Cluster Headache

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.

Women who have both migraines and a long-term history of hot flashes and/or night sweats have a slightly higher risk of heart disease and stroke, and young women who have migraines have a higher risk of later persistent menopause symptoms, according to two new papers based on a data from a long-term study of the same group of women from their young adult to middle-age years. For middle-aged women plagued by migraines, or hot flashes and night sweats, another worry may linger in the backs of their minds: whether these experiences have set them up for a heart attack, a stroke or another cardiovascular crisis. After all, past research suggesting such a link during and after menopause has gotten a lot of attention. But a pair of new studies in the journal Menopause suggest that most of them don't need to worry as much, especially if they don't have both migraines and long-term hot flashes and night sweats. Instead, they should focus on tackling the other factors that can raise their cardiovascular risk by getting more sleep, exercise and healthy foods, quitting tobacco, and minding their blood pressure, blood sugar, cholesterol and weight. For women who have experienced both migraines and hot flashes or night sweats over many years, one of the new studies does suggest an extra level of cardiovascular risk. That makes heart disease and stroke prevention even more important in this group, says study leader Catherine Kim, M.D., M.P.H., of the University of Michigan. And for women currently in their 20s and 30s who experience migraines, the new research suggests that they might be heading for a higher risk of long-term menopause-related symptoms when they get older. Long-term study yields important insights Kim and her colleagues at Michigan Medicine, U-M's academic medical center, published the new pair of studies based on an in-depth analysis of data from a long-term study of more than 1,900 women who volunteered to have regular physical exams and blood tests, and to take yearly health surveys, when they were in their late teens to early 30s. Those women, now in their 50s and 60s, have provided researchers with a priceless view of what factors shape health in the years leading up to menopause and beyond, through their continued participation in the CARDIA study. "The anxiety and dread that women with migraines and menopausal symptoms feel about cardiovascular risk is real -- but these findings suggest that focusing on prevention, and correcting unhealthy habits and risk factors, could help most women," said Kim, who is an associate professor of internal medicine at U-M and a primary care physician. "For the subgroup with both migraines and early persistent hot flashes and night sweats, and for those currently experiencing migraines in their early adulthood, these findings point to an added need to control risks, and address symptoms early," she adds. Just over 30% of the middle-aged women in the study reported they had persistent hot flashes and night sweats, which together are called vasomotor symptoms or VMS because they relate to changes in the diameter of blood vessels. Of them, 23% had reported also having migraines. This was the only group for whom Kim and her colleagues found extra risk of stroke, heart attack or other cardiovascular events that couldn't be explained by other risk factors that have long been known to be linked to cardiovascular problems. In addition to those with persistent vasomotor symptoms starting in their 40s or before, 43% of the women in the study had minimal levels of such symptoms in their 50s, and 27% experienced an increase in VMS over time into their 50s and early 60s. The latter two groups had no excess cardiovascular risk once their other risk factors were taken into account, whether or not they had migraines. Use of hormone-based birth control and estrogen to address medical issues did not affect this risk. Controlling destiny In the study of data from the same women in their earlier stages of life, the researchers found that the biggest factors in predicting which ones would go on to have persistent hot flashes and night sweats were having migraines, having depression, and smoking cigarettes, as well as being Black or having less than a high school education. "These two studies, taken together, underscore that not all women have the same experiences as they grow older, and that many can control the risk factors that might raise their chances of heart disease and stroke later in life," said Kim. "In other words, women can do a lot to control their destiny when it comes to both menopause symptoms and cardiovascular diseases." She notes that the American Heart Association calls these risk factors the "Essential 8" and offers guides for what women, men and even children and teens can do to address them. Evolving knowledge and treatment The long-term study that the two new findings come from was specifically designed to look at cardiovascular risks when it launched in the mid-1980s. CARDIA stands for Coronary Artery Risk Development in Young Adults. Back in the 80s, knowledge about the biology of blood vessels, down to the cellular and molecular level, was nowhere near where it is today. Both vasomotor symptoms in menopause and migraines have to do with blood vessel contraction and dilation. But decades of research has shown the microscopic impacts on blood vessels of years of smoking, poor sleep, poor eating habits and lack of activity, as well as a person's genetic inheritance, life experiences and hormonal history. Newer injectable migraine medications called calcitonin gene-related peptide (CGRP) antagonists have reached the market in recent years. Using monoclonal antibodies, they target a key receptor on the surface of blood vessel cells to prevent migraines and cluster headaches. But they are expensive and not covered by insurance for all people with migraines. While the new study is based on data from years before these medications became available, Kim said she recommends them to her patients with persistent migraines, as well as working with them to understand what triggers their migraines and how to use other medications including pain relievers and antiseizure medications to prevent them. She also notes that the paper on future risk of persistent hot flashes and night sweats echoes the recent trend of using antidepressant medications to try to ease these menopause effects. Kim also says that evidence has grown about the importance of healthy sleep habits for reducing hot flashes, as well the short-term use of estradiol-based hormone therapy patches, which have not been shown to have a link to cardiovascular risk. And, she notes that research has not shown any over-the-counter supplement or herbal remedy to be effective, and that these are far less regulated than medications.

VANCOUVER, British Columbia--( BUSINESS WIRE )--Lobe Sciences Ltd. (OTCQB: LOBEF) (CSE: LOBE) ("Lobe" or the "Company"), a biopharmaceutical company focused on developing transformative medicines to treat rare diseases today provided an update from the Company’s lead clinical program, L-130, a proprietary stabilized psilocin conjugate drug candidate. The Phase 1 study (NCT06035900) was an open label clinical trial in 10 normal and healthy individuals designed to determine the safety and pharmacokinetic parameters of L-130 after a single oral dose. All subjects were evaluated for impacts on cognition and anxiolytic effects on day 1, 7 and 28. All subjects were dosed with no significant adverse events. The study confirmed the improved pharmacokinetics of L-130 delivered as a shelf-stable, capsule over its inactive prodrug, psilocybin. The mean maximum plasma concentration (C max ) for L-130 was significantly higher than expected, demonstrating superior bioavailability compared to published literature of psilocybin. Additionally, time to achieve the maximum plasma concentration (T max ) was lower for L-130 due to elimination of first-pass metabolism and immediate absorption in the gut. Full results are expected to be published in peer reviewed journals in the first half of 2024. “L-130 was designed based on the needs for a shelf stable oral molecule that can cleanly and consistently deliver psilocin directly, therefore eliminating the inconsistencies we see with the variability of psilocybin due to its need for first-pass metabolism,” stated Philip Young, Chairman and CEO of Lobe Sciences. Collectively, the superior pharmacokinetics of L-130 offers significant therapeutic advantages over other psilocybin formulations as psilocybin itself is not biologically active in humans and must be converted into psilocin via dephosphorylation in the gut. By eliminating this first pass metabolism, industry experts believe the direct administration of psilocin may offer therapeutic benefits such as faster onset time, improved dosing consistency, increased bioavailability and importantly, the potential for reduced side effects. “These initial Phase 1 results with L-130 support the industry’s hypothesis regarding the improved characteristics from a pharmacological standpoint of a stabilized psilocin vs that of psilocybin. We look forward to completing the remaining planned Phase 1 trials to further elucidate the dosing regimen and initiate our Phase 2 study in chronic cluster headache in 2024,” Mr. Young concluded. Management will be meeting with prospective investors and corporate partners during the 42 nd Annual J.P. Morgan Healthcare Conference in San Francisco on January 8-11. To schedule a meeting please contact ir@lobesciences.com About Lobe Sciences Ltd. Lobe Sciences is a biopharmaceutical company focused on developing transformative medicines to treat rare diseases. The Company, through collaborations with industry-leading partners, is additionally engaged in drug research and development using non-hallucinatory doses of stabilized psilocin based compounds to address unmet medical needs in orphan neurological therapeutic applications. NEITHER THE CSE NOR ITS REGULATION SERVICES PROVIDER HAVE REVIEWED OR ACCEPT RESPONSIBILITY FOR THE ACCURACY OR ADEQUACY OF THIS RELEASE. This does not constitute an offer to sell or a solicitation of offers to buy any securities. Forward Looking Statements This news release contains forward-looking statements relating to the future operations of the Company and other statements that are not historical facts. Forward-looking statements are often identified by terms such as "will", "may", "should", "anticipate", "expects" and similar expressions. All statements other than statements of historical fact included in this news release (including, without limitation, statements regarding the future plans and objectives of the Company, research and development using psychedelic compounds, and the development of innovative devices and delivery mechanisms to improve mental health and wellness) are forward-looking statements that involve risks and uncertainties. There can be no assurance that such statements will prove to be accurate, and actual results and future events could differ materially from those anticipated in such statements. Readers are cautioned that assumptions used in the preparation of the forward-looking statements may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company, including changes to the regulatory environment; that the Company's drug research and development activities may be unsuccessful; that drugs and medical devices produced by, or on behalf of, the Company, may not work in the manner intended or at all, and may subject the Company to product liability or other liability claims; that the Company may not be able to attain the Company's corporate goals and objectives; and other risk factors detailed in the Company's continuous disclosure filings from time to time, as available under the Company's profile at www.sedar.com . As a result, the Company cannot guarantee that any forward-looking statement will materialize and the reader is cautioned not to place undue reliance on any forward-looking information. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made only as of the date of this news release and the Company does not intend to update any of the included forward-looking statements except as expressly required by applicable Canadian securities laws.