Ischemic Attack, Transient

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.

Boy Band Icon and Allergy Sufferer Lance Bass Raises Awareness of First-of-its-Kind Navigation Tool Helping People Breathe Cleaner Air NEW YORK, March 5, 2024 /PRNewswire/ -- Allegra, a leading brand in allergy relief, announced today the nationwide launch of Allegra Airways, a groundbreaking navigation tool designed to help outdoor enthusiasts find real-time walking, biking, and running routes with cleaner air based on hyperlocal pollen and air pollution levels on a street-by-street basis. Recent studies show that air pollution alters the pollen structure, releasing more allergens and making pollen more "aggressive." 1,2 These allergens can likely penetrate deeper into your airways, provoking more severe allergy symptoms1,2. What's more concerning is that seasonal allergy symptoms are on the rise, with an estimated 50% of the global population expected to have an allergic disease by 2050.3 "As a brand dedicated to empowering allergy sufferers to live their greatness, Allegra is thrilled to introduce Allegra Airways, a tool that goes beyond traditional solutions, and brings true innovation to the category and deepens our engagement with our consumer," said Jordana Barish, US Allegra Brand Head. "By harnessing hyperlocal data on pollen and air pollution levels, Allegra Airways guides people along cleaner routes, making an invisible problem visible and enabling people to pursue their passions outdoors with confidence." Developed in collaboration with Ambee, a renowned climate and environmental data intelligence company, Allegra Airways enables users to input their start and end destinations at and calculate the cleanest routes based on real-time pollen concentrations and air pollution data from Ambee. "We are thrilled to partner with Allegra on this cutting-edge technology that provides a real time solution for allergy sufferers across the U.S.," explained Jaideep Singh Bachher, co-founder of Ambee. To mark the national launch, Allegra is partnering with boy band legend, Lance Bass, an allergy sufferer, LA outdoor enthusiast, and parent, to raise awareness of the increase in worsening allergy symptoms and how Allegra Airways helps him. "I use Allegra Airways to navigate the cleanest routes as I go about my day in LA including my daily walks with my twins," Lance shared. "I have a lot of exciting projects coming up this year and need to stay on my game and not let my allergy symptoms get in the way." Experience Allegra Airways at SXSW Allegra Airways will debut at SXSW, a global event that sits at the intersection of innovation and culture. On March 9th and 10th, purple Allegra-branded pedicabs fitted with Allegra Airways technology will transport visitors around downtown Austin to find the cleanest route based on real-time data from Ambee where pollen concentrations and air pollution are at its lowest. Join the Allegra Airways community to learn more about how air pollution impacts pollen and how Allegra Airways can help you breathe easy. Visit to find your path to clean air. About Allegra Allegra® Allergy is an oral antihistamine available over the counter at full prescription strength to relieve indoor and outdoor allergy symptoms, including sneezing, runny nose, itchy, watery eyes, and itchy nose or throat. It provides fast, non-drowsy relief that starts in just one hour and stays strong for 24 hours. Allegra can be used by adults and children 2 years of age and older. For more information, visit . Sanofi Consumer Healthcare, US, the makers of Allegra, was recently B Corp certified. This distinction highlights the company's commitment for an inclusive and regenerative economy through its social and environmental impact. Sanofi US CHC believes that healthier people and a healthy planet go hand in hand. About Ambee Ambee is a climate and environmental intelligence technology company that provides real-time and accurate data to empower businesses, individuals and communities to make informed decisions for better outcomes. Media Contact Tia Harris [email protected] (312) 515 – 0518 Annesi-Maesano I;Maesano CN;Biagioni B;D'Amato G;Cecchi L; "Call to Action: Air Pollution, Asthma, and Allergy in the Exposome Era." The Journal of Allergy and Clinical Immunology, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/34238507/. D'Amato, G.; Annesi-Maesano, I.; Biagioni, B.; Lancia, A.; Cecchi, L.; D'Ovidio, M.C.; D'Amato, M. New Developments in Climate Change, Air Pollution, Pollen Allergy, and Interaction with SARS-CoV-2. Atmosphere 2023, 14, 848. Cecchi L, D'Amato G, Annesi-Maesano I. External exposome and allergic respiratory and skin diseases. J Allergy Clin Immunol 2018;141:846-57. SOURCE Allegra

Sustained efficacy was confirmed with an annualized relapse rate of 0.098 and 67% of patients were relapse-free at six years Safety was consistent with prior findings and the established safety pro Zeposia with nearly 10 years of clinical experience In a separate DAYBREAK analysis, nearly 97% of followed patients were relapse-free at 90 days post Zeposia discontinuation; patients that did relapse showed no evidence of rebound effect PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb Company (NYSE: BMY) today announced new results from the Phase 3 DAYBREAK open-label extension trial, demonstrating the long-term efficacy and safety pro Zeposia (ozanimod) in patients with relapsing forms of multiple sclerosis (MS). These data (Poster #P090) and nine additional abstracts will be presented at the 9th annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2024 in West Palm Beach, Florida taking place February 29 to March 2. In the DAYBREAK long-term extension study, treatment with Zeposia demonstrated a low annualized relapse rate of 0.098. Three- and six-month confirmed disability progression was absent in 82.8% and 84.8% of participants in the trial respectively. At Month 60, the adjusted mean number of new/enlarging T2 lesions per scan (range: 0.79–0.93) and the adjusted mean number of gadolinium-enhancing lesions (0.06–0.08) were similar across patient cohorts. “These DAYBREAK data continue to validate the role of Zeposia in the long-term management of relapsing forms of multiple sclerosis, with two-thirds of patients relapse-free at six years of treatment,” said Bruce Cree, MD, PhD, MAS, study investigator and professor of Clinical Neurology, University of California San Francisco (UCSF) Weill Institute for Neurosciences and Clinical Research Director, UCSF MS Center. “These findings add to our confidence in Zeposia as an important treatment option for people living with the disease, highlighting its efficacy and safety over time.” In the DAYBREAK trial, 2,494 participants were exposed to Zeposia for an average of 60.9 months (12,664.7 person-years); 2,219 participants (89.0%) had any treatment-emergent adverse event (TEAE), 381 (15.3%) had a serious TEAE and 98 (3.9%) discontinued the study due to a TEAE. The most common TEAEs were nasopharyngitis (21.3%), headache (17.1%), COVID-19 infection (16.5%) and upper respiratory tract infection (12.4%). No new safety signals emerged; data from this long-term observational study of patients treated for up to 81.5 months were consistent with the established safety pro Zeposia. Additionally, a separate analysis (Poster #P097) was conducted to assess the risk of rebound after Zeposia discontinuation in the DAYBREAK trial. Five hundred forty-four participants (21.8%) discontinued the study early, while 1,950 participants (78.2%) remained on treatment until the end of the trial. Approximately 2.2% were known to have relapsed after permanently discontinuing Zeposia, with 87.3% of relapses occurring between 29 and 90 days (median time to onset: 61 days) after discontinuation. Nearly all patients were not taking any disease modifying therapy for MS at the time of relapse. Most relapses were mild (n=20 [36.4%]) or moderate (n=34 [61.8%]) and most patients made a complete recovery. No post-treatment relapse was associated with rebound effect, characterized by severe exacerbation of disease or severe persistent increase in disability. “Currently no cure exists for multiple sclerosis, but effective strategies and treatments can help slow disease progression and alleviate symptoms,” said Jonathan Sadeh, MD, MSc, senior vice president and head of global program leaders, Immunology, Cardiovascular and Neuroscience development, Bristol Myers Squibb. “These DAYBREAK efficacy, safety and rebound data underscore a consistent and sustained safety and efficacy pro add to the body of evidence supporting Zeposia’s role in the treatment armamentarium. We remain focused on advancing care and delivering meaningful innovations in neuroscience, including for the millions of people impacted by relapsing forms of multiple sclerosis.” At the ACTRIMS Forum 2024, Bristol Myers Squibb and collaborators will present multiple abstracts that reinforce the company’s growing body of research on Zeposia as a treatment for relapsing forms of MS and unwavering commitment to people living with the disease. Summary of Presentations: Bristol Myers Squibb presentations featured at the ACTRIMS Forum 2024 include: Zeposia clinical abstracts Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Final analysis of the DAYBREAK open-label extension study Author: Krzysztof Selmaj Presentation Number: P090 Session Number: Poster session 1 Absence of rebound effect following ozanimod discontinuation among participants in the DAYBREAK open-label extension study Author: Ralf Gold Presentation Number: P097 Session: Poster session 1 Patient-reported outcomes after 1 year of ozanimod use for early relapsing multiple sclerosis: An interim analysis of the ENLIGHTEN study Author: Sarah Morrow Presentation Number: P433 Session: Poster session 2 Baseline predictors of long-term disability progression in ozanimod-treated participants with relapsing multiple sclerosis from the SUNBEAM, RADIANCE, and DAYBREAK trials Author: Hans-Peter Hartung Presentation Number: P096 Session: Poster session 1 Changes in cognitive functioning over 1 year in ozanimod-treated patients with early relapsing multiple sclerosis: An interim analysis of the ENLIGHTEN study Author: John DeLuca Presentation Number: P354 Session: Poster session 2 Long-term efficacy of ozanimod in disease-modifying treatment–naive vs experienced patients with relapsing multiple sclerosis Author: Diego Centonze Presentation Number: P092 Session: Poster session 1 Long-term efficacy of the sphingosine 1-phosphate receptor modulator ozanimod by age category in patients with relapsing multiple sclerosis: Final results from two Phase 3 trials and an open-label extension trial Author: Bruce Cree Presentation Number: P091 Session: Poster session 1 Effects of ozanimod on cognitive processing speed: Updated findings from the Phase 3 SUNBEAM and DAYBREAK extension trials Author: John DeLuca Presentation Number: P353 Session: Poster session 2 Zeposia MS health economics outcomes research abstracts Real-world clinical outcomes for disease-modifying therapy–naïve and experienced patients with multiple sclerosis treated with ozanimod: A U.S. retrospective medical chart review Author: Damemarie Paul Presentation Number: P477 Session: Poster session 2 Ozanimod use in patients with multiple sclerosis treated in a large U.S. healthcare system: A retrospective case series Author: Jennifer Hadlock Presentation Number: P478 Session: Poster session 2 Bristol Myers Squibb thanks the patients and investigators who have participated in Zeposia clinical trials. About DAYBREAK DAYBREAK was a Phase 3, multi-center, long-term open-label extension study to evaluate the safety and efficacy of Zeposia (ozanimod) administered orally to patients with relapsing forms of multiple sclerosis (RMS). Eligible patients from the RADIANCE, SUNBEAM and RPC01-1001 trials diagnosed with RMS were enrolled to receive treatment until the end of the DAYBREAK. Patients in the trial received Zeposia 0.92 mg (equivalent to 1 mg). About Multiple Sclerosis Multiple sclerosis (MS) is a disabling, unpredictable disease in which the immune system attacks the protective myelin sheath that covers the nerves. The myelin damage disrupts communication between the brain and the rest of the body. Ultimately, the nerves themselves may deteriorate—a process that's currently irreversible. MS affects 700,000 people in Europe and approximately 2.9 million people worldwide. Relapsing forms of MS (RMS), including clinically isolated syndrome, relapsing remitting disease and active secondary progressive disease, is characterized by clearly defined attacks of worsening neurologic function. These attacks—often called relapses, flare-ups or exacerbations—are followed by partial or complete recovery periods. During these recovery periods, also called remissions, symptoms improve partially or completely with no apparent progression of disease. However, smoldering neuroinflammation can be present from the earliest stages of MS, which is underlying and continuous disease activity occurring simultaneously in different areas of the brain that contributes to disability accumulation. Since MS relapses are unpredictable, patients can feel frustrated, stressed or scared when they occur. RMS is the most common disease course at the time of diagnosis. Approximately 85% of patients are initially diagnosed with RMS, compared with 10%-15% diagnosed with progressive forms of the disease. Bristol Myers Squibb: Delivering Breakthrough Science for Meaningful Interventions in Neuroscience Neurological conditions represent some of the greatest challenges of our time because of their impact on society, including patients, caregivers, families and healthcare systems. At Bristol Myers Squibb, we are committed to advancing our robust pipeline of potential medicines for neurological disorders with the goal of modifying disease and improving quality of life. Leveraging genetics, biomarkers and predictive sciences, we target key pathways involved in the initiation and progression of neurological diseases to develop therapies with the potential to optimize patient outcomes. About Zeposia (ozanimod) Zeposia (ozanimod) is an oral, sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Zeposia blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which Zeposia exerts therapeutic effects in multiple sclerosis (MS) is unknown but may involve the reduction of lymphocyte migration into the central nervous system. Zeposia is approved in numerous countries around the world for the treatment of adults with relapsing forms of MS and adults with moderately to severely active ulcerative colitis. U.S. FDA APPROVED INDICATIONS ZEPOSIA® (ozanimod) is indicated for the treatment of: Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Moderately to severely active ulcerative colitis (UC) in adults. IMPORTANT SAFETY INFORMATION Contraindications: Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have a presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker Patients with severe untreated sleep apnea Patients taking a monoamine oxidase (MAO) inhibitor Infections: ZEPOSIA may increase the susceptibility to infections. Life-threatening and rare fatal infections have occurred in patients receiving ZEPOSIA. Obtain a recent (i.e., within 6 months or after discontinuation of prior MS or UC therapy) complete blood count (CBC) including lymphocyte count before initiation of ZEPOSIA. Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. Consider interruption of treatment with ZEPOSIA if a patient develops a serious infection. Continue monitoring for infections up to 3 months after discontinuing ZEPOSIA. Herpes zoster was reported as an adverse reaction in ZEPOSIA-treated patients. Herpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate (S1P) receptor modulators. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus (VZV), should be tested for antibodies to VZV before initiating ZEPOSIA. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with ZEPOSIA. Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another S1P receptor modulator. If CM is suspected, ZEPOSIA should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated. In the MS and UC clinical studies, patients who received ZEPOSIA were not to receive concomitant treatment with antineoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS and UC. Concomitant use of ZEPOSIA with any of these therapies would be expected to increase the risk of immunosuppression. When switching to ZEPOSIA from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects. Use of live attenuated vaccines should be avoided during and for 3 months after treatment with ZEPOSIA. If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA. Progressive Multifocal Leukoencephalopathy (PML): PML is an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability. PML has been reported in patients treated with S1P receptor modulators, including ZEPOSIA, and other MS and UC therapies and has been associated with some risk factors. If PML is suspected, withhold ZEPOSIA and perform an appropriate diagnostic evaluation. If confirmed, treatment with ZEPOSIA should be discontinued. Immune reconstitution inflammatory syndrome (IRIS) has been reported in MS patients treated with S1P receptor modulators who developed PML and subsequently discontinued treatment. IRIS presents as a clinical decline in the patient’s condition that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes on MRI. The time to onset of IRIS in patients with PML was generally within a few months after S1P receptor modulator discontinuation. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken. Bradyarrhythmia and Atrioventricular Conduction Delays: Since initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays, dose titration is recommended to help reduce cardiac effects. Initiation of ZEPOSIA without dose escalation may result in greater decreases in heart rate. If treatment with ZEPOSIA is considered, advice from a cardiologist should be sought for those individuals: with significant QT prolongation with arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugs with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension with a history of Mobitz type II second-degree or higher AV block, sick sinus syndrome, or sino-atrial heart block Liver Injury: Elevations of aminotransferases may occur in patients receiving ZEPOSIA. Obtain liver function tests, if not recently available (i.e., within 6 months), before initiation of ZEPOSIA. Patients who develop symptoms suggestive of hepatic dysfunction should have hepatic enzymes checked and ZEPOSIA should be discontinued if significant liver injury is confirmed. Fetal Risk: There are no adequate and well-controlled studies in pregnant women. Based on animal studies, ZEPOSIA may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during treatment and for 3 months after stopping ZEPOSIA. Women who become pregnant while taking ZEPOSIA for MS may enroll in the ZEPOSIA pregnancy registry by calling 1-877-301-9314 or visiting . Increased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatment and persisted throughout treatment. Blood pressure should be monitored during treatment and managed appropriately. Certain foods that may contain very high amounts of tyramine could cause severe hypertension in patients taking ZEPOSIA. Patients should be advised to avoid foods containing a very large amount of tyramine while taking ZEPOSIA. Respiratory Effects: ZEPOSIA may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy, if clinically indicated. Macular Edema: S1P modulators have been associated with an increased risk of macular edema. Patients with a history of uveitis or diabetes mellitus are at increased risk. Patients with a history of these conditions should have an ophthalmic evaluation of the fundus, including the macula, prior to treatment initiation and regular follow-up examinations. An ophthalmic evaluation is recommended in all patients at any time if there is a change in vision. Continued use of ZEPOSIA in patients with macular edema has not been evaluated; potential benefits and risks for the individual patient should be considered if deciding whether ZEPOSIA should be discontinued. Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a S1P receptor modulator. If a ZEPOSIA-treated patient develops unexpected neurological or psychiatric symptoms or any symptom/sign suggestive of an increase in intracranial pressure, a complete physical and neurological examination should be conducted. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, treatment with ZEPOSIA should be discontinued. Unintended Additive Immunosuppressive Effects From Prior Immunosuppressive or Immune-Modulating Drugs: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation. Initiating treatment with ZEPOSIA after treatment with alemtuzumab is not recommended. Severe Increase in Multiple Sclerosis (MS) Disability After Stopping ZEPOSIA: In MS, severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping ZEPOSIA treatment so patients should be monitored upon discontinuation. After stopping ZEPOSIA in the setting of PML, monitor for development of immune reconstitution inflammatory syndrome (PML-IRIS). Immune System Effects After Stopping ZEPOSIA: After discontinuing ZEPOSIA, the median time for lymphocyte counts to return to the normal range was 30 days with approximately 90% of patients in the normal range within 3 months. Use of immunosuppressants within this period may lead to an additive effect on the immune system, therefore caution should be applied when initiating other drugs 4 weeks after the last dose of ZEPOSIA. Most Common Adverse Reactions that occurred in the MS clinical trials of ZEPOSIA-treated patients (≥4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension. In the UC clinical trials, the most common adverse reactions that occurred in ≥4% of ZEPOSIA-treated patients and greater than in patients who received placebo were upper respiratory infection, liver test increased, and headache. Use in Specific Populations: Hepatic Impairment: Dosage adjustment in patients with mild or moderate hepatic impairment (Child-Pugh class A or B) is required, and use of ZEPOSIA in patients with severe hepatic impairment (Child-Pugh class C) is not recommended. For additional safety information, please see the full Prescribing Information and Medication Guide. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram. Cautionary Statement Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that results of future post-marketing studies will be consistent with the results of this study, that Zeposia (ozanimod) for the additional indication described in this release may not be commercially successful, any marketing approvals, if granted, may have significant limitations on their use, and that continued approval of such treatment for such additional indication may be contingent upon verification and description of clinical benefit in additional confirmatory trials. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise. corporatefinancial-news