Gabapentin

Tonmya is a potential new first-line, centrally acting non-opioid analgesic for the management of fibromyalgia, supported by statistically significant results from two Phase 3 trials Primary physician research found high level of interest in Tonmya as a potential new treatment option for fibromyalgia Significant dissatisfaction reported with drugs currently approved by FDA for the treatment of fibromyalgia Analysis of claims data revealed that addictive opioids are prescribed more frequently than currently approved drugs following fibromyalgia diagnosis New Drug Application (NDA) submission to the FDA on track for the second half of 2024 CHATHAM, N.J., May 21, 2024 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals, Inc. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, announced today that EVERSANA® Life Science Services, LLC, a leading provider of commercialization services to the global life sciences industry, completed the initial phase of an assessment of the U.S market opportunity for TonmyaTM (also known as TNX-102 SL, cyclobenzaprine HCl sublingual tablets), a potential new first line therapy for the management of fibromyalgia. Tonix previously announced that EVERSANA was selected to support the launch strategy and commercial planning of Tonmya. Specifically, EVERSANA is working with Tonix to assess the fibromyalgia landscape and help plan an efficient go-to-market (GTM) strategy. “The primary research and analysis conducted by EVERSANA provides valuable insights and informs the vision for the commercialization of Tonmya,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “We are excited to refine our business strategy for the anticipated launch of Tonmya in 2025. It has been approximately fifteen years since patients suffering with fibromyalgia have been provided a new therapeutic option. The market research conducted by EVERSANA with physicians indicates a continued high unmet need, with the need ranked > 4.0 on a 5-point scale.” Dr. Lederman continued, “We were surprised to learn that opioids dominate the fibromyalgia prescription market, despite the well-known risks of dependency. Opioids are prescribed to more patients following fibromyalgia diagnosis than all the FDA-approved fibromyalgia drugs combined. If approved, we believe that Tonmya can provide a non-opioid, centrally-acting solution for fibromyalgia patients. This is corroborated by EVERSANA’s primary market research in which physicians indicated median interest of 4.0 on a 5-point scale and intended use of Tomya in 40% of their fibromyalgia patients, upon approval.1 We look forward to submitting the NDA for Tonmya in the second half of this year and expect an FDA decision on approval in 2025.” EVERSANA’s analysis of the market size was based on medical claims databases and epidemiological studies on prevalence and diagnosis2. Primary research with physicians was conducted to test the potential adoption of Tonmya based on its activity and tolerability. Key findings from claims data analyses2: ~2.7 million adults in the U.S. currently diagnosed and treated for fibromyalgia. ~90 percent of patients diagnosed with fibromyalgia are female. Percentage of fibromyalgia patients who were prescribed certain drugs3: FDA-approved fibromyalgia drug prescriptions: Duloxetine (generic Cymbalta®): 23%, pregabalin (generic Lyrica®): 13%, and Savella® (milnacipran): 1% Off-label drug prescriptions: Gabapentin: 26%, hydroxycodone: 20%, cyclobenzaprine: 18%, oxycodone: 19%, tramadol: 13%, meloxicam: 12%, and amitriptyline: 6% Off-label opioids prescriptions: Hydroxycodone: 20%, oxycodone: 19%, and tramadol: 13% Targeted prescriber strategy for launch. High prescribers are rheumatologists, pain medicine specialists, primary care physicians, neurologists, and psychiatrists. ~50 percent of diagnosed fibromyalgia patients are covered by Medicare. Medicare population stands to benefit from a decrease in out-of-pocket prescription drug liability to $2,000 per year when the changes from the Inflation Reduction Act are enacted in 2025. Key findings from primary physician research4: High level of dissatisfaction with currently prescribed drugs. Physicians interviewed estimate that 85% of their patients fail first-line therapy due to efficacy and tolerability issues and 79% of their patients are on multiple therapies. Prescribers indicate high unmet need in fibromyalgia, ranked >4.0 on a 5-point scale. High level of interest in Tonmya from physicians interviewed as a potential new treatment option based on favorable activity and tolerability pro in Tonmya fibromyalgia clinical studies. Median interest in Tonmya of 4 on a 5-point scale. Physicians indicated intended use of Tonmya in 40% of their fibromyalgia patients.1 Tonmya is a centrally acting, non-opioid medication. As previously announced, Tonix’s second statistically significant Phase 3 study, RESILIENT, 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 (p=0.001 or better) were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue, and improving overall fibromyalgia symptoms and function. Tonix plans to submit an NDA to the U.S. Food and Drug Administration (FDA) in the second half of 2024 for Tonmya for the management of fibromyalgia and has scheduled a Type B pre-NDA meeting with FDA for the second quarter of 2024. 1 40% was the median preference share amongphysicians interviewed,assuming no market access barriers. 2EVERSANA analysis of claims database, May 2024; commissioned by Tonix 3Note: the total number of patients is greater than 100% because of switching between medications and polypharmacy. 4EVERSANA primary physician research, May 2024; commissioned by Tonix About Tonmya* (also known as TNX-102 SL) Tonmya is a centrally acting, non-opioid, non-addictive, bedtime medication. 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, a second positive Phase 3 clinical trial of Tonmya for the management of fibromyalgia. In the study, Tonmya 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 key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function. RELIEF, the first positive Phase 3 trial of Tonmya 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. *Tonmya™ is conditionally accepted by the U.S. Food and Drug Administration (FDA) as the tradename for TNX-102 SL for the management of fibromyalgia. Tonmya has not been approved for any indication. About EVERSANA® EVERSANA® is a leading independent provider of global services to the life sciences industry. The company’s integrated solutions are rooted in the patient experience and span all stages of the product life cycle to deliver long-term, sustainable value for patients, prescribers, channel partners and payers. The company serves more than 650 organizations, including innovative start-ups and established pharmaceutical companies, to advance life sciences solutions for a healthier world. To learn more about EVERSANA, visit eversana.com or connect through LinkedIn and X. 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’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. 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 . 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 commercialize 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 Morris Tonix Pharmaceuticals investor.relations@tonixpharma.com (862) 904-8182 Peter Vozzo ICR Westwicke peter.vozzo@westwicke.com (443) 213-0505 Media Contact Katie Dodge LaVoieHealthScience kdodge@lavoiehealthscience.com (978) 360-3151 Matt Braun EVERSANA Matt.braun@eversana.com

Conditions such as diabetes, heart attack and vascular diseases commonly diagnosed in people with spinal cord injuries can be traced to abnormal post-injury neuronal activity that causes abdominal fat tissue compounds to leak and pool in the liver and other organs, a new animal study has found. Conditions such as diabetes, heart attack and vascular diseases commonly diagnosed in people with spinal cord injuries can be traced to abnormal post-injury neuronal activity that causes abdominal fat tissue compounds to leak and pool in the liver and other organs, a new animal study has found. After discovering the connection between dysregulated neuron function and the breakdown of triglycerides in fat tissue in mice, researchers found that a short course of the drug gabapentin, commonly prescribed for nerve pain, prevented the damaging metabolic effects of the spinal cord injury. Gabapentin inhibits a neural protein that, after the nervous system is damaged, becomes overactive and causes communication problems -- in this case, affecting sensory neurons and the abdominal fat tissue to which they're sending signals. "We believe there is maladaptive reorganization of the sensory system that causes the fat to undergo changes, initiating a chain of reactions -- triglycerides start breaking down into glycerol and free fatty acids that are released in circulation and taken up by the liver, the heart, the muscles, and accumulating, setting up conditions for insulin resistance," said senior author Andrea Tedeschi, assistant professor of neuroscience in The Ohio State University College of Medicine. "Through administration of gabapentin, we were able to normalize metabolic function." The study is published today (April 24, 2024) in Cell Reports Medicine. Previous research has found that cardiometabolic diseases are among the leading causes of death in people who have experienced a spinal cord injury. These often chronic disorders can be related to dysfunction in visceral white fat (or adipose tissue), which has a complex metabolic role of storing energy and releasing fatty acids as needed for fuel, but also helping keep blood sugar levels at an even keel. Earlier investigations of these diseases in people with neuronal damage have focused on adipose tissue function and the role of the sympathetic nervous system -- nerve activity known for its "fight or flight" response, but also a regulator of adipose tissue that surrounds the abdominal organs. Instead, Debasish Roy -- a postdoctoral researcher in the Tedeschi lab and first author on the paper -- decided to focus on sensory neurons in this context. Tedeschi and colleagues have previously shown that a neuronal receptor protein called alpha2delta1 is overexpressed after spinal cord injury, and its increased activation interferes with post-injury function of axons, the long, slender extensions of nerve cell bodies that transmit messages. In this new work, researchers first observed how sensory neurons connect to adipose tissue under healthy conditions, and created a spinal cord injury mouse model that affected only those neurons -- without interrupting the sympathetic nervous system. Experiments revealed a cascade of abnormal activity within seven days after the injury in neurons -- though only in their communication function, not their regrowth or structure -- and in visceral fat tissue. Expression of the alpha2delta1 receptor in sensory neurons increased as they over-secreted a neuropeptide called CGRP, all while communicating through synaptic transmission to the fat tissue -- which, in a state of dysregulation, drove up levels of a receptor protein that engaged with the CGRP. "These are quite rapid changes. As soon as we disrupt sensory processing as a result of spinal cord injury, we see changes in the fat," Tedeschi said. "A vicious cycle is established -- it's almost like you're pressing the gas pedal so your car can run out of gas but someone else continues to refill the tank, so it never runs out." The result is the spillover of free fatty acids and glycerol from fat tissue, a process called lipolysis, that has gone out of control. Results also showed an increase in blood flow in fat tissue and recruitment of immune cells to the environment. "The fat is responding to the presence of CGRP, and it's activating lipolysis," Tedeschi said. "CGRP is also a potent vasodilator, and we saw increased vascularization of the fat -- new blood vessels forming as a result of the spinal cord injury. And the recruitment of monocytes can help set up a chronic pro-inflammatory state." Silencing the genes that encode the alpha2delta1 receptor restored the fat tissue to normal function, indicating that gabapentin -- which targets alpha2delta1 and its partner, alpha2delta2 -- was a good treatment candidate. Tedeschi's lab has previously shown in animal studies that gabapentin helped restore limb function after spinal cord injury and boosted functional recovery after stroke. But in these experiments, Roy discovered something tricky about gabapentin: The drug prevented changes in abdominal fat tissue and lowered CGRP in the blood -- and in turn prevented spillover of fatty acids into the liver a month later, establishing normal metabolic conditions. But paradoxically, the mice developed insulin resistance -- a known side effect of gabapentin. The team changed drug delivery tactics, starting with a high dose and tapering off -- and stopping after four weeks. "This way, we were able to normalize metabolism to a condition much more similar to control mice," Roy said. "This suggests that as we discontinue administration of the drug, we retain beneficial action and prevent spillover of lipids in the liver. That was really exciting." Finally, researchers examined how genes known to regulate white fat tissue were affected by targeting alpha2delta1 genetically or with gabapentin, and found both of these interventions after spinal cord injury suppress genes responsible for disrupting metabolic functions. Tedeschi said the combined findings suggest starting gabapentin treatment early after a spinal cord injury may protect against detrimental conditions involving fat tissue that lead to cardiometabolic disease -- and could enable discontinuing the drug while retaining its benefits and lowering the risk for side effects. This work was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institutes of Health, and by the Chronic Brain Injury program at Ohio State. Co-authors, all from Ohio State, were Elliot Dion, Jesse Sepeda, Juan Peng, Sai Rishik Lingam, Kristy Townsend, Andrew Sas and Wenjing Sun.