Naratriptan Hydrochloride

NEW YORK--(BUSINESS WIRE)--Kallyope is a late-stage biotechnology company focused on developing innovative migraine and metabolic disease therapies for health challenges faced by hundreds of millions of people globally. Today, the Company presented results from a Phase 2b dose-ranging and proof of concept study of elismetrep, a novel TRPM8 channel blocker and the only agent known to be in late-stage development for the acute treatment of migraine. The data were reported during an oral presentation titled, “TRPM8 Antagonism with Elismetrep: A Novel Approach for Treating Migraine,” at the 2026 American Academy of Neurology (AAN) Annual Meeting underway in Chicago, IL. “Migraine is a highly disabling neurological disorder with attacks of severe throbbing pain, light sensitivity, nausea, and other debilitating symptoms that routinely force people to put their lives on hold without notice. Many migraine patients remain dissatisfied with currently available therapeutic options and regularly switch between medicines to seek relief,” said Peter J. Goadsby, MD, PhD, FRS, King Abdullah University of Science and Technology, Saudi Arabia. “Elismetrep has the potential to introduce an entirely new class of medicines, the TRPM8 migraine-associated channel blockers (MACB), to the millions of people suffering from migraine in need of more effective relief.” Phase 2b Study Overview and Key Data The study was a randomized, placebo-controlled, double-blind Phase 2b study (NCT06848075). Participants with 2-10 migraine attacks/month were randomized 2:1:2:2:1 to treat one migraine of moderate-severe pain with placebo or 2, 5, 10, or 20 mg elismetrep. Randomization was stratified by use of migraine preventive agents. Efficacy endpoints, assessed at 2h, were pain freedom (primary), freedom from most bothersome symptom (secondary), and pain relief (secondary). Efficacy data were recorded in real time in a patient-reported electronic-diary (e-Diary). Two-hour data were also captured by interview for those subjects with missing 2h e-Diary entries (All Data). Primary analyses used only e-Diary data, and a pre-specified supporting analysis of the primary endpoint used All Data. Of 431 participants randomized, 398 treated a qualifying migraine (mean age 46 years; 87% female; 35% on migraine preventive agents; 31% triptan resistant). Overall, elismetrep showed dose- and time-dependent efficacy with the 20 mg dose providing the greatest effects (see graphs). In the primary and supporting analyses for 2h pain freedom, response rates for elismetrep 20 mg vs. placebo were 17.6% vs. 9.1% (odds ratio [OR]=2.1, P=0.0650) (e-Diary only) and 19.6% vs. 9.1% (OR=2.4, nominal P=0.0344) (All Data) respectively. Response rates for 2h freedom from most bothersome symptom for elismetrep 20 mg vs. placebo were 38.3 % vs. 24.2% (OR=1.9, nominal P=0.0425). Response rates for 2h pain relief for elismetrep 20 mg vs. placebo were 58.8% vs. 42.4% (OR=1.9, nominal P=0.0293). There were no serious adverse events (AEs). The incidence of AEs was dose dependent. At 20 mg, all AEs were mild (70%) or moderate. The most common AEs in the 20 mg group were oral paresthesia (9.8%), feeling hot (9.8%), paresthesia (7.8%), hot flush (7.8.%), and flushing (5.9%). “These data are incredibly exciting for migraine patients, their physicians, and Kallyope. With only ~30% of migraine sufferers experiencing adequate and consistent relief with current therapeutics, there is a dire need for innovation,” said Brett Lauring, MD, PhD, Chief Medical Officer, Kallyope. “By targeting an entirely new part of the migraine cascade, we are hopeful that elismetrep can provide a safe and effective option for patients. We believe these data support the initiation of the registrational trials for elismetrep, anticipated to begin in mid-2026.” New Elismetrep Formulation Kallyope has developed a new liquid-filled softgel capsule (LSGC) formulation of elismetrep that results in substantially more rapid absorption compared to the formulation used in Phase 2b. The LSGC formulation will be used in future trials and is expected to result in earlier onset of migraine relief and enhanced efficacy at 2 hours (the timepoint where the primary endpoints for registrational trials are assessed). Full pharmacokinetic data from the LSGC formulation will be presented at an upcoming medical meeting in 2026. “The opportunity to provide a new treatment option for millions of people who suffer the debilitating effects of migraine is unique and important. Kallyope is committed to advancing this program rapidly to bring this potentially meaningful new medicine to patients as quickly as possible,” said Jay Galeota, CEO and President, Kallyope. About Transient Receptor Potential Melastatin 8 (TRPM8) Migraine is increasingly understood as a disorder of trigeminal sensory neuron hyperexcitability, in which trigeminal sensory pathways become sensitized, leading to sensory hypersensitivity and amplified pain signaling. TRPM8 is a polymodal sensory ion channel expressed on a distinct subset of trigeminal sensory neurons relevant to migraine pain signaling, migraine-associated channels. In the context of migraine, TRPM8 activity is associated with trigeminal sensory neuron pathway activation, contributing to pain onset and heightened, sustained pain signaling. TRPM8 is a mechanistically distinct therapeutic target from current migraine treatments, including calcitonin gene-related peptide (CGRP) receptor antagonists and serotonergic (5-HT)-based agents, and is the only TRP channel with an established genetic association to migraine in genome-wide association studies. About Elismetrep Elismetrep (K-304) is an investigational, novel, oral, TRPM8 migraine-associated channel blocker (MACB) that is highly selective for TRPM8 migraine-associated channels versus other TRP channels. Specifically designed to block TRPM8 activity, elismetrep has been shown to reduce migraine pain and associated symptoms. The Phase 2b dose-ranging and proof of concept trial for elismetrep for the acute treatment of migraine in adults demonstrated clinically meaningful efficacy that is competitive with the current leading marketed therapies. Registrational trials for elismetrep for the acute treatment of migraine are planned to initiate by mid-2026. Elismetrep is an investigational product and has not been approved by the FDA or any other regulatory agency. About Kallyope Kallyope is a late-stage biotechnology company focused on developing innovative migraine and metabolic therapies for health challenges faced by hundreds of millions of people globally. Kallyope’s lead programs target previously unknown drivers of disease in neural signaling pathways. The Company’s most advanced candidate, elismetrep (K-304), is poised to begin registrational trials for the acute treatment of migraine in mid-2026. The metabolism pipeline includes agents that target a novel target identified and validated by the Company’s Klarity™ platform, as well as oral small molecule approaches to the highly validated amylin pathway for the treatment of obesity. Kallyope was founded by world-leading neuroscientists and continues to explore the role of neural circuits in driving disease. For more information, visit www.kallyope.com.

Intranasal oxytocin blocks the release of calcitonin gene-related peptide (CGRP) in animal models and is the core technology of TNX-1900 for craniofacial pain conditions, including migraine and trigeminal neuralgia TNX-1900 will be studied in the trigeminal neurovascular reactivity model, by measuring the forehead skin blood flow response to capsaicin and electrical stimulation by Laser Speckle Contrast Imaging (LSCI) Oxytocin treatment affects a pathway distinct from the recently available CGRP migraine treatment drug class BERKELEY HEIGHTS, N.J., March 26, 2026 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a fully integrated, commercial biotechnology company, today announced that the first participant has been dosed in a Phase 1 investigator-initiated study to evaluate the effect of TNX-1900 (intranasal potentiated oxytocin) on trigeminal nerve-mediated vasodilation of the forehead using capsaicin as well as electrical stimulation, a model for trigeminal neurovascular reactivity, in healthy female human volunteers. Dr. Antoinette Maassen van den Brink, Professor of Neurovascular Pharmacology, Erasmus University Medical Center, is serving as principal investigator and sponsor for the study in a collaborative research agreement with Tonix. In animal studies, intranasal oxytocin has been shown to bind to oxytocin receptors in the trigeminal ganglion, blocking the release of calcitonin gene-related peptide (CGRP), a potent vasodilator critically involved in the pathogenesis of migraine.1 Dr. Maassen van den Brink has previously found a CGRP inhibitor and a triptan to inhibit the forehead dermal blood flow response to capsaicin in migraineurs and healthy volunteers, respectively.2,3 “We are excited to collaborate with Professor Maassen van den Brink on this proof-of-concept study investigating the potential for TNX-1900 for treating migraine, craniofacial pain, and other related conditions,” said Seth Lederman, MD, Chief Executive Officer of Tonix Pharmaceuticals. “While there are several CGRP inhibitors approved for the treatment of migraine, TNX-1900’s oxytocin treatment affects a distinct pathway that could address unmet needs. The results of the new study will guide future development of this potential non-opioid treatment for migraine and other craniofacial pain conditions.” As part of the preliminary work in support of this study, Dr. Maassen van den Brink’s team recently validated a newer detection method for dermal blood flow known as Laser Speckle Contrast Imaging (LSCI) in the trigeminal neurovascular reactivity model.4 “We are excited to be using LSCI in this study of TNX-1900, which adds to our established model by providing real-time and higher resolution dermal blood flow measurements, compared to Laser Doppler Perfusion Imaging used in earlier studies,” said Dr. Maassen van den Brink. “Oxytocin represents a potential new therapeutic option, targeting a pathway in migraine and craniofacial pain that is distinct from both the triptan and CGRP inhibitor migraine treatment drug classes.” About Migraine Migraine is a neurovascular condition that typically manifests in a throbbing moderate to severe headache which lasts at least four hours, often on one side of the head and aggravated by routine physical activity. It can also be accompanied by nausea, vomiting, visual disturbances, and sensitivity to bright light and loud noises.5 Epidemiological studies indicate that globally, approximately 1.2 billion individuals suffer from migraines annually.6 In the U.S., approximately 39 million Americans suffer from migraines, and among these individuals, approximately four million experience chronic migraines (15 or more headache days per month, at least eight of which are migraines).6 About TNX-1900 TNX-1900 (intranasal potentiated oxytocin) is a proprietary formulation of oxytocin in development as a candidate for the treatment of migraine and craniofacial pain. TNX-1900 is a drug-device combination product, based on an intranasal actuator device that delivers oxytocin into the nasal cavity. Oxytocin is a naturally occurring human peptide hormone that also acts as a neurotransmitter in the brain. Oxytocin has no recognized addiction potential. Oxytocin when delivered via the nasal route, concentrates in the trigeminal system7 resulting in binding of oxytocin to receptors on neurons in the trigeminal system, inhibiting the release of CGRP and transmission of pain signals returning from the site of CGRP release.1 Blocking CGRP release is a distinct mechanism compared with CGRP receptor antagonist and anti-CGRP antibody drugs, which block the binding of CGRP to its receptor, or bind to the peptide CGRP. The addition of magnesium to the oxytocin formulation in TNX-1900 enhances oxytocin receptor binding8 as well as having an inhibitory effect on trigeminal neurons and resultant craniofacial analgesic effects, as demonstrated in animal models.9 Intranasal oxytocin has been shown to be well tolerated in several clinical trials in both adults and children.10 Targeted nasal delivery results in low systemic exposure and lower risk of non-nervous system, off-target effects, which could potentially occur with systemic CGRP receptor antagonists and anti-CGRP (receptor) antibodies.11 For example, CGRP has roles in dilating blood vessels in response to ischemia, including in the heart. The Company believes nasally targeted delivery of oxytocin could translate into selective blockade of CGRP release from neurons in the trigeminal ganglion and not throughout the body, which could be a potential safety advantage over systemic CGRP inhibition. This mechanism is being investigated in a Phase 1 study to evaluate the effect of TNX-1900 on trigeminal nerve-mediated vasodilation of the forehead model for craniofacial pain. In addition, daily dosing is more rapidly reversible, in contrast to monthly or quarterly dosing, as is the case with anti-CGRP antibodies, giving physicians and their patients greater control. In addition to craniofacial pain conditions, TNX-1900 is being developed for treatment of binge eating disorder, adolescent obesity, bone health in pediatric autism and arginine-vasopressin deficiency. Tonix also has a license with the University of Geneva to use TNX-1900 for the treatment of insulin resistance and related conditions. Citations 1Tzabazis A, et al. Oxytocin receptor: Expression in the trigeminal nociceptive system and potential role in the treatment of headache disorders. Cephalalgia. 2016. 36(10):943-50.2de Vries Lentsch S, et al. CGRP-mediated trigeminovascular reactivity in migraine patients treated with erenumab. J Neurol Neurosurg Psychiatry. 2022 Aug;93(8):911-912.3Ibrahimi K, et al. A human trigeminovascular biomarker for antimigraine drugs: A randomized double-blind, placebo-controlled, crossover trial with sumatriptan. Cephalalgia. 2017 Jan;37(1):94-98.4van Lohuizen et al. 2025. Trigeminovascular activity using a forehead dermal blood flow model: preliminary results of a validation study. J Headache and Pain 26 (Suppl 2): 138.5The International Classification of Headache Disorders, 3rd Edition. Cephalalgia. 2018. 38(1):1-211.6Burch et al. Migraine: Epidemiology, Burden, and Comorbidity. Neurol Clin 37 (2019):631–649.7Yeomans DC, et al. Nasal oxytocin for the treatment of psychiatric disorders and pain: achieving meaningful brain concentrations. Transl Psychiatry. 2021. 11(1):388.8Antoni FA and Chadio SE. Essential role of magnesium in oxytocin-receptor affinity and ligand specificity. Biochem J. 1989. 257(2):611-4.9Cai Q, et al. Systematic review and meta-analysis of reported adverse events of long-term intranasal oxytocin treatment for autism spectrum disorder. Psychiatry Clin Neurosci. 2018. 72(3):140-151.10Yeomans, DC et al. 2017. US patent US2017368095.11MaassenVanDenBrink A, et al. Wiping out CGRP: potential cardiovascular risks. Trends Pharmacol Sci. 2016. 37(9):779-788. Tonix Pharmaceuticals Holding Corp. Tonix Pharmaceuticals* is a fully-integrated, commercial-stage biotechnology company focused on central nervous system (CNS) and immunology treatments in areas of high unmet medical need. TONMYA® (cyclobenzaprine HCl sublingual tablets 2.8 mg), is the first new treatment for fibromyalgia in adults in more than 15 years. Tonix’s CNS commercial infrastructure supports its marketed products, including its acute migraine products, Zembrace® Symtouch® (sumatriptan injection 3 mg) and Tosymra® (sumatriptan nasal spray 10 mg). Tonix is investigating TONMYA® in Phase 2 clinical trials to evaluate its potential in major depressive disorder and acute stress disorder/acute stress reaction. In addition, the Company’s CNS portfolio includes TNX-2900 (intranasal oxytocin), which is Phase 2 ready for the treatment of Prader-Willi syndrome, a rare disease. Tonix is also advancing a pipeline of immunology programs, including long-acting human monoclonal antibody TNX-4800 for Lyme disease prophylaxis, and TNX-1500, a third-generation CD40 ligand inhibitor for the prevention of kidney transplant rejection. To learn more, visit www.tonixpharma.com and follow the Company on LinkedIn and X. *Tonix’s product development candidates are investigational new drugs or biologics; their efficacy and safety have not been established and have not been approved for any indication. Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. TONMYA is a registered trademark of Tonix Pharma Limited. All other marks are property of their respective owners. Forward Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995 including those relating to the completion of the offering, the satisfaction of customary closing conditions, the intended use of proceeds from the offering and other statements that are predictive in nature. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. 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 successfully launch and commercialize TONMYA and any of our approved products; risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; 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 Company’s Annual Report on Form 10-K for the year ended December 31, 2025, as filed with the SEC on March 12, 2026, and periodic reports filed with the SEC on or after the date thereof. Tonix does not undertake an obligation to update or revise any forward-looking statement. 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 ContactsJessica MorrisTonix Pharmaceuticalsinvestor.relations@tonixpharma.com (862) 799-8599 Brian Korbastr partners(917) 653-5122brian.korb@astrpartners.com Media ContactsDeborah ElsonTonix Pharmaceuticalsdeborah.elson@tonixpharmaceuticals.com Ray JordanPutnam Insightsray@putnaminsights.com