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Release – Tonix Pharmaceuticals Announces Results of Pre-IND Meeting with FDA for TNX-801 as a Potential Vaccine to Prevent Mpox and Smallpox

Posted on August 21, 2023August 21, 2023 by aweinsoff@channelchek.com

August 21, 2023 7:00am EDTDownload as PDF

Phase 1/2 Clinical Trial of TNX-801 for the Prevention of Mpox and Smallpox to Commence Following Submission of an IND

TNX-801 is Based on a Proprietary Live Virus Vaccine Platform Designed to Stimulate Durable T-Cell Immunity

TNX-801 Vaccination Protected Animals from a Lethal Challenge with Monkeypox in Preclinical Testing

CHATHAM, N.J., Aug. 21, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced that it received the official written response from a Type B pre-Investigational New Drug Application (IND) meeting with the U.S. Food and Drug Administration (FDA) to develop TNX-801¹ (recombinant horsepox virus, live vaccine) as a potential vaccine to protect against mpox disease (formerly known as monkeypox) and smallpox. Tonix believes the FDA feedback provides a path to agreement on the design of a Phase 1/2 study and the overall clinical development plan. The Phase 1/2 clinical trial will assess the safety, tolerability, and immunogenicity of TNX-801, following the submission and clearance of an IND.

“The FDA’s response to the pre-IND meeting marks an important milestone in the development of TNX-801 since we have FDA concurrence on the proposed manufacturing, toxicology studies, and the Phase 1/2 clinical design,” said Seth Lederman, M.D., President and Chief Executive Officer of Tonix. “TNX-801 is believed to be closely related to Edward Jenner’s original smallpox vaccine.^2-10 Jenner’s live virus smallpox vaccine – the first vaccine – remains one of the most effective vaccines in history, since it typically provided lifetime immunity with a single dose, prevented forward transmission of the smallpox virus, and ultimately eradicated the disease. TNX-801 has an attenuated phenotype relative to modern vaccinia viruses, which comprise a group of vaccine viruses that evolved from Jenner’s vaccine during passage in man and animals for over 100 years. When live virus vaccinia vaccination was routinely practiced in Africa, mpox was kept out of the human population.”^2,11

TNX-801 is a live replicating attenuated vaccine based on horsepox that is believed to protect against smallpox and mpox, primarily by eliciting a T-cell response evidenced by the “take”. The “take” is a functional measure of protective T-cell immunity validated by the eradication of smallpox. TNX-801 is administered with a single dose, can be readily scaled up for manufacturing using proven technology and can be distributed and stored without requiring a costly and cumbersome ultra-cold supply chain. Live replicating vaccines have the potential to induce durable T-cell immunity, prevent serious illness after infection and block forward transmission. Tonix reported positive preclinical efficacy data, demonstrating that TNX-801 vaccination protected non-human primates against lethal challenge with mpox.¹²

“More than 30,000 people have contracted mpox in the U.S. so far during the 2022-23 epidemic,”¹³ said Dr. Zeil Rosenberg, Executive Vice President, Medical at Tonix. “The recent cluster of mpox in Chicago revealed breakthrough cases of mpox in individuals who had been vaccinated with the currently authorized non-replicating vaccine, which is administered in two doses.¹⁴ In contrast, TNX-801 is delivered intradermally with only one dose and therefore may achieve higher rates of community protection by eliminating drop-out between doses and limiting forward transmission. Moreover, relying on only one approved mpox vaccine at present is a risk for the global supply chain that has already led to insufficient availability of vaccine to meet global health needs, especially in Africa.”

Dr. Rosenberg added, “We believe TNX-801 could make a global impact on mpox and the risk of smallpox because of its potential durable T-cell immune response, the ability to manufacture at scale, to use a lower dose than non-replicating vaccines. The current formulation is a frozen liquid, but we believe that future lyophilized versions can be stored and shipped at standard refrigeration. Moreover, we believe the low dose of TNX-801 makes this technology amenable for future implementation in microneedle delivery systems.”

Dr. Lederman concluded, “In addition to its potential use as a vaccine, TNX-801 also has the potential as a viral vector platform, for which versions can be developed to protect against a host of infectious diseases beyond smallpox and mpox, including COVID-19. In light of the recent resurgence in COVID cases across the country with the new EG.5 “Eris” variant, we believe that the horsepox recombinant pox virus platform may provide next generation vaccines to prevent future outbreaks.”

About TNX-801*
TNX-801 is a live virus vaccine based on horsepox^2,11. Horsepox and vaccinia are closely related orthopoxviruses that are believed to share a common ancestor. TNX-801 is believed to be more closely related to Jenner’s vaccinia vaccine than modern vaccinia vaccines, which appear to have evolved by deletions and mutations to a phenotype of larger plaque size in tissue culture and greater virulence in mice. Molecular analysis shows that horsepox is closer than modern vaccinia vaccines in DNA sequence to the vaccine discovered and disseminated by Dr. Edward Jenner.^2-10Vaccine genome researchers have recently shown the contemporaneous use of horsepox and horsepox-related viruses in the United States as smallpox vaccines in the 1860’s^9,10. Additionally they found a remarkable degree of identity with the circa 1860 U.S. smallpox vaccine VK05 and the 1976 Mongolian horsepox isolate called MNR-76, upon which Tonix’s TNX-801 is based.^3,5 These recent discoveries are further steps in establishing that what is called ’horsepox‘ today was used to vaccinate against smallpox in the 19^th century. Dr. Edward Jenner invented vaccination in 1798 and the procedure was called “vaccination” because the inoculum material was initially obtained from lesions on the udders of cows affected by a mild disease known as cowpox². ‘Cow’ is ‘vacca’ in Latin. However, Dr. Jenner suspected that cowpox originated from horsepox.² Subsequently, Dr. Jenner and others immunized against smallpox using material directly obtained from horses. The use of vaccines from horses was sometimes called ‘equination’ from the Latin ‘equus’ which means ‘horse’. Equination and vaccination were practiced side-by-side in Europe⁶. The small plaque size in culture of TNX-801 appears identical to the U.S. Centers for Disease Control publication of the natural isolate¹². Relative to vaccinia, horsepox has substantially decreased virulence in mice³. Tonix’s TNX-801 vaccine candidate is administered intradermally. The major cutaneous reaction or “take” to vaccinia vaccine was described by Dr. Edward Jenner in 1796 and has been used since then as a biomarker for protective immunity to smallpox, including in the World Health Organization’s (WHO) accelerated smallpox eradication program that successfully eradicated smallpox in the 1960’s.

TNX-801 is in the pre-IND stage and has not been approved for any indication.
Jenner E. “An Inquiry Into the Causes and Effects of the Variole Vaccinae, a Disease Discovered in Some of the Western Counties of England, Particularly Gloucestershire and Known by the Name of the cow‐pox.” London: Sampson Low, 1798.
Noyce RS, et al. (2018) PLoS One. 13(1):e0188453
Schrick L, et al. (2017) N Engl J Med 377:1491-1492
Tulman ER, et al. (2006) J Virol. 80(18):9244-58.
Esparza J, et al. (2017) Vaccine. 35(52):7222-7230.
Esparza J, et al. (2020) Vaccine. 38(30):4773-4779.
Qin L, et al. (2015) J Virol. 89(3):1809-24.
Brinkmann A, et al, (2020) Genome Biology 21:286
Duggan A, et al. (2020) Genome Biology 21:175 https://doi.org/10.1186/s13059-020-02079-z
Noyce RS, et al., (2023) Viruses. 15(2):356.
Trindade GS, et al. (2016) Viruses. 8(12):328.
McQuiston JH, et al. (2023) The CDC Domestic Mpox Response — United States, 2022–2023. MMWR Morb Mortal Wkly Rep. 72(20):547–552
Faherty EAG, et al.(2023) Emergence of an mpox cluster primarily affecting persons previously vaccinated against mpox-Chicago, Illinois, March 18-June 12, 2023. MMWR Morb Mortal Wkly Rep. , 72(25);696-698.

Tonix Pharmaceuticals Holding Corp.^*

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

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

Tonix Medicines has contracted to acquire the Zembrace SymTouch and Tosymra registered trademarks. Intravail is a registered trademark of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis, Inc.

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

Forward Looking Statements

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

Investor Contact

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

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

Media Contact

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

Source: Tonix Pharmaceuticals Holding Corp.

Released August 21, 2023

Release – Tonix Pharmaceuticals to Present at the August Virtual Investor Summit

Posted on August 17, 2023August 17, 2023 by aweinsoff@channelchek.com

Research News and Market Data on TNXP

August 17, 2023 7:00am EDT

CHATHAM, N.J., Aug. 17, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates, announced today that Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals, will present at the August 2023 Virtual Investor Summit on Thursday, August 24, 2023, at 10:00 a.m. ET.

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

Tonix Pharmaceuticals Holding Corp.^*

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

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

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

Forward Looking Statements

Investor Contact

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

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

Media Contact

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

Source: Tonix Pharmaceuticals Holding Corp.

Released August 17, 2023

Release – Tonix Pharmaceuticals Initiates Phase 1 Trial of TNX-1500 (Fc-modified humanized anti-CD40L mAb) in Healthy Volunteers

Posted on August 16, 2023August 16, 2023 by aweinsoff@channelchek.com

Research News and Market Data on TNXP

August 16, 2023 7:00am EDT

Single Ascending Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TNX-1500

Study Designed to Support Planned Phase 2 Trial in Prevention of Kidney Transplant Rejection

Multiple Possible Indications, Including Bone Marrow Transplantation and Autoimmune Diseases: Potential Pipeline in a Product

TNX-1500 is the First of Tonix’s Internally-Developed Biologic Candidates to Reach the Clinic

CHATHAM, N.J., Aug. 16, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced the initiation of a Phase 1 single ascending dose escalation study of TNX-1500 (Fc-modified humanized anti-CD40L monoclonal antibody or mAb) in healthy volunteers. The primary objectives of the study are to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous (IV) TNX-1500.

TNX-1500 is in development for the prevention of kidney transplant rejection and other potential transplant and autoimmune disorder indications. Recent animal studies indicate that TNX-1500 prevents organ rejection and preserves graft function either as a single agent or in combination with other drugs.^1,2 Eligible participants enrolled in the Phase 1 study will be evaluated regularly over a 120-day period after dosing. Target enrollment is 36 participants. Initiation of this first-in-human study is intended to support dosing in a planned Phase 2 trial in kidney transplant recipients.

“Despite advancements in the field of solid organ transplantation, there remains a significant need for new treatments with improved activity and tolerability,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “TNX-1500 has demonstrated single agent activity for long-term organ acceptance and induction of tolerance in animals.^1,2 Potentially related to its activity, in preclinical studies, TNX-1500 preserves T regulatory cells, or Tregs, which are key to maintaining tolerance to grafts as well as to self-antigens. We believe TNX-1500 has the potential to prevent organ transplant rejection and improve long-term graft survival with reduced long-term toxicity burden compared to current immunosuppressive regimens. In addition, TNX-1500 has the potential to address multiple indications, including a number of autoimmune diseases. The range of potential indications suggests ‘pipeline in a product’ potential.”

“We are excited to advance TNX-1500 into the clinic by initiating this Phase 1 trial,” said Dr. Greg Sullivan, Chief Medical Officer of Tonix. “TNX-1500 is a third generation anti-CD40L mAb that has been designed by protein engineering to decrease FcγRIIA binding. Preclinical studies in non-human primates demonstrated that TNX-1500 is active in preventing allograft organ rejection and is well tolerated. Specifically, thrombotic complications associated with first generation anti-CD40L mAbs, were not observed, suggesting that the protein engineering underlying TNX-1500 has achieved its design goals.”

Dr. Lederman continued, “Recently, positive clinical data with other CD40L blockers have been reported by Sanofi, with its Fc-modified humanized anti-CD40L mAb frexalimab in treating relapsing multiple sclerosis,³ and from Horizon Therapeutics plc with its tn03 fusion protein dazodalibep in treating Sjögren’s syndrome.^4,5 UCB is in Phase 3 development with its anti-CD40L pegylated Fab, dapirolizumab pegol, for the treatment of systemic lupus erythematosus.⁶ Based on results from animals, we consider Fc-modified humanized TNX-1500 to be a potential best-in-class therapeutic in the CD40L blocker space.”

CD40L is a member of the TNF-α superfamily, which includes TNF-α and RANKL. TNF-α is the target for several established drugs, including Humira^® (adalimumab), Remicade^® (infliximab), Enbrel^® (etanercept), and Cimzia® (certolizumab). RANKL is targeted by Prolia^® and Xgeva^® (denosumab). Emerging TNF-α superfamily targets for therapeutics include TL1A, CD30L, Ox40L, and 41BBL. Merck acquired Prometheus Biosciences for its anti-TL1A and anti-CD30L programs.

Dr. Lederman concluded, “TNX-1500 is the first of Tonix’s internally-developed biologic candidates to reach the clinic. Tonix owns worldwide rights to TNX-1500, which are unencumbered by royalties. Our ability to develop and advance protein therapeutics is facilitated by our Research and Development Center (RDC) in Frederick, Md. and our Advanced Development Center (ADC) in Dartmouth, Mass.”

About TNX-1500

TNX-1500 (Fc-modified humanized anti-CD40L mAb) is a humanized monoclonal antibody that interacts with the CD40-ligand (CD40L), which is also known as CD154. TNX-1500 is being developed for the prevention of allograft and xenograft rejection, for the treatment of autoimmune diseases and for the prevention of graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation (HCT). A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Two articles have recently published in the American Journal of Transplantation that demonstrate TNX-1500 prolongs non-human primate renal and heart allograft survival^1,2.

Lassiter, G., et al. (2023). TNX-1500, a crystallizable fragment–modified anti-CD154 antibody, prolongs non-human primate renal allograft survival. American Journal of Transplantation. April 3, 2023. https://doi.org/10.1016/j.ajt.2023.03.022
Miura, S., et al. (2023) TNX-1500, a crystallizable fragment–modified anti-CD154 antibody, prolongs non-human primate cardiac allograft survival. American Journal of Transplantation. April 6, 2023. https://doi.org/10.1016/j.ajt.2023.03.025
Sanofi press release May 31, 2023 “Press Release: Positive Phase 2 data of novel investigational anti-CD40L antibody frexalimab show significantly reduced disease activity in relapsing multiple sclerosis”: https://www.sanofi.com/en/media-room/press-releases/2023/2023-05-31-05-00-00-2678991 (accessed August 11 2023)
Horizon press release September 12, 2022 “Horizon Therapeutics plc Announces Phase 2 Trial Evaluating Dazodalibep for the Treatment of Sjögren’s Syndrome Meets Primary Endpoint” https://ir.horizontherapeutics.com/news-releases/news-release-details/horizon-therapeutics-plc-announces-phase-2-trial-evaluating (accessed August 11 2023)
Horizon Press Release January 18, 2023 “Horizon Therapeutics plc Announces Phase 2 Trial Evaluating Dazodalibep for the Treatment of Sjögren’s Syndrome Meets Primary Endpoint in the Second Study Population; Only Phase 2 Trial to Meet Primary Endpoint in Both Patient Populations ”https://ir.horizontherapeutics.com/news-releases/news-release-details/horizon-therapeutics-plc-announces-phase-2-trial-evaluating-0 (accessed August 11 2023)
https://www.ucb.com/our-science/pipeline (accessed August 11 2023)

Tonix Pharmaceuticals Holding Corp.^*

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

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

Forward Looking Statements

Investor Contact

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

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

Media Contact

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

Source: Tonix Pharmaceuticals Holding Corp.

Released August 16, 2023

Tonix Pharmaceuticals (TNXP) – Focus On CNS Transforms During 2Q23

Posted on August 14, 2023August 14, 2023 by cpereira@noblefcm.com

Monday, August 14, 2023

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics and diagnostics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of immunology, rare disease, infectious disease, and central nervous system (CNS) product candidates. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-15001 which is a humanized monoclonal antibody targeting CD40-ligand being developed for the prevention of allograft and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the second half of 2022. Tonix’s rare disease portfolio includes TNX-29002 for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan-Drug Designation by the FDA. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox called TNX-8013, next-generation vaccines to prevent COVID-19, and an antiviral to treat COVID-19. Tonix’s lead vaccine candidates for COVID-19 are TNX-1840 and TNX-18504, which are live virus vaccines based on Tonix’s recombinant pox vaccine (RPV) platform. TNX-35005 (sangivamycin, i.v. solution) is a small molecule antiviral drug to treat acute COVID-19 and is in the pre-IND stage of development. TNX-102 SL6, (cyclobenzaprine HCl sublingual tablets), is a small molecule drug being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix expects to initiate a Phase 2 study in Long COVID in the second quarter of 2022. The Company’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL, is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022. Finally, TNX-13007 is a biologic designed to treat cocaine intoxication that is expected to start a Phase 2 trial in the second quarter of 2022. TNX-1300 has been granted Breakthrough Therapy Designation by the FDA.

Robert LeBoyer, Senior Vice President, Equity Research Analyst, Biotechnology, Noble Capital Markets, Inc.

Refer to the full report for the price target, fundamental analysis, and rating.

Two Product Acquisitions Plus Four Topline Clinical Trial Results Expected. Tonix reported a loss of $28.4 million or $(2.68) per share, and a cash balance of $25.6 million in cash on June 30, 2023. During the quarter, the company acquired two currently marketed products for migraine headache that turn it into an operating company with product sales. These products fit with its focus on CNS drugs and its four clinical trials that are expected to announce topline results before the end of 2023.

Two CNS Products Have Been Acquired. In June, Tonix acquired two migraine headache products containing sumatriptan with proprietary delivery technologies. Zembrace SymTouch is an injectable sumatriptan packaged with an autoinjector for ease of use. Tosymra is a sumatriptan nasal spray with a permeation enhancer. These products have sales estimated at about $30 million during the previous 12 months. In addition, they add a sales force and CNS customer base for Tonix’s future products.

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Release – Tonix Pharmaceuticals Reports Second Quarter 2023 Financial Results and Operational Highlights

Posted on August 11, 2023August 11, 2023 by aweinsoff@channelchek.com

Research News and Market Data on TNXP

August 10, 2023 4:30pm EDT

Download as PDF

Release – Tonix Pharmaceuticals Completes Clinical Phase of PREVAIL Proof-of-Concept Study of TNX-102 SL for the Treatment of Fibromyalgia-Type Long COVID

Posted on August 7, 2023August 7, 2023 by aweinsoff@channelchek.com

Research News and Market Data on TNXP

August 07, 2023 7:00am EDT

Topline Results Expected Third Quarter 2023

Long COVID Afflicts Approximately 19% of Patients Following COVID-19¹, and is Expected to be a Global Health Burden

Fibromyalgia-Type Long COVID with Multi-Site Pain Affects Approximately 40% of Long COVID Patients

CHATHAM, N.J., Aug. 07, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company, today announced the completion of the clinical phase of the Phase 2 proof-of-concept PREVAIL study of TNX-102 SL as a potential treatment for fibromyalgia-type Long COVID. Topline results for the PREVAIL study are expected in the third quarter of 2023.

“Approximately 40% of U.S. Long COVID patients have fibromyalgia-like multi-site pain symptoms based on our observational studies of Long COVID patients from the TriNetX claims database,”^2,3 said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “In addition to multi-site pain, these individuals often suffer from one or more other symptoms typically associated with fibromyalgia such as fatigue, sleep disturbance, and brain fog. We have termed this subgroup, ‘Fibromyalgia-type Long COVID.’ Given our encouraging results with TNX-102 SL as a potential treatment for fibromyalgia⁴, we are testing TNX-102 SL as a bedtime medicine for the management of Fibromyalgia-type Long COVID. In completing this clinical milestone, marked by the last enrolled patient finishing their final visit, we can now begin to look forward to topline results from the 63-patient PREVAIL study later this quarter.”

Dr. Lederman continued, “TNX-102 SL improves sleep quality in fibromyalgia, and we believe this is the mechanism by which TNX-102 SL improves other symptoms, like multi-site pain.⁵ Recently, the U.S. National Institutes of Health (NIH) has identified improving sleep quality as a target for potential therapeutics for Long COVID^6,7,8, consistent with the proposed mechanism of TNX-102 SL.

“Common symptoms of Long COVID, including multi-site pain, fatigue, unrefreshing sleep, and cognitive dysfunction, or ‘brain fog,’ are also hallmarks of conditions like fibromyalgia and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME),”⁹ said Herbert Harris, M.D., Ph.D., Executive Vice President and Head of Translational Medicine of Tonix Pharmaceuticals. “Defining subgroups of Long COVID patients that overlap with fibromyalgia and CFS/ME is expected to facilitate the development of new treatments.⁴ It can be challenging to distinguish fibromyalgia and CFS/ME clinically, given the high level of symptom overlap between them. Each of these conditions is defined by a constellation of symptoms, and there is no widely recognized diagnostic laboratory test that distinguishes them.”

Dr. Harris continued, “The recent identification of Long COVID subgroups in the National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored RECOVER study¹⁰ was an important step. In their recent publication, cluster analysis of the symptom frequencies in the RECOVER study identified four subgroups of Long COVID patients. Cluster #4 represented approximately one-quarter of the population (28%) and reported the highest frequencies of pain (back pain (58%), joint pain (64%) or muscle pain (60%)), high frequencies of fatigue (94%) and ’Brain Fog,’ (94%) and a high level of impairment of Quality of Life. We believe Cluster #4 is a subgroup of Long COVID that shares many clinical features with fibromyalgia and may involve common disease mechanisms. We also believe that Cluster #3, representing another approximately 29% of the RECOVER cohort, includes many patients with fibromyalgia-type Long COVID because 100% of that group suffer from ‘Brain Fog’, 94% experience fatigue and approximately one-third experience pain (back pain (32%), joint pain (36%) or muscle pain (34%)).”

Dr. Harris concluded, “With no FDA approved treatment for Long COVID, we understand the need to better understand long COVID and to develop treatments for subgroups of this unserved population of patients. Fibromyalgia has been recognized by the U.S. Food and Drug Administration (FDA) with three approved medicines. Consequently, measuring daily pain is a validated endpoint for FDA registrational studies in fibromyalgia. We believe that daily pain has the potential to be an endpoint for registrational studies in fibromyalgia-like long COVID.”

About the Phase 2 PREVAIL Study

The Phase 2 PREVAIL study is a 14-week double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-102 SL taken daily at bedtime in patients with multi-site pain associated with post-acute sequelae of SARS-CoV-2 infection (PASC). The trial is being conducted at approximately 30 sites in the U.S. The primary efficacy endpoint will be the change from baseline in the weekly average of daily self-reported worst pain intensity scores at the Week 14 endpoint. Key secondary efficacy endpoints include change from baseline in self-reported scores for sleep disturbance, fatigue, and cognitive function. Topline results are expected in the third quarter of 2023.

For more information, see ClinicalTrials.gov Identifier: NCT05472090.

About Long COVID or Post-Acute Sequelae of COVID-19 (PASC)

Post-acute sequelae of COVID-19, or PASC is the formal name for a condition now widely known as Long COVID. Although most people recover from COVID-19 within weeks of the acute illness, a substantial portion develops a chronic syndrome called Long COVID.¹¹ These individuals experience a constellation of disabling symptoms long past the time of recovery from acute COVID-19. Most Long COVID patients who have been studied appear to have cleared the SARS-CoV-2 infection from their systems. The symptoms of Long COVID can include fatigue, sleep disorders, multi-site pain, fevers, shortness of breath, cognitive impairment described as “brain fog” or memory disturbance, gastrointestinal symptoms, anxiety, and depression. According to the Centers for Disease Control and Prevention (CDC), 1 in 13 adults in the U.S. (7.5%) have Long COVID symptoms.¹ Long COVID is typically associated with moderate or severe COVID-19, but can occur after mild COVID-19 or even after asymptomatic SARS-CoV-2 infection. More than 40% of adults in the United States reported having COVID-19 in the past, and nearly one in five of those (19%) are currently still having symptoms of Long COVID.¹ Long COVID is a chronic disabling condition that is expected to result in a significant global health and economic burden.^12-15 In response to the urgent need for therapies that address Long COVID, Congress awarded $1.15 billion to the National Institutes of Health to study Long COVID in December 2020¹⁶ The U.S. Department of Health and Human Services National Research Action Plan on Long COVID¹⁷, released in August 2022, addresses the overlap of Long COVID with CFS/ME, which, like fibromyalgia, is one of the overlapping chronic pain syndromes with central and peripheral sensitization.¹⁸ A published survey¹⁹ found comparable pain, fatigue, and functional impairment between Long COVID, fibromyalgia, and CFS/ME. This symptom overlap between these conditions has suggested that altered neurologic function is one of the leading hypotheses to explain them.²⁰ While the vaccines available in the U.S., through either FDA approval or under Emergency Use Authorization, have been shown to prevent acute COVID, their ability to prevent Long COVID is unknown. There is currently no approved drug for the treatment of Long COVID. Fibromyalgia-type Long COVID, like fibromyalgia and CFS/ME, appears to be one of several chronic overlapping pain conditions that have in common the neurological process called central and peripheral sensitization, which is increasingly known by the term nociplastic pain.

About TNX-102 SL

TNX-102 SL is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities at the 5-HT2A-serotonergic, α1-adrenergic, H1-histaminergic, and M1-muscarinic receptors, TNX-102 SL is in development as a daily bedtime treatment for fibromyalgia, Long COVID (formally known as post-acute sequelae of COVID-19 [PASC]), alcohol use disorder and agitation in Alzheimer’s disease. The United States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408 in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic™ protective eutectic and Angstro-Technology™ formulation claimed in the patent are important elements of Tonix’s proprietary TNX-102 SL composition. These patents are expected to provide TNX-102 SL, upon NDA approval, with U.S. market exclusivity until 2034/2035.

*TNX-102 SL is an investigational new drug and is not approved for any indication

NIH News Release. June 22, 2022. “Nearly One in Five American Adults Who Have Had COVID-19 Still Have ‘Long COVID’” https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/20220622.htm (accessed August 4, 2023).
Tonix Pharmaceuticals Press Release. Feb 22, 2023. https://ir.tonixpharma.com/news-events/press-releases/detail/1369/tonix-pharmaceuticals-describes-emerging-research-on-the
Harris, H. et al. Tonix data on file 2023
Lederman S, et al. Arthritis Care Res (Hoboken). 2023
Moldofsky H, et al. J Rheumatol. 2011. 38(12):2653-63
NIH News Release. July 31, 2023. “NIH launches long COVID clinical trials through the RECOVER Initiative, opening enrollment.” https://www.nih.gov/news-events/news-releases/nih-launches-long-covid-clinical-trials-through-recover-initiative-opening-enrollment (accessed August 4, 2023).
Howard, J. CNN. July 31, 2023. “Biden administration announces launch of HHS office focused on long Covid research” https://edition.cnn.com/2023/07/31/health/long-covid-research-office/index.html
Johnson, M and Goldstein A. Washington Post. July 31, 2023. “NIH announces long covid treatment studies with hundreds of patients” www.washingtonpost.com/health/2023/07/31/long-covid-treatment-studies-nih/
Clauw DJ, and Calabrese L. Ann Rheum Dis. 2023
Thaweethai T, et al. JAMA. 2023. 329(22):1934-1946
Clauw DJ, et al. Pain. 2020. 161(8):1694-1697
Briggs, A, and Vassall, A. Nature. 2021. 593(7860): 502-505
Nittas V, et al. Public Health Rev. 2022. 43:1604501
Davis, HE., et al. EClinicalMedicine. 2021. 38:101019
Martin C, et al. PLoS One. 2021. 16(12):e0260843
The NIH provision of Title III Health and Human Services, Division M–Coronavirus Response and Relief Supplemental Appropriations Act, 2021, of H.R. 133, The Consolidated Appropriations Act of 2021. The bill was enacted into law on 27 December 2020, becoming Public Law 116-260.
Department of Health and Human Services, Office of the Assistant Secretary for Health. 2022. National Research Action Plan on Long COVID, 200 Independence Ave SW, Washington, DC 20201. www.covid.gov/assets/files/National-Research-Action-Plan-on-Long-COVID-08012022.pdf
Maixner W, et al. J Pain. 2016. 17(9 Suppl):T93-T107
Haider S, et al. Pain. 2023. 164(2):385-401
Sutherland, S. Scientific American. 2023

Tonix Pharmaceuticals Holding Corp.^*

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

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

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

Forward Looking Statements

Investor Contact

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

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

Media Contact

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

Source: Tonix Pharmaceuticals Holding Corp.

Released August 7, 2023

Release – Tonix Pharmaceuticals Announces Closing of $7 Million Public Offering

Posted on August 1, 2023August 1, 2023 by aweinsoff@channelchek.com

Research News and Market Data on TNXP

August 01, 2023 4:01pm EDT

CHATHAM, N.J., Aug. 01, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (“Tonix” or the “Company”), a biopharmaceutical company, today announced the closing of its public offering of 7,000,000 shares of its common stock (or common stock equivalents in lieu thereof) and warrants to purchase up to an aggregate of 7,000,000 shares of common stock in a public offering at a combined offering price of $1.00 per share (or common stock equivalents in lieu thereof) and accompanying warrant. The warrants have an exercise price of $1.00 per share, became exercisable upon issuance, and will expire five years following the issuance date.

The gross proceeds of the offering were $7 million before deducting placement agent fees and other offering expenses payable by the Company. The Company intends to use the net proceeds from the offering for working capital and general corporate purposes, the build out of the Company’s manufacturing and research and development facilities, and the acquisition or licensing of approved products and products in development.

A.G.P./Alliance Global Partners acted as lead placement agent for the offering.

Brookline Capital Markets, a division of Arcadia Securities, LLC, acted as co-placement agent for the offering.

This offering was made pursuant to an effective shelf registration statement on Form S-3 (File No. 333-254975) previously filed with the U.S. Securities and Exchange Commission (the “SEC”). The offering was made only by means of a prospectus supplement and accompanying base prospectus. A final prospectus supplement and accompanying prospectus describing the terms of the offering have been filed with the SEC and are available on the SEC’s website located at http://www.sec.gov. Electronic copies of the final prospectus supplement may be obtained from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at prospectus@allianceg.com.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment in a potentially registration-enabling study, and with topline data expected in the fourth quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 study has been completed, and topline results are expected in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation being developed as a treatment for major depressive disorder (MDD). Enrollment is now complete in the UPLIFT trial of TNX-601 ER in MDD and topline results are expected in the fourth quarter of 2023. TNX-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. TNX-1900 (intranasal potentiated oxytocin), in development for chronic migraine, has completed enrollment with topline data expected in the fourth quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the third quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, classes of broad-spectrum small molecule oral antivirals.

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

Forward Looking Statements

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

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

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

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

Source: Tonix Pharmaceuticals Holding Corp.

Released August 1, 2023

Release – Tonix Pharmaceuticals Completes Enrollment in Potentially NDA-Enabling Phase 3 RESILIENT Trial of TNX-102 SL for Management of Fibromyalgia

Posted on August 1, 2023August 1, 2023 by aweinsoff@channelchek.com

Research News and Market Data on TNXP

August 01, 2023 7:00am EDT

Topline Data Expected Fourth Quarter 2023

Final Trial Required for Submission of a New Drug Application, if Successful

CHATHAM, N.J., Aug. 01, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company, today announced that it has completed enrollment of its potentially final, confirmatory Phase 3 RESILIENT trial of TNX-102 SL (cyclobenzaprine HCL sublingual tablets) 5.6 mg in fibromyalgia and expects topline data next quarter. A total of 457 participants were randomized. TNX-102 SL is in development as a non-opioid, centrally acting analgesic, to be taken daily at bedtime for the management of fibromyalgia. If successful, we believe this will be the final, well-controlled efficacy trial required for submission of a New Drug Application (NDA) for approval by the U.S. Food and Drug Administration (FDA).

“The completion of enrollment in our Phase 3 RESILIENT trial is a significant milestone for both Tonix and the fibromyalgia community,” said Seth Lederman, M.D., Chief Executive Officer of Tonix. “Currently-approved treatments have not fully met the needs of fibromyalgia patients and there has not been a new FDA-approved therapy for the condition since 2009. TNX-102 SL has the potential to be a new non-addictive, non-opioid bedtime medication with broad spectrum symptom coverage and which can be used on a chronic basis for the management of fibromyalgia. With all other clinical, nonclinical and CMC requirements for an NDA submission achieved, we are looking forward to the upcoming data readout and an expeditious filing of an NDA.”

In December 2020, Tonix reported positive results from the first Phase 3 study (RELIEF) of TNX-102 SL 5.6 mg for the management of fibromyalgia. TNX-102 SL met its pre-specified primary endpoint in the Phase 3 RELIEF trial, significantly reducing daily pain compared to placebo (p=0.01) in participants with fibromyalgia. Also, when the primary endpoint was analyzed as a ≥30% pain responder analysis, there was a higher rate of responders to TNX-102 SL (47%) than to placebo (35%; p=0.006). TNX-102 SL at 5.6 mg also showed activity in key secondary endpoints demonstrating improvements in sleep quality, mitigation of fatigue, and fibromyalgia-specific global symptomatic and functional recovery. TNX-102 SL was generally safe and well tolerated in patients with fibromyalgia, with overall adverse event profile comparable to prior fibromyalgia studies. The most common treatment-emergent adverse events were oral hypoesthesia, oral paresthesia, and product taste abnormal.

About the Phase 3 RESILIENT Study

The RESILIENT study is a double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) in the management of fibromyalgia. The two-arm trial randomized 457 participants in the U.S. The first two weeks of treatment consist of a run-in period in which participants start on TNX-102 SL 2.8 mg (1 tablet) or placebo. Thereafter, all participants increase their dose to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks. The primary endpoint is the daily diary pain severity score change (TNX-102 SL 5.6 mg vs. placebo) from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation.

For more information, see ClinicalTrials.gov Identifier: NCT05273749

About Fibromyalgia

Fibromyalgia is a chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system. Fibromyalgia afflicts an estimated 6-12 million adults in the U.S., approximately 90% of whom are women. Symptoms of fibromyalgia include chronic widespread pain, nonrestorative sleep, fatigue, and morning stiffness. Other associated symptoms include cognitive dysfunction and mood disturbances, including anxiety and depression. Individuals suffering from fibromyalgia struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products.

About TNX-102 SL

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment in a potentially registration-enabling study, with topline data expected in the fourth quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 study has been completed, and topline results are expected in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation being developed as a treatment for major depressive disorder (MDD). Enrollment has now completed in the UPLIFT trial of TNX-601 ER in MDD, with topline results expected in the fourth quarter of 2023. TNX-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. TNX-1900 (intranasal potentiated oxytocin), in development for chronic migraine, has completed enrollment with topline data expected in the fourth quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the third quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, classes of broad-spectrum small molecule oral antivirals.

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

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

Forward Looking Statements

Investor Contact

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

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

Media Contact

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

Zembrace^® SymTouch^® (sumatriptan Injection): IMPORTANT SAFETY INFORMATION

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

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

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.

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

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

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

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.

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 August 1, 2023

Release – Tonix Pharmaceuticals Announces Enrollment Initiated in the MGH Phase 2 ‘STROBE’ Study of TNX-1900 (Intranasal Potentiated Oxytocin) for the Treatment of Binge-Eating Disorder

Posted on July 31, 2023July 31, 2023 by aweinsoff@channelchek.com

Research News and Market Data on TNXP

July 31, 2023 7:00am EDT

Preliminary Data Show that Oxytocin Decreases Impulsivity and Reduces Food Intake

TNX-1900 (Intranasal Potentiated Oxytocin) May Serve as a Novel Neuroendocrine Treatment for Binge-Eating Disorder

CHATHAM, N.J., July 31, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that the first participant was enrolled in the investigator-initiated Phase 2 Study of The Results of Oxytocin in Binge Eating ‘STROBE’ study of TNX-1900 (intranasal potentiated oxytocin) for the treatment of binge-eating disorder at the Massachusetts General Hospital (MGH). The aim of the study is to investigate the efficacy and safety of TNX-1900 as a novel therapeutic agent to reduce binge eating frequency in adults with binge-eating disorder. Tonix is supporting the STROBE study through a clinical trial agreement with MGH. MGH is the sponsor of the trial, which is being conducted under an investigator-initiated investigational new drug (IND) application.

The 8-week double-blind, placebo-controlled trial has a target enrollment of at least 60 participants 18-45 years old with binge-eating disorder.

“Binge-eating disorder is identified as a reduced ability to control behavioral impulses and formed habits, disrupting the regulation of food intake and energy balance,”^1-4 said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “While existing treatment options may produce remission from binge eating in some cases, up to 50% of patients continue to engage in binge eating.”^5-7

Elizabeth A. Lawson, M.D., M.M.Sc., Director, Interdisciplinary Oxytocin Research Program in the Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and principal investigator of the study added, “Individuals with binge-eating disorder experience loss of control over eating that is thought to be driven by increased hedonic drive to eat as well as impulsivity.^8-10 The oxytocin system has been linked to likelihood of lifetime binge eating in women¹¹, and our preliminary studies of intranasal oxytocin at the dose used in this trial show that oxytocin modulates areas of the brain responsible for hedonic eating and impulse control¹², improves impulsivity¹³, and reduces caloric intake.¹⁴ The goal of the STROBE study is to assess whether 8 weeks intranasal administration of oxytocin will decrease binge eating frequency by lowering the drive to eat and improving impulse control.”

About the Phase 2 STROBE Study

The Phase 2 STROBE study is a randomized, double blind, placebo-controlled study to evaluate the efficacy and safety of TNX-1900 for the treatment of binge-eating disorder in adults. The 8-week trial has a target enrollment of at least 60 participants 18-45 years old with binge-eating disorder. Subjects will be randomized to receive TNX-1900 or placebo and will be studied at Massachusetts General Hospital. Subjects will self-administer TNX-1900 or placebo as two sprays total (one spray in each nostril) up to four times per day for 8 weeks. The primary endpoint is 8-week change from baseline in binge frequency.

For more information, see ClinicalTrials.gov Identifier: NCT05664516

About Binge Eating Disorder

Binge-eating disorder (BED) is a psychiatric illness characterized by frequent episodes of uncontrollable consumption of large amounts of food. It is the most common eating disorder and often leads to obesity-associated complications and later psychopathology¹⁵. BED is characterized by increased homeostatic appetite and sensitivity to reward (including food reward)¹⁶, which may lead to initiation of binge episodes, and a reduced ability to control behavioral impulses and formed habits, creating an imbalance in the sensitive interplay between these bottom-up and top-down processes governing the adaptive regulation of food intake and energy balance^1-4.

About TNX-1900

TNX-1900 (intranasal potentiated oxytocin) is a proprietary formulation of oxytocin in development as a candidate for prevention of chronic migraine and other conditions. In 2020, TNX-1900 was acquired from Trigemina, Inc. who had licensed the technology underlying the composition and method from Stanford University. TNX-1900 is a drug-device combination product, based on an intranasal actuator device that delivers oxytocin into the nasal cavity. Oxytocin is a naturally occurring human peptide hormone that also acts as a neurotransmitter in the brain. Oxytocin has no recognized addiction potential. It has been observed that low oxytocin levels in the body are associated with increases in migraine headache frequency, and that increased oxytocin levels are associated with fewer migraine headaches. Certain other chronic pain conditions are also associated with decreased oxytocin levels. Migraine attacks are caused, in part, by the activity of pain-sensing trigeminal neurons which, when activated, release of calcitonin gene-related peptide (CGRP) which binds to receptors on other nerve cells and starts a cascade of events that is believed to result in headache. Oxytocin when delivered via the nasal route, concentrates in the trigeminal system¹⁷ resulting in binding of oxytocin to receptors on neurons in the trigeminal system, inhibiting the release of CGRP and transmission of pain signals returning from the site of CGRP release.¹⁸ Blocking CGRP release is a distinct mechanism compared with CGRP antagonist and anti-CGRP antibody drugs, which block the binding of CGRP to its receptor. With TNX-1900, the addition of magnesium to the oxytocin formulation enhances oxytocin receptor binding¹⁹ as well as its inhibitory effects on trigeminal neurons and resultant craniofacial analgesic effects, as demonstrated in animal models²⁰. Intranasal oxytocin has been shown to be well tolerated in several clinical trials in both adults and children²¹. Targeted nasal delivery results in low systemic exposure and lower risk of non-nervous system, off-target effects, which could potentially occur with systemic CGRP antagonists such as anti-CGRP antibodies²². For example, CGRP has roles in dilating blood vessels in response to ischemia, including in the heart. The Company believes nasally targeted delivery of oxytocin could translate into selective blockade of CGRP release from neurons in the trigeminal ganglion and not throughout the body, which could be a potential safety advantage over systemic CGRP inhibition. In addition, daily dosing is more rapidly reversible, in contrast to monthly or quarterly dosing, as is the case with anti-CGRP antibodies, giving physicians and their patients greater control. In addition to chronic migraine, TNX-1900 will be developed for treatment of episodic migraine, binge eating disorder, craniofacial pain conditions, and insulin resistance. Tonix also has a license with the University of Geneva to use TNX-1900 for the treatment of insulin resistance and related conditions.

About TNX-2900

TNX-2900 is another intranasal potentiated oxytocin-based therapeutic candidate, being developed for the treatment of Prader-Willi syndrome, or PWS. The technology for TNX-2900 was licensed from the French National Institute of Health and Medical Research. PWS, an orphan condition, is a rare genetic disorder of failure to thrive in infancy, associated with uncontrolled appetite later in childhood.

¹Dawe S and Loxton NJ. Neurosci Biobehav Rev. 2004; 28(3):343-351
²Giel KE, et al. Nutrients. 2017; 9(11)
³Hernandez D, et al. Obesity (Silver Spring). 2019; 27(4):629-635
⁴Schag K, et al. Obes Rev. 2013; 14(6):477-495
⁵Hilbert A, et al. Int J Eat Disord. 2020; 53(9):1353-1376
⁶Reas DL and Grilo CM. Expert Opin Emerg Drugs. 2014; 19(1):99-142
⁷Wilson GT. Psychiatr Clin North Am. 2011; 34(4):773-783
⁸Giel KE, et al. Nutrients. 2017. 9(11)
⁹Hernandez D, et al. Obesity (Silver Spring). 2019. 27(4):629-635
¹⁰Schag K, et al. Obes Rev. 2013. 14(6):477-95
¹¹Micali N, et al. Eur Eat Disord Rev. 2017; 25(1):19-25
¹²Plessow F, et al. Neuropsychopharmacology. 2018. 43(3):638-645
¹³Plessow F, et al. Obesity (Silver Spring), 2021. 29(1):56-61
¹⁴Lawson EA, et al. Obesity (Silver Spring). 2015; 23(5):950-956
¹⁵Field A, et al. Pediatrics. 2012; 130 (2):e289–e295
¹⁶Bulik CM, et al. Nature Neuroscience. 2022. 25(5):543-554
¹⁷Yeomans DC, et al. Transl Psychiatry. 2021. 11(1):388
¹⁸Tzabazis A, et al. Cephalalgia. 2016. 36(10):943-50
¹⁹Antoni FA and Chadio SE. Biochem J. 1989. 257(2):611-4
²⁰Cai Q, et al. Psychiatry Clin Neurosci. 2018. 72(3):140-151
²¹Yeomans, DC et al. 2017. US patent US2017368095
²²MaassenVanDenBrink A, et al. Trends Pharmacol Sci. 2016. 37(9):779-788

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, nearing complete enrollment in a potentially registration-enabling study, with topline data expected in the fourth quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 study has been completed, and topline results are expected in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation being developed as a treatment for major depressive disorder (MDD), is nearing complete enrollment with topline results expected in the fourth quarter of 2023. TNX-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. TNX-1900 (intranasal potentiated oxytocin), in development for chronic migraine, is currently enrolling with topline data expected in the fourth quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the third quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, classes of broad-spectrum small molecule oral antivirals.

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

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

Forward Looking Statements

Investor Contact

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

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

Media Contact

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

Zembrace^® SymTouch^® (sumatriptan Injection): IMPORTANT SAFETY INFORMATION

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

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

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.

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

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

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

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.

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 July 31, 2023

Release – Tonix Pharmaceuticals Announces Pricing of $7 Million Public Offering

Posted on July 28, 2023July 28, 2023 by aweinsoff@channelchek.com

Research News and Market Data on TNXP

July 27, 2023 9:31pm EDT

CHATHAM, N.J., July 27, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (“Tonix” or the “Company”), a biopharmaceutical company, today announced it has entered into a securities purchase agreement for the purchase and sale of 7,000,000 shares of its common stock (or common stock equivalents in lieu thereof) and warrants to purchase up to an aggregate of 7,000,000 shares of common stock in a public offering at a combined offering price of $1.00 per share (or common stock equivalents in lieu thereof) and accompanying warrant. The warrants have an exercise price of $1.00 per share, will become exercisable commencing the date of issuance, and will expire five years following the issuance date. The closing of the public offering is expected to take place on or about August 1, 2023, subject to the satisfaction of customary closing conditions.

The gross proceeds of the offering will be approximately $7 million before deducting placement agent fees and other estimated offering expenses payable by the Company. The Company intends to use the net proceeds from the offering for working capital and general corporate purposes, the build out of the Company’s manufacturing and research and development facilities, and the acquisition or licensing of approved products and products in development.

A.G.P./Alliance Global Partners is acting as lead placement agent for the offering.

Brookline Capital Markets, a division of Arcadia Securities, LLC is acting as co-placement agent for the offering.

This offering is being made pursuant to an effective shelf registration statement on Form S-3 (File No. 333-254975) previously filed with the U.S. Securities and Exchange Commission (the “SEC”). The offering will be made only by means of a prospectus supplement and accompanying base prospectus, as may be further supplemented by any free writing prospectus and/or pricing supplement that Tonix may file with the SEC. A preliminary prospectus supplement and accompanying prospectus describing the terms of the proposed offering have been filed with the SEC and are available on the SEC’s website located at http://www.sec.gov. Electronic copies of the final prospectus supplement may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at prospectus@allianceg.com. Before investing in this offering, interested parties should read in their entirety the prospectus supplement and the accompanying prospectus and the other documents that Tonix has filed with the SEC that are incorporated by reference in such prospectus supplement and the accompanying prospectus, which provide more information about Tonix and such offering.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, nearing complete enrollment in a potentially registration-enabling study, with topline data expected in the fourth quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 study has been completed, and topline results are expected in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation being developed as a treatment for major depressive disorder (MDD), is nearing complete enrollment with topline results expected in the fourth quarter of 2023. TNX-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. TNX-1900 (intranasal potentiated oxytocin), in development for chronic migraine, is currently enrolling with topline data expected in the fourth quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the third quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, classes of broad-spectrum small molecule oral antivirals.

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

Forward Looking Statements

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

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

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

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

Source: Tonix Pharmaceuticals Holding Corp.

Released July 27, 2023

Release – Tonix Pharmaceuticals Announces Accelerating Completion of Enrollment in Phase 2 UPLIFT Study of TNX-601 ER (Racemic Tianeptine) for Major Depressive Disorder: Topline Data Now Expected in Fourth Quarter 2023

Posted on July 27, 2023July 27, 2023 by aweinsoff@channelchek.com

Research News and Market Data on TNXP

July 26, 2023 4:05pm EDTDownload as PDF

Reallocating Resources to Development of Single Isomer TNX-4300 (Estianeptine)

Estianeptine in Preclinical Development Has Demonstrated Key Activities Related to in vivo Novel Object Recognition and in vitro Neuroplasticity, Without the µ-Opioid Receptor Activity of Racemic and (R)-Tianeptine

New Findings Support Development of TNX-4300 as a First-in-Class Oral Therapy in Depression, Alzheimer’s Disease and Other Psychiatric and Neurodegenerative Conditions with Memory Deficits

CHATHAM, N.J., July 26, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company, today announced that development of TNX-4300* (estianeptine), the single (S)-isomer of tianeptine will be prioritized over TNX-601 ER*, which is being studied in the Phase 2 UPLIFT¹ trial for the treatment of major depressive disorder (MDD). TNX-4300 is in preclinical development for mood disorders, Alzheimer’s disease and Parkinson’s disease. Recent findings have shown estianeptine possesses the ability to improve memory and cognition in vivo as measured in the rat Novel Object Recognition (NOR) test, and the ability to restore neuroplasticity to neurons in cell culture. The finding that estianeptine is responsible for improving memory and cognition in vivo suggests a role for peroxisome proliferator-activated receptor PPAR-β/δ activation in memory. For these reasons, Tonix intends to accelerate completion of enrollment for the Phase 2 UPLIFT¹ trial to reallocate resources to the preclinical development of TNX-4300 and now expects to report topline data from this study in the fourth quarter of 2023. Tonix is also accelerating completion of enrollment in the RESILIENT study of TNX-102 SL for the management of fibromyalgia so that approximately 450 patients will be enrolled, and topline results are expected in the fourth quarter of 2023.

Racemic tianeptine is an antidepressant that has been marketed outside the U.S. for more than 30 years. Tianeptine is also a racemic drug composed of a 1:1 mixture of two mirror-image isomers. Tonix recently reported that the (S)-isomer (estianeptine) is responsible for its positive effects on neuroplasticity in cell culture, while the (R)-isomer is responsible for racemic tianeptine’s off-target activity on the µ-opioid receptor.^2,3 Tonix also recently reported that estianeptine activates PPAR-β/δ. These activities on molecular targets in neurons and glia in the brain are believed to relate to tianeptine’s ability to restore connectivity between neurons that atrophy in conditions of stress or depression in animal models.⁴ Tianeptine’s mechanism is distinct from traditional antidepressants that alter the level or activity of serotonin, norepinephrine, and dopamine neurotransmitters, which are believed to indirectly induce neurons to make new connections.⁵

“Given the time and expense of developing new drugs, the scientific and clinical advantages of TNX-4300 lead us to focus our efforts on this preclinical program as a potential treatment for mood disorders like depression and neurodegenerative conditions like Alzheimer’s disease,” said Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals. “The finding that TNX-4300 possesses the desirable attributes of racemic tianeptine and at the same time lacks a measurable opioid liability supports the focus of our resources on this candidate. Multiple studies around the world have already shown that racemic tianeptine is effective in treating depression. However, our in vivo animal studies and in vitro lab studies have indicated that TNX-4300 is potentially a more active and safer drug.”

Dr. Sullivan continued, “TNX-601 ER, which contains racemic tianeptine, has informed the future development of TNX-4300 which contains the single isomer, estianeptine. We believe that estianeptine bypasses the synapse and activates intracellular PPAR-β/δ and PPAR-γ targets. The finding that estianeptine is responsible for tianeptine’s ability to improve memory and cognition in the NOR test implicates PPAR-β/δ activation specifically as a molecular target. This finding is consistent with the impaired memory of mice lacking the PPAR-β/δ gene.”⁸

Tonix has filed patents claiming single (S)-isomer estianeptine, the active ingredient in TNX-4300, which is devoid of activity on the µ-opioid receptor in tissue culture. Tonix has filed patent claims that describe crystalline salt forms of estianeptine that appear well suited to formulation. TNX-4300 is currently in preclinical development for depression, bipolar disorder, Alzheimer’s disease, and Parkinson’s disease. Key experiments were performed by scientists at Tonix’s Research and Development Center (RDC) in Frederick, Maryland.

^*TNX-601 ER and TNX-4300 are investigational new drugs and are not approved for any indication. TNX-601 ER is being developed under an IND. TNX-4300 is at the pre-IND stage of development.

About Tianeptine

Racemic tianeptine sodium (amorphous) immediate release (dosed 3 times daily) was first marketed for depression in France in 1989 and has been available for decades in Europe, Russia, Asia, and Latin America for the treatment of depression. Tianeptine sodium has an established tolerability profile from decades of use in these jurisdictions. Currently no tianeptine-containing product is approved in the U.S. and no extended-release once-daily tianeptine product is approved in any jurisdiction. In animal models, tianeptine restores dendritic arborization of pyramidal neurons in the CA3 region of hippocampus and in the dentate gyrus region promotes new neuron formation and integration into hippocampal networks.⁴ Tianeptine’s enhancement of neuroplasticity in animal models of stress is believed to be mediated by activation of PPAR isoforms PPAR-β/δ and PPAR-γ, which is mechanistically distinct from traditional monoaminergic antidepressants marketed in the U.S. and contributes to its potential for clinical indications beyond depression and stress disorders. Tianeptine and its MC5 metabolite are also weak µ-opioid receptor (MOR) agonists that present a potential abuse liability if illicitly misused in large quantities.^3,9 In cases where tianeptine has been abused, the dose has been approximately 8-80 times the therapeutic dose in depression on a daily basis.⁹ In patients who were prescribed tianeptine for depression, the French Transparency Committee found an incidence of misuse of approximately 1 case per 1,000 patients treated¹⁰ suggesting low abuse liability when used at the antidepressant dose in patients prescribed tianeptine for depression. Clinical trials have shown that cessation of a therapeutic course of tianeptine does not appear to result in dependence or withdrawal symptoms following 6-weeks^11-15, 3-months,¹⁶ or 12-months¹⁷ of treatment. Estianeptine is believed to mimic naturally occurring polyunsaturated fatty acid ligands in low affinity interactions with PPAR-β/δ and PPAR-γ. Estianeptine’s activation of nuclear PPAR-β/δ and PPAR-γ receptors appears to be a more direct mechanism to achieve the goal of restoring neuronal connectivity than the active ingredients of current pharmacologic therapies for depression. Tianeptine’s proposed mechanism as a plastogen is consistent with its clinical effects in promoting cognition in depressed patients with Alzheimer’s disease⁵ and in patients with bipolar disorder.⁶ The PPAR-β/δ target is validated by prior work on agonists treating animal models of neurodegenerative and autoimmune diseases of the central nervous system.¹⁸ Alzheimer’s disease has been proposed to be a form of diabetes that affects the CNS, sometimes termed type-III diabetes.”¹⁹The PPAR superfamily plays key roles in metabolic processes, and activation of PPAR-β/δ in brain by tianeptine shows promise to prevent the cognitive dysfunction associated with CNS insulin resistance. Tianeptine’s reported pro-cognitive and anxiolytic effects as well as its ability to attenuate the neuropathological effects of excessive stress responses suggest other potential uses including as a treatment for posttraumatic stress disorder (PTSD), as well as for preventing neurocognitive dysfunction associated with corticosteroid use.

References

Clinical Trials.gov I.D. NCT05686408
Sullivan, GM et al. June 1, 2023. Poster presentation at the American Society of Clinical Psychopharmacology, Miami, FL. https://www.tonixpharma.com/wp-content/uploads/2023/06/ASCP-Poster-2023-A-Randomized-Placebo-Controlled-Multicenter-Trial-of-Monotherapy-with-TNX-601-ER.pdf
Samuels et al., Neuropsychopharmacology. 2017, 42(10):2052-2063
McEwen, B. S., et al. Mol. Psychiatry 2010, 15 (3), 237–249
Duman RS, et al. Nat Med. 2016 22(3):238-49.
García-Alberca JM, et al. J Alzheimer’s Dis 2022, 88 (2), 707-720.
Kauer-Sant’Anna M, et al. J Psychopharmacol 2019, 33 (4), 502-510.
Barroso et al., Biochim Biophys Acta. 2013. 1832:1241–1248
Lauhan, R., et al. Psychosomatics 2018, 59 (6), 547–53.
Haute Authorite de Sante; Transparency Committee Opinion. Stablon 12.5 Mg, Coated Tablet, Re- Assessment of Actual Benefit at the Request of the Transparency Committee. December 5, 2012.
Emsley, R., et al. J. Clin. Psychiatry 2018, 79 (4)
Bonierbale M, et al. Curr Med Res Opin 2003, 19(2):114-124.
Guelfi, J. D., et al. Neuropsychobiology 1989, 22 (1), 41–48.
Invernizzi, G. et al., Neuropsychobiology 1994, 30 (2–3), 85–93.
Lepine, J. P., et al. Hum. Psychopharmacol. 2001, 16 (3), 219–227.
Guelfi, J. D. et al., Neuropsychobiology 1992, 25 (3), 140–148.
Lôo, H. et al., Br. J. Psychiatry. Suppl. 1992, 15, 61–65.
Kahremany S et al. Br J Pharmacol 2015, 172(3):754-70
Nguyen et al., Int J Mol Sci. 2010, 21(9):3165

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, nearing complete enrollment in a potentially registration-enabling study with topline data expected in the fourth quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 proof-of-concept study has been completed, and topline results are expected in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation being developed as a treatment for major depressive disorder (MDD), is nearing complete enrollment with topline results of a proof-of-concept study expected in the fourth quarter of 2023. TNX-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. TNX-1900 (intranasal potentiated oxytocin), in development for chronic migraine, has completed enrollment with topline data expected in the fourth quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the third quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, classes of broad-spectrum small molecule oral antivirals.

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

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

Forward Looking Statements

Investor Contact

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

Peter Vozzo
ICR Westwicke
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(443) 213-0505

Media Contact

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Zembrace® SymTouch® (sumatriptan Injection): IMPORTANT SAFETY INFORMATION

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

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

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.

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

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

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

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.

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 July 26, 2023

Tonix Pharmaceuticals (TNXP) – New Tianeptine Data In Memory and Cognition Announced

Posted on July 25, 2023July 25, 2023 by cpereira@noblefcm.com

Tuesday, July 25, 2023

Robert LeBoyer, Senior Vice President, Equity Research Analyst, Biotechnology, Noble Capital Markets, Inc.

Refer to the full report for the price target, fundamental analysis, and rating.

New Tianeptine Data In Memory and Cognition. Tonix announced new preclinical findings for tianeptine, the active molecule in two pipeline products. The two products are TNX-601 EP, in development for major depressive disorder, and TNX-4300, in preclinical development for Alzheimer’s disease, Parkinson’s disease, and mood disorders. The TNX-601 Phase 2 UPLIFT trial is expected to release results in 1Q24.

New Data Supports Previous Tianeptine Findings. As discussed in our Research Note on May 30, Tonix presented data showing that tianeptine restores neuronal sprouting and reconnections in cell culture. The data showed its two isomers have different targets, with the (S)-isomer affecting neuroplasticity, and the (R)-isomer binding to the mu-opioid receptor and causing undesirable off-target effects. A new molecule, TNX-4300 or estianeptine, was developed as a purified version containing only the (S)-isomer.

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This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).

Release – Tonix Pharmaceuticals Announces Data Supporting the Memory- and Cognition-Enhancing Effects of Racemic Tianeptine and (S)-Tianeptine, but not (R)-Tianeptine, in the In Vivo Rat Novel Object Recognition (NOR) Test

Posted on July 24, 2023July 24, 2023 by aweinsoff@channelchek.com

Research News and Market Data on TNXP

July 24, 2023 7:00am EDT

New Findings Support Development of Racemic Tianeptine and (S)-Tianeptine (Estianeptine) as First-in-Class Oral Therapies in Alzheimer’s Disease and Other Psychiatric and Neurodegenerative Conditions with Memory Deficits

(S)-Tianeptine Effects on Novel Object Recognition are Consistent with a Role for PPAR-β/δ Activation in Improving Memory and Cognition

Topline Results Expected First Quarter 2024 from the Currently Enrolling Potentially Pivotal Phase 2 UPLIFT Study of TNX-601 ER (Racemic Tianeptine) in Major Depressive Disorder

CHATHAM, N.J., July 24, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company, today announced data supporting the memory- and cognition-enhancing effects of two Tonix drug candidates, TNX-601 ER (tianeptine hemioxalate extended release) and TNX-4300 (estianeptine), the single (S)-isomer of tianeptine. TNX-601 ER is being tested in the potentially pivotal Phase 2 UPLIFT¹ trial for the treatment of major depressive disorder (MDD), with topline results expected in the first quarter of 2024. TNX-4300 is in preclinical development for mood disorders, Alzheimer’s disease and Parkinson’s disease.^* The findings reported today show that tianeptine and estianeptine improve memory and cognition as measured in the rat Novel Object Recognition (NOR) test. The finding that estianeptine is responsible for improving memory and cognition suggests a role for PPAR-β/δ activation in memory.

Tianeptine is an antidepressant that has been marketed outside the U.S. for more than 30 years. Tianeptine is also a racemic drug composed of a 1:1 mixture of two mirror-image isomers. Tonix recently reported that the (S)-isomer (estianeptine) is responsible for its positive effects on neuroplasticity in cell culture, while the (R)-isomer is responsible for racemic tianeptine’s off-target activity on the µ-opioid receptor.^2,3 Tonix also recently reported that estianeptine activates peroxisome proliferator-activated receptors PPAR-β/δ and PPAR-γ. These activities on molecular targets in neurons and glia in the brain are believed to relate to tianeptine’s ability to restore connectivity between neurons that atrophy in conditions of stress or depression in animal models.⁴ Tianeptine’s mechanism is distinct from traditional antidepressants that alter the level or activity of serotonin, norepinephrine, and dopamine neurotransmitters, which are believed to indirectly induce neurons to make new connections.⁵

“The memory- and cognition-enhancing effects of racemic tianeptine and estianeptine seen in the NOR test are consistent with human clinical studies in which racemic tianeptine treatment improved cognition and memory in patients with Alzheimer’s disease and depression⁶ and in patients with bipolar disorder,⁷” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “We recently reported that estianeptine induces neuroplasticity in cell culture.² The new findings indicate that estianeptine also improves memory and cognition in the in vivo rat NOR test. We believe that together these findings support the development of tianeptine and estianeptine in psychiatric and neurodegenerative diseases. Tianeptine’s ability to restore atrophied neuronal connections in animals² suggests the potential to achieve durable outcomes.”

“The rat NOR test is an experimental tool to assess drug effects on memory and evaluate their potential as treatments for neurodegenerative conditions like Alzheimer’s disease,” said Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals. “Since the main initial clinical feature in Alzheimer’s disease is impairment in newly learned facts or memories, improving learning and memory are important properties of potential new therapeutics. The specific type of learning and recognition memory measured by the NOR is believed to be relevant to the neurocircuitry impaired in Alzheimer’s disease.”

Dr. Sullivan continued, “Our ongoing clinical studies in major depression on TNX-601 ER, which contains racemic tianeptine, are expected to inform and potentially accelerate the development of TNX-4300 which contains the single isomer, estianeptine. We believe that estianeptine bypasses the synapse and activates intracellular PPAR-β/δ and PPAR-γ targets. The finding that estianeptine is responsible for tianeptine’s ability to improve memory and cognition in the NOR test implicates PPAR-β/δ activation specifically as a molecular target. This finding is consistent with the impaired memory of mice lacking the PPAR-β/δ gene.”⁸

In depression, estianeptine is believed to act on PPAR-β/δ and PPAR-γ targets in the nucleus to enhance genetic transactivation involved in restoring hippocampal neuroplasticity and neurogenesis. These findings also have applicability to neurodegenerative diseases in which neuronal connections are atrophied.² The reported PPAR mechanism has potential relevance to why tianeptine is not associated with sexual dysfunction, weight gain or several other treatment-limiting toxicities associated with the antidepressants currently marketed in the U.S. for long-term use. However, tianeptine has other potential side effects that are described in its labeling outside the U.S. where it is marketed as a prescription drug.

Tonix owns worldwide rights to the novel salt, racemic tianeptine hemioxalate and to the proprietary extended-release formulation employed in TNX-601 ER that allows once daily dosing. TNX-601 ER is currently being studied in the Phase 2 UPLIFT trial, which is targeting enrollment of approximately 300 patients at about 30 U.S. clinical sites. Tonix has also filed patents claiming single (S)-isomer estianeptine, the active ingredient in TNX-4300, which is devoid of activity on the µ-opioid receptor. TNX-4300 is currently in preclinical development for depression, bipolar disorder, Alzheimer’s disease, and Parkinson’s disease.

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

^*TNX-601 ER and TNX-4300 are investigational new drugs and are not approved for any indication. TNX-601 ER is being developed under an IND. TNX-4300 is at the pre-IND stage of development.

About Tianeptine

Racemic tianeptine sodium (amorphous) immediate release (dosed 3 times daily) was first marketed for depression in France in 1989 and has been available for decades in Europe, Russia, Asia, and Latin America for the treatment of depression. Tianeptine sodium has an established tolerability profile from decades of use in these jurisdictions. Currently no tianeptine-containing product is approved in the U.S. and no extended-release once-daily tianeptine product is approved in any jurisdiction. In animal models, tianeptine restores dendritic arborization of pyramidal neurons in the CA3 region of hippocampus and in the dentate gyrus region promotes new neuron formation and integration into hippocampal networks.⁴ Tianeptine’s enhancement of neuroplasticity in animal models of stress is believed to be mediated by activation of PPAR isoforms PPAR-β/δ and PPAR-γ, which is mechanistically distinct from traditional monoaminergic antidepressants marketed in the U.S. and contributes to its potential for clinical indications beyond depression and stress disorders. Tianeptine and its MC5 metabolite are also weak µ-opioid receptor (MOR) agonists that present a potential abuse liability if illicitly misused in large quantities.^3,9 In cases where tianeptine has been abused, the dose has been approximately 8-80 times the therapeutic dose in depression on a daily basis.⁹ In patients who were prescribed tianeptine for depression, the French Transparency Committee found an incidence of misuse of approximately 1 case per 1,000 patients treated⁹ suggesting low abuse liability when used at the antidepressant dose in patients prescribed tianeptine for depression. Clinical trials have shown that cessation of a therapeutic course of tianeptine does not appear to result in dependence or withdrawal symptoms following 6-weeks^11-15, 3-months,¹⁶ or 12-months¹⁷ of treatment. Estianeptine is believed to mimic naturally occurring polyunsaturated fatty acid ligands in low affinity interactions with PPAR-β/δ and PPAR-γ. Estianeptine’s activation of nuclear PPAR-β/δ and PPAR-γ receptors appears to be a more direct mechanism to achieve the goal of restoring neuronal connectivity than the active ingredients of current pharmacologic therapies for depression. Tianeptine’s proposed mechanism as a plastogen is consistent with its clinical effects in promoting cognition in depressed patients with Alzheimer’s disease⁵ and in patients with bipolar disorder.⁶ The PPAR-β/δ target is validated by prior work on agonists treating animal models of neurodegenerative and autoimmune diseases of the central nervous system.¹⁸ Alzheimer’s disease has been proposed to be a form of diabetes that affects the CNS, sometimes termed “type-III diabetes.”¹⁹The PPAR superfamily plays key roles in metabolic processes, and activation of PPAR-β/δ in brain by tianeptine shows promise to prevent the cognitive dysfunction associated with CNS insulin resistance. Tianeptine’s reported pro-cognitive and anxiolytic effects as well as its ability to attenuate the neuropathological effects of excessive stress responses suggest other potential uses including as a treatment for posttraumatic stress disorder (PTSD), as well as for preventing neurocognitive dysfunction associated with corticosteroid use.

About the Novel Object Recognition Test (NOR)

NOR is one of several cognitive tests that engage working memory and is considered a model for testing therapeutics or co-factors for Alzheimer’s disease.²⁰ The NOR task depends on the accurate comparison of novel information with recently stored memories. Among animal behavioral models for assessing cognitive functioning, the NOR test measures a specific form of recognition memory without assumptions about drug mechanism. The NOR is based on the spontaneous behavior of rodents without the need for external motivation, reward, or punishment. Impairments of NOR are seen in many animal models, including mice that overexpress the amyloid protein associated with Alzheimer’s disease.²¹ The NOR tests on tianeptine and estianeptine were performed by a third-party contract research organization. In the NOR test, rats were assessed for cognitive ability in a test apparatus comprising an open-field arena and were scored by an observer blind to treatments. The positive control for a drug effect was the acetylcholinesterase inhibitor medication galantamine, which is the active ingredient of Razadyne^®, approved by the U.S. Food and Drug administration as a treatment for Alzheimer’s disease. On Days 1 and 2, rats were allowed to freely explore the empty arena for a 10-minute habituation period. On Day 3, rats were administered saline, galantamine or test article (racemic tianeptine or estianeptine) and following the pretreatment time of 60 min, rats were then placed into the test arena in the presence of two identical objects. The time spent actively exploring the objects during a 3-minute training (T1) session was recorded. Each rat was returned to its home cage following training. After 48 hours, the rats were administered saline, galantamine or test article again, and, after 60 min, they were placed into the test arena in the presence of two objects: one familiar and one novel. The times spent exploring each object were recorded for 5 minutes in the testing session (T2). The outcome measure known as the Recognition Index was employed in these studies, defined as the ratio of the time spent exploring the novel object over the total time spent exploring both objects. These results are being prepared for presentation at a scientific meeting and for publication.

References

Clinical Trials.gov I.D. NCT05686408
Sullivan, GM et al. June 1, 2023. Poster presentation at the American Society of Clinical Psychopharmacology, Miami, FL. https://www.tonixpharma.com/wp-content/uploads/2023/06/ASCP-Poster-2023-A-Randomized-Placebo-Controlled-Multicenter-Trial-of-Monotherapy-with-TNX-601-ER.pdf
Samuels et al., Neuropsychopharmacology. 2017, 42(10):2052-2063
McEwen, B. S., et al. Mol. Psychiatry 2010, 15 (3), 237–249
Duman RS, et al. Nat Med. 2016 22(3):238-49.
García-Alberca JM, et al. J Alzheimer’s Dis 2022, 88 (2), 707-720.
Kauer-Sant’Anna M, et al. J Psychopharmacol 2019, 33 (4), 502-510.
Barroso et al., Biochim Biophys Acta. 2013. 1832:1241–1248
Lauhan, R., et al. Psychosomatics 2018, 59 (6), 547–53.
Haute Authorite de Sante; Transparency Committee Opinion. Stablon 12.5 Mg, Coated Tablet, Re- Assessment of Actual Benefit at the Request of the Transparency Committee. December 5, 2012.
Emsley, R., et al. J. Clin. Psychiatry 2018, 79 (4)
Bonierbale M, et al. Curr Med Res Opin 2003, 19(2):114-124.
Guelfi, J. D., et al. Neuropsychobiology 1989, 22 (1), 41–48.
Invernizzi, G. et al., Neuropsychobiology 1994, 30 (2–3), 85–93.
Lepine, J. P., et al. Hum. Psychopharmacol. 2001, 16 (3), 219–227.
Guelfi, J. D. et al., Neuropsychobiology 1992, 25 (3), 140–148.
Lôo, H. et al., Br. J. Psychiatry. Suppl. 1992, 15, 61–65.
Kahremany S et al. Br J Pharmacol 2015, 172(3):754-70
Nguyen et al., Int J Mol Sci. 2010, 21(9):3165
Bengoetxea X, et al. Front Biosci (Schol Ed). 2015, 7(1):10-29.
Romberg C, et al., Brain. 2012, 135(Pt 7):2103-14.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra^® (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with topline data expected in the first quarter of 2024. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 study has been completed, and topline results are expected in the third quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation being developed as a treatment for major depressive disorder (MDD), is also currently enrolling with topline results expected in the first quarter of 2024. TNX-4300 (estianeptine) is a small molecule oral therapeutic in preclinical development to treat MDD, Alzheimer’s disease and Parkinson’s disease. TNX-1900 (intranasal potentiated oxytocin), in development for chronic migraine, is currently enrolling with topline data expected in the fourth quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the third quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, classes of broad-spectrum small molecule oral antivirals.

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

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

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

Forward Looking Statements

Investor Contact

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

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

Media Contact

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

Zembrace^® SymTouch^® (sumatriptan Injection): IMPORTANT SAFETY INFORMATION

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

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

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.

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

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

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

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.

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 July 24, 2023

TONIX PHARMACEUTICALS HOLDING CORP. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (In Thousands, Except Share and Per Share Amounts) (unaudited)
	Three Months Ended June 30,						Six Months Ended June 30,
	2023			2022			2023			2022
COSTS AND EXPENSES:
Research and development	$	21,976		$	16,579		$	48,487		$	35,001
General and administrative		7,026			6,757			14,417			14,771
		29,002			23,336			62,904			49,772

Operating loss		(29,002	)		(23,336	)		(62,904	)		(49,772	)

Interest and other income, net		646			196			1,543			215

Net loss		(28,356	)		(23,140	)		(61,361	)		(49,557	)

Preferred stock deemed dividend		—			4,255			—			4,255

Net loss available to common stockholders	$	(28,356	)	$	(27,395	)	$	(61,361	)	$	(53,812	)

Net loss per common share, basic and diluted	$	(2.68	)	$	(7.64	)	$	(5.88	)	$	(17.28	)

Weighted average common shares outstanding, basic and diluted		10,587,096			3,584,699			10,428,678			3,113,965
See the accompanying notes to the condensed consolidated financial statements

TONIX PHARMACEUTICALS HOLDING CORP. CONDENSED CONSOLIDATED BALANCE SHEETS (In Thousands) (Unaudited)
	June 30, 2023		December 31, 2022¹
Assets
Cash and cash equivalents	$	25,617	$	120,229
Inventory		13,700		–
Prepaid expenses and other		12,012		10,548
Total current assets		51,329		130,777
Other non-current assets		108,407		94,913
Total assets	$	159,736	$	225,690

Liabilities and stockholders’ equity
Total liabilities	$	19,273	$	18,508
Stockholders’ equity		140,463		207,182
Total liabilities and stockholders’ equity	$	159,736	$	225,690

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