Tag: Biopharmaceutical

Research News and Market Data on TNXP

November 02, 2023 8:00am EDTDownload as PDF

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

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

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

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

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

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

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

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

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

About Project NextGen

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

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

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

Tonix Pharmaceuticals Holding Corp.^*

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

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

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

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

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

Forward Looking Statements

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

Investor Contact

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

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

Media Contact

Ben Shannon
ICR Westwicke
ben.shannon@westwicke.com
443-213-0495

Source: Tonix Pharmaceuticals Holding Corp.

Released November 2, 2023

Research News and Market Data on TNXP

October 31, 2023 5:00pm EDT

The study did not achieve statistical significance on the primary endpoint

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

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

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

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

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

About the Phase 2 UPLIFT Study

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

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

About Major Depressive Disorder (Depression)

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

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

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

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

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

About TNX-601 ER

TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a novel oral formulation of tianeptine designed for once-daily daytime dosing in development as a candidate for the treatment of MDD. Tianeptine sodium (amorphous) immediate release (dosed 3 times daily) was first marketed for depression in France in 1989 and has been available for decades in Europe, Russia, Asia, and Latin America for the treatment of depression. Tianeptine sodium has an established safety profile from decades of use in these jurisdictions. Currently no tianeptine-containing product is approved in the U.S. and no extended-release tianeptine product is approved in any jurisdiction. Tonix discovered a novel oxalate salt of tianeptine that may provide improved stability, consistency, and manufacturability compared to known salt forms of tianeptine.

Tonix Pharmaceuticals Holding Corp.^*

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

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

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

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

Forward Looking Statements

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

Investor Contact

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

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

Media Contact

Ben Shannon
ICR Westwicke
ben.shannon@westwicke.com
443-213-0495

Research News and Market Data on TNXP

October 30, 2023 7:00am EDTDownload as PDF

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

TNX-1500 is currently in Phase 1 Clinical Development

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

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

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

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

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

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

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

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

Tonix Pharmaceuticals Holding Corp.^*

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

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

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

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

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

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

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

Media Contact
Ben Shannon
ICR Westwicke
ben.shannon@westwicke.com
443-213-0495

Source: Tonix Pharmaceuticals Holding Corp.

Released October 30, 2023

Research News and Market Data on TNXP

October 26, 2023 7:00am EDTDownload as PDF

Topline results expected early December 2023

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

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

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

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

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

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

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

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

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

About Migraine
Migraine is a neurological condition that typically manifests in a throbbing moderate to severe headache which lasts at least four hours, often on one side of the head and aggravated by routine physical activity. It can also be accompanied by nausea, vomiting, visual disturbances, and sensitivity to bright light and loud noises¹. Epidemiological studies indicate that globally, approximately 1.2 billion individuals suffer from migraines annually². In the U.S., approximately 39 million Americans suffer from migraines and among these individuals, approximately four million experience chronic migraines (15 or more headache days per month, at least eight of which are migraines)². The current FDA approved drugs for migraine prevention in chronic migraine include Botox^® (onabotulinumtoxinA), and the anti-CGRP/CGRP-R monoclonal antibodies Aimovig^® (erenumab), Vyepti^® (eptinezumab), Ajovy^® (fremanezumab) and Emgality^® (galcanezumab).

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

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

About TNX-1900
TNX-1900 (intranasal potentiated oxytocin) is a proprietary formulation of oxytocin in development as a candidate for prevention in chronic migraine and other conditions. In 2020, TNX-1900 was acquired from Trigemina, Inc. who had licensed the technology underlying the composition and method from Stanford University. TNX-1900 is a drug-device combination product, based on an intranasal actuator device that delivers oxytocin into the nasal cavity. Oxytocin is a naturally occurring human peptide hormone that also acts as a neurotransmitter in the brain. Oxytocin has no recognized addiction potential. It has been observed that low oxytocin levels in the body are associated with increases in migraine headache frequency, and that increased oxytocin levels are associated with fewer migraine headaches. Certain other chronic pain conditions are also associated with decreased oxytocin levels. Migraine attacks are caused, in part, by the activity of pain-sensing trigeminal neurons which, when activated, release of calcitonin gene-related peptide (CGRP) which binds to receptors on other nerve cells and starts a cascade of events that is believed to result in headache. Oxytocin, when delivered via the nasal route, concentrates in the trigeminal system¹ resulting in binding of oxytocin to receptors on neurons in the trigeminal system, inhibiting the release of CGRP and transmission of pain signals returning from the site of CGRP release². Blocking CGRP release is a distinct mechanism compared with CGRP antagonist and anti-CGRP antibody drugs, which block the binding of CGRP to its receptor. With TNX-1900, the addition of magnesium to the oxytocin formulation enhances oxytocin receptor binding³ as well as its inhibitory effects on trigeminal neurons and resultant craniofacial analgesic effects, as demonstrated in animal models⁴. Intranasal oxytocin has been shown to be well tolerated in several clinical trials in both adults and children⁵. Targeted nasal delivery results in low systemic exposure and lower risk of non-nervous system, off-target effects, which could potentially occur with systemic CGRP antagonists such as anti-CGRP antibodies⁶. For example, CGRP has roles in dilating blood vessels in response to ischemia, including in the heart. The Company believes nasally targeted delivery of oxytocin could translate into selective blockade of CGRP release from neurons in the trigeminal ganglion and not throughout the body, which could be a potential safety advantage over systemic CGRP inhibition. In addition, daily dosing is more rapidly reversible, in contrast to monthly or quarterly dosing, as is the case with anti-CGRP antibodies, giving physicians and their patients greater control. In addition to chronic migraine, TNX-1900 will be developed for treatment of episodic migraine, binge eating disorder, craniofacial pain conditions, and insulin resistance. Tonix also has a license with the University of Geneva to use TNX-1900 for the treatment of insulin resistance and related conditions.

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

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

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

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

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

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

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

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

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

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

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

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

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

Media Contact
Ben Shannon
ICR Westwicke
ben.shannon@westwicke.com
443-213-0495

Source: Tonix Pharmaceuticals Holding Corp.

Released October 26, 2023

Research News and Market Data on TNXP

October 19, 2023 7:00am EDTDownload as PDF

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

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

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

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

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

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

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

About TNX-801

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

About the Recombinant Pox Virus (RPV) Platform

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

About Mpox and Smallpox

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

Tonix Pharmaceuticals Holding Corp.

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

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

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

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

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Investor Contact

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

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

Media Contact

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

Source: Tonix Pharmaceuticals Holding Corp.

Released October 19, 2023