Cyclobenzaprine hydrochloride

Phase 1 data 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 Phase 2 investigator-initiated study in adult kidney transplant at Massachusetts General Hospital (MGH) expected to initiate in the 2 nd half of 2026 pending U.S. Food and Drug Administration (FDA) clearance of MGH’s Investigational New Drug (IND) application BERKELEY HEIGHTS, N.J., May 27, 2026 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (“Tonix” or the “Company”), a fully integrated, commercial-stage biotechnology company, today announced the publication of a paper, “First-in-Human, Phase 1, Randomized, Double-Blind, Placebo-Controlled Study of TNX-1500, an Fc-Modified anti-CD154 Monoclonal Antibody, Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses in Healthy Adults,” in the peer-reviewed Journal of Clinical Immunology . TNX-1500 is an investigational, third-generation Fc-modified IgG4 anti-CD40L (also known as CD154) monoclonal antibody (mAb) in development for the prevention of organ transplant rejection and the treatment of autoimmune diseases. The manuscript can be accessed at . “The CD40L is a validated target for preventing organ rejection in transplant and treating autoimmune disease, yet no anti-CD40L mAb has been approved for any indication,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “TNX-1500 is a Phase 2 ready humanized mAb engineered to improve safety and tolerability relative to first-generation anti-CD40L mAbs, while preserving the durable half-life and certain effector functions associated with the Fc or crystallizable fragment. We believe the Phase 1 results show that these design objectives were achieved in TNX-1500.” Dr. Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals added, “The Phase 1 study evaluated TNX-1500’s safety, tolerability, pharmacokinetics, and pharmacodynamics. TNX-1500 was generally well tolerated, demonstrated a favorable safety profile, suppressed the primary and secondary T cell-dependent antibody responses (TDARs) to keyhole limpet hemocyanin (KLH) antigen, and showed a half-life which supports monthly intravenous dosing. We expect a Phase 2, investigator-initiated study of TNX-1500 in the prevention of kidney allograft rejection at MGH to begin in the 2 nd half of 2026 pending clearance of the IND by the FDA.” The publication reports findings from a single-center, first-in-human, Phase 1, randomized, double-blind, placebo-controlled, single-ascending dose escalation study in 26 healthy adult volunteers. Participants were enrolled across three ascending dose cohorts (3, 10, and 30 mg/kg) or placebo and received a single intravenous infusion of TNX-1500 or placebo, followed by intramuscular injections of KLH on days 2 and 29 to assess the TDAR, and monitored over a 120-day follow-up period. TNX-1500 blocked the primary T cell–dependent antibody response to KLH at all doses, blocked the secondary response at the 10 and 30 mg/kg doses, and reduced peak secondary response to KLH by ~70% relative to placebo at the 3 mg/kg dose. TNX-1500 was generally well tolerated, with no serious adverse events, and no discontinuations due to adverse events. The only treatment-emergent adverse event (TEAE) deemed possibly related to study drug was aphthous ulcer, which occurred in 1 participant in each of the three TNX-1500 groups; all TEAEs were rated as mild and resolved in 2-10 days. No TEAEs were determined to be related to KLH administration. There were no administration or injection site reactions (one of the prespecified TEAEs of special interest). Pharmacokinetic analyses suggested approximately dose-proportional exposure across the 3 to 30 mg/kg range, with mean terminal elimination half-lives of 37.8 and 33.8 days at the 10 and 30 mg/kg dose levels, respectively. TNX-1500 at 10 and 30 mg/kg blocked the primary and secondary anti-KLH TDAR through day 120, and at 3 mg/kg reduced the peak secondary response by approximately 70% relative to placebo. Across all dose cohorts, TNX-1500 was associated with a rapid (less than one-hour post-dose) and sustained reduction in soluble CD40L (sCD154) over the 120-day study period. About TNX-1500 TNX-1500 (Fc-modified humanized anti-CD40L mAb) is a Phase 2 ready, humanized monoclonal antibody that interacts with the CD40-ligand (CD40L), also known as CD154. TNX-1500 is being developed for the prevention of kidney transplant rejection and the treatment of autoimmune diseases. Anti-CD40L has multiple potential indications in addition to solid organ and bone marrow transplantation including autoimmune diseases. Collaborations are ongoing with MGH on allo-heart and -kidney transplantation in nonhuman primates, as well as prevention of xenograft rejection, preclinical studies, and prevention of allograft rejection in sensitized patients. The Phase 2 investigator-initiated study by MGH is expected to initiate enrollment in the 2 nd half of 2026, pending FDA clearance of the IND, to evaluate TNX-1500 in five kidney transplant recipients. The study is designed to assess the safety, tolerability, and activity of TNX-1500 in preventing kidney transplant rejection while decreasing the exposure to conventional immunosuppressive drugs, which are associated with infection, cancer, cardiovascular side effects, and various metabolic derangements with long term use. Tonix Pharmaceuticals Holding Corp. Tonix Pharmaceuticals* is a fully integrated, commercial-stage biotechnology company focused on central nervous system (CNS) disorders, infectious diseases, immunology conditions, and rare diseases where there exists high unmet medical need. TONMYA® (cyclobenzaprine HCl sublingual tablets 2.8mg), the Company’s flagship internally conceived and developed medicine, is the first new 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 its potential 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 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 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 Jessica Morris Tonix Pharmaceuticals (862) 799-8599 investor.relations@tonixpharma.com Brian Korb astr partners (917) 653-5122 brian.korb@astrpartners.com Media Contacts Deborah Elson Tonix Pharmaceuticals deborah.elson@tonixpharma.com Ray Jordan Putnam Insights ray@putnaminsights.com

Real-world analysis of three years of closed claims data from Symphony Health focused on the third year of the study (2023-2024), comprised of more than 261,000 U.S. adults with fibromyalgia Data underscore high comorbidity burden, multimodal treatment approach, and extensive healthcare resource utilization (HCRU) among patients with fibromyalgia Tonix commercially launched TONMYA® in November 2025, the first new fibromyalgia drug for adults in the U.S. approved in over 15 years BERKELEY HEIGHTS, N.J., May 26, 2026 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) ("Tonix" or the "Company"), a fully integrated, commercial biotechnology company, presented data from a real-world claims analysis characterizing U.S. adults with fibromyalgia in a poster at ISPOR 2026, the Professional Society for Health Economics and Outcomes Research’s annual meeting, held May 17-20, 2026, in Philadelphia, Pennsylvania. “Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, sleep disturbance, cognitive dysfunction, and somatic symptoms, leading to substantial management challenges,” 1-4 said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. “More than 10 million adults in the U.S. suffer from fibromyalgia. In response to fibromyalgia’s complex and persistent symptoms, and extensive comorbidities, fibromyalgia patients face rotating treatment approaches, and high HCRU. These findings highlight the need for comprehensive disease management and more effective therapeutic interventions to reduce the clinical and economic burden of fibromyalgia. Tonix is focused on the commercial launch of TONMYA, a first-in-class, first-line, non-opioid analgesic medicine designed for daily bedtime administration and long-term use.” Data presented at ISPOR 2026 represent a retrospective, multi-year, multi-cohort study using the Symphony Health closed claims database, encompassing administrative medical and pharmacy claims collected between April 2021 and April 2024. The study’s objective was to evaluate real-world characteristics, including demographics, comorbidities, and HCRU among adults diagnosed with fibromyalgia (ICD-10-CM diagnosis code M79.7). The Year 3 cohort (April 2023 to March 2024) included 261,776 adult patients, with a median age of 53 years. Most patients were female (92.1%). Patients were White non-Hispanic (49.6%), Hispanic (22.4%), Other (19.6%), and Black (8.3%). Comorbidity burden was high, with 93.2% of patients having at least one fibromyalgia-related comorbidity, most commonly anxiety/depression (63.9%), dorsalgia/back pain (56.5%), hypertensive diseases (51.4%), and joint pain (48.4%). Among the 90.3% of patients with at least one co-existing condition (or comorbidity), 36.2% had four or more, and subgroups including Black/Brown women, women on opioids, women with gut health issues, and older women with sleep issues all carried higher rates of comorbidity than the overall cohort. Among insured patients (n=92,157), HCRU was extensive, and inpatient services represented the largest component of healthcare costs at $29,896 per patient annually, followed by pharmacy ($9,453) and outpatient ($6,196) costs, demonstrating the large burden on commercial and public healthcare programs. Antidepressants were the most frequently used medication class (48.2%), followed by NSAID analgesics (43.4%), anticonvulsants (41.6%), gastric acid secretion reducers (41.5%), skeletal muscle relaxants (40.7%), and opioid analgesics (39.4%). The medication use reflects reliance on multimodal pharmacologic strategies to manage fibromyalgia-related symptoms in routine clinical practice. A copy of the Company’s poster presentation, “Characterizing Patients with Fibromyalgia: A U.S. Real-World Claims Analysis,” is available under the Scientific Presentations tab on the Tonix website at . About Fibromyalgia Fibromyalgia is a chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system. Fibromyalgia afflicts more than 10 million adults in the U.S., approximately 90% of whom are women. Symptoms of fibromyalgia include chronic widespread pain, nonrestorative sleep, fatigue, and morning stiffness. Other associated symptoms include cognitive dysfunction and mood disturbances, including anxiety and depression. Individuals suffering from fibromyalgia struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products. About TONMYA® (cyclobenzaprine HCl sublingual tablets) TONMYA (cyclobenzaprine HCl sublingual tablets) is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities at the 5-HT 2A serotonergic, α 1 -adrenergic, H 1 -histaminergic, and M 1 -muscarinic receptors, TONMYA was approved on August 15, 2025, by the FDA for the treatment of fibromyalgia in adults. TONMYA is the first new prescription medicine approved for fibromyalgia in more than 15 years. TONMYA was investigated as TNX-102 SL. TNX-102 SL is also being developed to treat acute stress disorder (ASD)/acute stress reaction (ASR), and major depressive disorder (MDD). The United States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408 in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic™ protective eutectic and Angstro-Technology™ formulation claimed in the patent are important elements of Tonix’s proprietary TONMYA composition. These patents are expected to provide TONMYA with U.S. market exclusivity until 2034/2035. Citations 1. Bilge U, et al. Cardiovasc Dis . 2018;155:30–5. 2. Choy EH, Mease PJ. Rheum Dis Clin North Am . 2009;35(2):329–37. 3. Rivera FA, et al. Front Med (Lausanne) . 2023;10:1301944. 4. Winslow BT, et al. Am Fam Physician . 2023;107(2):137–44. Tonix Pharmaceuticals Holding Corp. Tonix Pharmaceuticals* is a fully integrated, commercial-stage biotechnology company focused on central nervous system (CNS) disorders, infectious diseases, immunology conditions, and rare diseases where there exists high unmet medical need. TONMYA® (cyclobenzaprine HCl sublingual tablets 2.8mg), the Company’s flagship internally conceived and developed medicine, is the first new 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 its potential 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 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 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 Jessica Morris Tonix Pharmaceuticals investor.relations@tonixpharma.com (862) 799-8599 Brian Korb astr partners (917) 653-5122 brian.korb@astrpartners.com Media Contacts Deborah Elson Tonix Pharmaceuticals deborah.elson@tonixpharma.com Ray Jordan Putnam Insights ray@putnaminsights.com INDICATION TONMYA is indicated for the treatment of fibromyalgia in adults. CONTRAINDICATIONS TONMYA is contraindicated: In patients with hypersensitivity to cyclobenzaprine or any inactive ingredient in TONMYA. Hypersensitivity reactions may manifest as an anaphylactic reaction, urticaria, facial and/or tongue swelling, or pruritus. Discontinue TONMYA if a hypersensitivity reaction is suspected. With concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after discontinuation of an MAO inhibitor. Hyperpyretic crisis seizures and deaths have occurred in patients who received cyclobenzaprine (or structurally similar tricyclic antidepressants) concomitantly with MAO inhibitors drugs. During the acute recovery phase of myocardial infarction, and in patients with arrhythmias, heart block or conduction disturbances, or congestive heart failure. In patients with hyperthyroidism. WARNINGS AND PRECAUTIONS Embryofetal toxicity: Based on animal data, TONMYA may cause neural tube defects when used two weeks prior to conception and during the first trimester of pregnancy. Advise females of reproductive potential of the potential risk and to use effective contraception during treatment and for two weeks after the final dose. Perform a pregnancy test prior to initiation of treatment with TONMYA to exclude use of TONMYA during the first trimester of pregnancy. Serotonin syndrome: Concomitant use of TONMYA with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors increases the risk of serotonin syndrome, a potentially life-threatening condition. Serotonin syndrome symptoms may include mental status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms. Treatment with TONMYA and any concomitant serotonergic agent should be discontinued immediately if serotonin syndrome symptoms occur and supportive symptomatic treatment should be initiated. If concomitant treatment with TONMYA and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dosage increases. Tricyclic antidepressant-like adverse reactions: Cyclobenzaprine is structurally related to TCAs. TCAs have been reported to produce arrhythmias, sinus tachycardia, prolongation of the conduction time leading to myocardial infarction and stroke. If clinically significant central nervous system (CNS) symptoms develop, consider discontinuation of TONMYA. Caution should be used when TCAs are given to patients with a history of seizure disorder, because TCAs may lower the seizure threshold. Patients with a history of seizures should be monitored during TCA use to identify recurrence of seizures or an increase in the frequency of seizures. Atropine-like effects: Use with caution in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure, and in patients taking anticholinergic drugs. CNS depression and risk of operating a motor vehicle or hazardous machinery: TONMYA monotherapy may cause CNS depression. Concomitant use of TONMYA with alcohol, barbiturates, or other CNS depressants may increase the risk of CNS depression. Advise patients not to operate a motor vehicle or dangerous machinery until they are reasonably certain that TONMYA therapy will not adversely affect their ability to engage in such activities. Oral mucosal adverse reactions: In clinical studies with TONMYA, oral mucosal adverse reactions occurred more frequently in patients treated with TONMYA compared to placebo. Advise patients to moisten the mouth with sips of water before administration of TONMYA to reduce the risk of oral sensory changes (hypoesthesia). Consider discontinuation of TONMYA if severe reactions occur. ADVERSE REACTIONS The most common adverse reactions (incidence ≥2% and at a higher incidence in TONMYA-treated patients compared to placebo-treated patients) were oral hypoesthesia, oral discomfort, abnormal product taste, somnolence, oral paresthesia, oral pain, fatigue, dry mouth, and aphthous ulcer. DRUG INTERACTIONS MAO inhibitors: Life-threatening interactions may occur. Other serotonergic drugs: Serotonin syndrome has been reported. CNS depressants: CNS depressant effects of alcohol, barbiturates, and other CNS depressants may be enhanced. Tramadol: Seizure risk may be enhanced. Guanethidine or other similar acting drugs: The antihypertensive action of these drugs may be blocked. USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, TONMYA may cause fetal harm when administered to a pregnant woman. The limited amount of available observational data on oral cyclobenzaprine use in pregnancy is of insufficient quality to inform a TONMYA-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Advise pregnant women about the potential risk to the fetus with maternal exposure to TONMYA and to avoid use of TONMYA two weeks prior to conception and through the first trimester of pregnancy. Report pregnancies to the Tonix Medicines, Inc., adverse-event reporting line at 1-888-869-7633 (1-888-TNXPMED). Lactation: A small number of published cases report the transfer of cyclobenzaprine into human milk in low amounts, but these data cannot be confirmed. There are no data on the effects of cyclobenzaprine on a breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TONMYA and any potential adverse effects on the breastfed child from TONMYA or from the underlying maternal condition. Pediatric use: The safety and effectiveness of TONMYA have not been established. Geriatric patients: Of the total number of TONMYA-treated patients in the clinical trials in adult patients with fibromyalgia, none were 65 years of age and older. Clinical trials of TONMYA did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients. Hepatic impairment: The recommended dosage of TONMYA in patients with mild hepatic impairment (HI) (Child Pugh A) is 2.8 mg once daily at bedtime, lower than the recommended dosage in patients with normal hepatic function. The use of TONMYA is not recommended in patients with moderate HI (Child Pugh B) or severe HI (Child Pugh C). Cyclobenzaprine exposure (AUC) was increased in patients with mild HI and moderate HI compared to subjects with normal hepatic function, which may increase the risk of TONMYA-associated adverse reactions. Please see additional safety information in the full Prescribing Information. To report suspected adverse reactions, contact Tonix Medicines, Inc. at 1-888-869-7633, or the FDA at 1-800-FDA-1088 or