Revolutionizing MDD Treatment: Tonix Pharmaceuticals Launches UPLIFT Study of TNX-601 ER for Major Depressive Disorder

Tonix Pharmaceuticals, Inc. (Nasdaq: TNXP) has announced the enrollment of the first participant in the Phase 2 ‘UPLIFT’ clinical trial for TNX-601 ER1 (tianeptine hemioxalate extended-release tablets) for the treatment of major depressive disorder (MDD). The double-blind, placebo-controlled, registrational-quality study is being conducted at 30 sites across the U.S. and is expected to enroll a total of 300 participants. Results from an interim analysis of the trial are expected to be released in the fourth quarter of 2023.

TNX-601 ER is a revolutionary once-daily formulation of tianeptine sodium that has been designed to be bioequivalent to the three-times-a-day formulation of tianeptine sodium (amorphous) immediate release (IR) tablets. This is a breakthrough in the treatment of Major Depressive Disorder (MDD), as tianeptine-containing products have been used to treat MDD in Europe, Asia, and Latin America for over 30 years, yet the U.S. Food and Drug Administration (FDA) has yet to approve a tianeptine-containing product for use in the US.

Tonix Pharmaceuticals’ Chief Executive Officer Seth Lederman, M.D. notes that there is still an unmet need for novel treatments for major depressive disorder (MDD) in the US, despite the availability of various classes of treatments that directly modulate neurotransmitters and their synaptic receptors. TNX-601 ER has shown promise in animal models with its unique mechanism of action that restores neuroplasticity by increasing the arborization of dendrites in critical hippocampal circuits, as well as reversing stress-induced impairments in synaptic glutamate neurotransmission and restoring hippocampal neurogenesis.2

After years of researching and developing our once-daily tianeptine formulation, TNX-601 ER, we are thrilled to move forward with the clinical testing necessary to make it available to those suffering from MDD in the U.S. TNX-601 ER could be a game-changer for millions of MDD sufferers, providing not only relief from depressive symptoms, but an improved quality of life and greater resiliency. The short and long-term safety of tianeptine sodium IR has been well-established in clinical studies outside of the US. Dr. Gregory Sullivan, Tonix Pharmaceuticals’ Chief Medical Officer, could not be more pleased.

Tianeptine sodium IR has been proven to be just as effective as selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants, with a significantly lower incidence of adverse side effects such as sexual dysfunction, sleep disruption, sedation, weight gain, and cognitive impairment.5-7 Furthermore, TNX-601 ER has a decreased risk of drug-drug interactions due to its independent metabolic pathway, which does not involve the hepatic cytochrome P450 system.7 As such, tianeptine sodium IR offers a safer and more effective alternative to many existing antidepressants.

Tianeptine is making waves in the treatment of major depressive disorder (MDD), offering a new way to combat a seriously disabling condition that is linked to suicidal behavior. Studies in animals have shown that tianeptine can restore stress-induced deficits in neuroplasticity and neurogenesis, leading to improved dendritic arborization, spine synapse remodeling and even new neurons in the hippocampus. This breakthrough could provide relief to the estimated 21 million people in the U.S. who suffer from MDD, offering a way to combat MDD by enhancing a resilient biological phenotype of neurons and glial cells under stress.

About the Phase 2 UPLIFT Study

The TNX-TI-M201 Phase 2 UPLIFT study is an exciting double-blind, randomized, multicenter, placebo-controlled trial to explore the efficacy and safety of TNX-601 ER taken orally once-daily for six weeks in adults aged 18-65 suffering from depression. 300 participants will be randomly assigned to either the TNX-601 ER 39.4 mg arm or the placebo arm from 30 US sites. The primary endpoint of the study is the change from baseline in the Montgomery-├ůsberg Depression Rating Scale (MADRS) total score at Week 6, while the key secondary endpoints are the Clinical Global Impression of Severity Scale (CGI-S) and the Sheehan Disability Scale (SDS). An interim analysis is expected to be conducted after half of the participants have completed the study, with a 24-week open-label extension study, TNX-TI-M202, planned to follow for those who finish the study.

About Major Depressive Disorder (Depression)

Depression is a serious mental health condition that affects millions of people in the United States each year. In 2020, an estimated 21 million adults experienced at least one major depressive episode, with the highest prevalence among 18-25 year olds at 17.0%. Symptoms of depression include a depressed mood, loss of interest in daily activities, appetite changes, sleep disturbances, motor restlessness or retardation, loss of energy, feelings of worthlessness or excessive guilt, poor concentration, and suicidal thoughts and behaviors. Many people who suffer from depression do not respond adequately to traditional antidepressant treatments, such as SSRIs, TCAs, SNRIs, and Auvelity® (dextromethorphan HBr-bupropion HCl). Dextromethorphan is a powerful direct antagonist of the NMDA-type glutamate receptor, making it a promising option for long-term depression treatment.

About TNX-601 ER

TNX-601 ER is a novel and exciting extended-release formulation of tianeptine hemioxalate that is currently in development as a candidate for the treatment of MDD, posttraumatic stress disorder, and neurocognitive dysfunction associated with corticosteroid use. Tianeptine sodium, the immediate-release form of tianeptine, has been used for decades in Europe, Russia, Asia, and Latin America to treat depression. It has a well-established safety profile from decades of use. The oxalate salt of tianeptine used in TNX-601 ER has improved stability and manufacturability compared to known salt forms. Its mechanism of action involves indirect glutamatergic modulation, which makes it distinct from traditional monoaminergic antidepressants and could provide benefits in conditions beyond MDD and stress disorders. TNX-601 ER also contains several potentially abuse-deterrent ingredients, including gel forming polymers and a tablet hardness that makes it difficult to crush, cut, or grind. Additionally, tianeptine has been found to have pro-cognitive and anxiolytic effects, as well as the ability to attenuate the negative impact of excessive stress responses, suggesting it may be useful in the treatment of PTSD and

About Tonix Pharmaceuticals Holding Corp.*

Tonix is a biopharmaceutical company on the cutting edge of medical research, dedicated to creating groundbreaking therapeutics to prevent and treat human illness and improve quality of life. Its CNS portfolio covers a range of small molecules and biologics to manage pain, neurological, psychiatric and addiction issues, with a particular focus on fibromyalgia and Long COVID. Its rare disease portfolio includes a treatment for Prader-Willi syndrome, while in immunology it is developing biologics to tackle organ transplant rejection and autoimmunity. For infectious diseases, it is researching a smallpox and mpox vaccine and a broad-spectrum small molecule oral antiviral. Tonix’s lead candidate, TNX-102 SL, is in mid-Phase 3 development, with interim data expected in the second quarter of 2023. The company has been granted Breakthrough Therapy designation by the FDA for TNX-1300, a biologic designed to treat cocaine intoxication. Its other candidates, TNX-1900 and TNX-601 ER, are currently enrolling, with interim data expected in the fourth quarter of 2023.

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