A Single-Blind, Randomized Study Comparing The Efficacy And Safety Of A Single Dose Of TNX-1300 To Placebo With Usual Care For The Treatment Of Signs And Symptoms Of Acute Cocaine Intoxication In Emergency Department Subjects (CATALYST Study)

This is a Phase 2 single-blind, randomized, multicenter study to compare the efficacy and safety of a single dose of TNX-1300 to placebo with usual care in patients with acute cocaine intoxication within the emergency department setting.

开始日期2024-08-16

申办/合作机构

Tonix Pharmaceuticals, Inc.

[+2]

NCT04996056 / Withdrawn临床2期

An Open-Label, Randomized Pilot Study Comparing the Safety of a Single Dose of TNX-1300 to Usual Care (UC) Alone for the Treatment of Signs and Symptoms of Acute Cocaine Intoxication in Male Emergency Department (ED) Subjects

开始日期2021-09-03

申办/合作机构

Tonix Pharmaceuticals, Inc.

100 项与 Cocaine Esterase 相关的临床结果

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100 项与 Cocaine Esterase 相关的转化医学

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100 项与 Cocaine Esterase 相关的专利（医药）

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项与 Cocaine Esterase 相关的文献（医药）

2019-09-01·Drug and Alcohol Dependence2区 · 医学

Evaluation of the cholinesterase activity of a potential therapeutic cocaine esterase for cocaine overdose

2区 · 医学

Article

作者: Yin, Xiaopu ; Zhang, Yun ; Chen, Xiaoling ; Chen, Rong ; Kong, Yichao ; Xie, Tian ; Chen, Xiabin ; Zhang, Chao ; Hou, Shurong ; Zhu, Yao

BACKGROUNDCocaine is a commonly abused drug and there is no approved medication specifically to treat its addiction or overdose. Bacterial cocaine esterase (CocE)-derived RBP-8000 is currently under clinical development for cocaine overdose treatment. It is proven to be effective for human use to accelerate cocaine metabolism into physiologically inactive products. Besides cocaine, RBP-8000 may hydrolyze the neurotransmitter acetylcholine (ACh), however, no study has reported its cholinesterase activity. The present study aims to examine RBP-8000's cholinesterase activity and substrate selectivity to address the potential concern that this enzyme therapy might produce cholinergic side-effects.METHODSBoth computational modeling and experimental kinetic analysis were carried out to characterize the potential cholinesterase activity of RBP-8000. Substrates interacting with RBP-8000 were modeled for their enzyme-substrate binding complexes. In vitro enzymatic kinetic parameters were measured using Ellman's colorimetric assay and analyzed by Michaelis-Menten kinetics.RESULTSIt is the first demonstration that RBP-8000 catalyzes the hydrolysis of acetylthiocholine (ATC). However, its catalytic efficiency (k_cat/K_M) against ATC is 1000-fold and 5000-fold lower than it against cocaine at 25 °C and 37 °C, respectively, suggesting RBP-8000 has the desired substrate selectivity for cocaine over ACh.CONCLUSIONGiven the fact that clinically relevant dose of RBP-8000 displays insignificant cholinesterase activity relative to endogenous cholinesterases in human, administration of RBP-8000 is unlikely to produce any significant cholinergic side-effects. This study provides supplemental evidences in support of further development of RBP-8000 towards a clinically used pharmacotherapy for cocaine overdose.

2016-08-19·ACS Chemical Biology2区 · 生物学

Metabolic Enzymes of Cocaine Metabolite Benzoylecgonine

2区 · 生物学

Article

作者: Zhan, Chang-Guo ; Zhou, Ziyuan ; Zhan, Max ; Chen, Xiabin ; Zheng, Xirong ; Zheng, Fang

Cocaine is one of the most addictive drugs without a U.S. Food and Drug Administration (FDA)-approved medication. Enzyme therapy using an efficient cocaine-metabolizing enzyme is recognized as the most promising approach to cocaine overdose treatment. The actual enzyme, known as RBP-8000, under current clinical development for cocaine overdose treatment is our previously designed T172R/G173Q mutant of bacterial cocaine esterase (CocE). The T172R/G173Q mutant is effective in hydrolyzing cocaine but inactive against benzoylecgonine (a major, biologically active metabolite of cocaine). Unlike cocaine itself, benzoylecgonine has an unusually stable zwitterion structure resistant to further hydrolysis in the body and environment. In fact, benzoylecgonine can last in the body for a very long time (a few days) and, thus, is responsible for the long-term toxicity of cocaine and a commonly used marker for drug addiction diagnosis in pre-employment drug tests. Because CocE and its mutants are all active against cocaine and inactive against benzoylecgonine, one might simply assume that other enzymes that are active against cocaine are also inactive against benzoylecgonine. Here, through combined computational modeling and experimental studies, we demonstrate for the first time that human butyrylcholinesterase (BChE) is actually active against benzoylecgonine, and that a rationally designed BChE mutant can not only more efficiently accelerate cocaine hydrolysis but also significantly hydrolyze benzoylecgonine in vitro and in vivo. This sets the stage for advanced studies to design more efficient mutant enzymes valuable for the development of an ideal cocaine overdose enzyme therapy and for benzoylecgonine detoxification in the environment.

2014-10-02·Journal of Addictive Diseases4区 · 医学

A Randomized, Double-Blind, Placebo-Controlled Trial of RBP-8000 in Cocaine Abusers: Pharmacokinetic Profile of RBP-8000 and Cocaine and Effects of RBP-8000 on Cocaine-Induced Physiological Effects

4区 · 医学

Article

作者: Bo Zheng ; Yongzhen Liu ; Azmi F. Nasser ; Christian Heidbreder ; Paul J. Fudala

RBP-8000 is a double mutant cocaine esterase that rapidly metabolizes cocaine. This study was conducted to assess the pharmacokinetics of cocaine and cocaine-induced physiological effects in the absence (placebo) or presence of RBP-8000. Twenty-nine cocaine abusers were randomized 1:1 (active: placebo) to 4 sequences and 2 treatment periods. In the presence of RBP-8000, cocaine plasma exposures dropped by 90% within 2 min; cocaine-induced physiological effects were significantly reduced with higher extent and faster decrease in systolic blood pressure and pulse rate compared to placebo. This study provides strong evidence in support to use RBP-8000 as a pharmacotherapy for cocaine intoxication.

217

项与 Cocaine Esterase 相关的新闻（医药）

2024-11-18

·GlobeNewswire-Health Care

Tonix Pharmaceuticals Presented Data and Analyses of TNX-102 SL Treatment Effects on Fibromyalgia at the American College of Rheumatology (ACR) Convergence 2024 Annual Meeting

Poster presentation highlighted results from confirmatory Phase 3 RESILIENT study of TNX-102 SL (sublingual cyclobenzaprine HCl) treatment demonstrating statistically significant improvement in primary endpoint of fibromyalgia nociplastic pain and in all six key secondary endpoints, including sleep quality New Drug Application (NDA) submitted to FDA in October 2024; Fast Track designation previously granted by FDA; FDA decision on approval expected 2025 TNX-102 SL is a potential non-opioid analgesic targeting non-restorative sleep If approved by FDA, TNX-102 SL would be the first member of a new class of analgesic drugs for fibromyalgia and the first new drug for treating fibromyalgia in more than 15 years CHATHAM, N.J., Nov. 18, 2024 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, presented data in a poster presentation at the ACR Convergence 2024 Annual Meeting, held November 14-19, 2024, in Washington, D.C. A copy of the Company’s presentation, titled “Randomized, Double-Blind, Placebo-Controlled Confirmatory Phase 3 Trial of Bedtime Sublingual Cyclobenzaprine (TNX-102 SL) in Fibromyalgia” is available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com. In the Phase 3 RESILIENT study, TNX-102 SL met the pre-specified primary endpoint of significantly reducing daily pain compared to placebo (p-value=0.00005) in participants with fibromyalgia. In the RESILIENT study, TNX-102 SL demonstrated a broad spectrum of benefits with statistically significant improvement in all six pre-specified key secondary endpoints including those related to improved sleep quality, reduced fatigue, and improved patient global ratings and overall fibromyalgia symptoms and function. TNX-102 SL was generally well tolerated with an adverse event profile comparable to prior studies and no new safety signals observed. “Fibromyalgia is the prototypic nociplastic syndrome and one of the chronic overlapping pain conditions (COPCs)1,2,3,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “TNX-102 SL, designed as a bedtime treatment to target non-restorative sleep, has shown a statistically significant improvement in pain in two phase 3 studies. We believe TNX-102 SL has the potential to be the first new drug treatment option for fibromyalgia patients in 15 years.” Tonix submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) in October 2024 for TNX-102 SL for the management of fibromyalgia. The FDA typically has a 60-day filing review period to determine whether the submitted NDA is complete and accepted for review. If the FDA accepts the NDA for review, the Company expects a 2025 date for a FDA decision on approval, based on the Prescription Drug User Fee Act (PDUFA). 1Fitzcharles MA, et al. Lancet. 2021;397(10289):2098-2110. 2Clauw DJ. Ann Rheum Dis. 2024;83(11):1421-1427. 3Kaplan CM, et al. Nat Rev Neurol. 2024;20(6):347-363. About Fibromyalgia Fibromyalgia is a common chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system, called central sensitization. Brain imaging studies have localized the functional disorder to the brain’s insular and anterior cingulate cortex. Fibromyalgia afflicts more than 10 million adults in the U.S., the majority of whom are women. Symptoms of fibromyalgia include chronic widespread pain, non-restorative sleep, fatigue, and brain fog (or cognitive dysfunction). Other associated symptoms include mood disturbances, including depression, anxiety, headaches, and abdominal pain or cramps. Individuals suffering from fibromyalgia often struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products. Fibromyalgia is now recognized as the prototypic nociplastic syndrome. Nociplastic pain is the third primary type of pain in addition to nociceptive pain and neuropathic pain. Many patients present with pain syndromes that are combinations of the three primary types of pain. Nociplastic syndromes can involve components of both central and peripheral sensitization. Fibromyalgia can occur without any identifiable precipitating event. However, many fibromyalgia cases follow one or more precipitating event(s) including: chronic nociceptive or neuropathic pain states; recovery from an infectious illness; a cancer diagnosis or cancer treatment; a metabolic or endocrine stress; or a traumatic event. In the cases of recovery from an infectious illness, fibromyalgia is considered an Infection-Associated Chronic Condition. In addition to fibromyalgia cases associated with other conditions or stressors, the U.S. National Academies of Sciences, Engineering, and Medicine, has concluded that fibromyalgia is a diagnosable condition that occurs after recovery from COVID-19 in the context of Long COVID. Fibromyalgia is also recognized as a Chronic Overlapping Pain Condition, due to shared symptoms with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), irritable bowel syndrome, endometriosis, low back pain, post-concussive syndrome (also known as mild traumatic brain injury), chronic Lyme Disease, chronic diabetic neuropathy and chronic post-herpetic neuralgia. About TNX-102 SL TNX-102 SL is a centrally acting, non-opioid bedtime investigational drug, designed for chronic use. The tablet is a patented sublingual formulation of cyclobenzaprine hydrochloride developed for bedtime dosing for the management of fibromyalgia. Cyclobenzaprine interacts as an antagonist at four different receptors in the brain: serotonergic-5-HT2A, adrenergic-α1, histaminergic-H1, and muscarinic-M1-cholinergic receptors. Together, these interactions are believed to target the non-restorative sleep characteristic of fibromyalgia that was identified by Professor Harvey Moldofsky in 1975. Approved oral cyclobenzaprine products are not associated with risk of addiction or dependence. The TNX-102 SL tablet is based on a eutectic formation of cyclobenzaprine HCl and mannitol that provides a stable product which dissolves rapidly and efficiently delivers cyclobenzaprine by the transmucosal route into the bloodstream. The eutectic protects cyclobenzaprine HCl from interacting with the basifying agent that is also part of the formulation and required for efficient transmucosal absorption. Patents based on TNX-102 SL’s eutectic composition and its properties have issued in the U.S., E.U., Japan, China and many other jurisdictions around the world and provide market protection into 2034. The European Patent Office’s Opposition Division maintained Tonix’s European Patent EP 2 968 992 in unamended form after an Opposition was filed against it by a Sandoz subsidiary, Hexal AG. Hexal AG did not appeal that decision. The formulation of TNX-102 SL was designed specifically for sublingual administration and transmucosal absorption for bedtime dosing to target disturbed sleep, while reducing the risk of daytime somnolence. Clinical pharmacokinetic studies indicated that the addition of a basifying agent was necessary for efficient transmucosal absorption which results in higher levels of exposure during the first 2 hours after dosing and in deceased levels of the long-lived active metabolite, norcyclobenzaprine, relative to cyclobenzaprine, consistent with bypassing first pass hepatic metabolism. Tonix Pharmaceuticals Holding Corp.* Tonix is a fully-integrated biopharmaceutical company focused on transforming therapies for pain management and vaccines for public health challenges. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to advance TNX-102 SL, a product candidate for the management of fibromyalgia, for which an NDA was submitted based on two statistically significant Phase 3 studies for the management of fibromyalgia. The FDA has granted Fast Track designation to TNX-102 SL for the management of fibromyalgia. We expect an FDA decision on the acceptance of the NDA for review and an assigned PDUFA date in December and if accepted, a decision on NDA approval in 2025. TNX-102 SL is also being developed to treat acute stress reaction and acute stress disorder under a Physician-Initiated IND at the University of North Carolina in the OASIS study funded by the U.S. Department of Defense (DoD). Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase), a biologic in Phase 2 development designed to treat cocaine intoxication that has FDA Breakthrough Therapy designation and its development is supported by a grant from the U.S. National Institute on Drug Abuse. Tonix’s immunology development portfolio consists of biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is an Fc-modified humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. Tonix also has product candidates in development in the areas of rare disease, including TNX-2900 for Prader-Willi syndrome, and infectious disease, including a vaccine for mpox, TNX-801. Tonix recently announced a contract with the U.S. DoD’s Defense Threat Reduction Agency (DTRA) for up to $34 million over five years to develop TNX-4200, small molecule broad-spectrum antiviral agents targeting CD45 for the prevention or treatment of infections to improve the medical readiness of military personnel in biological threat environments. Tonix owns and operates a state-of-the art infectious disease research facility in Frederick, MD. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults. * Tonix’s product development candidates are investigational new drugs or biologics; their efficacy and safety have not been established and have not been approved for any indication. Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. All other marks are property of their respective owners. This press release and further information about Tonix can be found at www.tonixpharma.com. Forward Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission (the “SEC”) on April 1, 2024, and periodic reports filed with the SEC on or after the date thereof. All of Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof. Investor Contact Jessica MorrisTonix Pharmaceuticalsinvestor.relations@tonixpharma.com (862) 904-8182 Peter VozzoICR Healthcarepeter.vozzo@westwicke.com (443) 213-0505 Media Contact Ray JordanPutnam Insightsray@putnaminsights.com(949) 245-5432

临床3期快速通道临床结果临床2期申请上市

2024-11-13

·GlobeNewswire-Health Care

Tonix Pharmaceuticals Announces Poster Presentation at the American College of Rheumatology (ACR) Convergence 2024 Annual Meeting

CHATHAM, N.J., Nov. 13, 2024 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, today announced that Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals, will deliver a poster presentation at the ACR Convergence 2024 Annual Meeting, which will be held in Washington, D.C., November 14-19, 2024. A copy of the Company’s presentation will be available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com following the conference. Additional meeting information can be found on the ACR website here. Presentation Details Presenter:Seth Lederman, M.D. Title:Randomized, Double-Blind, Placebo-Controlled Confirmatory Phase 3 Trial of Bedtime Sublingual Cyclobenzaprine (TNX-102 SL) in Fibromyalgia Poster No.:1218 Session:Poster Session B, Pain in Rheumatic Disease Including Fibromyalgia Poster Location:Walter E. Washington Convention Center, Washington, D.C. Date:Sunday, November 17, 2024 Time:10:30 a.m. – 12:30 p.m. ET Tonix Pharmaceuticals Holding Corp.* Tonix is a fully-integrated biopharmaceutical company focused on transforming therapies for pain management and vaccines for public health challenges. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to advance TNX-102 SL, a product candidate for the management of fibromyalgia, for which an NDA was submitted based on two statistically significant Phase 3 studies for the management of fibromyalgia. The FDA has granted Fast Track designation to TNX-102 SL for the management of fibromyalgia. We expect an FDA decision on the acceptance of the NDA for review and a PDUFA date in December and if accepted, a decision on NDA approval in 2025. TNX-102 SL is also being developed to treat acute stress reaction and acute stress disorder under a Physician-Initiated IND at the University of North Carolina in the OASIS study funded by the U.S. Department of Defense (DoD). Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase), a biologic in Phase 2 development designed to treat cocaine intoxication that has FDA Breakthrough Therapy designation and its development is supported by a grant from the U.S. National Institute of Drug Abuse and Addiction. Tonix’s immunology development portfolio consists of biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is an Fc-modified humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. Tonix also has product candidates in development in the areas of rare disease, including TNX-2900 for Prader-Willi syndrome, and infectious disease, including a vaccine for mpox, TNX-801. Tonix recently announced a contract with the U.S. DoD’s Defense Threat Reduction Agency (DTRA) for up to $34 million over five years to develop TNX-4200, small molecule broad-spectrum antiviral agents targeting CD45 for the prevention or treatment of infections to improve the medical readiness of military personnel in biological threat environments. Tonix owns and operates a state-of-the art infectious disease research facility in Frederick, MD. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults. * Tonix’s product development candidates are investigational new drugs or biologics; their efficacy and safety have not been established and have not been approved for any indication. Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. All other marks are property of their respective owners. This press release and further information about Tonix can be found at www.tonixpharma.com. Forward Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Toni’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission (the “SEC”) on April 1, 2024, and periodic reports filed with the SEC on or after the date thereof. All of Toni’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 MorrisTonix Pharmaceuticalsinvestor.relations@tonixpharma.com (862) 904-8182 Peter VozzoICR Healthcarepeter.vozzo@westwicke.com (443) 213-0505 Media Contact Ray JordanPutnam Insightsray@putnaminsights.com(949) 245-5432

快速通道临床3期临床2期

2024-11-13

·GlobeNewswire-Health Care

Tonix Pharmaceuticals Announces Peer-Reviewed Publication in mSphere Journal Highlighting the Tolerability of Company’s Single-Dose Mpox and Smallpox Vaccine Candidate TNX-801, in Immune-Compromised Animals

The World Health Organization (WHO) declared the spread of new Clade Ib Mpox a public health emergency of international concern (PHEIC): Second Mpox-related WHO PHEIC declaration in two years Clade Ib Mpox cases detected in 16 African countries and outside of Africa, in Sweden, Thailand, Singapore, India, Germany and England Single-dose mpox vaccines with durable protection may be required to address global health emergency TNX-801 was shown to be more than 10- to 1,000-fold more attenuated (or less virulent) compared to the older vaccinia smallpox vaccines: Tolerability of TNX‐801 vaccination in immune-compromised animal models supports clinical development CHATHAM, N.J., Nov. 13, 2024 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, today announced the publication of a paper entitled, “Recombinant Chimeric Horsepox Virus (TNX-801) is Attenuated Relative to Vaccinia Virus Strains in Both In Vitro and In Vivo Models,” in the peer-reviewed journal mSphere. The publication presents data demonstrating that TNX‐801 is less virulent than 20th Century vaccinia vaccines in immune-compromised mice. Previously, single-dose vaccination with TNX-801 was shown to protect animals from a lethal challenge with Clade Ia monkeypox. On August 14, 2024, WHO determined that the upsurge of Clade Ib mpox in Africa constituted a public health emergency of international concern (PHEIC), the second such declaration in the past two years in response to an mpox outbreak. The recent ongoing outbreak is caused by Clade Ib monkeypox virus, while the PHEIC declared in 2022, and still ongoing, is caused by Clade IIb monkeypox virus. Mpox cases of the new clade Ib monkeypox virus have been detect in 16 African countries and Sweden, Thailand, Singapore, India, Germany and England. The new Clade Ib mpox is spreading in children in Africa and so far, has been carried by adult travellers from Africa into non-African countries. The global mpox outbreak from Clade IIb, which commenced in 2022, has affected over 90,000 people in countries where mpox had previously not been endemic, including Europe and the U.S. The Clade IIb mpox from the 2022 PHEIC predominantly affects gay men outside of Africa and already is an established endemic in the U.S. “Addressing the new Clade Ib mpox outbreak and the ongoing spread of Clade IIb mpox may require a single dose mpox vaccine that provides durable protection,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “TNX-801 previously has demonstrated the ability to protect animals from lethal challenge with Clade Ia monkeypox virus. The new findings reported in the peer-reviewed journal mSphere show tolerability of TNX-801 in immune-compromised animals which further supports testing in humans. In addition, we expect TNX-801 can be distributed and stored without a costly supply chain.” The publication describes data in which TNX-801 was compared with older vaccinia vaccine strains used in the eradication of smallpox for tolerability in both in vitro and in vivo models. Together, TNX-801 was shown to be more than 10- to 1,000-fold more attenuated (or less virulent) compared to the older vaccinia smallpox vaccines. Combined with the ability of TNX-801 to protect animals against lethal challenge with Clade Ia monkeypox virus, the Company believes that the new tolerability data support the idea that TNX-801 is a candidate vaccine to control the ongoing PHEICs with mpox Clade Ib and mpox Clade IIb. About TNX-801* TNX-801 (recombinant horsepox virus) is a minimally replicating, live virus vaccine based on horsepox in pre-clinical development to prevent mpox and smallpox. Tonix reported positive preclinical efficacy data, demonstrating that TNX-801 vaccination protected non-human primates against lethal challenge with monkeypox.1 After a single dose vaccination, TNX-801 prevented clinical disease and lesions and also decreased shedding in the mouth and lungs of non-human primates.1 The findings are consistent with mucosal immunity and suggest the ability to block forward transmission, similar to Dr. Edward Jenner’s vaccine, which eradicated smallpox and kept mpox out of the human population.1 TNX-801 is based on synthesized horsepox which is believed to be more closely related to Dr. Jenner’s vaccine than 20th Century vaccinia viruses.2 Smallpox vaccines, descended from Jenner’s vaccine, used prior to 1900 would be called horsepox by modern nomenclature.3-5 TNX-801 is delivered percutaneously with only one dose and therefore may achieve higher rates of community protection than two-dose vaccines by eliminating drop-out between doses and limiting forward transmission. 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.3 Tonix announced a collaboration to develop GMP manufacturing processes for its mpox vaccine with Bilthoven Biologics (Bbio), part of the world’s largest vaccine manufacturer, the Cyrus Poonawalla Group, which also includes the Serum Institute of India. Tonix also announced a collaboration with the Kenya Medical Research Institute (KEMRI) to design, plan and seek regulatory approval for a Phase I clinical study of TNX-801 in Kenya. The Company believes 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. The FDA-approved non-replicating mpox vaccine Jynneos® requires two doses and provides a relatively short duration of protection.7,8 FDA also recently approved ACAM2000, a live, replicating vaccinia vaccine for prevention of mpox.9 ACAM200 is a clone from DryVax®, a 20th Century vaccinia vaccine derived from the NYCBH strain. Pre-clinical results from an mRNA vaccine recently showed some protection from a Clade I monkeypox challenge, but with multiple break-through lesions in vaccinated animals.10 About the Recombinant Pox Vaccine (RPV) Vaccine Platform* On the horsepox platform, Tonix is developing TNX-1800 (horsepox expressing SARS-CoV-2 spike protein) for protecting against COVID-19. TNX-1800 is an engineered version of horsepox that expresses the spike protein of SARS-CoV-2. In preclinical studies of TNX-1800 highlighted in the presentation, TNX-1800 was tested for immunogenicity and efficacy of TNX-1800 in nonhuman primates following a SARS CoV-2 challenge.11,12 TNX-1800 vaccination results in a neutralizing antibody response that was associated with significant reduction in virus replication/shedding in the respiratory tract and tolerability.11,12 TNX-1800 was selected by the NIH’s, Project NextGen for inclusion in clinical trials as part of a select group of next generation COVID-19 vaccine candidates with the intent to identify promising vaccine platforms. NIH plans to conduct a Phase 1 trial of TNX-1800 and cover the full cost of the study, while Tonix provides the vaccine candidate. Tonix Pharmaceuticals Holding Corp.* Tonix is a fully integrated biopharmaceutical company focused on transforming therapies for pain management and vaccines for public health challenges. Our priority is to advance our TNX-102 SL product candidate for the management of fibromyalgia, for which a New Drug Application (“NDA”) was submitted to the U.S. Food and Drug Administration (“FDA”) in October 2024, based on two statistically significant Phase 3 studies. The FDA granted Fast Track designation to TNX-102 SL for the management of fibromyalgia in the third quarter. We expect an FDA decision on the acceptance of the NDA for review and PDUFA date in December and if accepted, a decision on NDA approval in 2025. Fibromyalgia is a common chronic pain condition that affect mostly women. Fibromyalgia is now recognized as the prototypic nociplastic pain syndrome. TNX-102 SL is a non-opioid, centrally acting analgesic developed for long-term use in fibromyalgia. If approved, TNX-102 SL would be the first new drug therapy for fibromyalgia in more than 15 years. TNX-102 SL is also being developed to treat acute stress reaction and acute stress disorder under a Physician-Initiated Investigational New Drug application (“IND”) at the University of North Carolina in the OASIS study funded by the U.S. Department of Defense (DoD). We expect to initiate enrollment in the OASIS study in the fourth quarter. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase), a biologic drug candidate in Phase 2 development designed to treat cocaine intoxication that has FDA Breakthrough Therapy designation and its development is supported by a grant from the U.S. National Institute of Drug Abuse and Addiction. Our immunology development portfolio includes TNX-1500, which is an Fc-modified humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) in Phase 1 development for the prevention of allograft rejection and for the treatment of autoimmune diseases. TNX-1700 is a fusion protein of TFF2 and albumin and is in the pre-IND stage of development to treat gastric and pancreatic cancer. Tonix also has pre-clinical product candidates in development in the areas of rare disease, including TNX-2900 for Prader-Willi syndrome, and infectious disease, including TNX-801 a potential vaccine to prevent mpox and smallpox. Tonix recently announced a contract with the U.S. DoD’s Defense Threat Reduction Agency (“DTRA”) for up to $34 million over five years to develop TNX-4200, small molecule broad-spectrum antiviral agents targeting CD45 for the prevention or treatment of infections to improve the medical readiness of military personnel in biological threat environments. Tonix owns and operates a state-of-the art infectious disease research facility in Frederick, MD. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults. * Tonix’s product development candidates are investigational new drugs or biologics; their efficacy and safety have not been established and have not been approved for any indication. Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. All other marks are property of their respective owners. (1)Noyce RS, et al. Viruses. 2023;15(2):356. https://doi-org.libproxy1.nus.edu.sg/10.3390/v15020356(2)Noyce RS, et al. PLoS One. 2018 Jan 19;13(1):e0188453. doi: 10.1371/journal.pone.0188453. PMID: 29351298; PMCID: PMC5774680.(3)Schrick L, et al. N Engl J Med. 2017;377(15):1491-1492(4)Duggan AT, et al. Genome Biol. 2020;21(1):175.(5)Brinkmann A, et al. Genome Biol. 2020;21(1):286.(6)TNX-801 PR pre-IND meeting 8/20/23: https://ir.tonixpharma.com/news-events/press-releases/detail/1417/tonix-pharmaceuticals-announces-results-of-pre-ind-meeting(7)Zaeck LM, et al. Low levels of monkeypox virus-neutralizing antibodies after MVA-BN vaccination in healthy individuals. Nat Med. 2023 Jan;29(1):270-278. doi: 10.1038/s41591-022-02090-w. Epub 2022 Oct 18. PMID: 36257333; PMCID: PMC9873555.(8)JAMA Collier AY, et al. JAMA. 2024 doi: 10.1001/jama.2024.20951. Epub ahead of print. PMID: 39361499. https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/39361499/(9)FDA Roundup August 30, 2024. www.fda.gov/news-events/press-announcements/fda-roundup-august-30-2024(10)Mucker et al., Cell, 2024 https://doi-org.libproxy1.nus.edu.sg/10.1016/j.cell.2024.08.043(11)Awasthi M, et al. Viruses. 2023 Oct 21;15(10):2131. doi: 10.3390/v15102131. PMID: 37896908; PMCID: PMC10612059.(12)Awasthi M et al Vaccines (Basel). 2023 Nov 2;11(11):1682. doi: 10.3390/vaccines11111682.PMID: 38006014 This press release and further information about Tonix can be found at www.tonixpharma.com. Forward Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission (the “SEC”) on April 1, 2024, and periodic reports filed with the SEC on or after the date thereof. All of Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof. Investor Contact Jessica MorrisTonix Pharmaceuticalsinvestor.relations@tonixpharma.com (862) 904-8182 Peter VozzoICR Healthcarepeter.vozzo@westwicke.com (443) 213-0505 Media Contact Ray JordanPutnam Insightsray@putnaminsights.com (949) 245-5432

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