Seizures

Zembrace® SymTouch® and Tosymra® will be marketed by Tonix Medicines, Tonix’s wholly-owned commercial subsidiary Commercial capabilities prepare Tonix for the potential launch in 2025 of Tonmya™ for the management of fibromyalgia, assuming FDA approval CHATHAM, N.J., March 19, 2024 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals, Inc. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced that it will achieve its goal of transitioning to a fully integrated pharmaceutical company on April 1, 2024. Since the acquisition of Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg on June 30, 2023, Tonix Pharmaceuticals has been putting in place the personnel, systems and contracts required to support a commercial organization. Both products are indicated for the treatment of acute migraine with or without aura in adults. “Tonix will become a fully integrated biopharmaceutical company with a mission of developing and marketing innovative, high-value therapeutics,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Tonix will assume responsibility for the distribution, selling and marketing of Zembrace SymTouch and Tosymra, as well as supply chain, regulatory and quality control of the two products.” Dr. Lederman added, “The assumption of commercial activities by Tonix represents an important milestone in the evolution of Tonix as we continue to build and strengthen our commercial organization for the potential launch of Tonmya™ (cyclobenzaprine HCl sublingual tablets) for fibromyalgia in 2025, assuming approval by the U.S. Food and Drug Administration (FDA).” About Zembrace® SymTouch® and Tosymra® Zembrace SymTouch is the only actively promoted brand of sumatriptan autoinjector in the United States (other sumatriptan autoinjector products on the market are Imitrex® and generics to Imitrex®). It has a unique low dose and has demonstrated onset of migraine pain relief in as few as 10 minutes (17% of patients vs. 5% for placebo).1 Zembrace SymTouch also demonstrated migraine pain freedom for 46% of patients (vs 27% for placebo) at 2 hours in a single-attack, double-blind study (N=230).1 Zembrace SymTouch currently has patent protection to 2036. Tosymra employs Intravail® permeation enhancer technology and is pharmacokinetically equivalent to 4 mg subcutaneous sumatriptan.2 Tosymra delivers migraine pain relief in as little as 10 minutes with just one spray for some patients (13% vs. 5% for placebo).2 Tosymra currently has patent protection to 2031. About Migraine Nearly 40 million people in the United States suffer from migraine3 and it has been recognized as the second leading cause of disability in the world.4 Migraine is characterized by debilitating attacks lasting four to 72 hours with multiple symptoms, including pulsating headaches of moderate to severe pain intensity often associated with nausea or vomiting, and/or sensitivity to sound (phonophobia) and sensitivity to light (photophobia).3 References: Zembrace SymTouch [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, LLC: February 2021. Tosymra [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, LLC: Feb 2021. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018;17(11):954-976. About Tonmya* (also known as TNX-102 SL) Tonmya is a centrally acting, non-opioid, non-addictive, bedtime medication. The tablet is a patented sublingual formulation of cyclobenzaprine hydrochloride developed for the management of fibromyalgia. In December 2023, the company announced highly statistically significant and clinically meaningful topline results in RESILIENT, a second positive Phase 3 clinical trial of Tonmya for the management of fibromyalgia. In the study, Tonmya met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia. Statistically significant and clinically meaningful results were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function. RELIEF, the first positive Phase 3 trial of Tonmya in fibromyalgia, was completed in December 2020. It met its pre-specified primary endpoint of daily pain reduction compared to placebo (p=0.010) and showed activity in key secondary endpoints. *Tonmya™ is conditionally accepted by the U.S. Food and Drug Administration as the tradename for TNX-102 SL for the management of fibromyalgia. Tonmya has not been approved for any indication. Tonix Pharmaceuticals Holding Corp.* Tonix is a biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya, a product candidate for which two positive Phase 3 studies have been completed for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction as well as fibromyalgia-type Long COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase) a biologic designed to treat cocaine intoxication with Breakthrough Therapy designation. Tonix’s immunology development portfolio consists of biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. Tonix also has product candidates in development in the areas of rare disease and infectious disease. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults. *Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication. Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. All other marks are property of their respective owners. This press release and further information about Tonix can be found at . Forward Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof. Investor Contact Jessica Morris Tonix Pharmaceuticals investor.relations@tonixpharma.com (862) 904-8182 Peter Vozzo ICR Westwicke peter.vozzo@westwicke.com (443) 213-0505 Media Contact Ben Shannon ICR Westwicke ben.shannon@westwicke.com (919) 360-3039 Zembrace® SymTouch® (sumatriptan Injection): IMPORTANT SAFETY INFORMATION Zembrace SymTouch (Zembrace) can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop use and get emergency help if you have any signs of a heart attack: discomfort in the center of your chest that lasts for more than a few minutes or goes away and comes back severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw pain or discomfort in your arms, back, neck, jaw or stomach shortness of breath with or without chest discomfort breaking out in a cold sweat nausea or vomiting feeling lightheaded Zembrace is not for people with risk factors for heart disease (high blood pressure or cholesterol, smoking, overweight, diabetes, family history of heart disease) unless a heart exam shows no problem. Do not use Zembrace if you have: history of heart problems narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease) uncontrolled high blood pressure hemiplegic or basilar migraines. If you are not sure if you have these, ask your provider. had a stroke, transient ischemic attacks (TIAs), or problems with blood circulation severe liver problems taken any of the following medicines in the last 24 hours: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, ergotamines, dihydroergotamine. are taking certain antidepressants, known as monoamine oxidase (MAO)-A inhibitors or it has been 2 weeks or less since you stopped taking a MAO-A inhibitor. Ask your provider for a list of these medicines if you are not sure. an allergy to sumatriptan or any of the components of Zembrace Tell your provider about all of your medical conditions and medicines you take, including vitamins and supplements. Zembrace can cause dizziness, weakness, or drowsiness. If so, do not drive a car, use machinery, or do anything where you need to be alert. Zembrace may cause serious side effects including: changes in color or sensation in your fingers and toes sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrhea, fever cramping and pain in your legs or hips; feeling of heaviness or tightness in your leg muscles; burning or aching pain in your feet or toes while resting; numbness, tingling, or weakness in your legs; cold feeling or color changes in one or both legs or feet increased blood pressure including a sudden severe increase even if you have no history of high blood pressure medication overuse headaches from using migraine medicine for 10 or more days each month. If your headaches get worse, call your provider. serotonin syndrome, a rare but serious problem that can happen in people using Zembrace, especially when used with anti-depressant medicines called SSRIs or SNRIs. Call your provider right away if you have: mental changes such as seeing things that are not there (hallucinations), agitation, or coma; fast heartbeat; changes in blood pressure; high body temperature; tight muscles; or trouble walking. hives (itchy bumps); swelling of your tongue, mouth, or throat seizures even in people who have never had seizures before The most common side effects of Zembrace include: pain and redness at injection site; tingling or numbness in your fingers or toes; dizziness; warm, hot, burning feeling to your face (flushing); discomfort or stiffness in your neck; feeling weak, drowsy, or tired. Tell your provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of Zembrace. For more information, ask your provider. This is the most important information to know about Zembrace but is not comprehensive. For more information, talk to your provider and read the Patient Information and Instructions for Use. You can also visit or call 1-888-869-7633. You are encouraged to report adverse effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. INDICATION AND USAGE Zembrace is a prescription medicine used to treat acute migraine headaches with or without aura in adults who have been diagnosed with migraine. Zembrace is not used to prevent migraines. It is not known if it is safe and effective in children under 18 years of age. Tosymra® (sumatriptan nasal spray): IMPORTANTSAFETYINFORMATION Tosymra can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop Tosymra and get emergency medical help if you have any signs of heart attack: discomfort in the center of your chest that lasts for more than a few minutes or goes away and comes back severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw pain or discomfort in your arms, back, neck, jaw, or stomach shortness of breath with or without chest discomfort breaking out in a cold sweat nausea or vomiting feeling lightheaded Tosymra is not for people with risk factors for heart disease (high blood pressure or cholesterol, smoking, overweight, diabetes, family history of heart disease) unless a heart exam is done and shows no problem. Do not use Tosymra if you have: history of heart problems narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease) uncontrolled high blood pressure severe liver problems hemiplegic or basilar migraines. If you are not sure if you have these, ask your healthcare provider. had a stroke, transient ischemic attacks (TIAs), or problems with blood circulation taken any of the following medicines in the last 24 hours: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, ergotamines, or dihydroergotamine. Ask your provider if you are not sure if your medicine is listed above. are taking certain antidepressants, known as monoamine oxidase (MAO)-A inhibitors or it has been 2 weeks or less since you stopped taking a MAO-A inhibitor. Ask your provider for a list of these medicines if you are not sure. an allergy to sumatriptan or any ingredient in Tosymra Tell your provider about all of your medical conditions and medicines you take, including vitamins and supplements. Tosymra can cause dizziness, weakness, or drowsiness. If so, do not drive a car, use machinery, or do anything where you need to be alert. Tosymra may cause serious side effects including: changes in color or sensation in your fingers and toes sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrhea, fever cramping and pain in your legs or hips, feeling of heaviness or tightness in your leg muscles, burning or aching pain in your feet or toes while resting, numbness, tingling, or weakness in your legs, cold feeling or color changes in one or both legs or feet increased blood pressure including a sudden severe increase even if you have no history of high blood pressure medication overuse headaches from using migraine medicine for 10 or more days each month. If your headaches get worse, call your provider. serotonin syndrome, a rare but serious problem that can happen in people using Tosymra, especially when used with anti-depressant medicines called SSRIs or SNRIs. Call your provider right away if you have: mental changes such as seeing things that are not there (hallucinations), agitation, or coma; fast heartbeat; changes in blood pressure; high body temperature; tight muscles; or trouble walking. hives (itchy bumps); swelling of your tongue, mouth, or throat seizures even in people who have never had seizures before The most common side effects of Tosymra include: tingling, dizziness, feeling warm or hot, burning feeling, feeling of heaviness, feeling of pressure, flushing, feeling of tightness, numbness, application site (nasal) reactions, abnormal taste, and throat irritation. Tell your provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of Tosymra. For more information, ask your provider. This is the most important information to know about Tosymra but is not comprehensive. For more information, talk to your provider and read the Patient Information and Instructions for Use. You can also visit or call 1-888-869-7633. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. INDICATION AND USAGE Tosymra is a prescription medicine used to treat acute migraine headaches with or without aura in adults. Tosymra is not used to treat other types of headaches such as hemiplegic or basilar migraines or cluster headaches. Tosymra is not used to prevent migraines. It is not known if Tosymra is safe and effective in children under 18 years of age.

Pictured: FDA signage at its headquarters in Maryland/iStock, hapabapa The FDA on Monday approved Orchard Therapeutics’ autologous gene therapy atidarsagene autotemcel, which will now be marketed as Lenmeldy, for the treatment of metachromatic leukodystrophy in pediatric patients. Lenmeldy is the first authorized gene therapy for children with pre-symptomatic late infantile or early juvenile metachromatic leukodystrophy (MLD), according to the FDA’s press release on the approval. Lenmeldy is also the first approved therapy for early juvenile or early symptomatic forms of the disease. Orchard CEO Bobby Gaspar in a statement said that Lenmeldy’s approval “opens up tremendous new possibilities” for children suffering from these early-onset forms of MLD, “who previously had no treatment options beyond supportive and end-of-life care.” The company on Monday did not provide specific launch details for Lenmeldy but promises to do so within the week. MLD is a rare and heritable metabolic disease that affects one in every 100,000 live births. It is characterized by a pathological build-up of sulfatides in the brain, liver, kidneys, spleen and other body parts, which over time can cause organ damage and neurological issues. Those with MLD often suffer from motor, behavioral and cognitive problems, as well as seizures. Patients also slowly lose the ability to move, talk, swallow and eat. Children with MLD often degenerate to a vegetative state and require round-the-clock care. Most patients die within five years of disease onset. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene, which under healthy circumstances produces an enzyme that breaks down sulfatides. Orchard’s Lenmeldy is an autologous gene therapy that uses a patient’s own stem cells to deliver a functioning copy of the ARSA gene. This mechanism of action won Lenmeldy the FDA’s Rare Pediatric Disease and Regenerative Medicine Advanced Therapy designations. Lenmeldy was also approved by the European Union in December 2020, where it is marketed as Libmeldy. The FDA’s approval of Lenmeldy is backed by data from two single-arm, open-label trials enrolling a total of 37 pediatric MLD patients. Over a median follow-up of 6.76 years, Lenmeldy led to significantly better overall survival compared with natural history data. The gene therapy also preserved motor and cognitive function in late-infantile MLD patients, whereas untreated counterparts had severe impairments. In terms of safety, Lenmeldy’s most common adverse events were febrile neutropenia, stomatitis, respiratory tract infections and rashes. These are reflected in the therapy’s label, which also bears warnings for thrombosis and thromboembolic events, encephalitis and the risk of hypersensitivity reactions. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

NEW YORK, March 19, 2024 /PRNewswire/ -- A new study in people undergoing surgery to treat seizures related to epilepsy shows that pauses in speech reveal information about how people's brains plan and produce speech. Led by researchers at NYU Grossman School of Medicine, the study results add to evidence that neighboring brain regions, the inferior frontal gyrus and the motor cortex, play an important role in such planning before words are said aloud. Both are part of the folded top layers of the brain, or cerebral cortex, which has long been known to control the muscle (motor) movements in the throat and mouth needed to produce speech. Less clear until now was how closely these regions determine the mix of sounds and words people want to say aloud, the authors report. Publishing in the journal Brain online March 19, the findings come from an analysis of hundreds of brain-mapping recordings made on 16 patients between the ages of 14 and 43 preparing for surgery to treat epilepsy at NYU Langone Health between 2018 and 2021. As a routine part of their procedures, surgeons electrically (and painlessly) stimulate specific parts of the brain while asking patients to perform standardized speaking tasks. Patients are asked, for example, to recite numbers or days of the week, or even the Pledge of Allegiance. The goal before surgery, researchers say, is to isolate and spare the parts of the brain nearby needed for speech, as marked by increased slurring or total loss of speech following electrical stimulation. This enables surgeons to remove only the brain tissue responsible for the errant electrical signals that cause seizures. What makes the new study unique, the researchers say, was their measurement and analysis of the time intervals, lasting less than two seconds, during which brain stimulation starts and speech becomes slurred and eventually stops. Previous research, they note, did not directly measure such latencies, but instead relied on behavioral observations to inform which brain regions were involved in whether a patient could continue to speak or not after stimulation of the cortex. Measuring the latencies, they say, provides new insight into the parts of the cortex involved in planning speech, even if not responsible for actually voicing and mouthing the words. Among the new study findings was that latencies between electrical stimulation and eventual loss of the ability to speak were different among brain regions. Latencies were longest in the inferior or lower regions of the motor cortex as well as another surface layer, the inferior frontal gyrus, at 1.0 second and 0.75 second, respectively. Because patients were able to keep speaking so long after stimulation, investigators say this suggests that these regions are more likely than other regions to be involved in planning what people want to say. Smaller latencies, lasting on average 0.5 second, were found in other parts of the motor cortex. Researchers say these shorter interruptions of speech indicate that these regions play a more crucial role in the physical mechanics of speaking. Based on these observations, researchers determined that a pattern of longer latencies corresponded to speech planning in different regions of the brain cortex more likely than shorter latencies, which corresponded to parts of the brain cortex involved in speech production. "Our study adds evidence for the role of the brain's motor cortex and inferior frontal gyrus in planning speech and determining what people are preparing to say, not just voicing words using the vocal cords or mouthing the words by moving the tongue and lips," said study lead investigator Heather Kabakoff, PhD, a speech pathologist at NYU Langone. "Our results show that mapping out the millisecond time intervals, or latencies, between electrical stimulation in parts of the brain to the disruption or slurring of words and eventual inability to speak can be used to better understand how the human brain works and the roles played by different brain regions in human speech," said study senior investigator and neuroscientist Adeen Flinker, PhD. "When it comes to mapping out functions of the brain cortex involved in speech, timing is key." Flinker, an associate professor in the Department of Neurology at NYU Langone, says the team's overall findings also confirm that motor execution and speech planning occur in distinctly different areas of the brain. Clinically, Flinker says the team findings, if further research confirms their work, could help surgeons better refine their brain mapping to protect patients' speech. Researchers say their next steps are to evaluate latency patterns in other parts of the brain to determine if they too play a role in the finer functions of planning speech or physically making sounds and words. Tasks include the naming of pictures aloud to determine if poststimulation latencies help distinguish parts of the brain needed to interpret visual inputs and process them into actual words. They also want to investigate whether latency patterns can expose real-time speech feedback mechanisms by measuring how long it takes patients to correct forced errors. This, they say, could provide insight into how people use the sound of their own voice to control the way they sound. Funding support for this research was provided by National Institutes of Health grants R01DC018805, R01NS109367, R01NS115929, and F32DC021094. Besides Flinker and Kabakoff, other NYU Langone researchers involved in the study are co-investigators Leyao Yu, BA; Daniel Friedman, MD; Patricia Dugan, MD; Werner Doyle, MD; and Orrin Devinsky, MD. Media Inquiries: David March 212-404-3528 david.march@nyulangone.org STUDY LINK STUDY DOI 10.1093/braincomms/fcae053 IMAGE ALSO AVAILABLE UPON REQUEST CAPTION Brain recordings in patients before surgery, as shown during electrical stimulation (as illustrated by sparks), reveal how neighboring regions, the inferior frontal gyrus (shaded center left) and the motor cortex (shaded center right), play a role in how people's brains plan and produce speech COURTESY CREDIT Adeen Flinker at NYU Langone Health/NYU Grossman School of Medicine View original content: SOURCE NYU Langone Health System