Sumatriptan Succinate

偏头痛作为神经-血管功能失调导致的高度失能的发作性疾病,已影响全球超过十亿人。其特征表现为中至重度头痛,常伴有恶心、呕吐、畏光、畏声。近日，夫瑞奈珠单抗注射液的获批让偏头痛这一疾病再次备受瞩目，除了CGRP这一靶点，我们还可以向哪一个方向探索？ 大鼠作为偏头痛经典模型构建动物，到今日为止仍因其易于手术操作、行为学表型丰富等原因占据偏头痛研究的半壁江山。表中多为较为经典的偏头痛前兆（CSD）和偏头痛发作期的经典模型，仅针对扩血管作用目前的经典模型包括辣椒素注射诱导局部血管扩张、PACAP注射诱导面部血管扩张等。 目前药康已针对经典NTG模型开发出稳定的急性偏头痛大鼠模型，其特点在于通过稳定的自发痛评估和诱发痛评估实现更精准的大鼠疼痛行为学判定。 动物模型构建 1、实验动物：6w 雄性SD大鼠 2、模型构建：通过在颈部皮下注射NTG（10mg/kg）诱导偏头痛。 给药方式解析：皮下、颈部or静脉？ 使用NTG造模早已成为偏头痛模型的主流方法，但是NTG的给药方式，不同文献仍存在差异。皮下注射后动物缓慢吸收NTG，偏头痛整体发作周期可达1-1.5h，时间窗更长，可在药效评估时进行多种行为学；腹腔注射后，NTG快速吸收，偏头痛发作周期0.5-1h，适用于机制研究；静脉滴注NTG可诱发动物延迟触发典型发作头痛。 造模剂配制差异：NTG用什么配制？ 目前已有文献报道，生理盐水溶解和丙二醇/乙醇混合物溶解NTG均可以诱发动物的偏头痛，动物的疼痛和畏光表型接近。也有文献报道，仅使用丙二醇/乙醇混合物（不添加NTG）也可诱发动物的畏光和活动减少，使得动物在明暗箱中的反应性有差异。 3、模型评价 我们通过注射NTG诱导了动物的面部抓挠（自发痛）和von Frey眶周疼痛阈值降低（诱发痛），从多个维度检测动物的疼痛表型。 图1. NTG注射后动物出现面部抓挠和眶周诱发痛 n=4-6/group. *: p < 0.05; **: p < 0.01; ***: p < 0.001; ****: p < 0.0001 面部抓挠是较为常见的偏头痛相关表型；持续观测NTG 给药后 1.5 h 内动物行为可见，该指标个体差异较大，通过Von Frey检测眶周的机械痛结果更稳定，个体差异性更小。 图2. 眶周机械痛检测位点（绿色）[1] 药效测试 为检测该模型对于药物的反应性，我们使用了舒马曲坦进行药效测试。舒马曲坦是一种小分子药物，通过对三叉神经系统的颅内血管和感觉神经上的5-HT1B/1D受体的激动作用，实现颅内血管收缩和抑制促炎性神经肽释放，从而缓解偏头痛。 通过分时相观察动物的面部抓挠，NTG注射后40-50min出现峰值。舒马曲坦的给药避免了峰值的出现，同时升高了眶周机械痛的阈值，缓解了动物的外周敏化。除此之外，文献中还会通过明暗箱来表征动物的畏光行为、面部血流变化表征血管扩张情况。 图3. NTG注射后不同时相的面部抓挠次数和眶周机械痛 n=6/group. *: p < 0.05; **: p < 0.01; ***: p < 0.001; ****: p < 0.0001 药康生物可提供多种急性和慢性偏头痛动物模型和行为学评估方法，急性模型适合快速筛选药物和初步探索NO相关偏头痛机制，慢性模型模拟临床中枢敏化过程，适用于研究长期效应和药效验证。 下期预告： Nav1.8作为大热门疼痛靶点，你的药物为何对靶点反应性不佳？什么模型适合用于Nav1.8的机制和药效研究？下期药康生物为你带来多种模型的疼痛靶点变化解析，一键解锁你的模型选择困难症。 参考文献 [1] Andersen VK, Hansen BS, Fungbrant E, Hestehave S, Haanes KA, Nordahl KML. Light-aversion and cephalic allodynia in an intravenous CGRP model of migraine-like behaviour in male and female rats. J Headache Pain. 2026;27(1):45. doi:10.1186/s10194-026-02278-2 作者｜杨彦容 审核｜吴正中 编辑｜Ning 有任何技术交流可咨询康仔 关于药康生物 江苏集萃药康生物科技股份有限公司（科创板代码：688046）是一家专注于实验动物小鼠模型研发、生产及非临床研究服务的国家级高新技术企业，同时是科技部认定的国家遗传工程小鼠资源库共建单位。 依托CRISPR/Cas9、ES打靶等在内的基因编辑技术，公司建立了国际一流的基因修饰动物模型研发平台，拥有近3万种自主知识产权的基因工程小鼠模型品系，其中包括基因敲除/条件性敲除小鼠品系（"斑点鼠计划"）、药靶基因人源化模型、复杂疾病模型、系列免疫缺陷小鼠品系、无菌小鼠品系以及用于抗体药物发现的NeoMab®全人源抗体转基因小鼠，为全球科研机构、CRO公司及医药企业提供全面的模型资源支持。公司提供从基因编辑定制（包括转基因TG、基因敲除KO、基因敲入KI及点突变PM等）、模型繁育到功能药效分析的全流程一站式服务，服务范围涵盖肿瘤、自身免疫性疾病、代谢心血管疾病、神经退行性疾病、感染性疾病及罕见病等重点疾病领域，具体包括靶点验证、药效学评价和非GLP安全性评价等临床前研究。 药康生物致力于成为全球实验动物模型领域的领导者，通过持续深化基因编辑技术的创新应用和资源整合，为生命科学研究和生物医药产业提供高质量的动物模型和技术服务，推动人类健康事业发展。 点赞 收藏 分享

TONMYA® net sales totaled approximately $11 million, an increase of 197% quarter-over-quarter Commercial and government payer coverage for TONMYA meaningfully expanded, now reaching approximately 136 million covered lives (43% of total U.S. lives) First patient enrolled in Phase 2 HORIZON study of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) 5.6 mg for the treatment of major depressive disorder (MDD) Phase 2 adaptive field study of TNX-4800 for the prevention of Lyme disease in the U.S. on track to start in the first quarter of 2027 pending final FDA review and agreement on study protocol ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); Approximately $176.2 million in cash and cash equivalents as of June 30, 2026 Conference call today at 8:30 a.m. ET BERKELEY HEIGHTS, N.J., Aug. 10, 2026 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (“Tonix” or the “Company”), a fully integrated, commercial-stage biopharmaceutical company, today announced financial results for the quarter ended June 30, 2026, and provided an overview of recent operational highlights. “We are pleased with the execution of TONMYA’s launch, including nearly tripling net sales and achieving growth across our key metrics in the second quarter,” said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. “We are seeing TONMYA’s value resonate among healthcare providers and patients as the first FDA-approved treatment for fibromyalgia in 15 years. It is a first-in-class, non-opioid analgesic designed for daily bedtime administration and long-term use. We are now beginning to see coverage translate into broader patient access following the execution of agreements with commercial payers, managed Medicare, and Medicaid. Our newly expanded sales force is expected to deploy in the field by September. We believe we are well positioned to reach more of our target prescribers and support the treatment of more patients with TONMYA.” Dr. Lederman continued, “We are also progressing our clinical development pipeline priorities. We enrolled the first patient in HORIZON, our potentially pivotal Phase 2 study of TNX-102 SL in MDD. For Lyme prevention, we expect to start enrollment in the first quarter of 2027 in a Phase 2 adaptive field study after we reached alignment with FDA on the development path for TNX-4800, an investigational long-acting borreliacidal human monoclonal antibody targeting OspA on Borrelia burgdorferi .” Commercial Updates TONMYA (cyclobenzaprine HCl sublingual tablets): a centrally acting, non-opioid analgesic for the treatment of fibromyalgia in adults; commercially launched on November 17, 2025 Performance Across Key Metrics In the second quarter of 2026, key metrics include: 12,592 total prescriptions, increasing 100% quarter-over-quarter. This includes bridge prescriptions that are facilitated through the Company’s digital pharmacy channel. Bridge prescriptions represent initial patient fills provided while coverage determinations are pending and do not immediately generate net product revenue. New patient prescriptions increased 36% quarter-over-quarter. Refills increased 207% quarter-over-quarter. Payer Access and Coverage The Company is prioritizing ongoing engagement with commercial payers, managed Medicare, and Medicaid to increase access: Tonix announced commercial payer agreements with two leading GPOs in May and June 2026, providing access to a combined approximate 52 million lives (29% of the total commercial lives in the U.S.). Currently, total coverage for TONMYA across commercial, managed Medicare, and Medicaid channels represents approximately 136 million covered lives (~43% of the approximately 314 million covered lives in the U.S.). When the managed Medicare payer coverage agreement goes into effect on January 1, 2027, it will add approximately nine million Medicare lives (16% of the approximately 55 million Medicare lives in the U.S.). Total coverage will then reach approximately 145 million covered lives (~46% of the 314 million covered lives in the U.S.). TONMYA is covered under Medicaid in most states, representing approximately 75 million lives. Commercial Execution Following these coverage milestones and encouraging trends across launch key performance indicators, Tonix is implementing its strategy to expand the TONMYA sales force. The Company expects to deploy 50 new sales representatives in the field by September 2026, bringing the full sales force to approximately 150 people. In parallel, the Company is advancing marketing activities to enhance understanding of fibromyalgia and product awareness among patients and healthcare providers, as well as non-commercial medical affairs initiatives. In the second quarter of 2026, Tonix presented data highlighting TONMYA at the European Alliance of Associations for Rheumatology (EULAR) 2026, 2026 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, and Professional Society for Health and Outcomes Research (ISPOR 2026) Annual Meeting, as well as published a manuscript in the peer-reviewed journal, Clinical Pharmacology in Drug Development . Key Product Pipeline Candidates: Recent Highlights Central Nervous System (CNS) Pipeline TNX-102 SL (cyclobenzaprine HCl sublingual tablets): in Phase 2 development for MDD In June 2026, Tonix enrolled the first patient in HORIZON, a potentially pivotal, 6-week, randomized, double-blind, placebo-controlled Phase 2 study of TNX-102 SL 5.6 mg as a first-line monotherapy in adults with MDD. Approximately 360 patients are expected to enroll at approximately 30 U.S. sites, with the primary endpoint of change from baseline in MADRS (Montgomery-Asberg Depression Rating Scale) total score at Week 6. TNX-102 SL targets disturbed sleep through antagonism at four neuronal receptors, an approach mechanistically distinct from currently available antidepressants. TNX-102 SL: in Phase 2 development for acute stress disorder (ASD) and acute stress reaction (ASR) The U.S. Department of Defense-funded Optimizing Acute Stress Reaction Interventions (OASIS) study is being conducted by the University of North Carolina under an investigator-initiated IND. Topline data is expected to be reported mid-2027. TNX-1300 (double-mutant cocaine esterase) for cocaine intoxication; Phase 2 program has Breakthrough Therapy designation from the FDA, with no products on the market for this indication The Company plans to meet with the FDA in 2026 to inform the clinical design of the next Phase 2 study (a Phase 2 study has been completed). Infectious Disease Pipeline TNX-4800 (anti-OspA mAb): Phase 2-ready long-acting human monoclonal antibody in development for the seasonal prevention of Lyme disease in the U.S., for which no FDA-approved vaccines or prophylactics are available The Company received final minutes from a Type C meeting held with the FDA in early third quarter of 2026. The adaptive Phase 2 field study is expected to start in the first quarter of 2027 pending final FDA review and agreement on the study protocol. The study will be a randomized, double-blind, placebo-controlled field study, with the primary efficacy endpoint of protection through six months, and a key secondary efficacy endpoint of protection through three months. Adults aged 18 and older from U.S. Lyme-endemic areas who engage in activities that increase their risk of deer tick bites will be randomized to receive placebo or two doses of TNX-4800: 450 mg subcutaneous (SC) dose at Day 1, and a second dose of 450 mg SC dose three months later at Day 85. In April 2026, Tonix presented Phase 1 data and announced plans for an adaptive Phase 2 field study of TNX-4800 at the 4 th Annual Ticks and Tickborne Diseases Symposium at Johns Hopkins University. The Company expects to deliver investigational product to the Phase 2 clinical study sites in the first quarter of 2027. TNX-801 (recombinant horsepox virus): an attenuated, minimally replicative, live virus vaccine candidate in pre-clinical development for the prevention of smallpox and mpox In July 2026, Tonix announced a new paper in the Journal of Virology describing new murine models for investigating mpox pathogenesis. TNX-801 is expected to enter a Phase 1 study in mid-2027 pending FDA clearance of the Investigational New Drug (IND) application. TNX-4200 (broad-spectrum antiviral targeting CD45) for the prevention or treatment of high-lethality infections to improve the medical readiness of military personnel in biological threat environments The ongoing TNX-4200 program is supported by an up to $34 million contract over five years from the Department of Defense’s Defense Threat Reduction Agency (DTRA). In the second quarter, the project began its next project phase. Immunology Pipeline TNX-1500 (dimeric Fc-modified anti-CD40L, humanized mAb): Phase 2-ready third-generation anti-CD40L for prophylaxis of kidney transplant rejection and treatment of autoimmune diseases In July 2026, the World Health Organization (WHO) included mosdaprubart as the proposed International Nonproprietary Name (pINN) for TNX-1500, pending publication as a recommended INN. In May 2026, Tonix announced the publication of Phase 1 clinical data for TNX-1500 in the Journal of Clinical Immunology that support TNX-1500 as a potentially first-in-class, best-in-class, third-generation anti-CD40L monoclonal antibody for the prevention of kidney transplant rejection. A Phase 2, open-label, investigator-initiated study in adult kidney transplant patients at Massachusetts General Hospital (MGH) is expected to initiate in the second half of 2026 pending FDA clearance of MGH’s IND application. The study is expected to enroll five adult kidney transplant recipients. Rare Disease Pipeline TNX-2900 (intranasal potentiated oxytocin): in development for Prader-Willi syndrome, with Orphan Drug and Rare Pediatric Disease designation that could potentially make Tonix eligible for a Priority Review Voucher upon approval Tonix plans to initiate a Phase 2, randomized, double-blind, placebo-controlled study in children and adolescents with Prader-Willi syndrome in the second half of 2027. Immuno-oncology Pipeline TNX-1700 (TFF2-albumin fusion protein): in preclinical development for gastric and colorectal cancer In June 2026, Tonix presented preclinical data at the Ninth JCA-AACR Special Joint Conference on Novel Therapies and Diagnostics in Upper Digestive and Head and Neck Cancers demonstrating TNX-1700 normalizes myelopoiesis and enhances anti-PD-1 therapy in gastric cancer. Financial: Recent Highlights Tonix had approximately $176.2 million of cash and cash equivalents as of June 30, 2026, compared to approximately $207.6 million as of December 31, 2025. Net cash used in operating activities was approximately $84.6 million for the six months ended June 30, 2026, compared to $31.4 million for the same period in 2025. Subsequent to quarter-end, the Company raised $3.7 million in proceeds under its At-the-Market facility. The Company believes that its cash resources as of June 30, 2026, together with the net proceeds that it raised from equity offerings in the third quarter of 2026 to date, will meet its planned operating and capital expenditure requirements into early second quarter of 2027. As of August 7, 2026, the Company had 17,151,024 shares of common stock outstanding. Second Quarter 2026 Financial Results Net product revenue for the second quarter 2026 was approximately $13.5 million, compared to $2.0 million for the same period in 2025, and consisted of combined net sales of TONMYA, Zembrace® SymTouch®, and Tosymra®. Net revenue from sales of TONMYA for the second quarter was approximately $11.0 million. Net revenue from sales of Zembrace SymTouch and Tosymra was approximately $2.5 million, compared to $2.0 million for the same quarter in 2025. Cost of sales for the second quarter 2026 was approximately $0.7 million, compared to $3.3 million for the same period in 2025. The decrease in the cost of sales is predominantly driven by a change in product mix and a write-off related to the migraine products in 2025. Research and development expenses for the second quarter 2026 were approximately $19.4 million, compared to $10.8 million for the same period in 2025. The increase of $8.6 million was primarily attributable to higher manufacturing and clinical trial costs associated with advancing the Company's prioritized pipeline programs, as well as increased employee-related costs reflecting expanded headcount. Selling, general, and administrative expenses for the second quarter 2026 were approximately $36.0 million, compared to $16.2 million for the same period in 2025. The increase of $19.8 million was primarily attributable to sales and marketing investment supporting the commercial launch of TONMYA and the Company's migraine products, together with increased employee-related and professional expenses. Net loss available to common stockholders was $40.6 million, or $2.44 per basic and diluted share, for the second quarter 2026, compared to net loss available to common stockholders of $28.3 million, or $3.86 per basic and diluted share, for the same period in 2025. The basic and diluted weighted average common shares outstanding for the second quarter 2026 was 16,635,254 compared to 7,327,257 shares for the same period in 2025. Conference Call and Webcast Information The Company will host a conference call and webcast to report second quarter 2026 financial results and operational highlights on Monday, August 10, 2026, at 8:30 a.m. ET. To listen to the conference call, register at this link . To view the webcast, register at this link . A replay will be available under “IR Events” in the Investors section of the Company’s website at . Tonix Pharmaceuticals Holding Corp. Tonix Pharmaceuticals* is a fully integrated, commercial-stage biopharmaceutical company focused on central nervous system (CNS) disorders, infectious diseases, immunology conditions, and rare diseases with high unmet medical needs. TONMYA® (cyclobenzaprine HCl sublingual tablets 2.8mg), the Company’s flagship internally conceived and developed medicine, is the first treatment for fibromyalgia 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 extending the science behind TONMYA in Phase 2 clinical studies to evaluate the potential of TNX-102 SL in major depressive disorder and acute stress disorder/acute stress reaction. Tonix is also advancing a pipeline of infectious disease programs, including monoclonal antibody TNX-4800 (anti-OspA mAb) for Lyme disease prevention in the U.S. and TNX-801 (horsepox, live virus vaccine), a vaccine in development for the prevention of mpox and smallpox. Within immunology, Tonix is developing TNX-1500 (anti-CD40L mAb), a third-generation CD40 ligand inhibitor for the prevention of kidney transplant rejection. Finally, the Company’s rare disease portfolio includes TNX-2900, which is Phase 2 ready for the treatment of Prader-Willi syndrome. To learn more, visit . *Tonix’s product development candidates, including TNX-102 SL for new, unapproved indications, 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 Company’s expected financial performance, the Company’s anticipated cash runway, the Company’s expected timelines regarding its clinical and pre-clinical programs, expected enrollment in the Company’s clinical trials, expected adoption by the medical community and patients of the Company’s products and expected timelines regarding the Company’s manufacturing processes. 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 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 Contacts Deborah Elson Tonix Pharmaceuticals deborah.elson@tonixpharma.com investor.relations@tonixpharma.com Brian Korb astr partners (917) 653-5122 brian.korb@astrpartners.com Media Contacts Andrea Cohen Sam Brown Inc. (917) 209-7163 andreacohen@sambrown.com TONIX PHARMACEUTICALS HOLDING CORP. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (In Thousands, Except Share and Per Share Amounts) (unaudited) Three Months Ended June 30, Six Months Ended June 30, 2026 2025 2026 2025 REVENUE: Product revenue, net $ 13,544 $ 1,998 $ 20,422 $ 4,427 COSTS AND EXPENSES: Cost of revenue 703 3,272 2,281 4,215 Research and development 19,417 10,820 37,630 18,256 Selling, general and administrative 35,959 16,202 64,583 26,306 56,079 30,294 104,494 48,777 Operating loss (42,535) (28,296) (84,072) (44,350) Grant income 600 1,036 600 1,959 Loss on extinguishment of debt — — — (2,092 ) Interest income, net 1,432 943 2,778 1,571 Other expense, net (49 ) (1,955 ) (52 ) (2,189 ) Net loss available to common stockholders $ (40,552) $ (28,272) $ (80,746) $ (45,101) Net loss per common share, basic and diluted $ (2.44) $ (3.86) $ (5.32) $ (6.80) Weighted average common shares outstanding, basic and diluted 16,635,254 7,327,257 15,179,268 6,631,111 TONIX PHARMACEUTICALS HOLDING CORP. CONDENSED CONSOLIDATED BALANCE SHEETS (In Thousands) (Unaudited) 1 June 30, 2026 December 31, 2025 Assets Cash and cash equivalents $ 176,232 $ 207,637 Accounts Receivable, net 11,805 6,271 Inventory 4,678 6,013 Prepaid expenses and other 10,717 8,955 Total current assets 203,432 228,876 Other non-current assets 50,656 48,295 Total assets $ 254,088 $ 277,171 Liabilities and stockholders’ equity Total liabilities $ 31,807 $ 32,021 Stockholders’ equity 222,281 245,150 Total liabilities and stockholders’ equity $ 254,088 $ 277,171 1 The condensed consolidated balance sheet for the year ended December 31, 2025, has been derived from the audited financial statements but do not include all of the information and footnotes required by accounting principles generally accepted in the United States for complete financial statements.