Obstetric Labor Complications

TNX-2900 is a proprietary magnesium-potentiated formulation of intranasal oxytocin, a naturally occurring hormone that reduces appetite and eating Prader Willi syndrome is the most common genetic cause of life-threatening childhood obesity CHATHAM, N.J., March 25, 2024 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation to TNX-2900* (intranasal potentiated oxytocin), a proprietary magnesium (Mg2+)-potentiated formulation of intranasal oxytocin, to treat Prader-Willi syndrome (PWS) in children and adolescents. TNX-2900 was previously granted Orphan Drug designation by the FDA in 2022 for the treatment of PWS and the investigational new drug (IND) application was cleared by the FDA in 2023. The Company may be eligible to receive a transferable Priority Review Voucher if TNX-2900 for PWS is approved for marketing. Recently, vouchers have sold for approximately $100 million. “The Rare Pediatric Disease Designation is an important regulatory milestone in the development of TNX-2900. With PWS being the most common genetic cause of life-threatening childhood obesity, we are excited that the FDA has recognized this significant unmet need in children and adolescents, particularly for PWS hyperphagia, which currently has no approved treatments1,2,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “As PWS is a genetic disorder associated with abnormalities of the oxytocin system, Tonix believes TNX-2900’s unique formulation has the potential to improve intranasal oxytocin’s therapeutic action by addressing limitations in efficacy observed at high-dose intranasal oxytocin that is not Mg2+-potentiated3,4.” The FDA defines a rare pediatric disease as a serious or life-threating disease that primarily affects individuals aged from birth to 18 years and affects under 200,000 people in the United States. About FDA’s Rare Pediatric Disease Priority Voucher Program The FDA’s Rare Pediatric Disease Priority Voucher Program is intended to encourage the development of new drugs to treat certain rare pediatric diseases. Under the FDA’s Rare Pediatric Disease Designation and Voucher Program, if TNX-2900 is approved for marketing, Tonix may qualify for a priority review voucher that can be redeemed to receive priority review of a subsequent marketing application for a different product. Priority review vouchers may also be sold or transferred to another sponsor. The new sponsor can redeem the voucher to receive priority review for a different product, which reduces the review time of NDAs from 10 months to six months. There is no limit on the number of times a priority review voucher can be transferred. A 2020 U.S. Government Accounting Office analysis5 of the voucher program found that in the ten years since launch of the program in 2009, the price of buying priority review vouchers ranged from $67 million to $350 million. More recently, priority review vouchers were acquired by Novo Nordisk for $110 million in June of 2022, and by Novartis for $100 million from Marinus in July of 2022.6 Bluebird Bio sold vouchers for $102 million, $95 million and $103 million in November 2022, January 2023, and October 2023, respectively.7-9 In June of 2023, Novartis bought a priority review voucher from Pharming for $21 million, a price that had been negotiated as part of a purchase agreement when Pharming acquired the asset from Novartis.5 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.10 There is no approved medication to treat poor feeding in newborns or hyperphagia in children and adolescents with PWS. Given the 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 correcting behavioral characteristics of the Magel2 knock-out mouse model for PWS and autism.11-13 Six clinical trials have investigated intranasal oxytocin as a treatment in pediatric patients with PWS. Four studies showed evidence for improvement in PWS-related behaviors/symptoms14-17; three clinical studies reported evidence for improvement in hyperphagia14,15,17; and one clinical study showed an improvement in sucking in infants16. About TNX-2900 and Tonix’s Potentiated Oxytocin Platform TNX-2900 is based on Tonix’s patented intranasal Mg2+-potentiated oxytocin formulation intended for use by children and adolescents. This formulation is believed to enhance the potency of oxytocin as well as increase specificity for oxytocin receptors relative to vasopressin receptors, potentially reducing unwanted side effects from activating vasopressin receptors. Tonix is also developing a different intranasal formulation, designated TNX-1900 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.18 It was initially 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 and control postpartum bleeding or hemorrhage. An intranasal formulation of oxytocin is marketed in some European countries to assist in breast milk production as Syntocinon®*** (oxytocin nasal 40 units/ml). Tonix Pharmaceuticals Holding Corp.* Tonix is a biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya, a product candidate for which two positive Phase 3 studies have been completed for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction as well as fibromyalgia-type Long COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase) a biologic designed to treat cocaine intoxication with Breakthrough Therapy designation. Tonix’s immunology development portfolio consists of biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. Tonix also has product candidates in development in the areas of rare disease and infectious disease. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults. *Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication. Tonmya™ is conditionally accepted by the U.S. Food and Drug Administration as the tradename for TNX-102 SL for the management of fibromyalgia. **Pitocin® is a trademark of Par Pharmaceutical, Inc. ***Syntocinon® is a trademark of BGP Products Operations GmbH Citations 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.U.S. Government Accounting Office, Jan 31, 2020. “Drug Development: FDA's Priority Review Voucher Programs”. GAO-20-251. https://www.gao.gov/products/gao-20-251.Waldron, J. Fierce Biotech. June 1, 2023. “Novartis buys priority review voucher from Pharming for discount price of $21 M.” www.fiercebiotech.com/biotech/novartis-buys-priority-review-voucher-pharming-discount-price-21mBlueBird bio Press Release. Nov. 30, 2022 “bluebird bio Sells Priority Review Voucher for $102 Million”. https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-sells-priority-review-voucher-102-millionKansteiner, F. Fierce Pharma. Jan 6, 2023 “Bluebird scores $95M nest egg after selling second FDA priority review voucher to BMS”. http://www.fiercepharma.com/pharma/bluebird-scores-another-nest-egg-after-selling-second-fda-review-voucher-bms-95m Business Wire. October 30, 2023. “bluebird bio Enters into Advance Agreement to Sell Priority Review Voucher, if Granted, for $103 Million.” http://finance.yahoo.com/news/bluebird-bio-enters-advance-agreement-120000768.htmlBellis SA, et al. Eur J Med Genet. 2022. 65(1):104379.Bertoni A, et al. Mol Psychiatry. 2021. 26(12):7582-7595.Schaller F, et al. Hum Mol Genet. 2010. 19:4895-4905.Meziane H, et al. Biol Psychiatry. 2015. 78: 85-94.Kuppens RJ, et al. Clin Endocrinol. 2016. 85:979-987.Miller JL et al. Am J Med Genet A. 2017. 173: 1243-1250.Tauber M, et al. Pediatrics. 2017. 139(2):e20162976.Damen L, et al. Clin Endocrinol. 2020. 94:774-785.Gruber CW. Exp Physiol. 2014. 99(1):55-61. doi: 10.1113/expphysiol.2013.072561. Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. All other marks are property of their respective owners. This press release and further information about Tonix can be found at www.tonixpharma.com. 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 MorrisTonix Pharmaceuticalsinvestor.relations@tonixpharma.com (862) 904-8182 Peter VozzoICR Westwickepeter.vozzo@westwicke.com (443) 213-0505 Media Contact Ben ShannonICR Westwickeben.shannon@westwicke.com443-213-0495

Defining a quantifiable threshold for embolization effectiveness FAIRFAX, Va., March 23, 2024 /PRNewswire/ -- Early intervention with a minimally invasive treatment called uterine artery embolization (UAE) can help women avoid hysterectomy due to severe bleeding after childbirth, according to a new study being presented at the Society of Interventional Radiology Annual Scientific Meeting in Salt Lake City. "These findings are important and may help more women avoid hysterectomy and other very serious complications of uncontrolled hemorrhage," said lead author Younes Jahangiri, M.D., a resident in the interventional and diagnostic radiology program at Michigan State University/Corewell Health. "As the medical community looks for ways to provide better care for women to address maternal health and peri-partum care, this is one more option on the table that could help many women." The study was a retrospective review of 66 patients (median age, 31) who underwent UAE for uncontrolled postpartum hemorrhage at a single, high-volume medical center between 2014 and 2022. UAE successfully controlled postpartum hemorrhaging in 62 of the 66 patients (94%). Four patients required hysterectomies to stop the bleeding, all of whom lost at least 2400 ml blood prior to presentation for UAE and symptoms of diffuse intravascular coagulopathy, a clotting abnormality that can happen after large-volume hemorrhage due to rapid consumption of clotting factors. Postpartum hemorrhage is a rare but potentially deadly complication of childbirth. To stop it, obstetricians will initially use conservative approaches to replace the lost blood or to promote clotting. If these measures are insufficient, hysterectomy is usually performed. Alternatively, interventional radiologists can be brought in to perform UAE, injecting tiny particles into the arteries that supply blood to the uterus using fluoroscopic imaging guidance. Once placed in the arteries, the particles temporarily block blood flow to stem uterine bleeding. "Based on these findings, we would encourage obstetricians to involve interventional radiologists early, to be ready to perform UAE if more conservative approaches are not managing postpartum hemorrhage," said senior author James Morrison, M.D., assistant professor of interventional radiology, also at Michigan State University's College of Human Medicine. Researchers in this study found a 36% incidence of post-embolization syndrome, which presents with abdominal pain and flu-like symptoms. The study found that it was more likely to occur in patients who experienced greater blood loss before embolization. Dr. Jahangiri, Dr. Morrison and their colleagues plan to expand their research to include multiple institutions and ultimately to conduct a prospective study that examines longer-term outcomes of UAE. Abstract #189: Short-Term and Long-Term Outcomes of Uterine Artery Embolization for Treatment of Uncontrolled Post-Partum Hemorrhage. Y. Jahangiri, J. Haan, O. Lane, O. Close, J. Morrison. Annual Scientific Meeting, March 23-28, 2024. This abstract can be found at sirmeeting.org. About the Society of Interventional Radiology The Society of Interventional Radiology is a nonprofit, professional medical society representing more than 8,000 practicing interventional radiology physicians, trainees, students, scientists and clinical associates, dedicated to improving patient care through the limitless potential of image-guided therapies. SIR's members work in a variety of settings and at different professional levels—from medical students and residents to university faculty and private practice physicians. Visit sirweb.org. The Society of Interventional Radiology is holding its Annual Scientific Meeting in Salt Lake City, March 23-28, 2024. Visit sirmeeting.org. SOURCE Society of Interventional Radiology

Centhaquine is a first-of-its-kind resuscitative agent to treat hypovolemic shock by increasing stroke volume and cardiac output due to an increase in (preload) venous blood return to the heart and a decrease in (afterload) due to arterial dilatationIndia is the first global territory where Centhaquine is being launched immediately WILLOWBROOK, Ill., March 22, 2024 (GLOBE NEWSWIRE) -- Pharmazz, Inc. ("Pharmazz"), a biopharmaceutical company developing and commercializing drug products to treat critically ill patients, announced that it has entered into a license agreement with Dr. Reddy's Laboratories Limited ("Dr. Reddy's"), a global pharmaceutical company, to commercialize a first-in-class innovative drug Centhaquine in India. Developed by Pharmazz for potential global use, Centhaquine is a resuscitative agent presently indicated for treating hypovolemic shock by Drugs Controller General of India (DCGI). As per the agreement, Dr. Reddy's has received exclusive rights to market and distribute Centhaquine in India. Pharmazz will be entitled to upfront payments and royalties. Dr. Reddy’s will market the product under the brand name Lyfaquin®, which it shall own. In addition to India, Dr. Reddy’s also receives marketing rights for Lyfaquin® from Pharmazz for Nepal. The inventor, Dr. Prof. Anil Gulati, M.D., Ph.D., who is the CEO and Chairman of the Board of Pharmazz, said: "India's emergence as a hub for developing and introducing innovative medicines is a remarkable achievement. It reflects the country's growing capabilities in research and development within the pharmaceutical sector. It is a large step for Pharmazz to partner with Dr. Reddy's, a leading global pharmaceutical company from India. For patients with hypovolemic shock, I believe Dr. Reddy's is the best partner for Pharmazz to market Centhaquine, an innovative, first-in-class novel resuscitative agent, in India." M.V. Ramana, Chief Executive Officer, Branded Markets (India and Emerging Markets), Dr. Reddy’s, said: “The partnership with Pharmazz and launch of this first-in-class drug marks the latest in our effort to enter into strategic collaborations to bring novel molecules to India to meet genuine unmet patient needs. The clinical studies for Lyfaquin® have demonstrated significantly better and promising outcomes, making it as a potential add-on drug in the management of hypovolemic shock and enhancing the current standard of care for its treatment in India.” Centhaquine is a frontline therapy used along with the standard of care and is well-positioned to a critical unmet need as a pharmacologically active resuscitative agent. A decrease in the volume of blood circulation from blood or fluid loss due to trauma, gastrointestinal bleeding, major surgery, postpartum hemorrhage, diarrhea, or vomiting can cause hypovolemic shock. About 1.9 million people worldwide die because of hemorrhagic shock every year, most dying within the first 6 hours. Centhaquine activates venous alpha2B adrenergic receptors to increase cardiac preload and activates central alpha2A adrenergic receptors to decrease cardiac afterload. Thereby, Centhaquine converts the venous unstressed blood volume to stressed blood volume and improves cardiac output and blood circulation, making it an ideal candidate for the resuscitation of patients with hypovolemic shock. Centhaquine was approved in India by Drugs Controller General of India following a successful Ph III clinical trial there, the results of which are published in a manuscript titled "A Multicentric, Randomized, Controlled Ph III Study of Centhaquine (Lyfaquin, as a Resuscitative Agent in Hypovolemic Shock Patients." The manuscript is published in DRUGS and is available at: https://link-springer-com.libproxy1.nus.edu.sg/article/10.1007/s40265-021-01547-5. Pharmazz received permission from the U.S. Food and Drug Administration (FDA) to conduct a Phase III clinical trial of Centhaquine in hypovolemic shock patients. It assesses the safety and efficacy of Centhaquine in patients with hypovolemic shock. The Phase III randomized double-blind, placebo-controlled study will be conducted in 430 patients, where patients will receive either an intravenous infusion of 0.01 mg/Kg of Centhaquine or a placebo. All patients will receive the standard of care. A 28-day all-cause mortality is the primary endpoint. The Phase III clinical trial is registered at clinicaltrials.gov (NCT05251181), providing details of the trial design and all the endpoints. U.S. FDA clearance of our Phase III IND is an important milestone for Pharmazz and the potential future treatment of hypovolemic shock patients. About Pharmazz, Inc. Pharmazz is a privately held company developing novel products in critical care medicine. Pharmazz, Inc. obtained marketing authorization for two of its first-in-class drug molecules, Centhaquine and Sovateltide, for hypovolemic shock and ischemic stroke, respectively, in India. In addition, the U.S. Food and Drug Administration (FDA) has approved two phase III INDs for Centhaquine as an agent for hypovolemic shock and Sovateltide for cerebral ischemic stroke. Additional information may be found on the Company's website, www.pharmazz.com. Contacts: Pharmazz, Inc. Investors David CostelloMediaShruti Gulati Tel:+1 630 780 6087 Tel:+1 630 780 6087Email:david.costello@pharmazz.com Email:shruti.gulati@pharmazz.com About Dr. Reddy’s: Dr. Reddy’s Laboratories Ltd. (BSE: 500124, NSE: DRREDDY, NYSE: RDY, NSEIFSC: DRREDDY) is a global pharmaceutical company headquartered in Hyderabad, India. Established in 1984, we are committed to providing access to affordable and innovative medicines. Driven by our purpose of ‘Good Health Can’t Wait’, we offer a portfolio of products and services including APIs, generics, branded generics, biosimilars and OTC. Our major therapeutic areas of focus are gastrointestinal, cardiovascular, diabetology, oncology, pain management and dermatology. Our major markets include – USA, India, Russia & CIS countries, China, Brazil and Europe. As a company with a history of deep science that has led to several industry firsts, we continue to plan ahead and invest in businesses of the future. As an early adopter of sustainability and ESG actions, we released our first Sustainability Report in 2004. Our current ESG goals aim to set the bar high in environmental stewardship; access and affordability for patients; diversity; and governance. For more information, log on to: www.drreddys.com. CONTACTS: Investor RelationsRicha PeriwalRichaperiwal@drreddys.com Media RelationsUsha IyerUshaiyer@drreddys.com