Nociceptive Pain

WALTHAM, Mass., Oct. 09, 2024 (GLOBE NEWSWIRE) -- Ardelyx, Inc. (Nasdaq: ARDX), a biopharmaceutical company founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs, today announced the recent publication of a review article, titled “Review of the Patient Burden and Therapeutic Landscape of Irritable Bowel Syndrome With Constipation in the United States” in Clinical and Experimental Gastroenterology, an international, peer reviewed, open access journal focusing on all aspects of gastroenterology research, as well as clinical results in human, animal and in vitro studies that shed light on disease processes and potential new therapies. The article provides an overview of treatment options and disease management for irritable bowel syndrome with constipation (IBS-C) from a U.S. perspective and discusses the importance of the relationship between patient and health care provider in diagnosis and treatment. It recommends a positive diagnostic strategy for IBS-C, based on clinical history, physical examination, and minimal laboratory tests. “IBS-C patients often experience a high level of disease burden across a variety of factors which extend beyond the physical symptoms associated with the condition. Patients often report negative economic, social and mental health impacts due to IBS-C, which makes even daily activities challenging,” said Morgan Allyn Sendzischew Shane, MD, Division of Gastroenterology and Digestive Disease, University of Miami and lead author of the article. “It’s critical that the larger healthcare community understands the full patient experience, especially as we see how important the patient and healthcare provider relationship is in regard to diagnosis and treatment.” The authors review the substantial societal burden in terms of health care costs, opportunity costs and decreased quality of life that comes with IBS-C. The article also reviews the treatment journey a patient with IBS-C may experience, beginning with lifestyle interventions and nonpharmacologic options, with progression to a U.S. FDA-approved therapy. IBSRELA® (tenapanor) is identified as one of the currently approved therapies, with data from the T3MPO-1 and T3MPO-2 studies included within the review. IBSRELA is a first-in-class treatment for IBS-C in adults that is approved by the U.S. Food and Drug Administration. The article is available online and can be accessed here. About IBSRELA® (tenapanor)IBSRELA (tenapanor) is a locally acting inhibitor of the sodium/hydrogen exchanger 3 (NHE3), an antiporter expressed on the apical surface of the small intestine and colon primarily responsible for the absorption of dietary sodium. By inhibiting NHE3 on the apical surface of the enterocytes, tenapanor reduces absorption of sodium from the small intestine and colon, thus retaining luminal water content, which accelerates intestinal transit time and results in a softer stool consistency. IBSRELA has also been shown to reduce abdominal pain by decreasing visceral hypersensitivity and by decreasing intestinal permeability in animal models. In a rat model of colonic hypersensitivity, tenapanor reduced visceral hyperalgesia and normalized colonic sensory neuronal excitability. Please see full Prescribing Information, including Boxed Warning, for additional risk information. About Irritable Bowel Syndrome with Constipation (IBS-C)Irritable bowel syndrome with constipation (IBS-C) is a gastrointestinal disorder characterized by both abdominal pain and altered bowel movements, estimated to affect 12 million people in the U.S. IBS-C is associated with significantly impaired quality of life, reduced productivity, and substantial economic burden. IMPORTANT SAFETY INFORMATION WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTSIBSRELA is contraindicated in patients less than 6 years of age; in nonclinical studies in young juvenile rats administration of tenapanor caused deaths presumed to be due to dehydration. Avoid use of IBSRELA in patients 6 years to less than 12 years of age. The safety and effectiveness of IBSRELA have not been established in patients less than 18 years of age. CONTRAINDICATIONSIBSRELA is contraindicated in: patients less than 6 years of age due to the risk of serious dehydrationpatients with known or suspected mechanical gastrointestinal obstruction WARNINGS AND PRECAUTIONSRisk of Serious Dehydration in Pediatric Patients IBSRELA is contraindicated in patients below 6 years of age. The safety and effectiveness of IBSRELA in patients less than 18 years of age have not been established. In young juvenile rats (less than 1 week old; approximate human age equivalent of less than 2 years of age), decreased body weight and deaths occurred, presumed to be due to dehydration, following oral administration of tenapanor. There are no data available in older juvenile rats (human age equivalent 2 years to less than 12 years).Avoid the use of IBSRELA in patients 6 years to less than 12 years of age. Although there are no data in older juvenile rats, given the deaths in younger rats and the lack of clinical safety and efficacy data in pediatric patients, avoid the use of IBSRELA in patients 6 years to less than 12 years of age. Diarrhea Diarrhea was the most common adverse reaction in two randomized, double-blind, placebo-controlled trials of IBS-C. Severe diarrhea was reported in 2.5% of IBSRELA-treated patients. If severe diarrhea occurs, suspend dosing and rehydrate patient. MOST COMMON ADVERSE REACTIONS The most common adverse reactions in IBSRELA-treated patients (incidence ≥2% and greater than placebo) were: diarrhea (16% vs 4% placebo), abdominal distension (3% vs <1%), flatulence (3% vs 1%) and dizziness (2% vs <1%). INDICATION IBSRELA (tenapanor) is indicated for the treatment of Irritable Bowel Syndrome with Constipation (IBS-C) in adults. Please see full Prescribing Information, including Boxed Warning, for additional risk information. About ArdelyxArdelyx was founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs. Ardelyx has two commercial products approved in the United States, IBSRELA® (tenapanor) and XPHOZAH® (tenapanor). Ardelyx has agreements for the development and commercialization of tenapanor outside of the U.S. Kyowa Kirin commercializes PHOZEVEL® (tenapanor) for hyperphosphatemia in Japan. A New Drug Application for tenapanor for hyperphosphatemia has been submitted in China with Fosun Pharma. Knight Therapeutics commercializes IBSRELA in Canada. For more information, please visit https://ardelyx.com/ and connect with us on X (formerly known as Twitter), LinkedIn and Facebook. Investor and Media Contacts: Caitlin Lowieclowie@ardelyx.com

HALETHORPE, Md., Sept. 24, 2024 /PRNewswire/ -- Fzata, Inc. is pleased to announce a five-year UG3/UH3 non-dilutive grant (UG3NS135350) of up to $7 million, plus in-kind contributions, awarded by the NIH National Institute of Neurological Disorders and Stroke (NINDS). Grant participants include Fzata and the University of Maryland, Baltimore (UMB). The grant supports development of BioPYM™ drug candidate FZ006 as a safe and effective oral treatment for chronic visceral pain associated with inflammatory bowel syndrome (IBS). Work under the grant will include IND-enabling studies, GLP toxicology, cGMP manufacturing, phase 1 trial design, IND submission, and Phase 1a clinical trial. Continue Reading Fzata's FZ006 drug candidate is in development as an effective, safe, non-addictive option to treat chronic abdominal pain. Dr. Zhiyong Yang, President and CEO of Fzata, commented, "Chronic visceral pain associated with IBS is a serious unmet need. Ten to 15 percent of Americans suffer with severe pain, but treatment options are often inadequate. The most effective opioid treatments come with a high risk of addiction, a national problem. FZ006 will be the first effective, safe, non-addictive option to treat chronic abdominal pain. We are excited to work with the outstanding team we assembled, including labs at UMB and NINDS, to bring a real game-changer to IBS patients and their families." "This NIH award presents a wonderful opportunity for Fzata, one of UMB's startup portfolio companies, to advance development of their platform technology for an important medical need. It's gratifying that the funded work will be in collaboration with UMB scientists," said Phil Robilotto, DO, MBA, associate vice president of technology transfer at UMB and director of UM Ventures, Baltimore. "We are excited by Fzata's continued pipeline advancements, including ("FZ002") for C. difficile infections, which is based on technology licensed from UMB and expected to start first-in-human clinical trials in 2025." About Fzata, Inc . The Company has innovated and developed a next-generation therapeutics platform called Bioengineered Probiotic Yeast Medicines (BioPYM™) for oral live biotherapeutics. BioPYM enables probiotic yeast to function as a micro-factory within the gut, producing therapeutics on site where disease pathologies occur. The "plug and play" platform accepts any gene to make biotherapeutic proteins including monoclonal antibodies, enzymes, cytokines, and hormones. Leveraging BioPYM, the Company has a pipeline of proprietary drug candidates to treat a wide variety of gastrointestinal diseases and gut-health axis disorders. Learn more at or follow us on LinkedIn. For investment opportunities, licensing, or collaboration inquiries, please contact: Elizabeth Smith, PhD, MBA, Chief Business Officer, Fzata E-mail: [email protected] SOURCE Fzata, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Oral presentation highlighted results from confirmatory Phase 3 RESILIENT study of TNX-102 SL (sublingual cyclobenzaprine HCl) treatment demonstrating statistically significant improvement in primary endpoint of fibromyalgia nociplastic pain and in all six key secondary endpoints, including sleep quality NDA submission on track for second half 2024; Fast Track designation granted by FDA; FDA decision expected 2025 TNX-102 SL is a potential non-opiod analgesic targeting non-restorative sleep in fibromyalgia: Post hoc analyses highlight strong correlations between improvements in nociplastic pain and sleep quality Nociplastic pain originates from altered pain perception in the brain and is the type of pain that manifests in fibromyalgia and other chronic overlapping pain conditions (COPCs) CHATHAM, N.J., Aug. 28, 2024 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, presented data in an oral presentation at the 2024 Military Health System Research Symposium (MHSRS), held August 26-29, 2024, in Kissimmee, Fla. A copy of the Company’s presentation, titled “Assuaging Agony: Novel Pain Therapeutics”, is available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com. In the Phase 3 RESILIENT study, TNX-102 SL met the pre-specified primary endpoint of significantly reducing daily pain compared to placebo (p-value=0.00005) in participants with fibromyalgia. TNX-102 SL demonstrated broad syndromal benefits with statistically significant improvement in all six pre-specified key secondary endpoints including those related to improving sleep quality, reducing fatigue, and improving patient global ratings and overall fibromyalgia symptoms and function. A post hoc analysis showed strong correlations between improvements in pain and sleep quality at Week 14, supporting the concept that targeting sleep quality has the potential to achieve syndromal improvement in fibromyalgia. TNX-102 SL was well tolerated with an adverse event profile comparable to prior studies and no new safety signals observed. “Traditional analgesics like NSAIDs or opioids often prove ineffective, if not deleterious, as strategies for treating fibromyalgia,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “In contrast, TNX-102 SL provided broad-spectrum symptom relief in the Phase 3 RESILIENT study and was designed as a bedtime treatment to target non-restorative sleep and improve sleep quality. With the statistically significant results of two positive Phase 3 studies of TNX-102 SL in fibromyalgia we believe TNX-102 SL has the potential to be the first new treatment option for fibromyalgia patients in 15 years.” Dr. Lederman continued, “Fibromyalgia is the prototypic nociplastic syndrome and chronic overlapping pain condition (COPC)3,4,5. Our results in fibromyalgia suggest potential for TNX-102 SL in treating other COPCs like post-concussive syndrome6, in which sleep disturbances correlate with persistence and severity. In addition, we expect to begin enrolling this quarter in a trial of TNX-102 SL for acute stress disorder/acute stress reaction in the immediate aftermath of motor vehicle collision in the U.S. Department of Defense (DoD)-funded Optimizing Acute Stress Reaction Interventions (OASIS) trial conducted by the University of North Carolina under an investigator-initiated investigational new drug (IND) application. Tonix remains on track to submit a new drug application (NDA) to the FDA in the second half of 2024 for TNX-102 SL for the management of fibromyalgia. A decision on approval is expected in 2025. 1Moldofsky H, et al. Psychosom Med. 1975;37:341-51 2Moldofsky H, Scarisbrick P. Psychosom Med. 1976;38:35-44 3Fitzcharles MA, et al. Lancet. 2021;397:2098-110 4Clauw DJ. Ann Rheum Dis. Published Online First: 2024 5Kaplan CM, et al. Nat Rev Neurol. 2024;20, 347–363 6Kureshi S et al. Healthcare (Basel) 2024 12(3): 289. 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., the majority of whom are women. Symptoms of fibromyalgia include chronic widespread pain, non-restorative sleep, fatigue, and brain fog (or cognitive dysfunction). Other associated symptoms include mood disturbances, including anxiety and depression, headaches, and abdominal pain or cramps. 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. According to the recent report from the U.S. National Academies of Sciences, fibromyalgia is a diagnosable condition that may also occur in the context of Long COVID About TNX-102 SL TNX-102 SL is a centrally acting, non-opioid, non-addictive, bedtime investigational drug. The tablet is a patented sublingual formulation of cyclobenzaprine hydrochloride developed for the management of fibromyalgia. In December 2023, the company announced highly statistically significant and clinically meaningful topline results in RESILIENT, the second pivotal Phase 3 clinical trial of TNX-102 SL for the management of fibromyalgia. In the study, TNX-102 SL met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo (p=0.00005) in participants with fibromyalgia. Statistically significant and clinically meaningful results were also seen in all six key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function. RELIEF, the first statistically significant Phase 3 trial of TNX-102 SL in fibromyalgia, was completed in December 2020. It met its pre-specified primary endpoint of daily pain reduction compared to placebo (p=0.010) and showed activity in key secondary endpoints. In both pivotal studies, the most common treatment-emergent adverse event was tongue or mouth numbness at the administration site, which was temporally related to dosing, self-limited, never rated as severe, and rarely led to study discontinuation (one participant in each study). TNX-102 SL was recently granted Fast Track Designation by the FDA for the management of fibromyalgia and remains on track to submit an NDA to FDA in the second half of 2024. About Nociplastic Pain Nociplastic pain is the third category of pain distinct from nociceptive pain and neuropathic pain. Nociplastic pain is characterized by pain arising from altered nociception despite no evidence of actual or threatened tissue damage causing activation of peripheral nociceptors or somatosensory system disease or lesion. Its underlying pathophysiology involves altered pain processing by the central nervous system (CNS). Nociplastic syndromes, officially recognized by the International Association for the Study of Pain (IASP) in 2017, also include several other chronic overlapping pain conditions: myalgic encephalomyelitis/chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorders, forms of chronic back pain and chronic headache. The pathophysiology of nociplastic pain involves central sensitization (CS), where neurons of the CNS become hyperexcitable, amplifying pain signals. CS can be triggered by peripheral pain stimuli, emotional stress, or other factors, leading to persistent pain despite no peripheral nociceptive input. Tonix Pharmaceuticals Holding Corp.* Tonix is a fully-integrated biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix recently announced the U.S. DoD, Defense Threat Reduction Agency (DTRA) awarded it a contract for up to $34 million over five years to develop TNX-4200 small molecule broad-spectrum antiviral agents targeting CD45 for the prevention or treatment of infections to improve the medical readiness of military personnel in biological threat environments. Tonix owns and operates a state-of-the art infectious disease research facility in Frederick, MD. The company also owns a Good Manufacutring Practice (GMP)-capable advanced manufacturing facility in Dartmouth, MA, which was purpose-built to manufacture TNX-801, a potential mpox vaccine, and the GMP suites are ready to be reactivated in case of a national emergency. Tonix’s development portfolio is focused on CNS disorders. Tonix’s priority is to submit an NDA to the FDA in the second half of 2024 for TNX-102 SL, a product candidate for which two statistically significant Phase 3 studies have been completed for the management of fibromyalgia. The FDA has granted Fast Track designation to TNX-102 SL for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase), a biologic designed to treat cocaine intoxication that has Breakthrough Therapy designation, which is enrolling in a potential pivotal Phase 2 trial. 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. 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, 2023, as filed with the Securities and Exchange Commission (the “SEC”) on April 1, 2024, 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 Lisa DeScenzaLaVoieHealthScienceldescenza@lavoiehealthscience.com(617) 351-0243