Tonix Pharmaceuticals
Tonix Pharmaceuticals (Tonix Pharmaceuticals Holding Corp.) is a pharmaceutical company based in Chatham, New jersey that focuses on repurposed drugs for central nervous system conditions and as of 2020 was also pursuing a vaccine for COVID-19 and a biodefense project. History. The company's predecessors were Tamandare Explorations Inc. which had been formed in 2007 as a mining wildcat vehicle focused on land in Nevada and the shares of which were traded over the counter, and L & L Technologies, LLC, which had been formed in 1996 by Seth Lederman and Donald Landry to repurpose drugs for CNS development . L&L had formed Janus Pharmaceuticals, Inc., which later became Vela Pharmaceuticals, Inc. to develop some of its inventions, and Vela returned those assets to L&L in 2006. L&L placed them in a subsidiary called Krele Pharmaceuticals, Inc., and that subsidiary and Tamandare Explorations Inc. performed a reverse merger in October 2011; the new entity was renamed Tonix Pharmaceuticals Holding Corp. and Lederman was named CEO. It was listed on the NASDAQ exchange in 2013 under the symbol TNXP. Ernest Mario, a scientist and former CEO of Glaxo Holdings Inc, served on the board of Tonix in the past. Tonix finalized  the purchase of a 40,000 square foot facility in Massachusetts in 2020 to house its new Advanced Development Center (ADC) for accelerated development and manufacturing of vaccines, including vaccines for COVID-19. In December 2020, Tonix purchased an approximately 44-acre parcel of land in Hamilton, Montana for the construction of a vaccine production facility. Tonix licensed from University of Geneva, their technology for oxytocin-based treatments for treating insulin resistance, diabetes, and obesity allowing Tonix to expand its intranasal potentiated oxytocin development program, TNX-1900, into cardiometabolic syndromes. In March 2021, Tonix announced the issuance of a U.S. patent for compositions  and uses of tianeptine oxalate salt, the active ingredient in TNX-601 CR. The patent provides Tonix with U.S. market exclusivity until December 2037 for claims directed to pharmaceutical compositions comprising crystalline tianeptine oxalate salts, to methods of using those compositions to treat various disorders, and to methods of producing oxalate salts. Indications and Programs. Since its formation in 2011, Tonix Pharmaceuticals has developed therapeutics for patients suffering from chronic conditions. Today, its programs primarily focus on central nervous system (CNS) and immunology indications. Fibromyalgia. Fibromyalgia is a medical condition characterized by chronic widespread pain and a heightened pain response to  pressure. Other symptoms include tiredness to a degree that normal activities are affected, sleep problems and troubles with memory. Some people also report restless legs syndrome, bowel or bladder problems, numbness and tingling and sensitivity to noise, lights or temperature. Fibromyalgia is frequently associated with depression, anxiety and posttraumatic stress disorder. Other types of chronic pain are also frequently present. Tonix announced in September 2020 their plan to complete the Phase 3 RELIEF study of TNX-102 SL for management of fibromyalgia with currently enrolled participants. The enrollment of this study was completed in July 2020. An independent statistical team, the  independent data monitoring committee (IDMC), conducted the unblinded interim analysis of the primary endpoint and made the non-binding recommendation that the trial continue to completion with the addition of 210 participants to the original sample size of 470 participants, which is the maximum number of participants that could be added under the interim statistical analysis plan. In early September 2020, Tonix had enrolled the first participant in the Pivotal Phase 3 RALLY study of TNX-102 SL for the management of fibromyalgia. and in December 2020, the company announced top-line data results from the RELIEF Phase 3 trial that  showed that TNX-102 SL safely and effectively eased pain and fatigue in people with fibromyalgia while also improving their sleep. Post Traumatic Stress Disorder. Post-traumatic stress disorder is a mental disorder that can develop after a person is exposed to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, or other threats on a person's life. Symptoms may include disturbing thoughts, feelings, or dreams related to the events, mental or physical distress to trauma-related cues, attempts to avoid trauma-related cues, alterations in how a person thinks and feels, and an increase in the  fight-or-flight response. These symptoms last for more than a month after the event. Young children are less likely to show distress, but instead may express their memories through play. A person with PTSD is at a higher risk of suicide and intentional self-harm. Tonix continued work on TNX-102 SL in PTSD; the IND for that use had been accepted in 2014 and in December 2016 after the Phase IIa trial was done, TNX-102 was granted Breakthrough Therapy designation by the FDA in December 2017 which was rescinded in January 2019, but then restored in March 2019. A  Phase 3 trial of military-related PTSD began in February 2017, but was stopped in July 2018 after an interim analysis of 50% of target participants were evaluated, for "inadequate separation on primary efficacy endpoint". In March 2020, a later Phase 3 trial of TNX-102 SL for PTSD in from mostly civilian traumas also showed futility at an interim analysis of 50% of its target participants patients were evaluated and enrollment was discontinued. FDA Breakthrough Therapy designation was rescinded again in May 2020. COVID-19. Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2  (SARS-CoV-2). The first case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, leading to an ongoing pandemic. In February 2020 Tonix began development of a potential vaccine to protect against COVID-19 with collaboration with Southern Research based on its live horsepox vaccine platform. In May 2020 it announced an additional collaboration with the University of Alberta to develop more horsepox-based vaccines, TNX-1810, TNX-1820 and TNX-1830, partnering with FUJIFILM Diosynth Biotechnologies in College Station, TX, to manufacture the TNX-1800 vaccine candidate. In July 2020, Tonix solidified a research collaboration with Columbia University in  NY to study the immune responses to COVID-19 in healthy volunteers who have recovered from COVID-19 or were asymptomatic. In October 2020, the first participant was enrolled in the PRECISION Study as part of the ongoing collaboration with Columbia University to examine the immune responses to COVID-19 in healthy volunteers. The research focuses on T cell and antibody responses to SARS-CoV-2 (CoV-2) virus. This is an observational study to facilitate development of precision medicine techniques for COVID-19 vaccines and therapeutics. To further facilitate COVID-19 vaccine development, Tonix entered into a preclinical research and exclusive license agreement in July 2020  with Kansas State University. This research collaboration will focus on developing a vaccine candidate utilizing a novel live virus vaccine vector platform and the CD40-ligand to stimulate T cell immunity. In September 2020, Tonix Pharma hosted and participated in a virtual webinar with Merck & Co. and IAVI to discuss the potential of T Cell Immunity in offering protection from COVID-19 infection. The live panel titled “Antibody vs. T Cell Immunity: Is a Single Vaccine Enough to Stop COVID-19?” was moderated by science journalist Clive Cookson of the "Financial Times". Also in September 2020, Tonix enrolled the first patient in  COV-LOGIC (TNX-C001), an observational study to assess antibody and T Cell responses to the SARS-CoV-2 virus. This is part of the ongoing collaborations between Tonix and Southern Research to develop and test TNX-1800, a live replicating, attenuated virus vaccine candidate being tested for protection against COVID-19. In November 2020, Tonix announced preliminary, non-human primate results for TNX-1800 in which the reaction of the skin showed a functional T cell immunity in the subjects. The result of the given vaccine led to the counteracting of antibodies in each of the cases. Tonix announced in February 2021 that  it received written guidance from the U.S. Food and Drug Administration (FDA) to develop their COVID-19 skin test to measure SARS-CoV-2 exposure and T Cell immunity. TNX-2100 is a diagnostic skin test to measure the delayed-type hypersensitivity (DTH) reaction to SARS-CoV02 (CoV-2) and is being tested for its ability to be administered in a wide range of settings, including a doctor's office or a remote outpost without running water or in inclement or extreme weather. TNX-2100 comprises three different mixtures of synthetic peptides (TNX-2110, -2120, and -2130). In March 2021, Tonix reported positive COVID-19 vaccine efficacy  results in non-human primates vaccinated with TNX-1800 and challenged with the live SARS-CoV-2 virus. Vaccine candidate TNX-1800 protected both upper and lower airways and produced anti-CoV-2 neutralizing antibodies after animals were challenged with live SARS-CoV-2 through intra-nasal and intra-tracheal routes. In April 2021, Tonix entered into an exclusive worldwide licensing agreement with OyaGen to develop its investigational antiviral SARS-CoV-2 inhibitor, TNX-3500, for the treatment of COVID-19 and potentially other viral disorders. TNX-3500 consists of sangivamycin and has demonstrated broad-spectrum antiviral activity in laboratory-based assays against the coronaviruses SARS-CoV-2 and MERS -CoV. Horsepox Platform and Smallpox. In July 2017 the news division of the journal, "Science", reported that Tonix had sponsored research and collaborating with scientists at the University of Alberta, David Evans and Ryan Noyce, and that the work had led to the generation of an extinct horsepox virus using synthetic biology — the lab had bought pieces of DNA from a reagent company and had built the horsepox genome with them. This invention was licensed to Tonix and Tonix announced that it intended to further develop it into a smallpox vaccine, TNX-801, which is a biodefense business model. The research  was published in 2018. In December 2020, Tonix announced that independent researchers reported 99.7% colinear identity between a circa 1860 U.S. smallpox vaccine and horsepox virus. Tonix's TNX-801 is a horsepox-based live virus vaccine being developed as a potential vaccine to prevent smallpox and monkeypox. Tonix's TNX-801 is also the vector on which Tonix's COVID-19 experimental vaccine is based. Alcohol Use Disorder. Alcohol Use Disorder is a diagnostic classification of excessive alcohol use that results in significant mental or physical health problems. In August 2020, TNX-102 SL's Investigational New Drug (IND) application was also cleared  by the U.S. Food and Drug Administration (FDA) for the initiation of a Phase 2 proof-of-concept study using TNX-102 SL for treatment of alcohol use disorder (AUD). Cocaine Intoxication. In May 2019, Tonix reported in-licensing the Phase 2 asset, TNX-1300 (T172R/G173Q double-mutant cocaine esterase 200 mg, "i.v." solution), for the treatment of cocaine intoxication. TNX-1300 (formerly known as RBP-8000) 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 rDNA technology in a non-disease-producing strain of "E. coli" bacteria . Cocaine Esterase (CocE) was identified in bacteria ("Rhodococcus") that use cocaine as its sole source of carbon and nitrogen and that grow in soil surrounding coca plants. The gene encoding CocE was identified and the protein was extensively characterized. CoCE catalyzes the breakdown of cocaine into metabolite ecgonine methyl ester and benzoic acid. Wild-type CocE is unstable at 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. In a Phase 2 study, TNX-1300 at 100 mg or 200  mg "i.v." doses was well tolerated and interrupted cocaine effects after cocaine 50 mg "i.v." challenge. TNX-1300 is designated as a breakthrough therapy by the U.S. Food and Drug Administration (FDA). Organ Transplant. In January 2021, Tonix announced a second collaboration with Massachusetts General Hospital to work on TNX-1500, a monoclonal antibody targeting CD40-ligand with a focus on organ rejection in kidney transplantation. In August 2019, Tonix announced the signing of the first research collaboration agreement with Massachusetts General Hospital to develop TNX-1500, a humanized monoclonal antibody (mAb) that targets CD154 for the prevention and treatment of organ transplant  rejection. In January 2021, Tonix filed a patent application with the World Intellectual Property Organization covering the use of TNX-1500 for the prevention and treatment of autoimmune diseases such as multiple sclerosis (MS) and organ transplant rejection. Prader-Willi Syndrome. Prader-Willi Syndrome is a genetic condition caused by the loss of function of specific genes on chromosome 15. Symptoms of Prader-Willi Syndrome include a lack of suckling in infants that often leads to malnutrition, while older children and adults may experience insatiable hunger which leads to severe obesity. In February 2021, Tonix announced that it had licensed technology  from the French National Institute of Health and Medical Research (Inserm) to treat the rare genetic disorder Prader-Willi Syndrome. TNX-2900 (intranasal potentiated oxytocin) will be investigated for its ability to address feeding behavior issues in patients. A recent study suggests that oxytocin improves suckling in newborn animals and suppresses feeding behaviors in adult animal models. Major Depressive Disorder. Major depressive disorder is a mental disorder characterized by at least two weeks of pervasive low mood with symptoms of low self-esteem, loss of interest in normally enjoyable activities, low energy, and pain without a clear cause. In March 2021 , Tonix announced that it received the official minutes from a Type B pre-investigational new drug (IND) meeting with the U.S. Food and Drug Administration (FDA) on its development plan for TNX-601 CR tablet for the treatment of major depressive disorder.