Tag: Tonix Pharmaceuticals Holding Corp.

Research News and Market Data on TNXP

May 13, 2024 4:30pm EDT

On track to submit NDA in the second half of 2024 for Tonmya™ for fibromyalgia; pre-NDA meeting with FDA scheduled for second quarter 2024

Commercial planning continues for U.S. launch of Tonmya, a potential new first-line, centrally-acting, non-opioid analgesic for the management of fibromyalgia

CHATHAM, N.J., May 13, 2024 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, today announced financial results for the first quarter ended March 31, 2024, and provided an overview of recent operational highlights.

“Our near-term priority continues to be the submission of our New Drug Application (NDA) for Tonmya™ (cyclobenzaprine HCl sublingual tablets) for the management of fibromyalgia, while continuing to build out our commercial strategy for the anticipated product launch in the event of FDA approval, which we currently estimate to occur in the second half of 2025,” said Seth Lederman, M.D., Chief Executive Officer of Tonix.

Dr. Lederman added, “The well-known treatment-limiting side effects of the three currently approved drugs have led to widespread patient dissatisfaction, creating what we believe is a significant opportunity for a new therapeutic. Tonmya has a differentiated mechanism of action and is generally free of common side effects associated with the currently approved products, including weight gain, fatigue, insomnia, increased blood pressure, gastrointestinal issues or sexual dysfunction. As such, we believe Tonmya, if approved, could become the treatment of choice for the approximately 10 million people in the U.S. suffering the debilitating effects of fibromyalgia.”

The Company is also advancing other key pipeline programs including those for immunology, obesity, eating disorders, infectious and rare diseases, many through a capital efficient strategy involving partnerships, grants and in-kind contributions.

Recent Highlights – Key Product Candidates*

Central Nervous System (CNS) Pipeline

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

• In January 2024, Tonix presented additional safety and tolerability data from the pivotal Phase 3 RESILIENT study that showed Tonmya treatment was not associated with increases in systolic or diastolic blood pressure or body weight, nor were there any reported sexual side effects. The Company had previously announced in December 2023 that the Phase 3 RESILIENT study, a registration-quality, double-blind, placebo-controlled study evaluating Tonyma met its pre-specified primary endpoint in the second of two positive Phase 3 clinical trials, significantly reducing daily pain compared to placebo (p-value=0.00005) in participants with fibromyalgia. Statistically significant and clinically meaningful results were also seen in all pre-specified key secondary endpoints including those related to improving sleep quality, reducing fatigue, and improving patient global ratings and overall fibromyalgia symptoms and function. Tonmya was well tolerated with an adverse event profile comparable to prior studies and no new safety signals observed. In addition, Tonmya therapy showed activity on improving female sexual function relative to placebo with a nominal p-value=0.010 by the Changes in Sexual Functioning Questionnaire short-form, female version.
• Tonix plans to submit an NDA to the FDA in the second half of 2024 for Tonmya for the management of fibromyalgia. In February 2024, Tonix announced the engagement of Rho, Inc. as our contract research organization (CRO) to support NDA submission.
• In February 2024, Tonix announced statistically significant results from its clinical pharmacokinetic (PK) bridging study of Tonmya in healthy adult male and female ethnic Japanese and Chinese volunteers. Results indicate that key PK parameters of cyclobenzaprine are comparable in ethnic Japanese and Chinese volunteers to Caucasian volunteers from a prior PK study. Tonmya was generally well tolerated in the ethnic Japanese and Chinese healthy volunteers. The company expects these data to fulfill the requirement for a bridging study, and enables Tonix to rely on Phase 3 studies RESILIENT and RELIEF results to support regulatory filings for clinical studies in Japan and China where cyclobenzaprine is a new chemical entity (NCE). Tonix holds issued patents for market exclusivity rights of Tonmya in Japan, China, Hong Kong and Taiwan.
• In March 2024, Tonix announced the selection of two contract manufacturing organizations (CMOs), including Almac Pharma Services, as dual supply sources for the potential launch and commercialization of Tonmya in the U.S.
• In March 2024, Tonix selected EVERSANA, a leading provider of commercialization services to the global life sciences industry, to support the launch strategy and commercial planning of Tonmya in the U.S.
• Tonix presented additional efficacy data from RESILIENT at the 6^th International Congress on Controversies in Fibromyalgia in Brussels, Belgium, March 7-8, 2024. The data showed that Tonmya treatment resulted in an improvement in cognitive dysfunction, or ‘brain fog’, measured by the change in the Fibromyalgia Impact Questionnaire-Revised (FIQ-R) memory item. The FIQ-R cognitive item showed nominal improvement in Tonmya-treated patients vs placebo-treated patients with a nominal p-value=0.001 and effect size of 0.31.

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

• In February 2024, the Company announced the FDA cleared the Investigational New Drug (IND) application for the Phase 2 investigator-initiated OASIS trial to evaluate TNX-102 SL in reducing the severity of ASR and the frequency of ASD and PTSD. The trial is sponsored by the University of North Carolina Institute for Trauma Recovery and supported by a $3 million grant from the U.S. Department of Defense, which was awarded in September 2023. 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. The study will enroll approximately 180 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 5.6 mg or placebo.
• Tonix anticipates the Phase 2 OASIS trial will initiate in the second quarter of 2024.

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

• In January 2024, the Company announced the online publication of a research paper in the Journal Pain. The article titled, “Chronic Overlapping Pain Conditions Increase the Risk of Long COVID Features, Regardless of Acute COVID Status,” by Bergmans, et al.¹, found that patients with pre-existing chronic overlapping pain conditions (COPCs) had an increased risk of being diagnosed with symptoms of Long COVID¹. Faculty at the University of Michigan directed the research. Commentary on the article titled, “A step towards better understanding chronic overlapping pain conditions” by Fitzcharles, et al,² is in the same issue of the journal. COPCs include fibromyalgia, chronic fatigue syndrome, migraine headache, irritable bowel syndrome, endometriosis and low back pain. These results contribute to a growing body of evidence that common symptoms of Long COVID in many patients are at least partly driven by central nervous system mechanisms.

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 emergency rooms in the second quarter of 2024. In 2022, Tonix was awarded a Cooperative Agreement grant from the National Institutes of Health (NIH)’s National Institute of Drug Abuse (NIDA) to support development of TNX-1300.
• TNX-1300 has been granted Breakthrough Therapy designation by the FDA.

TNX-1900 (intranasal potentiated oxytocin): small peptide in development through investigator-initiated studies for adolescent obesity, binge eating disorder, bone health in autism and social anxiety disorder (SAD).

• TNX-1900 continues to be studied in four ongoing investigator-initiated Phase 2 studies as follows: Massachusetts General Hospital (MGH): (1) Phase 2 study for binge-eating disorder (BED); (2) Phase 2 study for adolescent obesity; (3) Phase 2 study for improving bone health in children with autism spectrum disorder (BOX); and at University of Washington, (4) Phase 2 study for social anxiety disorder (SAD). The BED study and the adolescent obesity study will investigate whether TNX-1900 has effects on eating behaviors in specialized populations.

Rare Disease Pipeline

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

• In March 2024, Tonix announced that it received Rare Pediatric Disease designation from the FDA for TNX-2900 for the treatment of PWS. Tonix has an IND to support clinical development of TNX-2900 to treat PWS in children and adolescents. The planned Phase 2 study is a dose-finding study involving approximately 36 PWS patients divided into four groups with approximately nine per group. One group will receive placebo and three groups will receive different dosage regimens of TNX-2900. TNX-2900 for the treatment of PWS was granted Orphan Drug designation by the FDA in 2022. PWS is a genetic disorder that affects several body systems, with cognitive and behavioral symptoms including pathological over-eating beginning in childhood and leading to severe metabolic sequelae.

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.

• The first proposed indication for TNX-1500 is 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 with TNX-1500 at the Massachusetts General Hospital (MGH) on allogeneic transplants in animals.^3,4
• Preclinical studies have shown that TNX-1500 maintains the activity of first-generation monoclonal antibodies (mAbs), yet with reduced risk of thrombotic complications.^3-5 Modeling studies from animal pharmacokinetic data³ predict a half-life of greater than three weeks for TNX-1500 in humans, which supports a monthly i.v. dosing regimen. This analysis together with TNX-1500’s activity and tolerability in animals, suggests that the protein engineering of TNX-1500’s Fc region has achieved its design goals.
• In February 2024, Tonix announced the completion of the clinical stage of its 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.
• In March of 2024, the MGH announced the first transplant of a genetically modified pig kidney into a living patient in collaboration with eGenesis, which produced the pig donors and used an anti-CD40L mAb from another company.⁵ Some of the pre-clinical work that supported the living human transplant was performed in collaboration with Tonix and used TNX-1500.⁶ The patient was able to return home after the transplant, but died after approximately two months.⁷

Marketed Products – Recent Highlights

• As of April 1, 2024, Tonix completed the transition to becoming a fully integrated pharmaceutical company. Tonix Pharmaceuticals has implemented personnel, systems and contracts required to support a commercial organization and has assumed responsibility for distribution, selling and marketing of Zembrace SymTouch and Tosymra, as well as supply chain, regulatory and quality control of the two products.

Facilities – Recent Highlights

• In the fourth quarter of 2023, Tonix engaged CBRE, an international real estate brokerage firm, to potentially find a strategic partner for, or buyer of, its Advanced Development Center (ADC) to align with the Company’s current business objectives and priorities. At this time, the Company does not have a commitment in place to sell the building. ADC, located in the New Bedford business park in Dartmouth, Massachusetts, is an approximately 45,000 square foot BSL-2 facility intended for clinical scale manufacturing of live-virus vaccines and biologics.

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

Tonmya™ is conditionally accepted by the U.S. Food and Drug Administration (FDA) as the tradename for TNX-102 SL for the management of fibromyalgia. Tonmya has not been approved for any indication.

¹ Bergmans RS, et al. PAIN. 2023. DOI: 10.1097/j.pain.0000000000003110.

² Fitzcharles M-A, et al. PAIN. 2023. DOI: 10.1097/j.pain.0000000000003129.

³ Lassiter G., et al. Am J Transplantation. 2023. https://doi.org/10.1016/j.ajt.2023.03.022

⁴ Miura S., et al. Am J Transplantation. 2023. https://doi.org/10.1016/j.ajt.2023.03.025

⁵ Massachusetts General Hospital press release. March 21, 2024. “World’s First Genetically Edited Pig Kidney Transplant into Living Recipient Performed at Massachusetts General Hospital.” www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient (accessed March 29, 2024)

⁶ Anand, R.P., et al Nature. 622, 393–401 (2023). https://doi.org/10.1038/s41586-023-06594-4

⁷ Stoico, N. Boston Globe. May 11, 2023. “Mass Man who received first kidney transplant from genetically engineered pig has died, family says”.

Recent Highlights – Financial

As of March 31, 2024, Tonix had $7.0 million of cash and cash equivalents, compared to $24.9 million as of December 31, 2023. Net cash used in operations was approximately $17.6 million for first quarter 2024, compared to net cash used in operations of $32.9 million for the same period in 2023.

On April 1, 2024, the Company closed a financing with existing healthcare-focused institutional investors for upfront gross proceeds of approximately $4.4 million through a registered direct offering. 

First Quarter 2024 Financial Results

Net product revenue for the first quarter 2024 was approximately $2.5 million. Net product revenue consisted of combined net sales of Zembrace® SymTouch® and Tosymra®, which were acquired from Upsher-Smith Laboratories, LLC on June 30, 2023. Cost of Sales for the first quarter 2024 was approximately $1.7 million.

Research and development expenses for the first quarter 2024 were $12.9 million, compared to $26.5 million for the same period in 2023. This decrease is predominantly due to decreased clinical, non-clinical and manufacturing expenses.

General and administrative expenses for the first quarter 2024 were $9.3 million, compared to $7.4 million for the same period in 2023. The increase was primarily due to sales and marketing and the transition services expenses associated with the Company’s recently acquired marketed products offset by a decrease in financial reporting expenses.

Net loss was $(14.9) million, or $(0.18) per share, basic and diluted, for the first quarter 2024, compared to net loss of $(33.0) million, or $(3.21) per share, basic and diluted, for the same period in 2023. The basic and diluted weighted average common shares outstanding for the first quarter 2024 was 80,879,108 compared to 10,268,500 shares for the same period in 2023.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a fully-integrated biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya¹, a product candidate for which two statistically significant Phase 3 studies have been completed for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction as well as fibromyalgia-type Long COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase), a biologic designed to treat cocaine intoxication that has Breakthrough Therapy designation. Tonix’s immunology development portfolio consists of 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. Tonix also has product candidates in development in the areas of rare disease and infectious disease. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults.

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

¹Tonmya™ is conditionally accepted by the U.S. Food and Drug Administration (FDA) as the tradename for TNX-102 SL for the management of fibromyalgia. Tonmya has not been approved for any indication.

Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. 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, 2023, as filed with the Securities and Exchange Commission (the “SEC”) on April 1, 2024, 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.

View full release here.

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

Katie Dodge
LaVoieHealthScience
kdodge@lavoiehealthscience.com
(978) 360-3151

Research News and Market Data on TNXP

April 01, 2024 4:15pm EDT

Positive results from confirmatory Phase 3 RESILIENT study reported in December 2023 position Tonmya™ for fibromyalgia for NDA submission second half of 2024; pre-NDA meeting with FDA scheduled for second quarter 2024

Commercial planning underway, including go-to-market, supply chain and manufacturing strategies, for U.S. launch of Tonmya, a potential new first-line, centrally-acting, non-opioid analgesic for the management of fibromyalgia

CHATHAM, N.J., April 01, 2024 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, today announced financial results for the fourth quarter and full year ended December 31, 2023, and provided an overview of recent operational highlights.

“Our near-term focus is seeking U.S. marketing approval for Tonmya (cyclobenzaprine HCl sublingual tablets) for the treatment of fibromyalgia from the U.S. Food and Drug Administration (FDA),” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Our pre-NDA meeting with the FDA is scheduled to take place this quarter and we plan to submit our New Drug Application (NDA) for Tonmya™ in the second half of 2024. We believe the positive Phase 3 RESILIENT results reported in December of 2023 together with the positive results from the first Phase 3 RELIEF study should satisfy the requirements for approval and, if so, would provide the opportunity for Tonix to launch the first FDA-approved drug for fibromyalgia in more than a decade. We believe the activity of Tonmya on improving pain, sleep quality, fatigue and brain fog in the RESILIENT study are indicative of the broad-spectrum of activity in fibromyalgia.”

Dr. Lederman added, “While Tonix is focusing its resources on progressing Tonmya toward NDA submission and potential FDA approval, we are seeking partnerships and collaborations on our pipeline programs from government agencies, non-profit organizations and other biotechnology or pharmaceuticals companies. Tonix has already shifted portions of our research and development (R&D) expenses to U.S. government agencies and other institutions through partnerships involving grants and in-kind contributions. These outside collaborations leverage our internal resources, and we believe they provide a capital efficient strategy for progress.”

Selected Product Candidates* — Recent Highlights

Central Nervous System (CNS) Pipeline

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

• The Company announced in December 2023 that the Phase 3 RESILIENT study, a registration-quality, double-blind, placebo-controlled study evaluating TNX-102 SL met its pre-specified primary endpoint in the second of two positive Phase 3 clinical trials, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia. Statistically significant and clinically meaningful results were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue, and improving patient global ratings and overall fibromyalgia symptoms and function. Additionally, as it relates to improving daily pain, treatment with TNX-102 SL showed a robust and clinically meaningful analgesic Cohen’s d effect size of 0.38, with rapid onset of action, separating from placebo for every week of the study. TNX-102 SL was well tolerated with an adverse event profile comparable to prior studies and no new safety signals observed. Tonix plans to submit an NDA to the FDA in the second half of 2024 for TNX-102 SL for the management of fibromyalgia.
• In January 2024, Tonix presented additional safety and tolerability data from the Phase 3 RESILIENT study that showed TNX-102 SL treatment was not associated with increases in systolic or diastolic blood pressure or body weight, nor were there any reported sexual side effects.
• In January 2024, Tonix announced that the FDA has conditionally accepted the trade name, Tonmya, for the Company’s drug product candidate TNX-102 SL for the management of fibromyalgia.
• In February 2024, Tonix announced positive results from its clinical pharmacokinetic (PK) bridging study of Tonmya in healthy adult male and female ethnic Japanese and Chinese volunteers. Results indicate that key PK parameters of cyclobenzaprine are comparable in ethnic Japanese and Chinese volunteers to Caucasian volunteers from a prior PK study. Tonmya was generally well tolerated in the ethnic Japanese and Chinese healthy volunteers. The company expects these data to fulfill the requirement for a bridging study, and enables Tonix to rely on Phase 3 studies RESILIENT and RELIEF results to support regulatory filings for clinical studies in Japan and China where cyclobenzaprine is a new chemical entity (NCE). Tonix holds issued patents for market exclusivity rights of Tonmya in Japan, China, Hong Kong and Taiwan.
• In February 2024, Tonix selected Rho, Inc., a global contract research organization, to support Tonix’s preparation and planned submission of its NDA to the FDA for the approval of Tonmya for the management of fibromyalgia.
• In March 2024, Tonix announced the selection of two CMOs, including Almac Pharma Services, as dual supply sources for the potential launch and commercialization of Tonmya in the U.S.
• In March 2024, Tonix selected EVERSANA, a leading provider of commercialization services to the global life sciences industry, to support the launch strategy and commercial planning of Tonmya in the U.S.
• Tonix presented additional efficacy data from RESILIENT at the 6^th International Congress on Controversies in Fibromyalgia in Brussels, Belgium, March 7-8, 2024. The data showed that Tonmya treatment resulted in an improvement in cognitive dysfunction, or ‘brain fog’, measured by the change in the Fibromyalgia Impact Questionnaire-Revised (FIQ-R) memory item. The FIQ-R cognitive item showed nominal improvement in Tonmya-treated patients vs placebo-treated patients with p-value=0.001 and effect size of 0.31.

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

• In February 2024, the Company announced the FDA cleared the Investigational New Drug (IND) application for the Phase 2 investigator-initiated OASIS trial to evaluate TNX-102 SL in reducing the severity of ASR and the frequency of ASD and PTSD. The trial is sponsored by The UNC Institute for Trauma Recovery and supported by a $3 million grant from the U.S. Department of Defense (DoD), which was awarded in September 2023. 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 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 5.6 mg or placebo.
• Tonix expects the Phase 2 OASIS trial will initiate in the second quarter of 2024.

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

• In January 2024, the Company announced the online publication of a research paper in the Journal Pain. The article titled, “Chronic Overlapping Pain Conditions Increase the Risk of Long COVID Features, Regardless of Acute COVID Status,” by Bergmans, et al. ¹, found that patients with pre-existing chronic overlapping pain conditions (COPCs) had an increased risk of being diagnosed with symptoms of Long COVID¹. Faculty at the University of Michigan directed the research. Commentary on the article titled, “A step towards better understanding chronic overlapping pain conditions” by Fitzcharles, et al,² is in the same issue of the journal. COPCs include fibromyalgia, chronic fatigue syndrome, migraine headache, irritable bowel syndrome, endometriosis and low back pain. These results contribute to a growing body of evidence that common symptoms of Long COVID in many patients are at least partly driven by central nervous system mechanisms.
• In September 2023, the Company reported 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 0.50 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.

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 emergency rooms in the second quarter of 2024. In 2022, Tonix was awarded a Cooperative Agreement grant from the National Institutes of Health (NIH)’s National Institute of Drug Abuse (NIDA) to support development of TNX-1300.
• TNX-1300 has been granted Breakthrough Therapy designation by the FDA.

TNX-1900 (intranasal potentiated oxytocin): small peptide in development through investigator-initiated studies for bone health in autism, social anxiety disorder (SAD), adolescent obesity and binge eating disorder

• In November 2023, Tonix announced that the first participant was enrolled in an investigator-initiated Phase 2 study of TNX-1900 for improving bone health in children with autism spectrum disorder, named the BOX study, at Massachusetts General Hospital (MGH). The aim of this DoD funded study is to investigate the efficacy and safety of TNX-1900 as a novel therapeutic agent to increase bone density and improve bone structure and strength in children with autism spectrum disorder. Tonix is providing active drug and placebo for the BOX study as part of a drug donation agreement with MGH. MGH is the sponsor of the trial, which is being conducted under an investigator-initiated IND application.
• TNX-1900 is also being studied in three other ongoing investigator-initiated Phase 2 studies as follows:
  
  
  • MGH Phase 2 study for binge-eating disorder (BED)
  • University of Washington Phase 2 study for social anxiety disorder (SAD)
  • MGH Phase 2 study for adolescent obesity

Rare Disease Pipeline

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

• In December 2023, Tonix announced that the FDA has cleared the IND application to support clinical development of TNX-2900 to treat PWS in children and adolescents. The Phase 2 study approved under the IND is a dose-finding study involving approximately 36 PWS patients divided into four groups with approximately nine per group. One group will receive placebo and three groups will receive different dosage regimens of TNX-2900. TNX-2900 for the treatment of PWS was granted Orphan Drug designation by the FDA in 2022.
• In March 2024, Tonix announced that it received Rare Pediatric Disease designation from the FDA for TNX-2900 for the treatment of PWS.

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.

• The first indication for TNX-1500 is 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 Massachusetts General Hospital (MGH) on allogeneic transplants in animals were published.^3,4
• Preclinical studies have shown that TNX-1500 maintains the activity of first-generation monoclonal antibodies (mAbs), yet with reduced risk of thrombotic complications.^3-5 Modeling studies from animal pharmacokinetic data³ predict a half-life of approximately three weeks for TNX-1500 in humans, which supports a monthly i.v. dosing regimen. This analysis together with TNX-1500’s activity and tolerability in animals, suggests that the protein engineering of TNX-1500’s Fc region has achieved its design goals.
• In October 2023, the Company announced data from two oral presentations delivered at medical meetings in 2023. 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 xenogeneic 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 Nature⁵ 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 February 2024, Tonix announced the completion of the clinical stage of its 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. Topline results are expected in the third quarter of 2024. This first-in-human study is intended to support dosing in a planned Phase 2 trial in kidney transplant recipients.
• In March of 2024, the MGH announced the first transplant of a genetically modified pig kidney into a living patent in collaboration with eGenesis, which produced the pig donors.⁶ Some of the pre-clinical work that supported this transplant was performed in collaboration with Tonix and used TNX-1500.⁵

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

• Results from a study with our TNX-1800 vaccine that showed animals were protected from challenge with SARS-CoV-2 were published as an article in the peer reviewed journal, Viruses in 2023.⁷
• In November 2023, Tonix announced that NIH and National Institute of Allergy and Infectious Diseases (NIAID) will conduct a Phase 1 clinical trial with TNX-1800 as part of Project NextGen. 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 recombinant pox vaccine (RPV) platform.
• We believe the TNX-1800 vaccine development plan addresses several priority vaccine attributes advanced by the White House Office of Science and Technology Policy’s Pandemic Preparedness Plan,⁸ the National Biodefense Science Board⁹ and BARDA.¹⁰ Tonix believes its RPV platform can address a wide variety of disease targets of public health interest. 

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

• Results from a study with our TNX-801 vaccine that showed animals were protected from mpox were reported at a meeting in the first quarter of 2020 and published as an article in the peer reviewed journal, Viruses in 2023.¹¹
• On December 14, 2023, Dr. Lederman participated in a panel discussion on Vaccine Research & Development at the National Academies of Sciences, Engineering, and Medicine (NAS) Committee on the Current State of Research, Development, and Stockpiling of Smallpox Medical Countermeasures public meeting. Discussions explored lessons learned from the recent COVID-19 pandemic and mpox multi-country outbreak to inform an evaluation of the current state of research, development, and stockpiling of smallpox readiness and response measures. The Consensus Study Report was issued on March 28, 2024.¹² Some of the conclusions included recommendations for single dose vaccines, safer vaccines, vaccine platforms and attention to supply chain and manufacturing. Tonix believes TNX-801 has the potential to address some of the recommendations from the NAS Committee since it provides single dose protection to animals, and has the potential for favorable dose, manufacturing and cold chain requirements.
• 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.
• Concerns about current state of new smallpox and mpox vaccines in development have been raised by the U.S. Bipartisan Commission on Biodefense¹³ and by an outbreak of mpox in the Democratic Republic of the Congo.¹⁴
• Results from a study with our TNX-801 vaccine that showed decreased virulence relative to traditional live vaccinia vaccine strains were posted on the website BioRxiv in 2023.¹⁵

Broad-spectrum anti-viral programs

Tonix is developing potential broad-spectrum antiviral drugs in three programs: CD45-targeted therapeutics (TNX-4200), cathepsin inhibitors (TNX-3900) and viral glycan-targeted engineered biologics (TNX-4000). In 2020, the DoD announced that they are seeking broad spectrum antiviral drugs since it would be hard to predict which or how many viruses may be deployed on the battlefield.¹⁶ Tonix hopes that one or more of our programs may help the DoD address that goal.

Marketed Products — Recent Highlights

• Tonix completed the acquisition of Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra (sumatriptan nasal spray) 10 mg from Upsher-Smith Laboratories, LLC on June 30, 2023. Both products are indicated for the treatment of acute migraine with or without aura in adults.
• Combined net product revenue of $7.8 million reported for the period July 1, 2023 – December 31, 2023 for Zembrace Symtouch and Tosymra.
• As of April 1, 2024, Tonix completed the transition to becoming a fully integrated pharmaceutical company. Tonix Pharmaceuticals has implemented personnel, systems and contracts required to support a commercial organization and has assumed responsibility for distribution, selling and marketing of Zembrace SymTouch and Tosymra, as well as supply chain, regulatory and quality control of the two products.

Facilities — Recent Highlights

• Tonix’s Advanced Development Center (ADC) located in the New Bedford business park in Dartmouth, Massachusetts, is an approximately 45,000 square foot BSL-2 facility and is intended to accelerate development and clinical scale manufacturing of live-virus vaccines and biologics to support clinical trials. Tonix has engaged CBRE, an international real estate brokerage firm, to find a strategic partner for, or buyer of, ADC.
• Tonix’s Research and Development Center (RDC) in Frederick, Maryland, consisting of one building totaling approximately 48,000 square feet, conducts research on central nervous system, immunology, and infectious disease candidates. The RDC facility is mostly biosafety level 2 (BSL-2), with some components designated BSL-3.

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

¹ Bergmans RS, et al. PAIN. 2023. DOI: 10.1097/j.pain.0000000000003110^.
2 Fitzcharles M-A, et al. PAIN. 2023. DOI: 10.1097/j.pain.0000000000003129.
³ Lassiter G., et al. Am J Transplantation. 2023. https://doi.org/10.1016/j.ajt.2023.03.022
⁴ Miura S., et al. Am J Transplantation. 2023. https://doi.org/10.1016/j.ajt.2023.03.025
⁵ Anand, R.P., et al Nature. 622, 393–401 (2023). https://doi.org/10.1038/s41586-023-06594-4
⁶ Massachusetts General Hospital press release. March 21, 2024. “World’s First Genetically Edited Pig Kidney Transplant into Living Recipient Performed at Massachusetts General Hospital.” www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient (accessed March 29, 2024)
⁷ Awasthi M, et al. 2023. Vaccines (Basel) 11(11):1682. https://doi:10.3390/vaccines11111682
⁸ Office of Science and Technology Policy (OSTP). American Pandemic Preparedness: Transforming Our Capabilities. September 2021
⁹ National Biodefense Science Board (NBSB). Prioritization of Product Attribute Categories to Maximize Access for Next Generation COVID-19 Vaccines and Therapeutics. August 2023
¹⁰ BARDA Strategic Plan 2022-2026.
¹¹ Noyce RS, et al. Viruses. 2023 26;15(2):356. doi: 10.3390/v15020356
¹² U.S. National Academy of Sciences. March 28, 2024. “Consensus Study Report: Future State of Smallpox Medical Countermeasures.” https://nap.nationalacademies.org/catalog/27652/future-state-of-smallpox-medical-countermeasures
¹³ Bipartisan Commission on Biodefense. (2024). Box the Pox: Reducing the
Risk of Smallpox and Other Orthopoxviruses. Bipartisan Commission on
Biodefense: Washington, DC. https://biodefensecommission.org/reports/box-the-pox-reducing-the-risk-of-smallpox-and-other-orthopoxviruses/
¹⁴ Emanuel, G. NPR. March 27, 2024. “Why the mpox outbreak in the Democratic Republic of Congo is worrying disease docs.” URL: www.npr.org/sections/goatsandsoda/2024/03/27/1239276957/mpox-outbreak-democratic-republic-of-congo-deadlier-strain
¹⁵ Trefry, SV et al., BioRxiv 2023.10.25.564033; doi: https://doi.org/10.1101/2023.10.25.564033
¹⁶ U.S. Department of Defense. Chemical and Biological Defense Program. 2022. “Approach for Research, Development, and Acquisition of Medical Countermeasure and Test Products.” U.S. Department of Defense. https://media.defense.gov/2023/Jan/10/2003142624/-1/-1/0/APPROACH-RDA-MCM-TEST-PRODUCTS.PDF (accessed March 5, 2024)

Recent Highlights — Financial

As of December 31, 2023, Tonix had approximately $24.9 million of cash and cash equivalents, compared to $120.2 million as of December 31, 2022. Additionally, Tonix had inventory totaling approximately $13.6 million as of December 31, 2023. Net cash used in operations was approximately $102.0 million for the full year ended December 31, 2023, compared to $98.1 million for the same period in 2022. Net cash used by investing activities for the full year ended December 31, 2023 was approximately $29.1 million compared to $48.1 million for the same period in 2022.

In August 2022, the Company announced that it received a Cooperative Agreement grant from the National Institute on Drug Abuse (“NIDA”), part of the National Institutes of Health, to support the development of its TNX-1300 product candidate for the treatment of cocaine intoxication. During the year ended December 31, 2023, Tonix received $2.7 million in funding as a reduction of related research and development expenses. Included in prepaid expense and other is an additional $0.2 million that was not received until January 2024.

On December 8, 2023, the Company executed a Loan and Guaranty Agreement (the “Loan Agreement”) to issue a 36-month term loan (the “Term Loan”) in the principal amount of $11.0 million with a maturity date of December 8, 2026 (the “Maturity Date”). The Term Loan was funded with an original issue discount of 9% of the principal amount of the Term Loan, or $1.0 million, which is being amortized over the term of the debt as an adjustment to the effective interest rate on the outstanding borrowings.

On December 20, 2023, the Company announced it had signed securities purchase agreements with existing healthcare-focused institutional investors for upfront gross proceeds of approximately $30 million through a registered direct offering.

On March 28, 2024, the Company announced it had signed securities purchase agreements with existing healthcare-focused institutional investors for upfront gross proceeds of approximately $4.4 million through a registered direct offering.

As of April 1, 2024, there were 84,490,862 shares of Tonix Pharmaceuticals common stock outstanding.

Fourth Quarter 2023 Financial Results

Net product revenue for the fourth quarter 2023 was approximately $3.8 million. Cost of Sales for the fourth quarter 2023 was approximately $2.4 million. Tonix completed the acquisition of two currently marketed products from Upsher-Smith Laboratories, LLC on June 30, 2023.

R&D expenses for the fourth quarter 2023 were approximately $17.1 million, compared to $24.7 million for the same period in 2022. This decrease is predominantly due to decreased non-clinical and manufacturing expenses.

SG&A expenses for the fourth quarter 2023 were $11.6 million, compared to $8.1 million for the same period in 2022. The increase was primarily due to sales and marketing and the transition services expenses associated with the Company’s recently acquired marketed products offset by a decrease in compensation-related expenses.

Net loss available to common stockholders was $27.3 million, or $0.86 per share, basic and diluted, for the fourth quarter 2023, compared to net loss available to common stockholders of $34.1 million, or $3.42 per share, basic and diluted, for the same period in 2022. The basic and diluted weighted average common shares outstanding for the fourth quarter 2023 was 31,756,759 compared to 9,952,780 shares for the same period in 2022.

Full Year 2023 Financial Results

Net product revenue for the full year 2023 was approximately $7.8 million. Cost of sales for the full year 2023 was approximately $4.7 million.

R&D expenses for the full year 2023 were approximately $86.7 million, compared to $81.9 million for the same period in 2022. This increase is predominantly due to decreased non-clinical and regulatory expenses, offset by an increase in clinical, manufacturing, employee-related and professional expenses.

SG&A expenses for the full year 2023 were $34.8 million, compared to $30.2 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 $116.7 million, or $6.85 per share, basic and diluted, for the full year 2023, compared to net loss available to common stockholders of $116.9 million, or $20.01 per share, basic and diluted, for the same period in 2022. The basic and diluted weighted average common shares outstanding for the full year 2023 was 17,039,309 compared to 5,841,447 shares for the same period in 2022.

Tonix Pharmaceuticals Holding Corp.*

Tonix is a biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya, a product candidate for which two positive Phase 3 studies have been completed for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction as well as fibromyalgia-type Long COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase), a biologic designed to treat cocaine intoxication that has Breakthrough Therapy designation. Tonix’s immunology development portfolio consists of 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. Tonix also has product candidates in development in the areas of rare disease and infectious disease. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults.

*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. 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 as filed with the Securities and Exchange Commission (the “SEC”) and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Research News and Market Data on TNXP

March 25, 2024 8:00am EDT

TNX-2900 is a proprietary magnesium-potentiated formulation of intranasal oxytocin, a naturally occurring hormone that reduces appetite and eating

Prader Willi syndrome is the most common genetic cause of life-threatening childhood obesity

CHATHAM, N.J., March 25, 2024 (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 the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation to TNX-2900* (intranasal potentiated oxytocin), a proprietary magnesium (Mg2⁺)-potentiated formulation of intranasal oxytocin, to treat Prader-Willi syndrome (PWS) in children and adolescents. TNX-2900 was previously granted Orphan Drug designation by the FDA in 2022 for the treatment of PWS and the investigational new drug (IND) application was cleared by the FDA in 2023. The Company may be eligible to receive a transferable Priority Review Voucher if TNX-2900 for PWS is approved for marketing. Recently, vouchers have sold for approximately $100 million.

“The Rare Pediatric Disease Designation is an important regulatory milestone in the development of TNX-2900. With PWS being the most common genetic cause of life-threatening childhood obesity, we are excited that the FDA has recognized this significant unmet need in children and adolescents, particularly for PWS hyperphagia, which currently has no approved treatments^1,2,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “As PWS is a genetic disorder associated with abnormalities of the oxytocin system, Tonix believes TNX-2900’s unique formulation has the potential to improve intranasal oxytocin’s therapeutic action by addressing limitations in efficacy observed at high-dose intranasal oxytocin that is not Mg2⁺-potentiated^3,4.”

The FDA defines a rare pediatric disease as a serious or life-threating disease that primarily affects individuals aged from birth to 18 years and affects under 200,000 people in the United States.

About FDA’s Rare Pediatric Disease Priority Voucher Program

The FDA’s Rare Pediatric Disease Priority Voucher Program is intended to encourage the development of new drugs to treat certain rare pediatric diseases. Under the FDA’s Rare Pediatric Disease Designation and Voucher Program, if TNX-2900 is approved for marketing, Tonix may qualify for a priority review voucher that can be redeemed to receive priority review of a subsequent marketing application for a different product. Priority review vouchers may also be sold or transferred to another sponsor. The new sponsor can redeem the voucher to receive priority review for a different product, which reduces the review time of NDAs from 10 months to six months. There is no limit on the number of times a priority review voucher can be transferred. A 2020 U.S. Government Accounting Office analysis⁵ of the voucher program found that in the ten years since launch of the program in 2009, the price of buying priority review vouchers ranged from $67 million to $350 million. More recently, priority review vouchers were acquired by Novo Nordisk for $110 million in June of 2022, and by Novartis for $100 million from Marinus in July of 2022.⁶   Bluebird Bio sold vouchers for $102 million, $95 million and $103 million in November 2022, January 2023, and October 2023, respectively.^7-9 In June of 2023, Novartis bought a priority review voucher from Pharming for $21 million, a price that had been negotiated as part of a purchase agreement when Pharming acquired the asset from Novartis.⁵

About Prader-Willi Syndrome (PWS)

PWS is recognized as the most common genetic cause of life-threatening childhood obesity and affects males and females with equal frequency and all races and ethnicities. PWS results from the absence of expression of a group of genes on the paternally acquired chromosome 15. The hallmarks of PWS are lack of suckling in newborns and, in children and adolescents, severe hyperphagia – an overriding physiological drive to eat, leading to severe obesity and other complications associated with significant mortality. A systematic review of the morbidity and mortality as a consequence of hyperphagia in PWS found that the average age of death in PWS was 22.1 years.¹⁰ There is no approved medication to treat poor feeding in newborns or hyperphagia in children and adolescents with PWS. Given the serious or life-threatening manifestations of these conditions, there is a critical need for effective treatments to decrease morbidity and mortality, improve quality of life, and increase life expectancy in people with PWS. Oxytocin has potent effects in correcting behavioral characteristics of the Magel2 knock-out mouse model for PWS and autism.^11-13 Six clinical trials have investigated intranasal oxytocin as a treatment in pediatric patients with PWS. Four studies showed evidence for improvement in PWS-related behaviors/symptoms^14-17; three clinical studies reported evidence for improvement in hyperphagia^14,15,17; and one clinical study showed an improvement in sucking in infants¹⁶.

About TNX-2900 and Tonix’s Potentiated Oxytocin Platform

TNX-2900 is based on Tonix’s patented intranasal Mg²⁺-potentiated oxytocin formulation intended for use by children and adolescents. This formulation is believed to enhance the potency of oxytocin as well as increase specificity for oxytocin receptors relative to vasopressin receptors, potentially reducing unwanted side effects from activating vasopressin receptors. Tonix is also developing a different intranasal formulation, designated TNX-1900 for adolescent obesity, binge eating disorder, bone health in autism, and social anxiety disorder. Oxytocin is a naturally occurring human hormone that acts as a neurotransmitter in the brain. Oxytocin is believed to be more than 600 million years old and is present in vertebrates including mammals, birds, reptiles, amphibians, and fish.¹⁸ It was initially 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 and control postpartum bleeding or hemorrhage. An intranasal formulation of oxytocin is marketed in some European countries to assist in breast milk production as Syntocinon®*** (oxytocin nasal 40 units/ml).

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya, a product candidate for which two positive Phase 3 studies have been completed for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction as well as fibromyalgia-type Long COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase) a biologic designed to treat cocaine intoxication with Breakthrough Therapy designation. Tonix’s immunology development portfolio consists of 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. Tonix also has product candidates in development in the areas of rare disease and infectious disease. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults.

*Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication. Tonmya™ is conditionally accepted by the U.S. Food and Drug Administration as the tradename for TNX-102 SL for the management of fibromyalgia.

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

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

Citations

1. Meyerowitz JG, et al. Nat Struct Mol Biol. 2022. 29(3):274-281.
2. Meziane H, et al. Biol Psychiatry. 2015. 78(2):85-94.
3. Correa-da-Silva F, et al. J Neuroendocrinol. 2021. 33(7):e12994.
4. Bharadwaj VN, et al. Pharmaceutics. 2022. 14(5):1105.
5. U.S. Government Accounting Office, Jan 31, 2020. “Drug Development: FDA’s Priority Review Voucher Programs”. GAO-20-251. https://www.gao.gov/products/gao-20-251.
6. Waldron, J. Fierce Biotech. June 1, 2023. “Novartis buys priority review voucher from Pharming for discount price of $21 M.” www.fiercebiotech.com/biotech/novartis-buys-priority-review-voucher-pharming-discount-price-21m
7. BlueBird bio Press Release. Nov. 30, 2022 “bluebird bio Sells Priority Review Voucher for $102 Million”. https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-sells-priority-review-voucher-102-million
8. Kansteiner, F. Fierce Pharma. Jan 6, 2023 “Bluebird scores $95M nest egg after selling second FDA priority review voucher to BMS”. http://www.fiercepharma.com/pharma/bluebird-scores-another-nest-egg-after-selling-second-fda-review-voucher-bms-95m 
9. Business Wire. October 30, 2023. “bluebird bio Enters into Advance Agreement to Sell Priority Review Voucher, if Granted, for $103 Million.” http://finance.yahoo.com/news/bluebird-bio-enters-advance-agreement-120000768.html
10. Bellis SA, et al. Eur J Med Genet. 2022. 65(1):104379.
11. Bertoni A, et al. Mol Psychiatry. 2021. 26(12):7582-7595.
12. Schaller F, et al. Hum Mol Genet. 2010. 19:4895-4905.
13. Meziane H, et al. Biol Psychiatry. 2015. 78: 85-94.
14. Kuppens RJ, et al. Clin Endocrinol. 2016. 85:979-987.
15. Miller JL et al. Am J Med Genet A. 2017. 173: 1243-1250.
16. Tauber M, et al. Pediatrics. 2017. 139(2):e20162976.
17. Damen L, et al. Clin Endocrinol. 2020. 94:774-785.
18. Gruber CW. Exp Physiol. 2014. 99(1):55-61. doi: 10.1113/expphysiol.2013.072561.

Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. 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 March 25, 2024

Research News and Market Data on TNXP

March 19, 2024 8:00am EDTDownload as PDF

Zembrace^® SymTouch^® and Tosymra^® will be marketed by Tonix Medicines, Tonix’s wholly-owned commercial subsidiary

Commercial capabilities prepare Tonix for the potential launch in 2025 of Tonmya™ for the management of fibromyalgia, assuming FDA approval

CHATHAM, N.J., March 19, 2024 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced that it will achieve its goal of transitioning to a fully integrated pharmaceutical company on April 1, 2024. Since the acquisition of Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg on June 30, 2023, Tonix Pharmaceuticals has been putting in place the personnel, systems and contracts required to support a commercial organization. Both products are indicated for the treatment of acute migraine with or without aura in adults.

“Tonix will become a fully integrated biopharmaceutical company with a mission of developing and marketing innovative, high-value therapeutics,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Tonix will assume responsibility for the distribution, selling and marketing of Zembrace SymTouch and Tosymra, as well as supply chain, regulatory and quality control of the two products.”

Dr. Lederman added, “The assumption of commercial activities by Tonix represents an important milestone in the evolution of Tonix as we continue to build and strengthen our commercial organization for the potential launch of Tonmya™ (cyclobenzaprine HCl sublingual tablets) for fibromyalgia in 2025, assuming approval by the U.S. Food and Drug Administration (FDA).”   

About Zembrace^® SymTouch^® and Tosymra^®

Zembrace SymTouch is the only actively promoted brand of sumatriptan autoinjector in the United States (other sumatriptan autoinjector products on the market are Imitrex^® and generics to Imitrex^®). It has a unique low dose and has demonstrated onset of migraine pain relief in as few as 10 minutes (17% of patients vs. 5% for placebo).¹ Zembrace SymTouch also demonstrated migraine pain freedom for 46% of patients (vs 27% for placebo) at 2 hours in a single-attack, double-blind study (N=230).¹ Zembrace SymTouch currently has patent protection to 2036. Tosymra employs Intravail^® permeation enhancer technology and is pharmacokinetically equivalent to 4 mg subcutaneous sumatriptan.² Tosymra delivers migraine pain relief in as little as 10 minutes with just one spray for some patients (13% vs. 5% for placebo).² Tosymra currently has patent protection to 2031.

About Migraine

Nearly 40 million people in the United States suffer from migraine³ and it has been recognized as the second leading cause of disability in the world.⁴ Migraine is characterized by debilitating attacks lasting four to 72 hours with multiple symptoms, including pulsating headaches of moderate to severe pain intensity often associated with nausea or vomiting, and/or sensitivity to sound (phonophobia) and sensitivity to light (photophobia).³

References:

1. Zembrace SymTouch [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, LLC: February 2021.
2. Tosymra [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, LLC: Feb 2021.
3. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211.
4. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018;17(11):954-976.

About Tonmya* (also known as TNX-102 SL)

Tonmya is a centrally acting, non-opioid, non-addictive, bedtime medication. The tablet is a patented sublingual formulation of cyclobenzaprine hydrochloride developed for the management of fibromyalgia. In December 2023, the company announced highly statistically significant and clinically meaningful topline results in RESILIENT, a second positive Phase 3 clinical trial of Tonmya for the management of fibromyalgia. In the study, Tonmya met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia. Statistically significant and clinically meaningful results were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function. RELIEF, the first positive Phase 3 trial of Tonmya in fibromyalgia, was completed in December 2020. It met its pre-specified primary endpoint of daily pain reduction compared to placebo (p=0.010) and showed activity in key secondary endpoints.

*Tonmya™ is conditionally accepted by the U.S. Food and Drug Administration as the tradename for TNX-102 SL for the management of fibromyalgia. Tonmya has not been approved for any indication.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya, a product candidate for which two positive Phase 3 studies have been completed for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction as well as fibromyalgia-type Long COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase) a biologic designed to treat cocaine intoxication with Breakthrough Therapy designation. Tonix’s immunology development portfolio consists of 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. Tonix also has product candidates in development in the areas of rare disease and infectious disease. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults.

*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. 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

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.tonixpharma.com or call 1-888-869-7633.

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.tonixpharma.com or call 1-888-869-7633.

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 March 19, 2024

Research News and Market Data on TNXP

February 28, 2024 8:00am ESTDownload as PDF

Topline results expected in the third quarter of 2024; planning a Phase 2 Trial for prevention of kidney transplant rejection

Anti-CD40L has multiple possible indications in addition to solid organ and bone marrow transplantation including autoimmune diseases: potential pipeline in a product

Sanofi recently published results on their Fc-modified humanized anti-CD40L mAb, frexalimab, for multiple sclerosis in the New England Journal of Medicine¹

CHATHAM, N.J., Feb. 28, 2024 (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 stage of its Phase 1, single ascending dose escalation trial of TNX-1500 (Fc-modified humanized anti-CD40L monoclonal antibody, or mAb)* in healthy volunteers. TNX-1500 is in development for the prevention of rejection in solid organ and bone marrow transplant and for the treatment of autoimmune disorders.

“Despite advancements in the field of solid organ transplantation, there remains a significant need for new treatments with improved activity and tolerability,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Anti-CD40L modulates T cell function and has the potential to promote tolerance of transplanted organs. We are excited to have completed the clinical stage of this Phase 1 trial of TNX-1500, a third-generation Fc-modified anti-CD40L mAb that has been designed by protein engineering to eliminate the risk of thrombosis associated with first-generation anti-CD40L mAbs. Preclinical studies in non-human primates did not result in any thrombotic complications, suggesting that the protein engineering of TNX-1500’s Fc region has achieved its design goals.”

Dr. Lederman continued, “Recently, positive clinical data with other CD40L blockers have been reported by Sanofi, with its Fc-modified humanized anti-CD40L mAb frexalimab in treating relapsing multiple sclerosis.² Eledon Pharmaceuticals is developing tegoprubart, a non-covalent dimer antibody with no heavy-light or heavy-heavy interchain disulfide bridges for the prevention of rejection of kidney transplants³.”

Dr. Lederman concluded, “We believe TNX-1500 has the potential to prevent organ transplant rejection and improve graft survival with reduced long-term toxicity burden of current immunosuppressive regimens. In addition, TNX-1500 has the potential to address multiple other indications, including several autoimmune diseases. We look forward to the results of this Phase 1 trial, which are expected in the third quarter of this year, and to continuing the development of TNX-1500 as a promising candidate in an important therapeutic space.”

About TNX-1500

TNX-1500 (Fc-modified humanized anti-CD40L mAb) is a humanized monoclonal antibody that interacts with the CD40-ligand (CD40L), also known as CD154. TNX-1500 is being developed for the prevention of allograft and xenograft rejection, for the prevention of graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation (HCT) and for the treatment of autoimmune diseases. The first-in-human Phase 1 trial of TNX-1500 was initiated in the third quarter of 2023. The primary objective of the Phase 1 trial is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous (i.v.) TNX-1500. Eligible participants enrolled in the Phase 1 trial were distributed across three dosing cohorts (3 mg/kg, 10 mg/kg, and 30 mg/kg, respectively) and evaluated regularly over a 120-day period after dosing. This first-in-human trial is intended to support dosing in a planned Phase 2 trial in kidney transplant recipients. Two published articles in the American Journal of Transplantation demonstrate TNX-1500 prevents rejection, prolongs survival and preserves graft function as a single agent or in combination with other drugs in non-human primate renal and heart allografts.^4,5

About anti-CD40L Therapeutics in Development

No anti-CD40L mAb has been approved in any jurisdiction. In addition to TNX-1500, frexalimab and tegoprubart, tn03 fusion protein dazodalibep is being developed by Amgen (formerly Horizon Therapeutics Public Limited Company) for the treatment of Sjögren’s Syndrome .^6,7 Dapirolizumab pegol, an anti-CD40L pegylated Fab, is being developed by UCB for the treatment of systemic lupus erythematosus.⁸

*TNX-1500 is an investigational new biologic and is not approved for any indication

1. Vermersch P., et al. N Engl J Med. 2024. 390(7):589-600 https://doi.org/10.1056/nejmoa2309439
2. Sanofi press release. May 31, 2023. https://www.sanofi.com/en/media-room/press-releases/2023/2023-05-31-05-00-00-2678991 (accessed August 2023)
3. Eledon press release. November 2, 2023. https://ir.eledon.com/news-releases/news-release-details/eledon-reports-updated-data-ongoing-phase-1b-trial-evaluating (accessed February 2024)
4. Lassiter G., et al. Am J Transplantation. 2023. https://doi.org/10.1016/j.ajt.2023.03.022
5. Miura S., et al. Am J Transplantation. 2023. https://doi.org/10.1016/j.ajt.2023.03.025
6. 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 (accessed February 2024)
7. BioSpace. January 18, 2023. https://www.biospace.com/article/horizon-bags-second-phase-ii-win-in-sjoegren-s-syndrome (accessed February 2024)
8. https://www.ucb.com/our-science/pipeline (accessed August 2023)

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya¹, a product candidate for which two positive Phase 3 studies have been completed for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction as well as fibromyalgia-type Long COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase) a biologic designed to treat cocaine intoxication with Breakthrough Therapy designation. Tonix’s immunology development portfolio consists of 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. Tonix also has product candidates in development in the areas of rare disease and infectious disease. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults.

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

¹Tonmya™ is conditionally accepted by the U.S. Food and Drug Administration (FDA) as the tradename for TNX-102 SL for the management of fibromyalgia. Tonmya has not been approved for any indication.

Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. 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 February 28, 2024

Research News and Market Data on TNXP

February 27, 2024 8:00am ESTDownload as PDF

Tonix plans to File a Clinical Trial Notification (CTN) in Japan and Investigational New Drug (IND) application in China to support a registration-enabling Asian Phase 3 study without dosage adjustment based on U.S. registrational Phase 3 data

Tonmya’s market exclusivity is supported by issued patents in Japan, China, Hong Kong and Taiwan; cyclobenzaprine is a new chemical entity in Japan and China

New Drug Application (NDA) submission to the U.S. FDA for the approval of Tonmya for the management of fibromyalgia planned for second half of 2024

CHATHAM, N.J., Feb. 27, 2024 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, announced positive results from its clinical pharmacokinetic (PK) bridging study of Tonmya™ (also known as TNX-102 SL, cyclobenzaprine HCl sublingual tablets) in healthy adult male and female ethnic Japanese and Chinese volunteers. Results indicate that key pharmacokinetic parameters of cyclobenzaprine are comparable in ethnic Japanese and Chinese volunteers to Caucasian volunteers from a prior PK study. Tonmya was generally well tolerated in the ethnic Japanese and Chinese healthy volunteers. The company expects these data to fulfill the requirement for a bridging study, and to support regulatory filings for clinical studies in Japan and China where cyclobenzaprine is a new chemical entity (NCE). Tonix holds issued patents for market exclusivity rights of Tonmya in Japan, China, Hong Kong and Taiwan.

This study characterized the PK profile and dose proportionality of Tonmya following administration in 20 healthy volunteers of documented Japanese or Chinese ancestry, and compared these findings to an existing PK dataset conducted under similar conditions in Caucasian volunteers.

“This bridging study is an important first step as we begin evaluating the potential for approval and marketing Tonmya in Japan and China. The results show a similar pharmacokinetic profile in ethnic Japanese and Chinese volunteers with a Caucasian comparator group,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “As a result, we believe that these data, with supporting results recently reported from the positive Phase 3 RESILIENT study, are the only clinical data needed to support regulatory filings in Japan and China.”

Dr. Lederman continued, “With patents issued in Japan, China, Hong Kong and Taiwan expected to provide market exclusivity into 2034, we believe that Tonmya would be a welcome addition to the therapeutic options for fibromyalgia patients in East Asia and an attractive asset for the right development and commercialization partners in these markets. Cyclobenzaprine is an NCE in both of these countries. We plan to meet with Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) and China’s National Medical Products Administration (NMPA) to seek agreement on the development of Tonmya in Japan and China, respectively.”

About the Asia Bridging Study

The study was a randomized, single-dose, open-label, 2-way, crossover study design in ethnic Japanese (N=10) and Chinese (N=10) healthy male and female volunteers. The primary objective of the study was to characterize the PK profile and dose proportionality of Tonmya following administration of 2.8 mg and 5.6 mg (one and two 2.8 mg tablets) under fasting conditions in Japanese and Chinese volunteers, and to retrospectively compare these PK data with existing PK data of both cyclobenzaprine and norcyclobenzaprine from a prior Phase 1 study in Caucasian volunteers dosed under the same conditions. Safety and tolerability were also assessed. A 2.8 mg or 5.6 mg dose (2 X 2.8 mg tablet) of Tonmya was administered sublingually in the morning under fasted conditions. Blood samples were collected pre-dose and up to 15 days post-dose for analyte measurements, with a 28-day washout between periods. The primary PK endpoints were the total amount of cyclobenzaprine and metabolite norcyclobenzaprine in the blood (expressed as the area under the curve (AUC_0-T)) and maximum concentration (expressed as C_max).

Study Results

Pharmacokinetics
Ethnic Japanese and Chinese volunteers were considered comparable on PK parameters for cyclobenzaprine following a 2.8 mg and 5.6 mg dose of Tonmya, and dose proportionality was demonstrated in both samples. Given that the similarity in PK profile between Japanese and Chinese volunteers was confirmed, the PK data from the two ethnic groups were pooled for the comparison between Asian (n=20) and Caucasian (n=16) volunteers. The PK parameters of cyclobenzaprine for Japanese, Chinese, and Caucasian groups were similar, with geometric mean ratios falling within the 90% confidence interval.

Safety

• Tonmya was shown to be safe and well-tolerated at doses up to 5.6 mg as single sublingual administrations in healthy adult Japanese and Chinese volunteers.
• The incidence of adverse events (AEs) and investigational product-related AEs was low. No volunteer discontinued due to an AE.
• No clinically significant abnormal findings in laboratory parameters, ECGs, or other safety assessments were noted during the study. No severe AEs and no deaths were reported during the study.
  
  

Issued Patents in Japan, China, Hong Kong and Taiwan

EUTECTIC FORMULATIONS	Country	Patent Number	Expected Expiry
	China	ZL 201480024011.1	03/14/2034
	China	ZL201910263541.6	03/14/2034
	Hong Kong	HK1218727	03/14/2034
	Japan	6310542	03/14/2034
	Taiwan R.O.C.	I661825	03/14/2034
TRANSMUCOSAL ABSORPTION	Japan	6259452	06/14/2033
	Taiwan R.O.C.	I590820	06/14/2033
	Taiwan R.O.C.	I683660	06/14/2033
	Taiwan R.O.C.	I642429	06/14/2033
	Hong Kong	1209361	06/14/2033

About Tonmya* (also known as TNX-102 SL)

Tonmya is a centrally acting, non-opioid, non-addictive, bedtime medication. The tablet is a patented sublingual formulation of cyclobenzaprine hydrochloride developed for the management of fibromyalgia. In December 2023, the Company announced highly statistically significant and clinically meaningful topline results in RESILIENT, a second positive Phase 3 clinical trial of Tonmya for the management of fibromyalgia. In the study, Tonmya met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia. Statistically significant and clinically meaningful results were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function. RELIEF, the first positive Phase 3 trial of Tonmya in fibromyalgia, was completed in December 2020. It met its pre-specified primary endpoint of daily pain reduction compared to placebo (p=0.010) and showed activity in key secondary endpoints.

Tonix plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the second half of 2024 for Tonmya for the management of fibromyalgia.

*Tonmya™ is conditionally accepted by the U.S. Food and Drug Administration (FDA) as the tradename for TNX-102 SL for the management of fibromyalgia. Tonmya has not been approved for any indication.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya, a product candidate for which two positive Phase 3 studies have been completed for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction as well as fibromyalgia-type Long COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase) a biologic designed to treat cocaine intoxication with Breakthrough Therapy designation. Tonix’s immunology development portfolio consists of 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. Tonix also has product candidates in development in the areas of rare disease and infectious disease. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults.

*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. 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 February 27, 2024

Research News and Market Data on TNXP

February 14, 2024 8:00am EST

Clinical results show that Tonyma™ has broad-spectrum activity, addressing the three core fibromyalgia symptoms: pain, fatigue, and sleep disturbance

Tonmya™ has a favorable tolerability profile well-suited for chronic treatment

CHATHAM, N.J., Feb. 14, 2024 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, held a key opinion leader (KOL) webinar to discuss the positive Phase 3 data of Tonmya™ (also known as TNX-102 SL, cyclobenzaprine HCl sublingual tablets) for the management of fibromyalgia, and the path to file for FDA approval in the second half of 2024. The webinar was held on January 31, 2024 and hosted by Alliance Global Partners (A.G.P.).

The webinar featured two thought leaders in the field of fibromyalgia: Daniel Clauw, M.D., Professor of Anesthesiology, Medicine and Psychiatry, Director Chronic Pain & Fatigue Research Center, University of Michigan, and Lesley Arnold, M.D., Professor of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine.

A replay of the webinar is available here.

Tonmya™ is a centrally acting, non-opioid, non-addictive, bedtime medication. As previously announced, Tonix’s second positive Phase 3 study, RESILIENT, met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia. Statistically significant and clinically meaningful results (p=0.001 or better) were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue, and improving overall fibromyalgia symptoms and function.

Tonix plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the second half of 2024 for Tonmya™ for the management of fibromyalgia.

“These data offer new hope for patients with fibromyalgia,” said Dr. Arnold. “Many of my patients have required combination treatments to combat their multiple fibromyalgia-related symptoms. We haven’t seen a medication that can treat fatigue, sleep, and pain all together. Having a compound like Tonmya™ that may address all three is very exciting.”

“The fact that cyclobenzaprine was beneficial in many other key symptom domains, including sleep quality, is important to fibromyalgia patients,” said Dr. Clauw. “We’re really beginning to understand how crucial sleep is in alleviating and potentially preventing fibromyalgia symptoms.”

Dr. Arnold stated that most patients are open to new treatment options, citing lack of efficacy in some cases, tolerability issues and unwanted side effects associated with the currently approved fibromyalgia treatments. “Since patients typically need to be treated for prolonged periods of time, it is important to develop a therapeutic which is well-tolerated.”

“We believe that these positive results show that fibromyalgia can be successfully treated by Tonmya™ and may provide the opportunity for Tonix to have the first FDA-approved drug for fibromyalgia in more than a decade,” said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. “We are now an important step closer to bringing a new, first-line treatment to fibromyalgia patients that offers broad symptom relief and favorable tolerability for chronic use and adherence.”

About the Phase 3 RESILIENT Study
The RESILIENT study was a double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of Tonmya™ (TNX-102 SL: cyclobenzaprine HCl sublingual tablets) for the management of fibromyalgia. The two-arm trial randomized 457 participants in the U.S. across 33 sites. The first two weeks of treatment consisted of a run-in period in which participants started on TNX-102 SL 2.8 mg (1 tablet) or placebo. Thereafter, all participants increased their dose to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks. The study met the pre-specified primary endpoint of daily diary pain severity score change (TNX-102 SL 5.6 mg vs. placebo) from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation (p=0.00005).

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

About Fibromyalgia
Fibromyalgia is a chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system. Fibromyalgia afflicts an estimated 6 million to 12 million adults in the U.S., the majority of whom are women. Symptoms of fibromyalgia include chronic widespread pain, nonrestorative sleep, fatigue, and morning stiffness. Other associated symptoms include cognitive dysfunction and mood disturbances, including anxiety and depression. Individuals suffering from fibromyalgia struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products.

About Tonmya™ (also known as TNX-102 SL)
Tonmya is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which is designed for daily administration at bedtime with a proposed mechanism of improving sleep quality in fibromyalgia. Tonmya provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities at the 5-HT2A-serotonergic, α1-adrenergic, H1-histaminergic, and M1-muscarinic cholinergic receptors, Tonmya is in development as a daily bedtime treatment for fibromyalgia. TNX-102 SL is also in development fibromyalgia-type Long COVID (formally known as post-acute sequelae of COVID-19 [PASC]), alcohol use disorder, and agitation in Alzheimer’s disease. The United States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408 in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic™ protective eutectic and Angstro-Technology™ formulation claimed in the patent are important elements of Tonix’s proprietary Tonmya composition. These patents are expected to provide Tonmya, upon NDA approval, with U.S. market exclusivity until 2034/2035. In addition, Tonix has pending but not issued U.S. patent applications directed to the transmucosal absorption of CBP-HCl, with U.S. market exclusivity expected until 2033, for treating depressive symptoms in fibromyalgia, with U.S. market exclusivity expected until 2032, and for treating pain in fibromyalgia with U.S. market exclusivity expected until 2041.

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’s development portfolio is focused on central nervous system disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA for Tonmya, which has completed two positive Phase 3 studies for the management of fibromyalgia. Tonix intends to meet with the FDA in the first half of 2024 and submit an NDA for the approval of Tonmya for the management of fibromyalgia in the second half of 2024. TNX-102 SL is being developed to reduce the severity of acute stress reaction and the frequency of acute stress disorder and posttraumatic stress disorder. This trial is being sponsored by the University of North Carolina and received funding support from the U.S. Department of Defense. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition, and topline results from a proof-of-concept study were reported in the third quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA and received funding from the National Institute on Drug Abuse (NIDA). A Phase 2 study of TNX-1300 is expected to be initiated in the first quarter of 2024. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome (PWS). TNX-2900 has been granted Orphan Drug designation by the FDA and an investigational new drug (IND) application has been cleared to support a Phase 2 study in PWS patients. 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 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 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. 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 February 14, 2024

Research News and Market Data on TNXP

February 13, 2024 8:00am ESTDownload as PDF

Tonmya™ is a potential new first-line therapy, non-opioid analgesic for the management of fibromyalgia, supported by statistically significant results from two Phase 3 trials

New Drug Application (NDA) submission to the FDA planned for second half of 2024

Fibromyalgia is a chronic pain condition affecting approximately 10 million U.S. adults that typically persists for years or decades

CHATHAM, N.J., Feb. 13, 2024 (GLOBE NEWSWIRE) —  Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced that it has engaged Rho, Inc. (Rho), a global contract research organization (CRO), to support Tonix’s preparation and planned submission of its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the approval of Tonmya™ (cyclobenzaprine HCl sublingual tablets) for the management of fibromyalgia.

“We are excited by our most recent positive Phase 3 study results of Tonmya and look forward to Rho’s support in preparing our NDA,” said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. “We intend to meet with the FDA in the first half of this year and to submit our NDA in the second half of the year. We believe we have completed all development work required for the NDA, including CMC requirements and the completion of two positive Phase 3 studies.”

Tonmya is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride developed for the management of fibromyalgia. In December 2023, the Company announced highly statistically significant and clinically meaningful topline results in RESILIENT, a second positive Phase 3 clinical trial of Tonmya for the management of fibromyalgia. In the study, Tonmya met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia. Statistically significant and clinically meaningful results were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function. RELIEF, the first positive Phase 3 trial of Tonmya in fibromyalgia, was completed in December 2020. It met its pre-specified primary endpoint of daily pain reduction compared to placebo (p=0.010) and showed activity in key secondary endpoints.

“We are delighted in our continued support of Tonix and their Tonmya program,” said Tara Gladwell, President and COO at Rho. “We are hopeful that this work may result in a new treatment for the millions of Americans that suffer from this debilitating, chronic disorder.”

About Fibromyalgia

Fibromyalgia is a chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system. Fibromyalgia afflicts an estimated 6 million to 12 million adults in the U.S., the majority of whom are women. Symptoms of fibromyalgia include chronic widespread pain, nonrestorative sleep, fatigue, and morning stiffness. Other associated symptoms include cognitive dysfunction and mood disturbances, including anxiety and depression. Individuals suffering from fibromyalgia struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products.

About Tonmya™ (also known as TNX-102 SL)

Tonmya is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which is designed for daily administration at bedtime with a proposed mechanism of improving sleep quality in fibromyalgia. Tonmya provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities at the 5-HT2A-serotonergic, α1-adrenergic, H1-histaminergic, and M1-muscarinic cholinergic receptors, Tonmya is in development as a daily bedtime treatment for fibromyalgia. TNX-102 SL is also in development fibromyalgia-type Long COVID (formally known as post-acute sequelae of COVID-19 [PASC]), alcohol use disorder, and agitation in Alzheimer’s disease. The United States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408 in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic™ protective eutectic and Angstro-Technology™ formulation claimed in the patent are important elements of Tonix’s proprietary Tonmya composition. These patents are expected to provide Tonmya, upon NDA approval, with U.S. market exclusivity until 2034/2035. In addition, Tonix has pending but not issued U.S. patent applications directed to the transmucosal absorption of CBP-HCl, with U.S. market exclusivity expected until 2033, for treating depressive symptoms in fibromyalgia, with U.S. market exclusivity expected until 2032, and for treating pain in fibromyalgia with U.S. market exclusivity expected until 2041.

About Rho

Rho is a global, privately held contract research organization (CRO) headquartered in Research Triangle Park, a biotech hub in North Carolina, US. Rho provides a full range of drug development services, from program strategy through to clinical trials and marketing applications. Since 1984, Rho has been a trusted partner to some of the most innovative pharmaceutical, biotechnology and medical device companies as well as academic and government organizations. Dedicated to service excellence and cross-functional collaboration, Rho’s therapeutic expertise, employee focus and commitment to strong site relationships change what it means to work with a CRO – accelerating time to market, maximizing ROI, and delivering consistent, smarter and more efficient programs. Experience Rho by following the company on LinkedIn.

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’s development portfolio is focused on central nervous system disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA for Tonmya, which has completed two positive Phase 3 studies for the management of fibromyalgia. Tonix intends to meet with the FDA in the first half of 2024 and submit an NDA for the approval of Tonmya for the management of fibromyalgia in the second half of 2024. TNX-102 SL is being developed to reduce the severity of acute stress reaction and the frequency of acute stress disorder and posttraumatic stress disorder. This trial is being sponsored by the University of North Carolina and received funding support from the U.S. Department of Defense. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition, and topline results from a proof-of-concept study were reported in the third quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA and received funding from the National Institute on Drug Abuse (NIDA). A Phase 2 study of TNX-1300 is expected to be initiated in the first quarter of 2024. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome (PWS). TNX-2900 has been granted Orphan Drug designation by the FDA and an investigational new drug (IND) application has been cleared to support a Phase 2 study in PWS patients. 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 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 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. 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 February 13, 2024

Research News and Market Data on TNXP

January 29, 2024 7:00am EST

Results from two positive Phase 3 studies point to Tonmya’s (TNX-102 SL) potential as a new first-line medicine for chronic use in managing fibromyalgia, a debilitating condition suffered by 6-12 million adults in the U.S.

New Drug Application (NDA) submission to the FDA planned for second half of 2024 under the 505(b)(2) regulatory pathway

CHATHAM, N.J., Jan. 29, 2024 (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 the U.S. Food and Drug Administration (FDA) has conditionally accepted the trade name, Tonmya™, for the Company’s drug product candidate TNX-102 SL for the management of fibromyalgia.

Tonmya is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride developed for the management of fibromyalgia. In December 2023, the Company announced highly statistically significant and clinically meaningful topline results in RESILIENT, a second positive Phase 3 clinical trial of Tonmya for the management of fibromyalgia. In the study, Tonmya met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia. Statistically significant and clinically meaningful results were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function. RELIEF, the first positive Phase 3 trial of Tonmya in fibromyalgia, was completed in December 2020. It met its pre-specified primary endpoint of daily pain reduction compared to placebo (p=0.010) and showed activity in key secondary endpoints. Tonix plans to have a pre-NDA meeting with U.S. Food and Drug Administration (FDA) in the first half of 2024 and to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya for the management of fibromyalgia.

“We are very pleased with the FDA’s conditional acceptance of Tonmya as the brand name for TNX-102 SL,” said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. “With this acceptance, we remain excited for what we believe is an important opportunity to offer the first FDA-approved drug for fibromyalgia patients in more than a decade.”

About Tonmya™ (formerly known as TNX-102 SL)

Tonmya is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which is designed for daily administration at bedtime with a proposed mechanism of improving sleep quality in fibromyalgia. Tonmya provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities at the 5-HT2A-serotonergic, α1-adrenergic, H1-histaminergic, and M1-muscarinic cholinergic receptors, Tonmya is in development as a daily bedtime treatment for fibromyalgia, fibromyalgia-type Long COVID (formally known as post-acute sequelae of COVID-19 [PASC]), alcohol use disorder, and agitation in Alzheimer’s disease. The United States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408 in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic™ protective eutectic and Angstro-Technology™ formulation claimed in the patent are important elements of Tonix’s proprietary Tonmya composition. These patents are expected to provide Tonmya, upon NDA approval, with U.S. market exclusivity until 2034/2035. In addition, Tonix has pending but not issued U.S. patent applications directed to the transmucosal absorption of CBP-HCl, with U.S. market exclusivity expected until 2033, for treating depressive symptoms in fibromyalgia, with U.S. market exclusivity expected until 2032, and for treating pain in fibromyalgia with U.S. market exclusivity expected until 2041.

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’s development portfolio is focused on central nervous system disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA for Tonmya, which has completed two positive Phase 3 studies for the management of fibromyalgia. Tonix intends to meet with the FDA in the first half of 2024 and submit an NDA for the approval of Tonmya for the management of fibromyalgia in the second half of 2024. TNX-102 SL is being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition, and topline results from a proof-of-concept study were reported in the third quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the first quarter of 2024. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome (PWS). TNX-2900 has been granted Orphan Drug designation by the FDA and an investigational new drug (IND) application has been cleared to support a Phase 2 study in PWS patients. 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 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 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. 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 January 29, 2024