MAGEL2

-- Phase 3 trial evaluating setmelanotide in pediatric patients ages 2-<6yo (N=12) over 52 weeks achieved primary endpoint -- -- Setmelanotide achieved 3.04 mean reduction in BMI-Z score and 18.4 percent mean reduction in BMI in patients ages 2-<6yo with obesity due to POMC/LEPR deficiency or BBS -- -- RM-718 showed potential to reduce body weight and hyperphagia with no off-target cardiovascular effects and no hyperpigmentation observed in pre-clinical studies; first in-human studies anticipated to begin in the first half of 2024 -- -- Responder rates of 25 to 56 percent demonstrated in six genetic cohorts of Phase 2 DAYBREAK trial of setmelanotide -- -- Company to host R&D webcast today at 8:00 a.m. ET-- BOSTON, Dec. 06, 2023 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a global commercial-stage biopharmaceutical company focused on transforming the lives of patients and their families living with hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) pathway diseases, today hosted an R&D event for investors and analysts, “Rhythm Update on MC4R Pathway Programs.” During the event, the Company announced new topline data from its ongoing Phase 3, open-label pediatrics trial evaluating one year of setmelanotide therapy in patients between the ages of 2 and younger than 6 years with Bardet-Biedl syndrome (BBS) or proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency obesity and new preliminary data from the first stage of its exploratory Phase 2 DAYBREAK trial. Rhythm also presented pre-clinical data on its new drug candidate, RM-718, which is designed to be a more selective MC4R agonist with weekly administration, and its plans for Phase 1 clinical development. The Company hosted Amy Wood, Executive Director and Co-Founder of the Raymond A. Wood Foundation, and Jennifer Miller, MD, Professor of Pediatric Endocrinology, University of Florida, who shared insights on hypothalamic obesity and the severe impact of the disease on patient quality of life. Rhythm continues to advance the development of setmelanotide in patients with hypothalamic obesity and remains on track to complete Phase 3 study enrollment by the end of 2023. “Today, we are excited to showcase our commitment to understanding the MC4R pathway and developing the next generation of therapies,” said David Meeker, M.D., Chair, President and Chief Executive Officer of Rhythm. “Setmelanotide has demonstrated its potential to effect a clinically significant weight loss in children ages 2 to younger than 6 years old, potentially enabling us to treat patients younger in life when these diseases first present. With our DAYBREAK trial, we have shown potential for a meaningful, positive response to setmelanotide in several new gene cohorts.” Setmelanotide demonstrated clinically meaningful reductions in BMI and BMI-Z score in patients aged 2 to <6 (N=12)Today, Rhythm presented new data from its 52-week, Phase 3 pediatrics trial in patients between 2 and younger than 6 years old. The hyperphagia and severe obesity of rare genetically-caused MC4R pathway diseases can present early in life, and these data show potential efficacy in patients younger than 6. This trial is a multi-center, one-year, open-label trial in pediatric patients with obesity due to biallelic POMC, PCSK1 or LEPR deficiency or a clinical diagnosis of BBS with genetic confirmation. The primary efficacy endpoint is a responder analysis, based on the proportion of patients who experience a decrease from baseline in BMI-Z score of ≥0.2. Highlights from the data include: 83.3% of all patients (10 of 12) achieved ≥ 0.2 reduction in BMI-Z score from baseline to week 52;18.4 percent mean reduction from baseline in BMI at week 52 (N=12);3.04 mean reduction from baseline in BMI-Z score at week 52 (N=12);11 patients completed the trial, and all remain on therapy, as of Dec. 5, 2023; one patient discontinued and was lost to follow-up; andThe safety profile is consistent with past trials evaluating setmelanotide. Rhythm today also announced it has submitted a Type II variation application to the European Medicines Agency seeking regulatory approval and authorization for setmelanotide to treat obesity and control of hunger in pediatric patients between 2 and younger than 6 years old with BBS or POMC, PCSK1 or LEPR deficiency in the European Union. The Company anticipates submitting a supplementary New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) in the first half of 2024 seeking a similar label expansion. RM-718 demonstrated potential to reduce body weight and hyperphagia with a favorable safety profile and no hyperpigmentation in pre-clinical studiesRhythm presented data from several pre-clinical studies showing that RM-718, a new, weekly, MC4R-specific agonist, demonstrated the potential to reduce body weight and hunger with a favorable safety profile. RM-718 is designed to be more highly targeted and MC1R sparing with the potential to not cause hyperpigmentation. The Company also showed data from pre-clinical studies demonstrating that RM-718 had no off-target cardiovascular effects in non-human primate studies. Rhythm also announced today that it completed submission of a new investigational drug application for RM-718 to the FDA. The Company anticipates beginning Phase 1 in-human trials in the first half of 2024, including a multiple-ascending dose study in patients with hypothalamic obesity. Data from Phase 2 DAYBREAK trial demonstrate potential efficacy of setmelanotide in multiple genetically-defined cohortsRhythm today also announced data from the open-label part of its exploratory Phase 2 DAYBREAK trial that demonstrate potential efficacy in patients in multiple genetically-defined cohorts. The Company presented data from the full analysis set for DAYBREAK, which includes 164 patients. A total of 112 patients completed the 16-week Stage 1 of the Phase 2 trial, with 52 patients who discontinued. The primary endpoint of the trial is the proportion of patients by genotype who achieve a BMI reduction of ≥5% from baseline in response to setmelanotide at the end of Stage 1. The rates of response from Stage 1 of the trial were: 30% of patients (12 of 40) with variants in the SEMA3 gene cohort;35.6% of patients (16 of 45) with variants in the PLXNs gene cohort;56.3% of patients (9 of 16) with variants in the PHIP gene cohort;40% of patients (2 of 5) with variants in the TBX3 gene cohort;30% of patients (3 of 10) with variants in the MAGEL2 gene cohort; and25% of patients (5 of 20) with variants in the SIM1 gene cohort. For those who completed Stage 1, the rates of response of patients who achieved a BMI reduction of greater than 5% from a post-hoc analysis were: 44.4% of patients (12 of 27) with variants in the PLXNs gene cohort;61.5% of patients (16 of 26) with variants in the SEMA3 gene cohort than 5%; and69.2% of patients (9 of 13) with variants in the PHIP gene cohort. A total of 49 patients who completed Stage 1 with a response to setmelanotide were randomized into Stage 2 of the trial. Stage 2 is a 24-week, double-blind, placebo-controlled withdrawal study. These patients were stratified into genetically defined cohorts and randomized 2:1 to receive setmelanotide or placebo. Rhythm anticipates announcing DAYBREAK Stage 2 data in the second half of 2024. Conference Call InformationA live webcast of the R&D call will be available under "Events and Presentations" in the Investor Relations section of the Rhythm Pharmaceuticals website at https://ir.rhythmtx.com/. The archived webcast will be available on Rhythm Pharmaceuticals’ website approximately two hours after the conference call and will be available for 30 days following the call. About Rhythm PharmaceuticalsRhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) diseases. Rhythm’s lead asset, IMCIVREE (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity caused by rare MC4R pathway diseases, is approved by the U.S. Food and Drug Administration (FDA) for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare MC4R pathway diseases, as well as a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA. Setmelanotide IndicationIn the United States, setmelanotide is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to POMC, PCSK1 or LEPR deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1 or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS) or BBS. In the European Union, setmelanotide is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed Bardet-Biedl syndrome (BBS) or genetically confirmed loss-of-function biallelic proopiomelanocortin (POMC), including PCSK1, deficiency or biallelic leptin receptor (LEPR) deficiency in adults and children 6 years of age and above. Limitations of UseIn the United States and Europe, Setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. Setmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective: Obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC, PCSK1 or LEPR variants classified as benign or likely benignOther types of obesity not related to POMC, PCSK1 or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity. WARNINGS AND PRECAUTIONS Skin Monitoring: Setmelanotide may lead to generalized increased skin pigmentation and darkening of pre-existing naevi because of its pharmacologic effect. Full body skin examinations should be conducted annually to monitor pre-existing and new skin pigmentary lesions before and during treatment with setmelanotide. Heart rate and blood pressure monitoring: Heart rate and blood pressure should be monitored as part of standard clinical practice at each medical visit (at least every 6 months) for patients treated with setmelanotide. Prolonged penile erection: Spontaneous penile erections have been reported in clinical trials with setmelanotide. Patients who have a penile erection lasting longer than 4 hours should be instructed to seek emergency medical attention for potential treatment of priapism. Depression: In clinical trials, depression has been reported in patients treated with setmelanotide. Patients with depression should be monitored at each medical visit during treatment with setmelanotide. Consideration should be given to discontinuing setmelanotide if patients experience suicidal thoughts or behaviors. Pediatric Population: The prescribing physician should periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated. The prescribing physician should monitor growth (height and weight) using age- and sex-appropriate growth curves. Excipients: This medicinal product contains 10 mg benzyl alcohol in each ml. Benzyl alcohol may cause allergic reactions. Patients who are pregnant or breastfeeding should be advised of the potential risk from the excipient benzyl alcohol, which might accumulate over time and cause metabolic acidosis. This medicinal product should be used with caution in patients with hepatic or renal impairment, because of the potential risk from the excipient benzyl alcohol which might accumulate over time and cause metabolic acidosis. Sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free.” ADVERSE REACTIONSThe most frequent adverse reactions are hyperpigmentation (51%), injection site reaction (39%), nausea (33%), and headache (26%). USE IN SPECIFIC POPULATIONS PregnancyThere are no data from the use of setmelanotide in pregnant women. Animal studies do not indicate direct harmful effects with respect to reproductive toxicity. However, administration of setmelanotide to pregnant rabbits resulted in decreased maternal food consumption leading to embryo-fetal effects. As a precautionary measure, setmelanotide should not be started during pregnancy or while attempting to get pregnant as weight loss during pregnancy may result in fetal harm. If a patient who is taking setmelanotide has reached a stable weight and becomes pregnant, consideration should be given to maintaining setmelanotide treatment as there was no proof of teratogenicity in the nonclinical data. If a patient who is taking setmelanotide and still losing weight gets pregnant, setmelanotide should either be discontinued, or the dose reduced while monitoring for the recommended weight gain during pregnancy. The treating physician should carefully monitor weight during pregnancy in a patient taking setmelanotide. Breast-feedingIt is unknown whether setmelanotide is excreted in human milk. A nonclinical study showed that setmelanotide is excreted in the milk of nursing rats. No quantifiable setmelanotide concentrations were detected in plasma from nursing pups. A risk to the newborn/infant cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from setmelanotide therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother. FertilityNo human data on the effect of setmelanotide on fertility are available. Animal studies did not indicate harmful effects with respect to fertility. To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337. See Summary of Product Characteristics’ APPENDIX V for a list of European national reporting systems to communicate adverse reactions. Please see the full Prescribing Information for additional Important Safety Information. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical progress of setmelanotide, including the anticipated timing for initiation of clinical trials and release of clinical trial data and our expectations surrounding potential regulatory submissions, approvals and timing thereof, including for our Phase 2 DAYBREAK trial, anticipated development plan for RM-718 and regulatory submissions for our Phase 3 pediatrics program, our business strategy and plans, including regarding commercialization of setmelanotide in the United States and Europe, the application of genetic testing and related growth potential, and expectations surrounding the potential market opportunity for our product candidates.. Statements using word such as “expect”, “anticipate”, “believe”, “may”, “will”, "aim" and similar terms are also forward-looking statements. Such statements are subject to numerous risks and uncertainties, including, but not limited to, risks relating to our liquidity and expenses, our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the ability to achieve necessary regulatory approvals, risks associated with data analysis and reporting, failure to identify and develop additional product candidates, unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, risks associated with the laws and regulations governing our international operations and the costs of any related compliance programs, the impact of competition, risks relating to product liability lawsuits, inability to maintain our collaborations, or the failure of these collaborations, our reliance on third parties, risks relating to intellectual property, our ability to hire and retain necessary personnel, the impact of the COVID-19 pandemic and general economic conditions on our business and operations, including our preclinical studies, clinical trials and commercialization prospects, failure to realize the anticipated benefits of our acquisition of Xinvento B.V. or significant integration difficulties related to the acquisition, and the other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 and our other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise. Corporate Contact:David ConnollyExecutive Director, Investor Relations and Corporate CommunicationsRhythm Pharmaceuticals, Inc.857-264-4280dconnolly@rhythmtx.com Media Contact:Adam DaleyBerry & Company Public Relations212-253-8881adaley@berrypr.com

TNX-2900 is a proprietary magnesium-potentiated formulation of intranasal oxytocin, a naturally occurring hormone that reduces appetite and eating Preclinical data show magnesium-potentiation increases the potency of exogenous oxytocin Formulations of intranasal oxytocin without magnesium have reported inconsistent results in clinical trials of Prader Willi Syndrome1,2 CHATHAM, N.J., Dec. 04, 2023 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals, Inc. (Nasdaq: TNXP), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application to support clinical development of TNX-2900 (intranasal potentiated oxytocin), a proprietary magnesium (Mg2+)-enhanced formulation of intranasal oxytocin, to treat Prader-Willi syndrome (PWS) in children and adolescents. TNX-2900 for the treatment of PWS was granted Orphan Drug designation by the FDA in 2022. The Phase 2 study approved by the IND is a dose-finding study involving approximately 36 PWS patients divided into four groups with approximately nine PWS patients per group. One group will receive placebo and three groups will receive different dosage regimens of TNX-2900. Tonix intends to seek a partner to advance TNX-2900 for PWS in clinical development. “We are pleased that TNX-2900 is cleared for clinical studies for the treatment of PWS in children and adolescents as there remains a significant need for new therapies, particularly for PWS hyperphagia, which currently has no approved treatments,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “PWS is the most common genetic cause of life-threatening childhood obesity.3,4 We believe adding Mg2+ to the formulation has the potential to improve intranasal oxytocin’s therapeutic action.” The IND application for TNX-2900 was supported by preclinical data demonstrating that Mg2+ enhances the potency of oxytocin. Oxytocin is a naturally-occurring hormone that reduces appetite and eating and regulates hunger, anxiety and prosocial behavior. PWS is a genetic disorder associated with abnormalities of the oxytocin system5. Several previous clinical studies in PWS of intranasal oxytocin without Mg2+-potentiation have shown trends toward improvement, but the results have been inconsistent.1,2 Tonix believes that Mg2+-potentiation of intranasal oxytocin in PWS may improve consistency in clinical trials because in animal studies Mg2+-potentiation appears to eliminate the high-dose suppression of oxytocin’s inverted “U”-shaped dose response.6 Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals added, “Recent reports show Mg2+ is necessary for oxytocin to fully activate the oxytocin receptor.3,6 Oxytocin has potent effects in adult mice correcting behavioral characteristics of the Magel2 knock-out mouse model for PWS and autism.4 Oxytocin has many potential therapeutic roles in reducing appetite, eating, weight, migraine pain and autistic spectrum behaviors. Tonix recently completed enrollment in a Phase 2 study of TNX-1900, a related Mg2+-potentiated intranasal oxytocin candidate, for the prevention of migraine headaches, and is also studying TNX-1900 through external collaborations for the treatment of obesity in adolescents, binge eating disorder, bone health in autism, and social anxiety disorder.” About Prader-Willi Syndrome (PWS) PWS is recognized as the most common genetic cause of life-threatening childhood obesity and affects males and females with equal frequency and all races and ethnicities. PWS results from the absence of expression of a group of genes on the paternally acquired chromosome 15. The hallmarks of PWS are lack of suckling in newborns and, in children and adolescents, severe hyperphagia, an overriding physiological drive to eat, leading to severe obesity and other complications associated with significant mortality. A systematic review of the morbidity and mortality as a consequence of hyperphagia in PWS found that the average age of death in PWS was 22.1 years.7 There is no approved medication to treat poor feeding in newborns or hyperphagia in children and adolescents with PWS. Given these serious or life-threatening manifestations of these conditions, there is a critical need for effective treatments to decrease morbidity and mortality, improve quality of life, and increase life expectancy in people with PWS. Oxytocin has potent effects in adult mice correcting behavioral characteristics of the Magel2 knock-out mouse model for PWS and autism.4 In addition, oxytocin has potent effects in correcting behavioral characteristics of the neonatal Magel2 knock-out mouse model for PWS and autism8 and intriguing effects in a clinical trial of neonates with PWS.9 About TNX-2900 and Tonix’s Potentiated Oxytocin Platform TNX-2900 is based on Tonix’s patented intranasal potentiated oxytocin formulation intended for use by adults and adolescents. Tonix’s patented potentiated oxytocin formulation is believed to increase specificity for oxytocin receptors relative to vasopressin receptors as well as to enhance the potency of oxytocin. Tonix is also developing a different intranasal formulation, designated TNX-1900, for prophylaxis of chronic migraine as well as for adolescent obesity, binge eating disorder, bone health in autism and social anxiety disorder. Oxytocin is a naturally occurring human hormone that acts as a neurotransmitter in the brain. Oxytocin is believed to be more than 600 million years old and is present in vertebrates including mammals, birds, reptiles, amphibians and fish.10,11 It was originally approved by the U.S. Food and Drug Administration as Pitocin®*, an intravenous infusion or intramuscular injection drug, for use in pregnant women to induce labor. An intranasal formulation of oxytocin is marketed in some European countries to assist in the production of breast milk as Syntocinon®** (oxytocin nasal 40 units/ml). *Pitocin® is a trademark of Par Pharmaceutical, Inc. **Syntocinon® is a trademark of BGP Products Operations GmbH Citations Shalma NM, et al. Diabetes Metab Syndr. 2023. 17(2):102711. Rice LJ, et al. Curr Opin Psychiatry. 2018. 31(2):123-127. Meyerowitz JG, et al. Nat Struct Mol Biol. 2022. 29(3):274-281. Meziane H, et al. Biol Psychiatry. 2015. 78(2):85-94. Correa-da-Silva F, et al. J Neuroendocrinol. 2021. 33(7):e12994. Bharadwaj VN, et al. Pharmaceutics. 2022. 14(5):1105. Bellis SA, et al. Eur J Med Genet. 2022. 65(1):104379. Bertoni A, et al. Mol Psychiatry. 2021. 26(12):7582-7595. Tauber M, et al. Pediatrics. 2017. 139(2):e20162976. Oxytocin in Wikipedia (accessed 8-8-23) Gruber CW. Exp Physiol. 2014. 99(1):55-61. doi: 10.1113/expphysiol.2013.072561. Tonix Pharmaceuticals Holding Corp.* Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed the clinical phase of a potentially confirmatory Phase 3 study in the fourth quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition, and topline results were reported in the third quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), is in development as a preventive treatment in chronic migraine, and enrollment has completed in a Phase 2 proof-of-concept study with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the fourth quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes 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. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases, including TNX-1800, in development as a vaccine to protect against COVID-19. During the fourth quarter of 2023, TNX-1800 was selected by the U.S. National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) Project NextGen for inclusion in Phase 1 clinical trials. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum small molecule oral antivirals. *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. Intravail is a registered trademark of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis, Inc. 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 (443) 213-0495