No Evidence of Sexual Dysfunction or Weight Gain with its Active Ingredient as a Prescription Drug Outside the U.S.

Tianeptine Rescues Neuron Connectivity in Animal Models of Stress

CHATHAM, NJ / ACCESSWIRE / April 27, 2023 / A new antidepressant drug candidate being developed by researchers at Tonix Pharmaceuticals Holding Corp. (Nasdaq:TNXP) is said to have mechanistic activity and therapeutic features that set it apart from almost all of the currently approved antidepressants in the U.S.

Tianeptine - the active ingredient in Tonix candidate TNX-601 ER^* - has been approved and marketed outside the U.S. for more than 30 years but has never before been available in the U.S. as a prescription drug.

Multiple clinical studies abroad have shown that tianeptine-based drugs provide similar treatment efficacy benefits as antidepressants currently sold in the U.S. but without the risk of sexual side effects and weight gain and other common side effects that limit use of the antidepressants widely used in the country.

"We think that's a very attractive baseline - a great starting point to build upon," notes Seth Lederman, M.D., CEO of Tonix. "What makes tianeptine even more special is the data collected and published during more than 30 years of use outside the U.S. showing that tianeptine is not associated with sexual impairment or weight gain - two features that may help us set a new high-water mark for tolerability of antidepressants in the U.S."

Traditional antidepressant medications work by ramping up the levels of certain brain chemicals, called neurotransmitters, such as serotonin, norepinephrine, and dopamine, in the synapses. Synapses are the specialized spaces between neurons through which one sends signals to another. By increasing the levels of neurotransmitters, traditional antidepressants control mood and emotions somewhat indirectly.

That's because many scientists believe that depression is a loss of connectivity between neurons and that the neurotransmitter effects of traditional antidepressants are an indirect way of slowing down the loss of connections and may induce new connections to some extent.

TNX-601 ER (tianeptine hemioxalate extended-release tablets) works very differently from traditional antidepressants and may become a new alternative antidepressant in the U.S. with a unique mechanism of action (MOA).

"Tianeptine doesn't do much with neurotransmitters," Dr. Lederman explains. "Instead, it increases the arborization of neurons - much like branches sprouting - more directly. Tianeptine appears to change the biology of neurons and their supporting glial cells. Whereas current antidepressants basically flog the remaining synapses left in depressed patients, tianeptine counteracts the attrition."

In animal models of depression and stress, tianeptine acts on neurons with stress-induced shrinkage and loss of connections and induces them to reach out and connect with each other. Tianeptine treatment of depressed animals causes atrophied neurons to grow again, increases arborization and restores the neuroplasticity that has been lost in a state of depression. These effects reflect the induction of the brain's normal repair mechanisms called, "synaptic plasticity."

Dr. Lederman said, "Tianeptine holds the hope of providing longer-term relief than current therapeutics without their treatment-limiting side effects. I won't be surprised if tianeptine is ultimately found to be helpful in treating other conditions involving stress and neurodegeneration."

Depression is one of the most common mental health disorders in the U.S. Approximately 21 million people experienced at least one major depressive episode in 2020. Although many medications exist to treat depression, most people do not get better with their treatment and may suffer from unacceptable or intolerable side effects. Depression is a chronic disease, and patients may require treatment for life, despite these ill effects of traditional antidepressant pharmacotherapies. Traditional antidepressant regimens and augmentation strategies showed that 30-40 percent of depression patients who are prescribed these antidepressants never achieve resolution - meaning their illness doesn't go away.

The tianeptine products available outside the U.S. are designed for three-times daily dosing. Tonix's formulation of TNX-601 ER is designed for once daily dosing. The company believes this will improve patient compliance which is crucial for achieving the therapeutic benefits of any drug.

Tonix is currently enrolling patients in a potentially pivotal Phase 2 study called "UPLIFT" to test the safety and effectiveness of once-daily TNX-601 ER in approximately 300 patients with major depressive disorder, or MDD. Tonix expects to release results of a pre-planned interim analysis on the first 50% who have completed the study in the fourth quarter of 2023.

Worldwide sales of antidepressant medications totaled about $15 billion in 2020, a market shared by such major players as Bristol-Myers Squibb Co, GlaxoSmithKline, Inc., and Eli Lilly and Co. The market is expected is to grow to $21 billion by 2030, with the growth expected to come from drugs with novel ways of working.

Tonix is dedicated to developing innovative therapeutics for the central nervous system, immunology conditions, infectious diseases and rare diseases.

Click here for more information on Tonix Pharmaceuticals.

^*TNX-601 ER is an investigational new drug and has not been approved for any indication.

Featured photo by Lidiia on Shutterstock

Important notice, please read: Certain statements in this document 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 failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; 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 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.

Contact

Jessica Morris 
investor.relations@tonixpharma.com

SOURCE: Tonix Pharmaceuticals