last of 88 enrolled patients completed their final study visit. PREVENTION is a registration-quality, double-blind, placebo-controlled study.
• Topline results from the PREVENTION Phase 2 trial are expected in early December 2023.
• In September 2023, the Company announced that David C. Yeomans, Ph.D. presented data relevant to the proposed mechanism of TNX-1900 in treating chronic migraine in a poster and an oral presentation at the 2023 International Headache Congress (IHC) in Seoul, South Korea. The poster and oral presentation titled, “Human trigeminal ganglia possess oxytocin receptors on CGRP positive neurons: expression increased by inflammation,” include research sponsored by and licensed to Tonix. The presentations show that oxytocin receptors are co-expressed with calcitonin gene-related peptide (CGRP) on human trigeminal ganglia neurons, which is similar to Professor Yeomans’ previous findings in animal trigeminal ganglia. The inflammatory cytokine IL-6 upregulated expression of oxytocin receptors on human trigeminal neurons, consistent with the previously observed impact of inflammation on the potency of oxytocin on its receptor. In animals, oxytocin has been shown to functionally inhibit the excitability of trigeminal neurons, which is consistent with oxytocin inhibiting the release of CGRP at trigeminal nerve terminals.¹
• Tonix announced in July 2023 that the first participant was enrolled in the investigator-initiated Phase 2 STROBE Study of TNX-1900 for the treatment of binge-eating disorder at MGH. Tonix is supporting the STROBE study through a clinical trial agreement with MGH.
• Tonix announced in July 2023 that the first participant was enrolled in a Phase 2 investigator-initiated, proof-of-concept study of TNX-1900 for enhancing social safety learning in SADSAD. Tonix entered into an agreement with the University of Washington to examine the potential role of TNX-1900 in enhancing vicarious extinction learning in SAD, compared to healthy controls.
• Tonix announced in July 2023 that the first participant was enrolled in the Phase 2 POWER study of TNX-1900 for the treatment of pediatric obesity with MGH. MGH is the sponsor of the NIH-funded trial, being conducted under an investigator-initiated IND.

TNX-1300 (recombinant double mutant cocaine esterase): biologic for life-threatening cocaine intoxication

• Tonix expects to initiate a Phase 2 clinical study of TNX-1300 for the treatment of cocaine intoxication in the fourth quarter of 2023. In 2022, Tonix was awarded a Cooperative Agreement grant from NIDA, part of the NIH, to support development of TNX-1300.
• TNX-1300 has been granted Breakthrough Therapy designation by the FDA.

Rare Disease Pipeline

TNX-2900 (intranasal potentiated oxytocin): small peptide for the treatment of Prader-Willi syndrome (PWS)

• In October 2023, Herbert Harris, M.D., Ph.D., Executive Vice President, Translational Medicine of Tonix Pharmaceuticals, provided an overview of Tonix’s TNX-2900 program at the Foundation for Prader-Willi Research (FPWR) Family Conference in Denver, CO. The presentation highlights preclinical data showing the enhancing effects of magnesium (Mg²⁺) on the activation of oxytocin receptors. The Mg²⁺ enhanced formulation of intranasal oxytocin is the basis for TNX-2900, in development to treat hyperphagia, or pathological over-eating, in children and adolescents with PWS. In preclinical studies, Mg²⁺ increases the potency of oxytocin, which is a peptide hormone that reduces appetite and signals fullness, potentially improving receptor binding and resulting in improved therapeutic action.

Immunology Pipeline

TNX-1500 (anti-CD40L Fc-modified humanized monoclonal antibody): third generation anti-CD40L monoclonal antibody for prophylaxis of organ transplant rejection and treatment of autoimmune disorders.

• In October 2023, the Company announced data from two oral presentations which were delivered recently at the American College of Surgeons (ACS) Clinical Congress 2023, and The International Pancreas and Islet Transplant Association (IPITA), the International Xenotransplantation Association (IXA), and the Cell Transplant and Regenerative Medicine Society (CTRMS) Joint Congress by faculty at the Center for Transplantation Sciences, MGH. The oral presentations titled, “Pilot Evaluation of a Clinical Xeno Heart Transplant Regimen in a Preclinical Model” and “Extended Survival of 9- and 10-Gene Edited Pig Heart Xenografts with Ischemia Minimization and CD154 Costimulation Blockade-Based Immunosuppression” by Dr. Ikechukwu Ileka et al. include data demonstrating the use of TNX-1500 as maintenance therapy after xeno heart transplant in non-human primates. In both studies, genetically engineered (GE) pigs in baboon transplants were treated with cold-perfused ischemia minimization and a novel costimulation-based immunosuppressive regimen that includes TNX-1500.
• In October 2023, Tonix announced that a study published in the Journal Nature² by faculty at the Center for Transplantation Sciences, MGH in collaboration with biotechnology company, eGenesis, utilized TNX-1500 as part of the immune modulating regimen to prevent organ transplant rejection. The Nature article titled, “Design and testing of a humanized porcine donor for xenotransplantation” includes data that provide additional support for TNX-1500’s activity in preventing pig xenograft organ rejection and for its safety and tolerability in non-human primates.
• In August 2023, Tonix announced the initiation of a Phase 1 single ascending dose study of TNX-1500 in healthy volunteers. The primary objectives of the study are to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous TNX-1500. This first-in-human study is intended to support dosing in a planned Phase 2 trial in kidney transplant recipients.
• The first indication for TNX-1500 will be prophylaxis of organ rejection in adult patients receiving a kidney transplant, but multiple additional indications are possible, including autoimmune diseases. Two peer reviewed publications described the work at the MGH on allogeneic transplants in animals were published.^3,4

Infectious Disease Pipeline

TNX-1800 (modified recombinant horsepox virus, live vaccine): potential vaccine to protect against COVID-19 designed to express the SARS-CoV-2 spike protein

• In November 2023, Tonix announced that NIAID, a part of the NIH, will conduct a Phase 1 clinical trial with TNX-1800 as part of Project NextGen. The Phase 1 trial of TNX-1800 is expected to start in the second half of 2024. NIAID will cover the full cost of the clinical trial, including operations and related analyses. Tonix will be responsible for providing clinical trial materials, and upon completion will have the right to rely on the findings in regulatory filings with the FDA to support the approval of its COVID-19 vaccine and other vaccines based on the RPV platform.

TNX-801 (recombinant horsepox virus, live vaccine): potential vaccine to protect against mpox disease and smallpox.

• In August 2023, Tonix received the official written response from a Type B pre-IND meeting with the FDA to develop TNX-801 as a potential vaccine to protect against mpox disease (formerly known as monkeypox) and smallpox. Tonix believes the FDA feedback provides a path to agreement on the design of a Phase 1/2 study and the overall clinical development plan. The Phase 1/2 clinical trial will assess the safety, tolerability, and immunogenicity of TNX-801, following the submission and clearance of an IND.

*All of Tonix’s product candidates are investigational new drugs or biologics and none have been approved for any indication.

¹Tzabazis A, et al. Cephalalgia. 2016. 36(10):943-50^.

²Anand R.P., et al. Nature. 2023. 622, 393–401.

³Lassiter, G., et al. (2023). TNX-1500, a crystallizable fragment–modified anti-CD154 antibody, prolongs non-human primate renal allograft survival. American Journal of Transplantation. https://doi.org/10.1016/j.ajt.2023.03.022

⁴Miura, S., et al. (2023). TNX-1500, a crystallizable fragment–modified anti-CD154 antibody, prolongs non-human primate cardiac allograft survival. American Journal of Transplantation. https://doi.org/10.1016/j.ajt.2023.03.025

      Recent Highlights—Financial

As of September 30, 2023, Tonix had approximately $6.9 million of cash and cash equivalents, compared to $120.2 million as of December 31, 2022. Additionally, Tonix had inventory totaling approximately $13.3 million as of September 30, 2023. In August 2023, Tonix received net proceeds of approximately $6.3 million through a public offering of common stock, after deducting underwriting discount and other offering expenses. Cash used in operations was approximately $79.7 million for the nine months ended September 30, 2023, compared to $75.8 million for the same period in 2022. Cash used by investing activities for the nine months ended September 30, 2023 was approximately $28.6 million.

On September 28, 2023, the Company sold 4,050,000 shares of common stock, pre-funded warrants to purchase up to 4,950,000 shares of common stock, and accompanying common A warrants to purchase 9,000,000 shares of common stock and common B warrants to purchase up to 9,000,000 shares of common stock in a public offering for net proceeds of approximately $4.0 million, after deducting underwriting discount and other offering expenses. This public offering closed on October 3, 2023.

Third Quarter 2023 Financial Results

Net product revenue for the third quarter 2023 was approximately $4.0 million. As a reminder, Tonix completed the acquisition of two currently marketed products from Upsher-Smith Laboratories, LLC on June 30, 2023.

During the three months ended September 30, 2023, Tonix received $0.4 million from NIDA for the TNX-1300 study to treat cocaine intoxication.

R&D expenses for the third quarter 2023 were approximately $21.1 million, compared to $22.2 million for the same period in 2022. This decrease is predominantly due to decreased non-clinical and manufacturing expenses, offset by an increase in clinical, employee-related and professional expenses.

SG&A expenses for the third quarter 2023 were $8.7 million, compared to $7.4 million for the same period in 2022. The increase was primarily due to sales and marketing associated with the Company’s recently acquired marketed products.

Net loss available to common stockholders was $28.0 million, or $1.83 per share, basic and diluted, for the third quarter 2023, compared to net loss available to common stockholders of $29.0 million, or $4.24 per share, basic and diluted, for the same period in 2022. The basic and diluted weighted average common shares outstanding for the third quarter 2023 was 15,327,558 compared to 6,843,099 shares for the same period in 2022.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition, and topline results were reported in the third quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), is in development as a preventive treatment in chronic migraine, and enrollment has completed in a Phase 2 proof-of-concept study with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the fourth quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases, including TNX-1800, in development as a vaccine to protect against COVID-19. During the fourth quarter of 2023, TNX-1800 was selected by the U.S. National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) Project NextGen for inclusion in Phase 1 clinical trials. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum small molecule oral antivirals.

*Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication.

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

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

TONIX PHARMACEUTICALS HOLDING CORP.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(In Thousands, Except Share and Per Share Amounts)
(unaudited)
			Three Months Ended September 30,								Nine Months Ended September 30,
			2023				2022				2023				2022
REVENUE:
Product revenue, net			$	3,989			$	—			$	3,989			$	—
COSTS AND EXPENSES:
Cost of revenue			$	2,374			$	—			$	2,374			$	—
Research and development				21,050				22,201				69,537				57,202
Selling, general and administrative				8,712				7,390				23,129				22,161
				32,136				29,591				95,040				79,363
Operating loss				(28,147	)			(29,591	)			(91,051	)			(79,363	)
Interest income, net				172				610				1,715				825
Net loss				(27,975	)			(28,981	)			(89,336	)			(78,538	)
Preferred stock deemed dividend				—				—				—				4,255
Net loss available to common stockholders			$	(27,975	)		$	(28,981	)		$	(89,336	)		$	(82,793	)
Net loss per common share, basic and diluted			$	(1.83	)		$	(4.24	)		$	(7.40	)		$	(18.58	)
Weighted average common shares outstanding, basic and diluted				15,327,558				6,843,099				12,079,583				4,455,943

See the accompanying notes to the condensed consolidated financial statements

TONIX PHARMACEUTICALS HOLDING CORP.
CONDENSED CONSOLIDATED BALANCE SHEETS
(In Thousands)
(Unaudited)
	September 30, 2023				December 31, 20221
Assets
Cash and cash equivalents	$	6,914			$	120,229
Inventory		13,317				–
Receivables, net		1,562				–
Prepaid expenses and other		9,544				10,548
Total current assets		31,337				130,777
Other non-current assets		107,945				94,913
Total assets	$	139,282			$	225,690
Liabilities and stockholders’ equity
Total liabilities	$	18,449			$	18,508
Stockholders’ equity		120,833				207,182
Total liabilities and stockholders’ equity	$	139,282			$	225,690

¹The condensed consolidated balance sheet for the year ended December 31, 2022 has been derived from the audited financial statements but do not include all of the information and footnotes required by accounting principles generally accepted in the United States for complete financial statements.

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^® (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.

Source: Tonix Pharmaceuticals Holding Corp.

Released November 9, 2023

Research News and Market Data on TNXP

November 02, 2023 8:00am EDTDownload as PDF

NIAID is conducting early phase clinical trials on select next generation COVID-19 vaccine candidates with the intent to identify promising vaccine candidates

TNX-1800, a live virus percutaneous vaccine candidate, is based on Tonix’s recombinant pox virus (RPV) platform

Phase 1 clinical trial of TNX-1800 expected to start in the second half of 2024

NIAID will cover the full cost of the clinical trial; Tonix will supply the vaccine candidate

CHATHAM, N.J., Nov. 02, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced that the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH), will conduct a Phase 1 clinical trial with TNX-1800 (recombinant horsepox virus, live vaccine),¹ Tonix Pharmaceuticals’ vaccine candidate to protect against COVID-19.

Tonix is developing a novel vaccine platform initially targeting COVID-19, smallpox and mpox (monkeypox). The intent is to provide durable protection against severe disease and prevent forward transmission, primarily by eliciting a T-cell immune response. TNX-1800 expresses the spike protein of SARS-CoV-2, was immunogenic, well tolerated² and showed promise in protecting animals from challenge with SARS-CoV-2 delivered directly into the lungs.³ A related horsepox-based vaccine, TNX-801¹, protected animals against challenge with monkeypox virus delivered directly into the lungs.⁴ TNX-801 is also the vector on which TNX-1800 is based and has been shown to be >1,000-fold more attenuated than modern vaccinia virus vaccine (VACV) strains in immunocompromised mice.⁵ The Phase 1 trial of TNX-1800 is expected to start in the second half of 2024. NIAID will study TNX-1800 by percutaneous administration.

“We believe our novel vaccine platform technology has the potential to provide durable protection from respiratory pathogens and slow their spread,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “TNX-1800 will be the first vaccine candidate using our live virus recombinant pox virus (RPV) platform technology to enter clinical trials. We hope to expand the portfolio of RPV-based vaccines to address several other known respiratory threats including smallpox, mpox and tuberculosis. We are committed to supporting NIAID in assembling a variety of vaccine platform options to ensure the availability of effective vaccines in the face of known and emerging threats. We look forward to participating in the Project NextGen initiative.”

“Project NextGen,” is an initiative by the U.S. Department of Health and Human Services (HHS) to advance a pipeline of new, innovative vaccines and therapeutics for COVID-19. NIAID will be conducting clinical trials to evaluate several early-stage vaccine candidates. The Phase 1 study involving TNX-1800 is designed to assess safety and immunogenicity in approximately 60 healthy adult volunteers. Upon completion of the trial, NIAID and Tonix Pharmaceuticals will assess the results and determine the next steps for the development of TNX-1800.

NIAID will cover the full cost of the clinical trial, including operations and related analysis. Tonix will be responsible for providing clinical trial materials, and upon completion will have the right to rely on the findings in regulatory filings with the U.S. Food and Drug Administration (FDA) to support the approval of its COVID-19 vaccine and other vaccines based on the RPV platform.

About Project NextGen

Project NextGen is a $5 billion initiative to develop the next generation of vaccines and therapeutics to combat COVID-19. Based at the HHS and led by the Administration for Strategic Preparedness and Response’s Biomedical Advanced Research and Development Authority and the NIH’s NIAID, Project NextGen will coordinate across the federal government and the private sector to advance the pipeline of new, innovative vaccines and therapeutics into clinical trials and potential review by the U.S. Food and Drug Administration (FDA) for authorization or approval, and commercial availability for the American people. The program will focus on several areas, including mucosal vaccines, vaccines that provide broader protection against variants of concern and a longer duration of protection, pan-coronavirus vaccines, and new and more durable monoclonal antibodies.

About TNX-1800*
TNX-1800 (recombinant horsepox virus) is a live virus vaccine for percutaneous administration that is designed to express the spike protein of the SARS-CoV-2 virus and to elicit a predominant T cell response. The RPV platform is based on a horsepox vector, which is a live replicating, attenuated virus that has been shown to be >1,000-fold more attenuated than modern VACV strains in immunocompromised mice.⁵ Horsepox and the vaccinia vaccine viruses are closely related orthopoxviruses that are believed to share a common ancestor. Molecular analysis shows that horsepox is closer than modern vaccinia vaccines in DNA sequence to the vaccine discovered and disseminated by Dr. Edward Jenner. ^6-9 Live replicating orthopoxviruses, like vaccinia or horsepox, can be engineered to express foreign genes and have been explored as platforms for vaccine development because they possess; (1) large packaging capacity for exogenous DNA inserts, (2) precise virus-specific control of exogenous gene insert expression, (3) lack of persistence or genomic integration in the host, (4) strong immunogenicity as a vaccine, (5) ability to rapidly generate vector/insert constructs, (6) readily manufacturable at scale, and (7) ability to provide direct antigen presentation. Relative to vaccinia, horsepox has substantially decreased virulence in mice.^4,6 The current formulation is a frozen liquid, but we believe that future lyophilized versions can be stored and shipped at standard refrigeration. Horsepox-based vaccines are designed to be single dose, vial-sparing vaccines that can be administered without sterile injection, manufactured using conventional cell culture systems with the potential for mass scale production, and packaged in multi-dose vials. Moreover, we believe the low dose of TNX-1800 makes this technology amenable for future implementation in microneedle delivery systems.

About TNX-801*
TNX-801 (recombinant horsepox virus) is a live virus vaccine based on horsepox^4-7 in pre-clinical development to prevent smallpox and mpox. Tonix reported positive preclinical efficacy data, demonstrating that TNX-801 vaccination protected non-human primates against lethal challenge with monkeypox.⁴ Tonix has received official written response from a Type B pre-Investigational New Drug Application (IND) meeting with the U.S. Food and Drug Administration (FDA) to develop TNX-801 as a potential vaccine to protect against mpox disease and smallpox.¹⁰ Tonix believes the FDA feedback provides a path to agreement on the design of a Phase 1 /2 study and the overall clinical development plan. The Phase 1/2 clinical trial will assess the safety, tolerability, and immunogenicity of TNX-801, following the submission and clearance of an IND. More than 30,000 people have contracted mpox in the U.S. so far during the 2022-23 epidemic,¹¹ The recent cluster of mpox in Chicago revealed breakthrough cases of mpox in individuals who had been vaccinated with the currently authorized non-replicating vaccine, which is administered in two doses.¹² In contrast, TNX-801 is delivered percutaneously with only one dose and therefore may achieve higher rates of community protection by eliminating drop-out between doses and limiting forward transmission. Moreover, relying on only one approved mpox vaccine at present is a risk for the global supply chain that has already led to insufficient availability of vaccines to meet global health needs, especially in Africa. TNX-801 has the potential to make a global impact on mpox and the risk of smallpox because of its durable T-cell immune response, the potential to manufacture at scale, and the use of a lower dose than non-replicating vaccines.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 proof-of-concept study has been completed, and topline results were reported in the third quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), is in development as a preventive treatment for chronic migraine, and enrollment has been completed in a Phase 2 proof-of-concept study with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the fourth quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases, including TNX-1800, in development as a vaccine to protect against COVID-19. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum small molecule oral antivirals.

*Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication.

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

¹ TNX-1800 and TNX-801 are experimental new vaccines and have not been approved for any indication.
² Awasthi, M. et al. Viruses. 2023. 15(10):2131.
³ Awasthi, M. et al. BioRxiv. 2023.
⁴ Trefry S, et al. BioRxiv. 2023.
⁵ Noyce RS, et al. Viruses. 2023. 15(2):356.
⁶ Jenner E. “An Inquiry Into the Causes and Effects of the Variole Vaccinae, a Disease Discovered in Some of the Western Counties of England, Particularly Gloucestershire and Known by the Name of the cow‐pox.” London: Sampson Low, 1798.
⁷ Noyce RS, et al. PloS One. 2018. 13(1):e0188453.
⁸ Schrick L et al. N Engl J Med. 2017. 377:1491-1492.
⁹ Tulman ER, et al. J Virol. 2006. 80(18):9244-58.
¹⁰ TNX-801 PR pre-IND meeting August 20, 2023: https://ir.tonixpharma.com/news-events/press-releases/detail/1417/tonix-pharmaceuticals-announces-results-of-pre-ind-meeting
¹¹ McQuiston JH, et al. MMWR Morb Mortal Wkly Rep. 2023. 72:547–552.
¹² Centers for Disease Control. MMWR Morb Mortal Wkly Rep. 2023. 72(25);696-698.

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

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
443-213-0495

Source: Tonix Pharmaceuticals Holding Corp.

Released November 2, 2023

Research News and Market Data on TNXP

October 31, 2023 5:00pm EDT

The study did not achieve statistical significance on the primary endpoint

Tonix is discontinuing development of TNX-601 ER based on the efficacy results of this study

Tonix expects topline data results in December 2023 for its Phase 2 study of TNX-1900 in chronic migraine and Phase 3 study of TNX-102 SL in fibromyalgia

CHATHAM, N.J., Oct. 31, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced topline results from the Phase 2 proof-of-concept double-blind, randomized, multi-center, placebo-controlled UPLIFT study of TNX-601 ER* (tianeptine hemioxalate extended-release tablets) in patients with major depressive disorder (MDD). The primary efficacy endpoint of change from baseline in depression severity, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) total score, did not achieve clinical or statistical significance.

“Based on these efficacy results, we are discontinuing development of TNX-601 ER. We look forward to topline results from our Phase 2 study of TNX-1900 in chronic migraine in early December and topline results from our Phase 3 potential NDA-enabling study of TNX-102 SL in fibromyalgia in late December,” said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. “We would like to thank the patients, their families, and all the investigators and researchers who participated in the Phase 2 UPLIFT study.”

In the Phase 2 UPLIFT study, TNX-601 ER was orally administered as monotherapy once a day to 132 patients who, upon entering the study, met a DSM-5 diagnosis of moderate-to-severe depression with a duration for the current major depressive episode of at least 12 weeks. Efficacy was assessed using the MADRS to measure any potential change in patients’ depression severity from baseline. In the study, TNX-601 ER was generally well-tolerated with a favorable safety profile. There was one serious adverse event (SAE) experienced in the placebo group, and two SAEs in the active treatment group deemed possibly related to study drug, both of which resolved without sequelae.

About the Phase 2 UPLIFT Study

The Phase 2 proof-of-concept UPLIFT study, TNX-TI-M201, is a double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-601 ER taken orally once-daily for 6 weeks for the treatment of moderate-to-severe MDD. It is a parallel design study with a TNX-601 ER 39.4 mg arm and a placebo arm. A total of 132 participants were randomized in a 1:1 ratio into the two arms across approximately 27 U.S. sites, enrolling adult patients 18-65 years old with a DSM-5 diagnosis of MDD and a duration for the current major depressive episode of at least 12 weeks. The primary efficacy endpoint is mean change from baseline in the MADRS total score at Week 6. Key secondary efficacy endpoints include the Clinical Global Impression – Severity Scale (CGI-S) and the Sheehan Disability Scale (SDS).

For more information, see ClinicalTrials.gov Identifier: NCT05686408.

About Major Depressive Disorder (Depression)

According to the National Institute of Mental Health, an estimated 21 million adults in the U.S. in 2020 experienced at least one major depressive episode¹, with highest prevalence among individuals aged 18-25 at a rate of 17.0%. For approximately 2.5 million adults in the U.S., adjunctive therapies are necessary for depression treatment.^2,3 Depression is a condition characterized by symptoms such as a depressed mood or loss of interest or pleasure in daily activities most of the time for two weeks or more, accompanied by appetite changes, sleep disturbances, motor restlessness or retardation, loss of energy, feelings of worthlessness or excessive guilt, poor concentration, and suicidal thoughts and behaviors. These symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. The majority of people who suffer from depression do not respond adequately to initial antidepressant therapy.⁴

¹ Data Courtesy of SAMHSA on Past Year Prevalence of Major Depressive Episode Among U.S. Adults 2020. Retrieved from http://www.nimh.nih.gov/health/statistics/major-depression.shtml

² IMS NSP, NPA, NDTI MAT-24-month data through Aug 2017.

³ Kubitz N, et al. PLoS One 2013, 8 (10), e76882.

⁴ Rush AJ, et al. Am J. Psychiatry 2007, 163 (11), 1905-1917.

About TNX-601 ER

TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a novel oral formulation of tianeptine designed for once-daily daytime dosing in development as a candidate for the treatment of MDD. 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. Tonix discovered a novel oxalate salt of tianeptine that may provide improved stability, consistency, and manufacturability compared to known salt forms of tianeptine.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition, and topline results were reported in the third quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), is in development as a preventive treatment in chronic migraine, and enrollment has completed in a Phase 2 proof-of-concept study with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the fourth quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases, including TNX-1800, in development as a vaccine to protect against COVID-19 . The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum small molecule oral antivirals.

*Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication.

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

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

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
443-213-0495

Research News and Market Data on TNXP

October 30, 2023 7:00am EDTDownload as PDF

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

TNX-1500 is currently in Phase 1 Clinical Development

Tonix is Developing TNX-1500 for Prevention of Kidney Allograft Rejection as the First Indication; Multiple Other Indications, including Autoimmune Disorders, are Planned

CHATHAM, N.J., Oct. 30, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced data from two oral presentations which were delivered recently at the American College of Surgeons (ACS) Clinical Congress 2023, and The International Pancreas and Islet Transplant Association (IPITA), the International Xenotransplantation Association (IXA), and the Cell Transplant and Regenerative Medicine Society (CTRMS) Joint Congress by faculty at the Center for Transplantation Sciences, Massachusetts General Hospital (MGH) in October 2023. The data involve Tonix’s TNX-1500 (Fc-modified dimeric anti-CD40L monoclonal antibody [mAb]) which is currently in Phase 1 development for the prevention of organ transplant rejection. Copies of the presentations are available under the Scientific Presentations tab of the Tonix Pharmaceuticals website at www.tonixpharma.com.

The oral presentations titled, “Pilot Evaluation of a Clinical Xeno Heart Transplant Regimen in a Preclinical Model” and “Extended Survival of 9- and 10-Gene Edited Pig Heart Xenografts with Ischemia Minimization and CD154 Costimulation Blockade-Based Immunosuppression” by Dr. Ikechukwu Ileka et al. include data demonstrating the use of TNX-1500 as maintenance therapy after xeno heart transplant in non-human primates. In both studies, genetically engineered (GE) pigs in baboon transplants were treated with cold-perfused ischemia minimization and a novel costimulation-based immunosuppressive regimen including TNX-1500. The multi-GE pigs were provided by eGenesis and Revivicor.

“The results of these preclinical studies are encouraging and demonstrate the potential of genetically engineered pig hearts in the context of a clinically applicable regimen,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Because anti-CD40L treatment is widely recognized as critical to the success of xeno organ transplant, no animals were transplanted without anti-CD40L treatment.”

“These and other data^1,2,3 confirm the rationale for us to pursue development of TNX-1500 to prevent rejection in human transplantation,” said Dr. Lederman. “We are currently enrolling in a Phase 1 trial in healthy volunteers to support the development of TNX-1500 for the prevention of allograft rejection. However, long term we hope to develop TNX-1500 for xenotransplantation in which the donor organ comes from genetically engineered pigs.”

¹Lassiter G., et al. Am. J. Transplant. 2023. https://doi.org/10.1016/j.ajt.2023.03.022

²Miura S., et al. Am. J. Transplant. 2023. https://doi.org/10.1016/j.ajt.2023.03.025

³Anand R.P., et al. Nature. 2023. 622, 393–401.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 proof-of-concept study has been completed, and topline results were reported in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily oral formulation being developed as a treatment for major depressive disorder (MDD), that completed enrollment in a Phase 2 study in the third quarter of 2023, with topline results expected in early November of 2023. TNX-4300 (estianeptine) is a single isomer version of TNX-601, a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. Relative to tianeptine, estianeptine lacks activity on the mu-opioid receptor while maintaining activity and the ability to activate PPAR-β/δ and neuroplasticity in tissue culture. TNX-1900 (intranasal potentiated oxytocin), is in development as a preventive treatment in chronic migraine, and the clinical phase of a Phase 2 proof-of-concept study is now completed with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the fourth quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases, including TNX-1800, in development as a vaccine to protect against COVID-19. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum small molecule oral antivirals.

*Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication.

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

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; 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
443-213-0495

Source: Tonix Pharmaceuticals Holding Corp.

Released October 30, 2023

Research News and Market Data on TNXP

October 26, 2023 7:00am EDTDownload as PDF

Topline results expected early December 2023

Novel formulation of intranasal oxytocin contains magnesium (Mg2+), shown to potentiate the analgesic
effects of oxytocin on the oxytocin receptor in animal models

TNX-1900 blocks release of CGRP, a key peptide in the pathogenesis of migraine, from trigeminal ganglia
neurons while limiting systemic exposure

CHATHAM, N.J., Oct. 26, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced the completion of the clinical phase of the Phase 2 proof-of-concept, double-blind, randomized, placebo-controlled PREVENTION¹ study of TNX-1900² (intranasal potentiated oxytocin) as a potential treatment for the prevention of migraine headaches in chronic migraineurs. A total of 88 patients were enrolled in this multi-site study in the U.S. Topline results are expected in early December 2023.

TNX-1900 is a proprietary formulation of oxytocin that contains magnesium, which Tonix has shown in animal models potentiates the action of oxytocin at oxytocin receptors and potentially improves the consistency of treatment by reducing paradoxical high-dose inhibition. Its unique, multimodal mechanism of action includes an ability to inhibit the release of the trigeminal neuropeptide calcitonin gene-related peptide (CGRP) in blood vessels within the brain, its lining and the brainstem, and to suppress signaling in pain neurons. Tonix believes that by engaging and activating oxytocin receptors in the trigeminal ganglia, TNX-1900 has the potential to help those suffering from chronic migraine.

“TNX-1900 is being developed as a novel, non-CGRP antagonist approach to treatment for chronic migraineurs,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “There are an estimated four million individuals in the U.S. suffering from this debilitating condition, and despite several classes of migraine preventives available, there remains an unmet need for novel approaches.”

“With the last patient now treated, we look forward to analysis of the results of this proof-of-concept study, which will help to inform our plans as we discuss next steps with the U.S. Food and Drug Administration (FDA),” said Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals. “We would like to thank the participants, their families, and all the investigators and researchers who have been an important part of this journey so far.”

¹Clinical Trials.gov I.D. NCT05679908
²TNX-1900 is an investigational new drug and is not approved for any indication.

About the Phase 2 PREVENTION Study
The Phase 2 PREVENTION study is a double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-1900 taken prophylactically on a daily basis to prevent chronic migraine. There are three arms: two treatment regimens of TNX-1900 and one placebo in a 1:1:1 ratio in a total of 88 participants across approximately 26 U.S. sites. After a four-week Run-In phase to confirm chronic migraine criteria are met, there are 12-weeks of a double-blind Treatment phase with study drug, followed by a 2-week safety Follow-Up phase. The primary efficacy endpoint is mean change in the number of migraine headache days between the 28-day Run-In phase and the last 28-days of the Treatment phase. Key secondary efficacy endpoints include proportion of patients experiencing a ≥ 50% reduction in the number of migraine headache days, mean change in the number of days using migraine abortive medications, and mean change in a migraine-specific quality of life measure.

For more information, see ClinicalTrials.gov Identifier: NCT05679908.

About Migraine
Migraine is a neurological 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 noises¹. Epidemiological studies indicate that globally, approximately 1.2 billion individuals suffer from migraines annually². 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)². The current FDA approved drugs for migraine prevention in chronic migraine include Botox^® (onabotulinumtoxinA), and the anti-CGRP/CGRP-R monoclonal antibodies Aimovig^® (erenumab), Vyepti^® (eptinezumab), Ajovy^® (fremanezumab) and Emgality^® (galcanezumab).

¹The International Classification of Headache Disorders, 3^rd Edition. Cephalalgia. 2018. 38(1):1-211.

²Burch et al., Migraine: Epidemiology, Burden, and Comorbidity. Neurol Clin. 2019. 631–649.

About TNX-1900
TNX-1900 (intranasal potentiated oxytocin) is a proprietary formulation of oxytocin in development as a candidate for prevention in 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 of calcitonin gene-related peptide (CGRP) which binds to receptors on other nerve cells and starts a cascade of events that is believed to result in headache. Oxytocin, when delivered via the nasal route, concentrates in the trigeminal system¹ resulting in binding of oxytocin to receptors on neurons in the trigeminal system, inhibiting the release of CGRP and transmission of pain signals returning from the site of CGRP release². Blocking CGRP release is a distinct mechanism compared with CGRP antagonist and anti-CGRP antibody drugs, which block the binding of CGRP to its receptor. With TNX-1900, the addition of magnesium to the oxytocin formulation enhances oxytocin receptor binding³ as well as its inhibitory effects on trigeminal neurons and resultant craniofacial analgesic effects, as demonstrated in animal models⁴. Intranasal oxytocin has been shown to be well tolerated in several clinical trials in both adults and children⁵. Targeted nasal delivery results in low systemic exposure and lower risk of non-nervous system, off-target effects, which could potentially occur with systemic CGRP antagonists such as anti-CGRP antibodies⁶. For example, CGRP has roles in dilating blood vessels in response to ischemia, including in the heart. The Company believes nasally targeted delivery of oxytocin could translate into selective blockade of CGRP release from neurons in the trigeminal ganglion and not throughout the body, which could be a potential safety advantage over systemic CGRP inhibition. In addition, daily dosing is more rapidly reversible, in contrast to monthly or quarterly dosing, as is the case with anti-CGRP antibodies, giving physicians and their patients greater control. In addition to chronic migraine, TNX-1900 will be developed for treatment of episodic migraine, binge eating disorder, craniofacial pain conditions, 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.

¹Yeomans DC, et al. Transl Psychiatry. 2021. 11(1):388.

²Tzabazis A, et al. Cephalalgia. 2016. 36(10):943-50.

³Antoni FA and Chadio SE. Biochem J. 1989. 257(2):611-4.

⁴Cai Q, et al., Psychiatry Clin Neurosci. 2018. 72(3):140-151.

⁵Yeomans, DC et al. 2017. US patent US2017368095.

⁶MaassenVanDenBrink A, et al. Trends Pharmacol Sci. 2016. 37(9):779-788.

Tonix Pharmaceuticals Holding Corp.^*
Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 proof-of-concept study has been completed, and topline results were reported in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily oral formulation being developed as a treatment for major depressive disorder (MDD), that completed enrollment in a Phase 2 study in the third quarter of 2023, with topline results expected in early November of 2023. TNX-4300 (estianeptine) is a single isomer version of TNX-601, a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. Relative to tianeptine, estianeptine lacks activity on the mu-opioid receptor while maintaining activity and the ability to activate PPAR-β/δ and neuroplasticity in tissue culture. TNX-1900 (intranasal potentiated oxytocin), is in development as a preventive treatment in chronic migraine, and the clinical phase of a Phase 2 proof-of-concept study is now completed with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the fourth quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases, including TNX-1800, in development as a vaccine to protect against COVID-19. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum small molecule oral antivirals.

*Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication.

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

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward-Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

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
443-213-0495

Source: Tonix Pharmaceuticals Holding Corp.

Released October 26, 2023

Research News and Market Data on TNXP

October 19, 2023 7:00am EDTDownload as PDF

Preclinical Data Demonstrate Attenuation of TNX‐801 (horsepox live virus vaccine) Compared to Modern Vaccinia Vaccines

TNX-801 is in Preclinical Development as a Novel Vaccine to Protect Against Smallpox and Mpox

CHATHAM, N.J., Oct. 19, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates, presented data on its horsepox-based live virus vaccine platform in an oral presentation at the World Vaccine Congress Europe being held in Barcelona, Spain, October 16-19, 2023. A copy of the Company’s presentation is available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com.

“Tonix’s horsepox-based live virus vaccine platform is designed to help protect against emerging infectious diseases by engaging T cell responses, which have the potential to provide durable protection and block forward transmission,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “In addition, we believe horsepox-based vaccines can be widely deployed without the need for sterile injection or ultra-cold shipping and storage. Our lead vaccine candidate, TNX-801¹, is in development to protect against Mpox (monkeypox) and smallpox. Tonix’s TNX-801 is based on the sequence of a natural field isolate.^2,3 Molecular analysis suggests that TNX-801 is closer than modern smallpox vaccines to the vaccine discovered and disseminated by Dr. Edward Jenner in 1798^4-6. Archaic smallpox vaccines based on horsepox were used in the U.S. and Europe to successfully control smallpox in the Nineteenth Century.”^4,7-9

The presentation, titled, “A Novel Mpox Vaccine (Horsepox virus) to Enhance Preparedness and Vaccine Equity,” includes recent preclinical data that indicate that the TNX-801 platform is naturally attenuated and potentially safer than the vaccines utilized to eradicate smallpox.

“TNX-801 was found to be up to 100-fold more attenuated than modern vaccinia vaccine viruses in primary human cell lines derived from dermal and respiratory tract cells, which are the two main poxvirus routes of entry and transmission,” said Zeil Rosenberg, M.D., M.P.H., Executive Vice President, Medical. “TNX-801 was also found to be more than 1,000-fold attenuated relative to modern vaccinia vaccine viruses (“VACV”) in an immunocompromised murine model with targeted knock-outs of the IFN- and/or IFN- receptors. In these mice, TNX-801 did not cause any observable clinical disease, and in most measured parameters (disease score, body temperature, weight loss, and survival), the TNX-801 infected mice were indistinguishable from the uninfected mice. Together, these data suggest that TNX-801 potentially should be a safer vaccine in immunocompromised populations than many VACV-based vaccines.”

Dr. Rosenberg added, “A new attenuated live-virus smallpox and Mpox vaccine has the potential to enhance vaccine equity and preparedness in the event of a global emergency.”

About TNX-801

TNX-801 is a live virus vaccine based on horsepox^2,3. Tonix is developing TNX-801 for percutaneous administration as a vaccine to protect against Mpox and smallpox. Tonix’s TNX-801 is based on the sequence of the 1976 natural isolate Mongolian horsepox clone MNR-76.^2,3 Molecular analysis of DNA sequences suggests that TNX-801 is closer than modern smallpox vaccines to the vaccine discovered and disseminated by Dr. Edward Jenner in 1798^4-6. For example, recent studies^7,8 have shown approximately 99.7% colinear identity between TNX-801 and the circa 1860 U.S. smallpox vaccine VK05.⁹ The small plaque size in the culture of TNX-801 appears identical to the U.S. Centers for Disease Control publication of the natural isolate¹⁰. Relative to vaccinia, horsepox has substantially decreased virulence in mice². Dr. Edward Jenner invented vaccination in 1798 and the procedure was called “vaccination” because ‘cow’ is ‘vacca’ in Latin and the inoculum material was initially obtained from lesions on the udders of cows affected by a mild disease known as cowpox. However, Dr. Jenner suspected that cowpox originated from horses⁶. Subsequently, Dr. Jenner and others immunized against smallpox using material directly obtained from horses. The use of vaccines from horses was sometimes called ‘equination’ from the Latin ‘equus’ which means ‘horse’¹¹. Equination and vaccination were practiced side-by-side in Europe^11,12. Tonix received an official written response from a Type B pre-Investigational New Drug Application (IND) meeting with the U.S. Food and Drug Administration (FDA) to develop TNX-801 as a potential vaccine to protect against Mpox disease and smallpox. Tonix believes the FDA feedback provides a path to agreement on the design of a Phase 1/2 study and the overall clinical development plan. The Phase 1/2 clinical trial will assess the safety, tolerability, and immunogenicity of TNX-801, following the submission and clearance of an IND.

About the Recombinant Pox Virus (RPV) Platform

Horsepox virus and vaccines based on its use as a vector are live replicating viruses that elicit strong immune responses. Live replicating orthopoxviruses, like vaccinia or horsepox, can be engineered to express foreign genes and have been exploited as platforms for vaccine development because they possess; (1) large packaging capacity for exogenous DNA inserts, (2) precise virus-specific control of exogenous gene insert expression, (3) lack of persistence or genomic integration in the host, (4) strong immunogenicity as a vaccine, (5) ability to rapidly generate vector/insert constructs, (6) manufacturable at scale, and (7) ability to provide direct antigen presentation. Horsepox-based vaccines are designed to be single-dose, vial-sparing vaccines, that can be manufactured using conventional cell culture systems, with the potential for mass-scale production and packaging in multi-dose vials. Tonix’s TNX-801 and RPV vaccine candidates are administered percutaneously using a two-pronged, or “bifurcated” needle, and are amendable to microneedle technology. The major cutaneous reaction or “take” to the vaccinia vaccine was described by Dr. Edward Jenner in 1796 and has been used since then as a biomarker for protective immunity to smallpox, including in the World Health Organization’s (WHO) accelerated smallpox eradication program that successfully eradicated smallpox in the 1960’s. The “take” is a measure of functional T cell immunity validated by the eradication of smallpox, a respiratory-transmitted disease caused by variola.

About Mpox and Smallpox

Mpox¹³ and smallpox¹⁴ are diseases in humans caused by the Mpox and smallpox (or variola) viruses, respectively. Mpox and variola are closely related orthopox viruses. Vaccination against smallpox with live virus vaccines based on horsepox or vaccinia protects against Mpox. After routine smallpox vaccination was stopped in about 1970, Mpox has become a growing problem in Africa. Since May of 2022, approximately 30,000 cases have been identified in the United States^15,16. There are two distinct clades of the Mpox virus: the central African (Congo Basin) clade, and the West African clade which is associated with the recent outbreak. Historically, the Congo Basin clade has caused more severe disease than the West African clade. In recent times, the case fatality ratio for the virus is about 3–6%¹⁷. In November 2022, the WHO began using a new preferred term “Mpox” as a synonym for monkeypox¹⁸. Smallpox is considered eradicated, but there are concerns about malicious reintroduction.

Tonix Pharmaceuticals Holding Corp.

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio¹⁹ is composed of central nervous system (CNS), rare disease, immunology, and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric, and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 proof-of-concept study has been completed, and topline results were reported in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily oral formulation being developed as a treatment for major depressive disorder (MDD), that completed enrollment in a Phase 2 proof-of-concept study in the third quarter of 2023, with topline results expected in early November of 2023. TNX-4300 (estianeptine) is a single isomer version of TNX-601, a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease, and Parkinson’s disease. Relative to tianeptine, estianeptine lacks activity on the µ-opioid receptor while maintaining activity in the rat Novel Object Recognition test in vivo and the ability to activate PPAR-β/δ and neuroplasticity in tissue culture. TNX-1900 (intranasal potentiated oxytocin), is in development for preventing headaches in chronic migraine, and has completed enrollment in a Phase 2 proof-of-concept study with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity, and social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the fourth quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and Mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum small-molecule oral antivirals.

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

This press release and further information about Tonix can be found at www.tonixpharma.com.

¹TNX-801 is an investigational new drug and has not been approved for any indication.
²Noyce RS, et al. (2018) PLoS One. 13(1):e0188453
³Tulman ER, et al. (2006) J Virol. 80(18):9244-58.PMID:16940536
⁴Schrick L et al. (2017) N Engl J Med. 377:1491.
⁵Qin et al. (2015) J. Virol. 89:1809.
⁶Jenner E. “An Inquiry Into the Causes and Effects of the Variolae Vaccinae: A Disease Discovered in Some of the Western Counties of England, Particularly Gloucestershire, and Known by the Name of the Cow Pox.” London: Sampson Low, 1798.
⁷Brinkmann A et al, Genome Biology (2020) 21:286.
⁸Duggan A et al. Genome Biology (2020) 21:175.
⁹Tonix press release. Dec 4, 2020 https://ir.tonixpharma.com/news-events/press-releases/detail/1236/vaccine-genome-researchers-report-99-7-colinear-identity
¹⁰Trindale GS et al. (2016) Viruses (12). Pii: E328. PMID:27973399
¹¹Esparza E, et al (2017) Vaccine. 35(52):7222-7230.
¹²Esparza J et al. (2020) Vaccine.; 38(30):4773-4779.
¹³www.cdc.gov/poxvirus/monkeypox/about.html
¹⁴www.cdc.gov/smallpox/research/
¹⁵Mandavilli, A. The New York Times. May 26, 2020. “Who is protected against monkeypox”
¹⁶www.cdc.gov/poxvirus/monkeypox/response/2022/us-map.html – Accessed October 18, 2023
¹⁷https://www.who.int/news-room/fact-sheets/detail/monkeypox#:~:text=There%20are%20two%20distinct%20genetic,thought%20to%20be%20more%20transmissible – Accessed October 18, 2023
¹⁸https://www.who.int/news/item/28-11-2022-who-recommends-new-name-for-monkeypox-disease – Accessed October 18, 2023
¹⁹Tonix’s product candidates in development are investigational new drugs and have not been approved for any indication

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

Source: Tonix Pharmaceuticals Holding Corp.

Released October 19, 2023

Research News and Market Data on TNXP

October 18, 2023 7:00am EDT

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

TNX-1500 is Enrolling in a Phase 1 Clinical Trial

Tonix is Developing TNX-1500 for Prevention of Kidney Allograft Rejection as the First Indication: Multiple Other Indications, including Autoimmune Disorders, are Planned

CHATHAM, N.J., Oct. 18, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced that a study published in the Journal Nature¹ by faculty at the Center for Transplantation Sciences, Massachusetts General Hospital (MGH) in collaboration with biotechnology company, eGenesis, utilized TNX-1500 (Fc-modified dimeric anti-CD40L monoclonal antibody [mAb]) as part of the immune modulating regimen to prevent organ transplant rejection. Tonix’s TNX-1500 is in development for the prevention of human kidney organ transplant rejection. The molecular target of TNX-1500 is CD40-ligand (CD40L), which is also known as CD154.

TNX-1500 was invented and developed in-house by Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals, and colleagues. TNX-1500 is a third generation anti-CD40L monoclonal antibody that has been designed by protein engineering to decrease FcγRII binding and to reduce the potential for thrombosis. Preclinical studies in non-human primates demonstrated that TNX-1500 showed activity in preventing allograft and xenograft organ rejection and was well tolerated. The research in the Nature paper was conducted at MGH, led by principal investigator Tatsuo Kawai, M.D., Professor of Surgery, Harvard Medical School and the Center for Transplantation Science. A “News and Views” editorial² and a News³ story appeared in the same issue of Nature.

The Nature article titled, “Design and testing of a humanized porcine donor for xenotransplantation” includes data that provide additional support for TNX-1500’s activity in preventing pig xenograft organ rejection and for its tolerability in non-human primates. Because anti-CD40L treatment is widely recognized as critical to the success of xeno organ transplant, no animals were transplanted without anti-CD40L treatment. Four of the transplanted animals received prophylactic treatment with TNX-1500. The other animals were treated with a primate-adapted version of mAb 5c8, which is an earlier antibody that was also discovered by Dr. Lederman, when he was an assistant professor at Columbia University.⁴ The primate-adapted 5c8 anti-CD40L mAb⁵ has been provided to qualified researchers at a nominal charge for more than 20 years in an National Institute of Health (NIH)-funded program called the “Non-human Primate Reagent Resource Center” (NHPRRC).

“The animal study described in the Nature publication¹ supports the growing evidence that the protein engineering behind the invention of TNX-1500 resulted in a dimeric antibody that retains activity to prevent rejection and preserve graft function. These and other data^6,7 confirm the rationale for us to pursue development of TNX-1500 to prevent rejection in human transplantation,” said Dr. Lederman. “We are currently enrolling in a Phase 1 trial with TNX-1500 in healthy volunteers to support the development of TNX-1500 for the prevention of allograft rejection. There remains a significant need for new treatments with improved activity and tolerability to prevent organ transplant rejection. We believe TNX-1500 has the potential for treating and preventing organ transplant rejection.”

Dr. Lederman added, “Our primary focus of early development will be allotransplantation in which the donor organ comes from a human volunteer or cadaver. However, long term we hope to develop TNX-1500 for xenograft transplantation in which the donor organ comes from genetically engineered pigs. Several lines of research indicate that anti-CD40L is required for long term xenograft acceptance. I believe it is unlikely for human xenotransplantation to proceed without CD40L blockade. In addition, anti-CD40L monoclonal antibodies have demonstrated efficacy in autoimmune diseases like systemic lupus erythematosus and Sjögren’s Syndrome.”

About TNX-1500

TNX-1500 (Fc-modified anti-CD40L mAb) is a humanized dimeric monoclonal antibody that interacts with the CD40-ligand (CD40L), which is also known as CD154. TNX-1500 is being developed for the prevention of allograft and xenograft rejection, for the treatment of autoimmune diseases including multiple sclerosis and for the prevention of graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation (HCT). A Phase 1 study of TNX-1500 is currently enrolling. 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. The disulfide-linked dimeric structure is similar to natural antibodies and in the case of anti-CD40L is believed to confer to TNX-1500 a higher avidity for cell-associated CD40L, relative to soluble CD40L. Two articles were recently published in the American Journal of Transplantation that demonstrate TNX-1500 prolongs nonhuman primate renal and heart allograft survival^6,7. Other anti-CD40L mAbs are in development for treating systemic lupus erythematosus, Sjögren’s syndrome and multiple sclerosis.^8-10 CD40-L is a member of the TNFα super gene family. Other members have been the targets of successful mAb: TNFα and RANKL for autoimmune diseases and osteoporosis, respectively. Other TNFα super gene family members are targeted by mAbs in development including, TNF-like ligand 1A (TL1A) and CD30L for ulcerative colitis.

1. Anand R.P., et al. Nature. 2023. 622, 393–401.
2. Mohiuddin M. Nature. News and Views. 2023. “Pig-to-primate organ transplants require genetic modifications of donor.”
3. Kozlov M. Nature. New, 2023. “Monkey survives two years after gene-edited pig-kidney transplant.”
4. Lederman S, et al. J Exp Med. 1992. 175(4):1091-101.
5. NHPRRC anti-CD154 clone 5C8H1D MassBiologics PR-1547
6. Lassiter G., et al. Am. J. Transplant. 2023. https://doi.org/10.1016/j.ajt.2023.03.022
7. Miura S., et al. Am. J. Transplant. 2023. https://doi.org/10.1016/j.ajt.2023.03.025
8. UCB Pipeline – https://www.ucb.com/our-science/pipeline
9. BioSpace. September 12, 2022 – https://www.biospace.com/article/releases/horizon-therapeutics-plc-announces-phase-2-trial-evaluating-dazodalibep-for-the-treatment-of-sjoegren-s-syndrome-meets-primary-endpoint/
10. Business Wire. January 18, 2023 – https://www.businesswire.com/news/home/20230118005359/en/Horizon-Therapeutics-plc-Announces-Phase-2-Trial-Evaluating-Dazodalibep-for-the-Treatment-of-Sj%C3%B6gren%E2%80%99s-Syndrome-Meets-Primary-Endpoint-in-the-Second-Study-Population-Only-Phase-2-Trial-to-Meet-Primary-Endpoint-in-Both-Patient-Populations

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 proof-of-concept study has been completed, and topline results were reported in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily oral formulation being developed as a treatment for major depressive disorder (MDD), that completed enrollment in a Phase 2 in the third quarter of 2023, with topline results expected in early November of 2023. TNX-4300 (estianeptine) is a single isomer version of TNX-601, a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. Relative to tianeptine, estianeptine lacks activity on the mu-opioid receptor while maintaining activity and the ability to activate PPAR-β/δ and neuroplasticity in tissue culture. TNX-1900 (intranasal potentiated oxytocin), is in development as a preventive treatment in chronic migraine, and enrollment has completed in a Phase 2 proof-of-concept study with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the fourth quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum small molecule oral antivirals.

*Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication.

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

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

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
443-213-0495

Source: Tonix Pharmaceuticals Holding Corp.

Released October 18, 2023

Research News and Market Data on TNXP

October 16, 2023 7:00am EDTDownload as PDF

Topline Results Expected Early November 2023

Tianeptine, the Active Ingredient in TNX-601 ER, is Not Associated with Sexual Dysfunction or Weight Gain Which are Treatment-Limiting Side Effects of Many Traditional Antidepressants

Tianeptine Acts by Directly Restoring Neuroplasticity and Neurogenesis and Limiting the Effects of Oxidative Stress in the Brain

CHATHAM, N.J., Oct. 16, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, today announced the completion of the clinical phase of the Phase 2 potential registration-quality, double-blind, randomized, multicenter, placebo-controlled UPLIFT¹ study of TNX-601 ER² (tianeptine hemioxalate extended-release tablets) as a potential treatment for major depressive disorder (MDD). Topline results from the intention-to-treat (ITT) sample (N=132) are expected in early November 2023.

TNX-601 ER is being developed as a monotherapy and first-line treatment for MDD and works by a distinct mechanism of action as compared to traditional monoaminergic antidepressants. Tonix recently reported that tianeptine activates peroxisome proliferator-activated receptors PPAR-β/δ and PPAR-γ. These activities on intracellular molecular targets in neurons and glia in the brain are believed to relate to tianeptine’s ability to restore connectivity between neurons that atrophy under conditions of stress, in animal models.^3,4 Tianeptine is the active ingredient of an antidepressant that has been marketed as a three-times-a-day medicine outside the U.S. for more than 30 years. Tonix has developed a novel, patented once-daily oral formulation.

“Because of its unique mechanism, tianeptine avoids some of the treatment-limiting side effects of traditional antidepressants, including sexual dysfunction and weight gain,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Tianeptine restores connectivity between neurons, or neuroplasticity, and limits the effects of oxidative stress in the brain in animal models of depression. In contrast to traditional antidepressants which alter the levels of neurotransmitters in the synapse, tianeptine directly induces mature neurons to sprout new connections and also induces formation of new neurons.”

“With the last patient now treated, we look forward to analysis of the results of this registration-quality study, which will help to inform our plans as we discuss next steps with the U.S. Food and Drug Administration (FDA),” said Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals. “We would like to thank the participants, their families, and all the investigators and researchers who have been an important part of this journey so far.”

1. Clinical Trials.gov I.D. NCT05686408
2. TNX-601 ER is an investigational new drug and is not approved for any indication.
3. McEwen, B. S., et al. Mol. Psychiatry 2010, 15 (3), 237–249
4. Sullivan, GM et al. June 1, 2023. Poster presentation at the American Society of Clinical Psychopharmacology, Miami, FL. https://www.tonixpharma.com/wp-content/uploads/2023/06/ASCP-Poster-2023-A-Randomized-Placebo-Controlled-Multicenter-Trial-of-Monotherapy-with-TNX-601-ER.pdf

About the Phase 2 UPLIFT Study

The Phase 2 UPLIFT study, TNX-TI-M201, is a potential registration-quality, double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-601 ER taken by mouth once-daily for 6 weeks for the treatment of moderate-to-severe MDD. It is a parallel design study with two arms, a TNX-601 ER 39.4 mg arm and a placebo arm. A total of 132 participants were randomized in a 1:1 ratio into the two arms across approximately 27 U.S. sites, enrolling adult patients 18-65 years old with a DSM-5 diagnosis of depression and a duration for the current major depressive episode of at least 12 weeks. The primary efficacy endpoint is mean change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6. Key secondary efficacy endpoints include the Clinical Global Impression of Severity Scale (CGI-S) and the Sheehan Disability Scale (SDS).

For more information, see ClinicalTrials.gov Identifier: NCT05686408.

About Major Depressive Disorder (Depression)

According to the National Institute of Mental Health, an estimated 21 million adults in the U.S. in 2020 experienced at least one major depressive episode¹, with highest prevalence among individuals aged 18-25 at a rate of 17.0%. For approximately 2.5 million adults in the U.S., adjunctive therapies are necessary for depression treatment.^2,3 Depression is a condition characterized by symptoms such as a depressed mood or loss of interest or pleasure in daily activities most of the time for two weeks or more, accompanied by appetite changes, sleep disturbances, motor restlessness or retardation, loss of energy, feelings of worthlessness or excessive guilt, poor concentration, and suicidal thoughts and behaviors. These symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. The majority of people who suffer from depression do not respond adequately to initial antidepressant therapy.⁴

¹ Data Courtesy of SAMHSA on Past Year Prevalence of Major Depressive Episode Among U.S. Adults 2020. Retrieved from http://www.nimh.nih.gov/health/statistics/major-depression.shtml

² IMS NSP, NPA, NDTI MAT-24-month data through Aug 2017.

³ Kubitz N, et al. PLoS One 2013, 8 (10), e76882.

⁴ Rush AJ, et al. Am J. Psychiatry 2007, 163 (11), 1905-1917.

About TNX-601 ER

TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a novel oral formulation of tianeptine designed for once-daily daytime dosing in development as a candidate for the treatment of MDD, posttraumatic stress disorder, and neurocognitive dysfunction associated with corticosteroid use. 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. Tonix discovered a novel oxalate salt of tianeptine that may provide improved stability, consistency, and manufacturability compared to known salt forms of tianeptine. 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 TNX-601 ER’s 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 basis²). 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. The ER formulation of TNX-601 includes several potentially abuse deterrent ingredients, such as gel forming polymers which impede extraction. In addition, the tablet’s hardness makes it difficult to crush, cut or grind to fine particle size, which potentially hinders efforts to misuse by insufflation or intravenous routes. 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. TNX-601 ER is expected to have patent protection through 2037.

¹ McEwen, B. S., et al. Mol. Psychiatry 2010, 15 (3), 237–249.

² Lauhan, R., et al. Psychosomatics 2018, 59 (6), 547–53.

³ Haute Authorite de Sante; Transparency Committee Opinion. Stablon 12.5 Mg, Coated Tablet, Re- Assessment of Actual Benefit at the Request of the Transparency Committee. December 5, 2012.

⁴ Emsley, R., et al. J. Clin. Psychiatry 2018, 79 (4)

⁵ Bonierbale M, et al. Curr Med Res Opin 2003, 19(2):114-124.

⁶ Guelfi, J. D., et al. Neuropsychobiology 1989, 22 (1), 41–48.

⁷ Invernizzi, G. et al., Neuropsychobiology 1994, 30 (2–3), 85–93.

⁸ Lepine, J. P., et al. Hum. Psychopharmacol. 2001, 16 (3), 219–227.

⁹ Guelfi, J. D. et al., Neuropsychobiology 1992, 25 (3), 140–148.

¹⁰ Lôo, H. et al., Br. J. Psychiatry. Suppl. 1992, 15, 61–65. 

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 proof-of-concept study has been completed, and topline results were reported in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily oral formulation being developed as a treatment for major depressive disorder (MDD), that completed enrollment in a Phase 2 in the third quarter of 2023, with topline results expected in early November of 2023. TNX-4300 (estianeptine) is a single isomer version of TNX-601, a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. Relative to tianeptine, estianeptine lacks activity on the mu-opioid receptor while maintaining activity and the ability to activate PPAR-β/δ and neuroplasticity in tissue culture. TNX-1900 (intranasal potentiated oxytocin), is in development as a preventive treatment in chronic migraine, and enrollment has completed in a Phase 2 proof-of-concept study with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the fourth quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum small molecule oral antivirals.

*Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication.

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

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

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
443-213-0495

Source: Tonix Pharmaceuticals Holding Corp.

Released October 16, 2023

Research News and Market Data on TNXP

October 09, 2023 7:00am EDTDownload as PDF

CHATHAM, N.J., Oct. 09, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, today announced that Herbert Harris, M.D., Ph.D., Executive Vice President, Translational Medicine of Tonix Pharmaceuticals, provided an overview of Tonix’s TNX-2900 (potentiated intranasal oxytocin) program at the Foundation for Prader-Willi Research (FPWR) Family Conference in Denver, CO. A copy of the presentation is available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com. Additional information can be found on the FPWR conference website here.

The presentation highlights preclinical data showing the enhancing effects of magnesium (Mg²⁺) on the activation of oxytocin receptors. The Mg²⁺ enhanced formulation of intranasal oxytocin is the basis for TNX-2900, in development to treat hyperphagia, or pathological over-eating, in children and adolescents with Prader-Willi syndrome (PWS). In preclinical studies, Mg²⁺ increases the potency of oxytocin, which is an anorexigenic hormone that reduces appetite and signals fullness, potentially improving receptor binding and resulting in improved therapeutic action.

TNX-2900 has been granted Orphan Drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of PWS. Tonix plans to submit an investigational new drug (IND) application to the FDA in the fourth quarter of 2023. There is no treatment currently approved for hyperphagia in PWS.

Tonix licensed the technology to treat PWS from Inserm Transfert, the private subsidiary of Inserm (the French National Institute of Health and Medical Research).

About Prader-Willi Syndrome

Prader-Willi syndrome is recognized as the most common genetic cause of life-threatening childhood obesity¹ and affects males and females with equal frequency and all races and ethnicities. The hallmarks of Prader-Willi syndrome are lack of suckling in infants and, in children, adolescents, and adults, severe hyperphagia, an overriding physiological drive to eat, leading to severe obesity and other complications associated with significant mortality. There is currently no approved treatment for either the suckling deficit in babies or the obesity and hyperphagia in older children associated with Prader-Willi syndrome.

¹ Foundation for Prader-Willi Research (fpwr.org).

About TNX-2900 and Tonix’s Potentiated Oxytocin Platform

TNX-2900 is based on Tonix’s patented intranasal potentiated oxytocin formulation which is believed to increase specificity for oxytocin receptors relative to vasopressin receptors as well as to enhance the potency of oxytocin. Tonix is also developing a different intranasal formulation and device, designated TNX-1900, for prophylaxis of chronic migraine and for the treatment of insulin resistance and related conditions. Oxytocin is a naturally occurring human hormone that acts as a neurotransmitter in the brain. It was originally approved by the U.S. Food and Drug Administration as Pitocin^®*, an intravenous infusion or intramuscular injection drug, for use in pregnant women to induce labor. An intranasal form of oxytocin was marketed in the U.S. by Novartis to assist in the production of breast milk as Syntocinon^®** (oxytocin nasal 40 units/ml), but the product was discontinued, and the New Drug Application was withdrawn.

*Pitocin^® is a trademark of Par Pharmaceutical, Inc.

**Syntocinon^® is a trademark of BGP Products Operations GmbH

About the Foundation for Prader-Willi Research (FPWR)

FPWR is a global nonprofit organization focused on funding research, advancing scientific understanding, and improving the lives of individuals with Prader-Willi syndrome. By supporting innovative research and forging strategic partnerships, FPWR seeks to find treatments and ultimately a cure for PWS. For more information please visit https://www.fpwr.org/. 

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 proof-of-concept study has been completed, and topline results were reported in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily oral formulation being developed as a treatment for major depressive disorder (MDD), that completed enrollment in a Phase 2 proof-of-concept study in the third quarter of 2023, with topline results expected in early November of 2023. TNX-4300 (estianeptine) is a single isomer version of TNX-601, small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. Relative to tianeptine, estianeptine lacks activity on the µ-opioid receptor while maintaining activity in the rat Novel Object Recognition test in vivo and the ability to activate PPAR-β/δ and neuroplasticity in tissue culture. TNX-1900 (intranasal potentiated oxytocin), is in development for preventing headaches in chronic migraine, and has completed enrollment in a Phase 2 proof-of-concept study with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the fourth quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum small molecule oral antivirals.

*Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication.

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

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

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

Source: Tonix Pharmaceuticals Holding Corp.

Released October 9, 2023