Tag: Tonix Pharmaceuticals

Research News and Market Data on TNXP

March 16, 2023 7:00am EDTDownload as PDF

Results from Planned Interim Analysis Expected Fourth Quarter 2023

Approximately 21 Million Adults in U.S. Suffer From a Major Depressive Episode Each Year

TNX-601 ER is a Once-Daily Tablet that is Bioequivalent to Three-Times-Daily Tianeptine Sodium Immediate Release (IR) that has been available in Europe, Asia and Latin America for More than Three Decades

Tianeptine IR is Associated with Low Incidences of Sexual Dysfunction, Sleep Disruption, Sedation, Weight Gain, and Cognitive Impairment Compared with Traditional Monoaminergic Antidepressants

TNX-601 ER is a New Chemical Entity in the U.S. and Represents a Potential Innovative Approach to Addressing Depression: Restoration of Neuroplasticity and Neurogenesis Rather than Modulation of Neurotransmitter Levels and Activity

CHATHAM, N.J., March 16, 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 Phase 2 ‘UPLIFT’ study of TNX-601 ER¹ (tianeptine hemioxalate extended-release tablets) for the treatment of major depressive disorder (MDD). The double-blind, placebo-controlled registrational-quality study has a target enrollment of 300 participants at approximately 30 sites across the U.S. Results from a planned interim analysis are expected to be released in the fourth quarter of 2023.

The proprietary once-daily formulation of TNX-601 ER was designed to be bioequivalent to the three-times-a-day formulation of tianeptine sodium (amorphous) immediate release (IR) tablets. IR tianeptine sodium has been available in Europe and many countries in Asia and Latin America for the treatment of MDD for more than three decades since being first marketed in France in 1989. No tianeptine-containing product has been approved by the U.S. Food and Drug Administration (FDA).

“Despite the availability of several classes of MDD treatments in the U.S. that directly modulate neurotransmitters and their synaptic receptors, there remains an unmet need for novel approaches,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “In animal studies, TNX-601 ER has a unique mechanism of action that restores brain neuroplasticity by exerting biological effects on neurons and glial cells that increase arborization of dendrites in critical hippocampal circuits.² In animal models, tianeptine also reverses stress-induced impairments in synaptic glutamate neurotransmission, and it restores hippocampal neurogenesis.²”

Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals said, “After a decade of development of our proprietary once-daily tianeptine formulation, it is very gratifying to enter the next stage of clinical testing required to make TNX-601 ER available to those suffering from MDD in the U.S. TNX-601 ER not only has the potential to relieve depressive symptoms, but also to improve the quality of life and resiliency for the millions of MDD sufferers. The short and long-term safety of tianeptine sodium IR has been well-established based on its clinical use outside the US.”

Dr. Sullivan added, “The efficacy of tianeptine sodium IR has repeatedly been shown to be comparable with that of either selective serotonin reuptake inhibitor (SSRI) or tricyclic antidepressants^3,4 while being associated with a lower incidence of sexual dysfunction, derangement of sleep architecture, sedation, weight gain, or cognitive impairment.^5-7 Given tianeptine’s metabolic pathway, which is independent of the hepatic cytochrome P450 system, we believe that TNX-601 ER has a reduced risk of drug-drug interactions compared to antidepressants marketed in the U.S.⁷

“MDD is a seriously disabling condition that is also often associated with suicidal behavior. Extensive animal studies have taught us that tianeptine restores the stress-induced deficits in neuroplasticity and neurogenesis. The dramatic impact of tianeptine on a brain experiencing many types of stress is best illustrated by the effects it has in restoring dendritic arborization and spine synapse remodeling of pyramidal neurons in the CA3 region of hippocampus, as well as new neuron formation and their microglia-mediated integration into neuronal networks of the hippocampal formation. With an estimated 21 million individuals suffering from a major depressive episode each year in the U.S., it’s exciting to move beyond neurotransmitter modulation and begin an era where MDD may be treated by enhancing a resilient biological phenotype of neurons and glial cells under stress.”

¹TNX-601 ER is in the Phase 2 stage of development and is not approved for any indication
²McEwen, B. S., et al. Mol. Psychiatry 2010, 15 (3), 237–249.
³Jeon, H. J., et al. .J. Clin. Psychopharmacol. 2014, 34 (2), 218–225.
⁴Emsley, R., et al. J. Clin. Psychiatry 2018, 79 (4)
⁵Bonierbale M, et al. Curr Med Res Opin 2003, 19(2):114-124.
⁶Costa e Silva, J. A., et al. Neuropsychobiology 1997, 35 (1), 24–29.
⁷Wagstaff, A. J. et al. CNS Drugs 2001, 15 (3), 231–259.

About the Phase 2 UPLIFT Study

The Phase 2 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 by mouth once-daily for 6 weeks for the treatment of MDD. It is a parallel design study with two arms,   a TNX-601 ER 39.4 mg arm and a placebo arm. A total of 300 participants will be randomized in a 1:1 ratio into the two arms across approximately 30 U.S. sites, enrolling adult patients 18-65 years old with a DSM-5 diagnosis of depression and a duration for the current major depressive episode (MDE) of at least 12 weeks. The primary efficacy endpoint is mean change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6. Key secondary efficacy endpoints include the Clinical Global Impression of Severity Scale (CGI-S) and the Sheehan Disability Scale (SDS). An interim analysis is expected to be completed after the first 50% of enrolled patients have completed the study for the purpose of potential sample size re-estimation, currently anticipated in the fourth quarter of 2023. A 24-week open-label extension study, TNX-TI-M202, is planned to receive patients completing the UPLIFT study.

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%. 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 behavior. 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.² The current FDA approved drugs for long term monotherapy treatment of MDD include selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and Auvelity® (dextromethorphan HBr-bupropion HCl).   Dextromethorphan is a direct antagonist of the NMDA-type glutamate receptor.

¹Data 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
²Rush AJ, et al. (2007) Am J. Psychiatry 163:11, pp. 1905-1917 (STAR*D Study).

About TNX-601 ER

TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a novel oral formulation of tianeptine hemioxalate designed for once-daily daytime dosing in development as a candidate for the treatment for MDD, posttraumatic stress disorder, and neurocognitive dysfunction associated with corticosteroid use. Tianeptine sodium (amorphous) immediate release (dosed 3 times daily) was first marketed for depression in France in 1989 and has been available for decades in Europe, Russia, Asia, and Latin America for the treatment of depression. Tianeptine sodium has an established safety profile from decades of use in these jurisdictions. Currently there is no tianeptine-containing product approved in the U.S. and no extended-release tianeptine product 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. Tianeptine is believed to work in depression as an indirect modulator of the glutamatergic system, without direct binding NMDA, AMPA or kainate receptors. Tianeptine reverses stress induced increases in AMPA receptor trafficking, restores hippocampal long-term potentiation and neurogenesis, and reverses the negative neuroplastic changes from stress and corticosteroid exposure. In contrast with the modulation of neurotransmitter levels and activity at synaptic receptors like traditional antidepressants, in animal models tianeptine restores dendritic arborization of pyramidal neurons in the CA3 region of hippocampus and in the dentate gyrus region promotes new neuron formation and integration into hippocampal networks.¹ Tianeptine’s enhancement of neuroplasticity in animal models of stress implies a mechanism of action involving indirect glutamatergic modulation, which makes TNX-601 ER’s properties distinct from traditional monoaminergic antidepressants in the U.S. and contributes to its potential for clinical indications beyond MDD and stress disorders. Tianeptine and its MC5 metabolite are also weak mu-opioid receptor (MOR) agonists that present a potential abuse liability if illicitly misused in large quantities (typically abused at 8-80 times the therapeutic dose on a daily basis²). In patients who were prescribed tianeptine for depression, the French Transparency Committee found an incidence of misuse of approximately 1 case per 1,000 patients treated³ suggesting low abuse liability when used at the antidepressant dose in patients prescribed tianeptine for depression. Clinical trials have shown that cessation of a therapeutic course of tianeptine does not appear to result in dependence or withdrawal symptoms following 6-weeks^4-8, 3-months⁹, or 12-months¹⁰ of treatment. The ER formulation of TNX-601 includes several potentially abuse deterrent ingredients include gel forming polymers which impede extraction. In addition, the tablet’s hardness makes it difficult to crush, cut or grind to fine particle size, which potentially hinders efforts to misuse by insufflation or intravenous routes. Tianeptine’s reported pro-cognitive and anxiolytic effects as well as its ability to attenuate the neuropathological effects of excessive stress responses suggest that it may also be used to treat posttraumatic stress disorder (PTSD), and neurocognitive dysfunction associated with corticosteroid use. TNX-601 ER is expected to have patent protection through 2037. 

¹McEwen, B. S., et al. Mol. Psychiatry 2010, 15 (3), 237–249.
²Lauhan, R., et al. Psychosomatics 2018, 59 (6), 547–53.
³Haute 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.
⁴Emsley, R., et al. J. Clin. Psychiatry 2018, 79 (4)
⁵Bonierbale M, et al. Curr Med Res Opin 2003, 19(2):114-124.
⁶Guelfi, J. D., et al. Neuropsychobiology 1989, 22 (1), 41–48.
⁷Invernizzi, G. et al., Neuropsychobiology 1994, 30 (2–3), 85–93.
⁸Lepine, J. P., et al. Hum. Psychopharmacol. 2001, 16 (3), 219–227.
⁹Guelfi, J. D. et al., Neuropsychobiology 1992, 25 (3), 140–148.
¹⁰Lôo, H. et al., Br. J. Psychiatry. Suppl. 1992, No. 15, 61–65.

About Tonix Pharmaceuticals Holding Corp.*

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition, for which a Phase 2 study was initiated in the third quarter of 2022. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is currently enrolling with interim data expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation of tianeptine being developed as a treatment for major depressive disorder (MDD), is also currently enrolling with interim data expected in the fourth quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the second quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft 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 quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox, for which a Phase 1 study is expected to be initiated in the second half of 2023. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease portfolio also includes TNX-3900, a class of broad-spectrum small molecule oral antivirals.

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

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

Forward Looking Statements

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

Contacts

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

Olipriya Das, Ph.D. (media)
Russo Partners
Olipriya.Das@russopartnersllc.com
(646) 942-5588

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

Source: Tonix Pharmaceuticals Holding Corp.

Released March 16, 2023

Research News and Market Data on TNXP

February 22, 2023 7:00am EST

Symptoms of Long COVID, Like Multi-Site Pain, Fatigue and Insomnia, are the Hallmarks of Chronic Pain Syndromes Like Fibromyalgia and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

Event Co-Hosted by the Biotechnology Innovation Organization (BIO) and Solve M.E., an Advocacy Group for CFS/ME

CHATHAM, N.J., Feb. 22, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that during a virtual event co-hosted by BIO and Solve M.E. titled, “Long COVID: What Will it Take to Accelerate Therapeutic Progress?”, Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals, presented emerging research describing the role of infections in triggering fibromyalgia or CFS/ME and other fibromyalgia-type illnesses, and discussed Tonix’s ongoing Phase 2 study of TNX-102 SL in fibromyalgia-type Long COVID. Symptoms of Long COVID, like multi-site pain, fatigue and insomnia, are the hallmarks of chronic pain syndromes like fibromyalgia and CFS/ME.

“The U.S. Department of Health and Human Services National Research Action Plan on Long COVID¹, 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 sensitization,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Furthermore, a recent survey² found comparable pain, fatigue and function between Long COVID, fibromyalgia and CFS/ME.”

Enrollment continues in the Phase 2 PREVAIL study of TNX-102 SL as a potential treatment for patients with Long COVID syndrome whose symptoms overlap with fibromyalgia. PREVAIL is a randomized, double-blind, placebo-controlled study in the U.S. that is expected to enroll approximately 470 patients. One unblinded interim analysis is anticipated based on the first 50% of randomized participants.

Dr. Lederman’s presentation is available under the Presentations tab of the Tonix website at www.tonixpharma.com.

¹Department 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.

²Haider S, et al. Pain. 2023;164(2):385-401.

About Solve M.E.

Solve M.E. is a non-profit organization that serves as a catalyst for critical research into diagnostics, treatments, and cures for CFS/ME, Long COVID and other post-infection conditions.

About BIO

BIO is the world’s largest advocacy association representing member companies, state biotechnology groups, academic and research institutions, and related organizations across the United States and in 30+ countries.

About Long COVID or Post-Acute Sequelae of SARS-CoV-2 (PASC)

Although most people recover from COVID-19 within weeks of the acute illness, a substantial portion develop a chronic syndrome called Long COVID. These individuals experience a constellation of 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 virus from their systems. The symptoms of Long COVID can include fatigue, sleep disorders, pain, fevers, shortness of breath, cognitive impairment described as “brain fog” or memory disturbance, gastrointestinal symptoms, anxiety, and depression. Long COVID can persist for months and can range in severity from mild to incapacitating. Several cohort studies have reported that persistence of symptoms following SARS-CoV-2 infection occurs in approximately 19% of people who recover from COVID.¹ While typically associated with moderate or severe COVID-19, Long COVID can occur after mild COVID-19 or even after asymptomatic SARS-CoV-2 infection. Patients with Long COVID are sometimes referred to as “long-haulers”. Long COVID is a chronic disabling condition that is expected to result in a significant global health and economic burden.² 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 2021.³ While the vaccines available in the U.S. 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.”

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022. 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 second quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is being studied in a potential pivotal Phase 2 study that initiated enrollment in the first quarter of 2023 and for which interim data is expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft 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 quarter of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801; a next-generation vaccine to prevent COVID-19, TNX-1850; a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600; and humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800; and a class of broad-spectrum small molecule oral antivirals, TNX-3900. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in the second half of 2023.

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

¹https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/20220622.htm – Accessed Feb. 21, 2023

²Briggs, Andrew, and Anna Vassall. “Count the cost of disability caused by COVID-19.” (2021): 502-505.

³The 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.

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, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Contacts

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

Olipriya Das, Ph.D. (media)
Russo Partners
Olipriya.Das@russopartnersllc.com
(646) 942-5588

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

Source: Tonix Pharmaceuticals Holding Corp.

Released February 22, 2023

Research News and Market Data on TNXP

February 16, 2023 7:00am EST

Co-Hosted by the Biotechnology Innovation Organization (BIO) and Solve M.E., an Advocacy Group for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

CHATHAM, N.J., Feb. 16, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals, will present at a virtual event co-hosted by BIO and Solve M.E. titled, “Long COVID: What Will it Take to Accelerate Therapeutic Progress?”, which is being held February 21, 2023 from 1:00 – 4:30 p.m. ET. Dr. Lederman will present during the session “Clinical Studies and Emerging Therapeutic Approaches”, which begins at approximately 3:10 p.m. ET.

According to Solve M.E., the session will cover emerging research in Long COVID, as well as the existing body of data in other post-infection diseases like CFS/ME. The session will feature perspectives from a host of participants, including government, academic, and industry researchers, patient groups, funding sources, and policymakers.

Registration is open to the general public and is required in advance through the BIO website found here. The presentation will be available after the event, under the Presentations tab of the Tonix website at www.tonixpharma.com.

About Solve M.E.

Solve M.E. is a non-profit organization that serves as a catalyst for critical research into diagnostics, treatments, and cures for CFS/ME, Long COVID and other post-infection conditions.

About BIO

BIO is the world’s largest advocacy association representing member companies, state biotechnology groups, academic and research institutions, and related organizations across the United States and in 30+ countries.

About Long COVID or Post-Acute Sequelae of SARS-CoV-2 (PASC)

Although most people recover from COVID-19 within weeks of the acute illness, a substantial portion develop a chronic syndrome called Long COVID. These individuals experience a constellation of 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 virus from their systems. The symptoms of Long COVID can include fatigue, sleep disorders, pain, fevers, shortness of breath, cognitive impairment described as “brain fog” or memory disturbance, gastrointestinal symptoms, anxiety, and depression. Long COVID can persist for months and can range in severity from mild to incapacitating. Several cohort studies have reported that persistence of symptoms following SARS-CoV-2 infection occurs in more than 30% of patients.¹ While typically associated with moderate or severe COVID-19, Long COVID can occur after mild COVID-19 or even after asymptomatic SARS-CoV-2 infection. Patients with Long COVID are sometimes referred to as “long-haulers”. Long COVID is a chronic disabling condition that is expected to result in a significant global health and economic burden.² 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 last December.³ While the vaccines available in the U.S. 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.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022. 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 second quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is being studied in a potential pivotal Phase 2 study that initiated enrollment in the first quarter of 2023 and for which interim data is expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft 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 quarter of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801; a next-generation vaccine to prevent COVID-19, TNX-1850; a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600; and humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800; and a class of broad-spectrum small molecule oral antivirals, TNX-3900. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in the second half of 2023.

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

¹Nalbandian, Ani, et al. “Post-acute COVID-19 syndrome.” Nature Medicine (2021): 1-15.

²Briggs, Andrew, and Anna Vassall. “Count the cost of disability caused by COVID-19.” (2021): 502-505.

³The 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.

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, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Contacts

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

Olipriya Das, Ph.D. (media)
Russo Partners
Olipriya.Das@russopartnersllc.com
(646) 942-5588

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

Source: Tonix Pharmaceuticals Holding Corp.

Released February 16, 2023

Research News and Market Data on TNXP

February 13, 2023 7:00am EST

Immunocompromised Individuals, Including Organ Transplant Recipients, Are at Increased Risk of Severe COVID-19 and Poor Clinical Outcomes

SARS-CoV-2 has Mutated to Evade the Formerly EUA-Approved Monoclonal Antibody Therapies and Preventatives

CHATHAM, N.J., Feb. 13, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, today announced that it has exercised an option to obtain an exclusive license from Columbia University for the development of a portfolio of fully human (TNX-3600) and murine (TNX-4100) monoclonal antibodies (mAbs) for the treatment or prophylaxis of SARS-CoV-2 infection. SARS-CoV-2 is the cause of COVID-19. The licensed mAbs were developed as part of a research collaboration and option agreement between Tonix and Columbia University, originally announced in 2020.

“The licensing of these mAbs strengthens our expanding pipeline of next-generation therapeutics to treat and prevent COVID-19,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Immunocompromised individuals, including organ transplant recipients, are at increased risk of severe COVID-19 and poor clinical outcomes¹. We believe there is a need for second-generation mAb treatments and prophylactics^2,3 to protect this population.”

Although five mAb products containing seven distinct mAbs received emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA) for either treatment or prophylaxis of COVID-19, none remain useful or available since January 26, 2023, when the FDA announced that the last remaining mAb, Evusheld®, is no longer authorized⁴. Previously, either the National Institutes of Health COVID Treatment Guidelines Panel or FDA had removed recommendations or approvals for the other mAbs^5,6.

Ilya Trakht, Ph.D., Associate Research Scientist at Columbia University Vagelos College of Physicians and Surgeons said, “We are excited to work with Tonix because of its commitment to developing therapeutics for COVID-19. Our antibody platform has proven robust and capable of rapidly making therapeutically relevant fully human mAbs to SARS-CoV-2. We have also generated murine mAbs, which represent a new approach. Murine mAbs have the potential for neutralizing a broader spectrum of SARS-CoV-2 variants and may be harder for SARS-CoV-2 to evade as we face a multitude of variants.”

To date, the formerly EUA-approved products were derived from the blood of COVID-convalescent patients or humanized mice^7-9. The fully human mAbs generated by Columbia University, TNX-3600, have been isolated using a proprietary system involving a human hybridoma fusion partner.

The Company believes that murine mAbs, such as TNX-4100, have the potential to generate high affinity antibodies that recognize different epitopes on the SARS-CoV-2 spike protein. This is because mice have a different repertoire of antibodies than humans and the technology for generating antibodies optimizes the selection of appropriate B cells by the timing of immunization, harvesting approach and screening platform.

Dr. Lederman added, “The potential therapeutic antibodies licensed from Columbia University leverage our expanding internal development and manufacturing capabilities for biologics. These fully human and murine mAbs and their humanized counterparts build on a base of knowledge from a distinct murine mAb platform in development, TNX-3800, from which we have licensed three humanized mAbs from Curia Global.”

About TNX-3600

TNX-3600 are fully human mAbs generated from SARS-CoV-2+ asymptomatic individuals or COVID-19 convalescent patients, on which Tonix is collaborating with Columbia University. Given the unpredictable trajectory of the SARS-CoV-2 virus and new variants, we seek to contribute to a broad set of mAbs that can be scaled up quickly and potentially combined with other mAbs for the treatment or prophylaxis of SARS-CoV-2 infection.

About TNX-4100

TNX-4100 are murine mAbs and their humanized counterparts generated from mice immunized with SARS-CoV-2 spike protein, on which Tonix is collaborating with Columbia University. Since mice have a different repertoire of antibodies than humans, murine mAbs have the potential for neutralizing a broader spectrum of SARS-CoV-2 variants than fully human mAbs.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022. 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 second quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is being studied in a potential pivotal Phase 2 study that initiated enrollment in the first quarter of 2023 and for which interim data is expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft 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 quarter of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801; a next-generation vaccine to prevent COVID-19, TNX-1850; a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600; and humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800; and a class of broad-spectrum small molecule oral antivirals, TNX-3900. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in the second half of 2023.

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

¹Haidar G, Mellors JW. Improving the Outcomes of Immunocompromised Patients With Coronavirus Disease 2019. Clin Infect Dis. 2021;73(6):e1397-e1401. Doi:10.1093/cid/ciab397

²Madison Muller, M. November 16, 2022 Bloomberg. “Doctors Are Running Out of Antibody Drugs to Treat Covid as Virus Mutates.” www.bloomberg.com/news/articles/2022-11-16/covid-s-mutations-leave-doctors-with-far-fewer-antibody-drugs-to-treat-virus?

³Callaway, E. Oct 28 2022. Nature (News). COVID ‘variant soup’ is making winter surges hard to predict: Descendants of Omicron are proliferating worldwide — and the same mutations are coming up again and again. www.nature.com/articles/d41586-022-03445-6

⁴https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-evusheld-not-currently-authorized-emergency-use-us – Accessed Feb 7, 2023

⁵https://www.covid19treatmentguidelines.nih.gov/therapies/anti-sars-cov-2-antibody-products/anti-sars-cov-2-monoclonal-antibodies/ – Accessed Nov 3, 2022

⁶“FDA Updates on Bebtelovimab” – “This information shows that bebtelovimab is not expected to neutralize Omicron subvariants BQ.1 and BQ.1.1.” – www.fda.gov/drugs/drug-safety-and-availability/fda-updates-bebtelovimab– Accessed Nov 4, 2022

⁷Hansen J et al. Science. 2020 Aug 21;369(6506):1010-1014.  Doi: 10.1126/science.abd0827

⁸Asdaq, S.M.B. et al. A Patent Review on the Therapeutic Application of Monoclonal Antibodies in COVID-19. Int. J. Mol. Sci. 2021, 22, 11953. https://doi.org/10.3390/ijms222111953

⁹Vir isolated sotrovimab from the blood of a SARS-CoV-1 patient

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, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

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

Olipriya Das, Ph.D. (media)
Russo Partners
Olipriya.Das@russopartnersllc.com
(646) 942-5588

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

Source: Tonix Pharmaceuticals Holding Corp.

Released February 13, 2023

Research News and Market Data on TNXP

February 09, 2023 7:00am EST

Preclinical data demonstrate the efficacy of TNX‐801 vaccination against monkeypox virus challenge in an animal model

Phase 1 trial with TNX-801 for the prevention of monkeypox and smallpox is expected to start in the second half of 2023

CHATHAM, N.J, Feb. 09, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced the publication of a paper entitled, “Single Dose of Recombinant Chimeric Horsepox Virus (TNX‐801) Vaccination Protects Macaques from Lethal Monkeypox Challenge,” in the journal Viruses. The publication demonstrates that a single dose vaccination with TNX‐801 was effective at protecting non-human primates from infection with monkeypox virus. The article can be accessed online at https://www.mdpi.com/1999-4915/15/2/356.

“The global monkeypox outbreak that started in the spring of 2022 reinforced the importance of protecting the population using live virus vaccines,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Consequently, there is a need for an effective and safer, single dose, live replicating vaccine against monkeypox virus. Given the encouraging preclinical data to date, one potential approach is to use a live virus vaccine based on horsepox, such as TNX-801.”

David Evans, Ph.D., FCAHS, Professor and former Vice-Dean (Research) Faculty of Medicine and Dentistry at the University of Alberta and an investigator in the study and author of the publication, said, “It is often forgotten that vaccines don’t always produce sterilizing immunity and so it’s very exciting to be able to report that a horsepox-based vaccine works so well in such a challenging infection model.”

The publication describes data from animals in which eight out of eight vaccinated with TNX-801 were fully protected with sterilizing immunity from a challenge with intra-tracheal monkeypox (central African, or Congo Basin, clade). The vaccinations with TNX-801 were well tolerated as indicated by the lack of any overt clinical disease. These data show that the immunity generated by TNX‐801 was able to provide protection against a lethal challenge with monkeypox virus and is the first study to demonstrate the efficacy of TNX‐801 vaccination against monkeypox virus challenge in a non‐human primate model. Synthetic horsepox virus is the basis for the Company’s TNX-801 vaccine in development to protect against monkeypox and smallpox and for the Company’s Recombinant Pox Virus (RPV) platform to protect against other pathogens, including SARS-CoV-2.

About TNX-801 and TNX-1850

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 monkeypox and smallpox. Tonix is also developing TNX-1850 (horsepox-based live virus vaccine) for the prevention of COVID-19. TNX-1850 is designed to express the spike protein from the BA.2 variant of SARS-CoV-2. Tonix has previously reported positive data from a SARS-CoV-2 challenge study in non-human primates in which animals were vaccinated with TNX-1800, a horsepox-based vaccine expressing spike protein from the Wuhan strain⁴. Tonix’s TNX-801 is based on the sequence of the 1976 natural isolate Mongolian horsepox clone MNR-763.² 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 1798^5-7. For example, recent studies^8,9 have shown approximately 99.7% colinear identity between TNX-801 and the circa 1860 U.S. smallpox vaccine VK05.¹⁰ The small plaque size in culture of TNX-801 appears identical to the U.S. Centers for Disease Control publication of the natural isolate¹¹. 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 horses⁷. 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’¹². Equination and vaccination were practiced side-by-side in Europe^12,13.

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. 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. The “take” is a measure of functional T cell immunity validated by the eradication of smallpox, a respiratory-transmitted disease caused by variola.

About Monkeypox and Smallpox

Monkeypox¹⁴ and smallpox¹⁵ are diseases in humans caused by the monkeypox and smallpox (or variola) viruses, respectively. Monkeypox and variola are closely related orthopox viruses. Vaccination against smallpox with live virus vaccines based on horsepox or vaccinia protects against monkeypox. After routine smallpox vaccination was stopped in about 1970, monkeypox has become a growing problem in Africa. Since May of 2022, approximately 30,000 cases have been identified in the United States.^16,17 There are two distinct clades of the monkeypox 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%.¹⁸ In November, 2022, the WHO began using a new preferred term “mpox” as a synonym for monkeypox.¹⁹ Smallpox is considered eradicated, but there are concerns about malicious reintroduction.

Tonix Pharmaceuticals Holding Corp.¹

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022. 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 second quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is being studied in a potential pivotal Phase 2 study that initiated enrollment in the first quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft 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 quarter of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801, a next-generation vaccine to prevent COVID-19, TNX-1850, a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600, and humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800, recently licensed from Curia. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in the second half of 2023.

¹All of Tonix’s product candidates are investigational new drugs or biologics and have 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
⁴Tonix Press Release March 16, 202a https://ir.tonixpharma.com/news-events/press-releases/detail/1255/tonix-pharmaceuticals-reports-positive-covid-19-vaccine
⁵Schrick L et al. (2017) N Engl J Med. 377:1491.
⁶Qin et al. (2015) J. Virol. 89:1809.
⁷Jenner 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.
⁸Brinkmann A et al, Genome Biology (2020) 21:286 https://doi.org/10.1186/s13059-020-02202-0
⁹Duggan A et al. Genome Biology (2020) 21:175 https://doi.org/10.1186/s13059-020-02079-z
¹⁰Tonix press release. Dec 4, 2020 https://ir.tonixpharma.com/news-events/press-releases/detail/1236/vaccine-genome-researchers-report-99-7-colinear-identity
¹¹Trindale GS et al. (2016) Viruses (12). Pii: E328. PMID:27973399
¹²Esparza E, et al (2017) Vaccine. 35(52):7222-7230.
¹³Esparza J et al. (2020) Vaccine.; 38(30):4773-4779.
¹⁴www.cdc.gov/poxvirus/monkeypox/about.html
¹⁵www.cdc.gov/smallpox/research/
¹⁶Mandavilli, A. The New York Times. May 26, 2020. “Who is protected against monkeypox”
¹⁷ www.cdc.gov/poxvirus/monkeypox/response/2022/us-map.html – Accessed Feb 8, 2023
¹⁸ https://www.who.int/news-room/fact-sheets/detail/monkeypox#:~:text=There%20are%20two%20distinct%20genetic,thought%20to%20be%20more%20transmissible – Accessed Feb 8, 2023
¹⁹ https://www.who.int/news/item/28-11-2022-who-recommends-new-name-for-monkeypox-disease – Accessed Feb 8, 2023

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, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Contacts

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

Olipriya Das, Ph.D. (media)
Russo Partners
Olipriya.Das@russopartnersllc.com
(646) 942-5588

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

Source: Tonix Pharmaceuticals Holding Corp.

Released February 9, 2023

Research News and Market Data on TNXP

February 06, 2023 7:00am EST

Results from Planned Interim Analysis Expected Fourth Quarter 2023

Approximately Four Million in U.S. Suffer from Chronic Migraine

Development of TNX-1900 Also Planned for Treatment of Episodic Migraine

CHATHAM, N.J., Feb. 06, 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 Phase 2 ‘PREVENTION’ study of TNX-1900 (intranasal potentiated oxytocin) for the prevention of migraine headache in chronic migraineurs.

The double-blind, placebo-controlled study has a target enrollment of 300 participants at approximately 25 sites across the U.S. Results from a planned interim analysis are expected to be released in the fourth quarter of 2023.

“Despite several classes of migraine preventatives available, there remains an unmet need for novel approaches with an estimated four million individuals in the United States suffering from chronic migraine, often a seriously disabling condition,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “TNX-1900 has a unique, multimodal mechanism of action, that includes an ability to inhibit the release of the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) in blood vessels within the brain, its lining and the brainstem, and to suppress signaling in pain neurons. We believe 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 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.”

Shashidar Kori, M.D., former Chief Medical Officer of Trigemina and consultant to Tonix added, “After a decade of development and optimization of our proprietary oxytocin formulation, it is very gratifying and exciting to enter the next stage of testing required to make TNX-1900 available to unfortunate chronic migraine sufferers who have few treatment options. This has the potential to improve the quality of life of people suffering from chronic migraine.”

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 300 participants across approximately 25 U.S. sites. After a four-week Run-In phase to confirm meeting chronic migraine criteria, 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. An interim analysis is expected to be completed after the first 50% of enrolled patients have completed the study for the purpose of potential sample size re-estimation, currently anticipated in the fourth quarter of 2023.

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 annually.² 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^® (onabotulinumtoxin), and the anti-CGRP/CGRP-R monoclonal antibodies Aimovig^® (erenumab), Vyepti^® (eptinezumab), Ajovy^® (fremanezumab) and Emgality^® (galcanezumab).

About TNX-1900
TNX-1900 (intranasal potentiated oxytocin) is a proprietary formulation of oxytocin in development as a candidate for prevention of chronic migraine and other conditions. In 2020, TNX-1900 was acquired from Trigemina, Inc. who had licensed the technology underlying the composition and method from Stanford University. TNX-1900 is a drug-device combination product, based on an intranasal actuator device that delivers oxytocin into the nasal cavity. Oxytocin is a naturally occurring human peptide hormone that also acts as a neurotransmitter in the brain. Oxytocin has no recognized addiction potential. It has been observed that low oxytocin levels in the body are associated with increases in migraine headache frequency, and that increased oxytocin levels are associated with fewer migraine headaches. Certain other chronic pain conditions are also associated with decreased oxytocin levels. Migraine attacks are caused, in part, by the activity of pain-sensing trigeminal neurons which, when activated, release 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 system³ 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.⁴ 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 binding⁵ as well as its inhibitory effects on trigeminal neurons and resultant craniofacial analgesic effects, as demonstrated in animal models⁷. Intranasal oxytocin has been shown to be well tolerated in several clinical trials in both adults and children⁶. 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 antibodies⁸. 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.

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 37 (2019):631–649.
³Yeomans DC, et al. Transl Psychiatry. 2021. 11(1):388.
⁴Tzabazis A, et al. Cephalalgia. 2016. 36(10):943-50.
⁵Antoni FA and Chadio SE. Biochem J. 1989. 257(2):611-4.
⁶Yeomans, DC et al. 2017. US patent US2017368095
⁷Cai Q, et al., Psychiatry Clin Neurosci. 2018. 72(3):140-151.
⁸MaassenVanDenBrink A, et al. Trends Pharmacol Sci. 2016. 37(9):779-788

About Tonix Pharmaceuticals Holding Corp.*

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022. 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 second quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, entered the clinic with a Phase 2 study in the first quarter of 2023 and interim data are expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft 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 quarter of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801; a next-generation vaccine to prevent COVID-19, TNX-1850; a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600; humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800; and a class of broad-spectrum small molecule oral antivirals,TNX-3900. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in the second half of 2023.

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

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

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Contacts

Jessica Morris (corporate)

Tonix Pharmaceuticals

investor.relations@tonixpharma.com

(862) 904-8182

Olipriya Das, Ph.D. (media)

Russo Partners

Olipriya.Das@russopartnersllc.com

(646) 942-5588

Peter Vozzo (investors)

ICR Westwicke

peter.vozzo@westwicke.com

(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Released February 6, 2023

Research News and Market Data on TNXP

February 03, 2023 7:00am EST

CHATHAM, N.J., Feb. 03, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals, will participate virtually in the BIO CEO & Investor Conference, which is being held February 6-9, 2023.

The Company’s pre-recorded presentation will be made available during the conference to registered conference participants through the BIO CEO & Investor Conference website at https://www.bio.org/events/bio-ceo-investor-conference/sessions. Beginning February 9, 2023, the presentation will also be available under the IR Events tab of the Investors section of the Tonix website at www.tonixpharma.com.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022. 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 second quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is expected to enter the clinic with a Phase 2 study in the first quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft 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 quarter of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801, a next-generation vaccine to prevent COVID-19, TNX-1850, a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600, humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800, and a class of broad-spectrum small molecule oral antivirals, TNX-3900. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in Kenya in the second half of 2023.

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

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

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Contacts

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

Olipriya Das, Ph.D. (media)
Russo Partners
Olipriya.Das@russopartnersllc.com
(646) 942-5588

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

Source: Tonix Pharmaceuticals Holding Corp.

Released February 3, 2023

Research News and Market Data on TNXP

January 31, 2023 7:00am EST

Preliminary Results from Human PET Study Show that Intranasal Application of a Radioisotope of Magnesium-Potentiated Oxytocin is Delivered to the Trigeminal Ganglia

Preliminary Results on Human Cadaveric Trigeminal Ganglia Show Co-expression of Oxytocin Receptors and CGRP

Preliminary Results Show Sex Differences in Oxytocin Potency in an Animal Model

CHATHAM, N.J., Jan. 31, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that David C. Yeomans, Ph.D., presented data from clinical and nonclinical studies in an oral presentation at the 16^th Annual Headache Cooperative of the Pacific (HCOP) Winter Conference on January 27, 2023. The oral presentation titled, “Primary vs Secondary Sex Hormones and Migraine,” includes research sponsored by and licensed to Tonix Pharmaceuticals. Professor Yeomans was a founder of Trigemina, which Tonix acquired, and he remains a consultant to Tonix. A copy of the presentation is available under the Scientific Presentations tab of the Tonix Pharmaceuticals corporate website at www.tonixpharma.com.

“In addition to data showing that magnesium (Mg⁺⁺) potentiates the analgesic effects of oxytocin, the presentation includes new preliminary data from a Positron Emission Tomography (PET) study in human volunteers dosed with a proprietary nitrogen-13 (¹³N) radioisotope of oxytocin formulated with Mg⁺⁺,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “A signal was observed in the trigeminal ganglia, indicating that intranasal oxytocin plus Mg⁺⁺ delivers oxytocin to the trigeminal ganglia which have known roles in migraine headache. These studies were a collaboration with Aarhus University and the principal investigator, Michael Winterdahl, PhD.”

In addition to the PET study, the presentation includes data collected from isolated human trigeminal ganglia neurons in vitro which show oxytocin receptor co-expressed with calcitonin gene-related peptide (CGRP). The results of these studies, which were performed by postdoctoral fellow Vimala Bharadwaj, PhD, are believed to represent the first observation of oxytocin receptors in human tissue rather than in an animal model. Previously, it has been shown that oxytocin receptors and CGRP co-localize in rat trigeminal ganglia neurons. The cytokine IL-6 functionally upregulated expression of human trigeminal oxytocin receptors in vitro, similar to what has been shown previously in rats, in which oxytocin has been shown to functionally inhibit electrically evoked activity of trigeminal neurons.

Finally, the presentation highlights data which suggest a sex difference in oxytocin potency. “The results indicate that oxytocin is more potent in inhibiting trigeminal ganglion neuronal excitability in female rats compared to males,” said Professor David C. Yeomans. “Moreover, treating male rats with estrogen for four days increased the responsiveness of their isolated trigeminal ganglia to oxytocin in vitro such that they show a similar level of responsiveness to oxytocin as female trigeminal ganglia. The Company believes that together, these findings have potential dosing implications in humans who suffer from chronic migraine.”

In late 2021, Tonix received Investigational New Drug clearance from the U.S. Food and Drug Administration to support the initiation of a Phase 2 study of TNX-1900 (intranasal magnesium potentiated oxytocin) for the prevention of migraine headache in chronic migraineurs. The Company expects to begin enrollment in the Phase 2 study during the first quarter of 2023.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022 and expects interim data in the third quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the first quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is expected to enter the clinic with a Phase 2 study in the first quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the first half of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801, a next-generation vaccine to prevent COVID-19, TNX-1850, a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600, and humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800, recently licensed from Curia. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in Kenya in the second half of 2023.

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

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

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Contacts

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

Olipriya Das, Ph.D. (media)
Russo Partners
Olipriya.Das@russopartnersllc.com
(646) 942-5588

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

Source: Tonix Pharmaceuticals Holding Corp.

Released January 31, 2023