Trinitrate

CATALYST is a Phase 2 single-blind, placebo-controlled, proof-of-concept study in patients presenting to the emergency department More than 27,569 individuals in the U.S. died from drug overdose deaths involving cocaine in 2022; there is currently no FDA-approved product for cocaine intoxication Topline results are expected in the first half of 2025 Aug. 20, 2024 -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, today announced the first patient has been dosed in the Phase 2, single-blind, placebo-controlled, proof of concept trial of TNX-1300 (double-mutant cocaine esterase 200 mg, i.v. solution) for the treatment of acute cocaine intoxication in the emergency department (ED). TNX-1300 is a recombinant enzyme that rapidly and efficiently degrades and metabolizes cocaine in cocaine users, as demonstrated in a prior Phase 2a randomized, double-blind, placebo-controlled, laboratory-based clinical study, providing support for the use of TNX-1300 as a treatment for life-threatening cocaine intoxication.1 Tonix has been awarded a Cooperative Agreement Grant from National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), to support development of TNX-1300 for the treatment of cocaine intoxication. In addition, TNX-1300 has been granted Breakthrough Therapy designation by the U.S Food and Drug Administration (FDA). “Cocaine abuse and dependence are major problems in the U.S. However, there is currently no FDA-approved treatment indicated for cocaine intoxication, a life-threatening state characterized by acute symptoms including agitation, hyperthermia, tachycardia, arrhythmias, hypertensive crisis, myocardial infarction, stroke, and seizures,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “In 2022, the number of overdose deaths involving cocaine reached 27,569 individuals.2 With approximately 505,000 emergency room visits annually involving cocaine use and approximately 61,000 of the visits involving detox services to treat cocaine overdose,3,4 we believe TNX-1300 has the potential to help address the morbidity and mortality caused by cocaine intoxication. By targeting the cause rather than the symptoms of cocaine intoxication, TNX-1300 may offer significant advantages to the current standard of care for cocaine overdose.” The Phase 2 trial is a single-blind, open-label, placebo-controlled, randomized study comparing the safety of a single 200 mg dose of TNX-1300 to placebo injection plus standard of care alone for the treatment of signs and symptoms of acute cocaine intoxication. The study is being conducted in the EDs of six academic medical centers in the U.S. It will include approximately 60 subjects presenting to the ED with cocaine intoxication. During the treatment period, subjects randomized to receive TNX-1300 will receive a single i.v. injection of TNX-1300 administered over two minutes or less; whereas subjects randomized to receive standard of care alone will receive a single i.v. saline injection over two minutes or less. For both study arms, signs and symptoms of cocaine intoxication will be assessed at pre-determined time points after treatment. After randomization, blood samples will be drawn at specific time points to assess the pharmacokinetics of TNX-1300 and levels of cocaine and its metabolites in the plasma. The primary endpoint of the study is reduction of systolic blood pressure associated with acute cocaine intoxication identified at study baseline comparing TNX-1300 to placebo with standard of care after 60 minutes. A variety of secondary endpoints will be measured, including reduction of circulating cocaine and levels of its metabolites at multiple post-baseline timepoints. TNX-1300 (T172R/G173Q double-mutant cocaine esterase 200 mg, i.v. solution) is being developed under an Investigational New Drug application (IND) for the treatment of cocaine intoxication. TNX-1300 is a recombinant protein enzyme produced through recombinant DNA technology in a non-disease-producing strain of E. coli bacteria. Cocaine esterase (CocE) was identified in bacteria (Rhodococcus) that uses cocaine as its sole source of carbon and nitrogen and that grows in soil surrounding coca plants.5 The gene encoding CocE was identified and the protein was extensively characterized.5-8 CocE catalyzes the breakdown of cocaine into metabolite ecgonine methyl ester and benzoic acid. Wild-type CocE is unstable at human body temperature, so targeted mutations were introduced in the CocE gene and resulted in the T172R/G173Q double-mutant CocE, which is active for approximately 6 hours at body temperature.8 In a Phase 2 laboratory-based study in volunteers who use cocaine, TNX-1300, at 100 mg or 200 mg i.v. doses, was well tolerated and rapidly reduced cocaine effects after cocaine 50 mg i.v. challenge.1 Cocaine is an illicit recreational drug which is taken for its pleasurable effects and associated euphoria. In 2022, over 5 million individuals in the U.S. reported current cocaine use, almost 2% of the population.9 Pharmacologically, cocaine blocks the reuptake of the neurotransmitter dopamine from central nervous system synapses, resulting in the accumulation of dopamine within the synapse and an amplification of dopamine signaling and its capacity to produce euphoric mood states. With the continued use of cocaine, however, intense cocaine cravings occur resulting in a high potential for abuse and addiction (dependence), as well as the risk of acute cocaine intoxication. Cocaine intoxication refers to the deleterious effects on several body systems, especially those involving the cardiovascular system. Common symptoms of cocaine intoxication include tachyarrhythmias and elevated blood pressure, either of which can be life-threatening. As a result, individuals with known or suspected cocaine intoxication are sent immediately to the emergency department (ED), preferably by ambulance in case cardiac arrest occurs during transit. The standard of care for treating cocaine intoxication in the ED focuses on symptom management, preventing complications, and supporting cardiovascular, respiratory, and neurological function, e.g. benzodiazepines for agitation, seizures, and sympathetic overdrive; antihypertensives for extremely elevated blood pressure; aspirin and nitroglycerine for cardiac ischemia. There are approximately 505,000 emergency room visits for cocaine abuse each year in the U.S., of which 61,000 require detoxification services.3,4 According to the National Institute on Drug Abuse, in 2022 the number of overdose death involving cocaine reached 27,569 individuals.2 In 2019, Black Americans experienced the highest death rate for overdoses involving cocaine, at 10.7 per 100,000.10 References 1 Nasser et al. A randomized, double-blind, placebo-controlled trial of RBP-8000 in cocaine abusers: pharmacokinetic profile of rbp-8000 and cocaine and effects of RBP-8000 on cocaine-induced physiological effects. J Addict Dis. 2014;33(4):289-302. 2 https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates; August 18, 2024 3 Substance Mental Health Services Administration, Drug Abuse Warning Network, 2011: National Estimates of Drug- Related Emergency Department Visits. HHS Publication No. (SMA) 13-4760, DAWN Series D-39. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013. 4 Drug Abuse Warning Network, 2011: Selected Tables of National Estimates of Drug-Related Emergency Department Visits. Rockville, MD: Center for Behavioral Health Statistics and Quality, SAMHSA, 2013. 5 Bresler, et al. Gene cloning and nucleotide sequencing and properties of a cocaine esterase from Rhodococcus sp. strain MB1. Appl Environ Microbiol. 2000. 66(3):904-8. 6 Larsen, et al. Crystal structure of a bacterial cocaine esterase. Nat Struct Biol. 2002. 9(1):17-21. 7 Turner, et al. Biochemical characterization and structural analysis of a highly proficient cocaine esterase. Biochemistry. 2002. 41(41):12297-307. 8 Gao, et al. Thermostable variants of cocaine esterase for long-time protection against cocaine toxicity. Mol Pharmacol. 2009. 75(2):318-23. 9 https://www.cdc.gov/drugoverdose/deaths/other-drugs.html; accessed August 18, 2024 10 Kariisa, et al. Drug overdose deaths involving cocaine and psychostimulants with abuse potential among racial and ethnic groups – United States, 2004-2019. Drug Alcohol Depend. 2021. 1;227:109001. Tonix is a fully integrated biopharmaceutical company focused on transforming therapies for pain management and modernizing solutions for public health challenges. Tonix’s development portfolio is focused on central nervous system (CNS) disorders, and its priority is to submit a New Drug Application (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 in Phase 2 development designed to treat cocaine intoxication that has 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, including TNX-2900 for Prader-Willi syndrome, and infectious disease, including a vaccine for mpox, TNX-801. Tonix recently announced the U.S. Department of Defense (DoD), Defense Threat Reduction Agency (DTRA) awarded it a contract for up to $34 million over five years in an Other Transaction Agreement (OTA) 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, instrumental in progressing this development. 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. 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OSLO, Norway, Feb. 15, 2024 /PRNewswire/ -- Navamedic ASA (OSE: NAVA) , a Nordic pharma company and reliable provider of high-quality products to hospitals and pharmacies, today announced its results for the fourth quarter and for the full year 2023. Revenues for the year was up 34 per cent to NOK 512 million, mainly by organic growth. For the first time all three product categories were above the NOK 100 million mark. The company's gross margin was 38.9 per cent for the year, down from 42.8 per cent in the year before. Adjusted EBITDA (EBITDA less acquisition cost) amounted to NOK 51.6 million, compared with NOK 51.7 million in 2022. Operating results (EBIT) amounted to NOK 23.6 million, compared to NOK 44.4 million in 2022. Operating costs were higher than in 2022, mostly due to continued investments in growth initiatives. Also included in the EBITDA is a negative contribution of 4.8 MNOK from the Sensidose business. "We are looking back at an eventful and transformative year. With the Sensidose acquisition, we gained a promising position in the market for treatment of Parkinson's Disease, and we renewed and secured new marketing and distribution agreements for several other high selling products, including Eroxon®, a clinically proven treatment of erectile dysfunction. Eroxon® was launched in Norway this week and will soon also be available in Sweden," said Kathrine Gamborg Andreassen, CEO of Navamedic. "Furthermore, in the fourth quarter 2023, we signed a term sheet with the Finnish pharmaceutical corporation Orion Pharma, which we are currently finalising into an agreement for a licensing and supply of Flexilev® and OraFID® in Europe, products that were acquired through Sensidose. In Sweden, Norway and Denmark, we will market and sell these products from our own proven platform," Andreassen added. Revenues in the fourth quarter of 2023 was NOK 125 million, up 8.1 percent from the same period last year. Gross margin was 36.5 per cent, down from 42.9 per cent, and Adjusted EBITDA was NOK 7.9 million, compared with NOK 15.7 million in the fourth quarter of 2022. Category update In the Consumer Health category, Modifast cemented its position with continued strong sales in Sweden, and Absolute Torr gained traction with a 54 per cent growth year-over-year in the fourth quarter. Further growth to be achieved through combination of consumer and pharmacy engagement, sale of unique and profitable products in home markets and out-licensing of own products elsewhere. The Hospital category saw double-digit growth year-over-year across the portfolio of antibiotics and medical nutrition products. It also renewed exclusive rights to Vitaflo's medical nutrition products across the Nordic for five more years. Winning new antibiotic tenders is core in the growth strategy, along with initiatives to expand and secure new marketing authorisations. The Prescription Drugs category had strong growth across various therapeutic areas, with continued high demand for Mysimba for obesity treatment, and strong sales of Imdur, Nitrolingual and Forlax. In this category, Navamedic is now preparing rollout of Flexilev with MyFID® and OraFID® in the Nordic countries and out-licensing in the rest of Europe. Outlook Navamedic sees continued strong growth and new expansion opportunities and reiterates its mid-term ambition of building a NOK 1 billion revenue company with a 15 per cent EBITDA margin. "We are building on a solid foundation. We will continue to strengthen our existing business by leveraging our highly scalable market access platform. We will explore opportunities for market expansion with own products and increase company value by acquiring and strengthening own products and brands while increasing gross margins through careful management of our product portfolio," Andreassen concluded. Navamedic will present the results for the fourth quarter and full year 2023 at 08.30 today. The presentation will take place at Dronning Eufemias Gate 16 in Oslo, and will be available to follow via webcast at the following link: Representatives from Navamedic's management team, CEO Kathrine Gamborg Andreassen and CFO Lars Hjarrand will host the presentation. EBITDA and other alternative performance measures (APMs) are defined and reconciled to the IFRS financial statements as a part of the APM section of the attached presentation on slide 23. For further information, please contact: Kathrine Gamborg Andreassen, CEO, Navamedic Mobile: +47 951 78 680 E-mail: [email protected] Lars Hjarrand, CFO, Navamedic Mobile: +47 917 62 842 E-mail: [email protected] About Navamedic Navamedic ASA is a full-service provider of high-quality healthcare products to hospitals and pharmacies. Navamedic meets the specific medical needs of patients and consumers by leveraging its highly scalable market access platform, leading category competence and local knowledge. Navamedic is present in all the Nordic countries, the Baltics and Benelux, with sales representation in the UK and Greece. Navamedic is headquartered in Oslo, Norway, and listed on the Oslo Stock Exchange (ticker: NAVA). For more information, please visit Navamedic.com. This information is subject to the disclosure requirements pursuant to section 5 -12 of the Norwegian Securities Trading Act. The following files are available for download: