Jump to content

Tonix Pharmaceuticals

Add links
From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by Nemo bis (talk | contribs) at 16:13, 9 May 2021 (remove URL redundant with identifier in autolinked citation). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Tonix Pharmaceuticals (Tonix Pharmaceuticals Holding Corp.) is a pharmaceutical company based in New York City 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.[1] The current lead candidates in the pipeline are the Phase 3 study of TNX-102 SL for the bedtime treatment of fibromyalgia, the Phase 2 study of TNX-1300 for cocaine intoxication and overdose and the preclinical study of TNX-1800, a potential coronavirus vaccine.[2]

History

Tonix Pharmaceuticals
Company typePublic
Nasdaq: TNXP
IndustryBiotechnology
Healthcare
Headquarters
New York, New York
,
United States
Key people
Websitewww.tonixpharma.com

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.[3] It was listed on the NASDAQ exchange in 2013 under the symbol TNXP.[3]

Ernest Mario, a scientist and former CEO of Glaxo Holdings Inc, served on the board of Tonix in the past.[4]

Towards the end of Q3 of 2020, Tonix finalized the purchase of a 40,000 square foot facility in Massachusetts to house its new Advanced Development Center (ADC) for accelerated development and manufacturing of vaccines, including vaccines for COVID-19.[5]

In December 2020, Tonix purchased an approximately 44-acre parcel of land in Hamilton, Montana for the construction of a vaccine production facility.[6]

In February 2021 Tonix closed on its previously announced registered direct offering, priced at-the-market, with gross proceeds of approximately $70.0 million before deducting fees and other estimated offering expenses.[7] The Company sold 58,333,334 shares of common stock at $1.20 per share.[8]

In September, 2019, Tonix licensed immuno-oncology treatment technology based on Trefoil Family Factor 2 (TFF2) from Columbia University.[9] A poster from that work was presented at the American Association of Cancer Research (AACR) meeting in June 2020.[10]

In December 2019, the Phase 1 trial for TNX-601 CR (tianeptine oxalate), an indirect glutamatergic pathway modulator, was completed and results were reported at the American Society of Clinical Psychopharmacology (ASCP) meeting in May 2020.[11]

In June 2020, Tonix acquired the migraine and pain treatment technologies of Trigemina, Inc. for the TNX-1900 program based on a proprietary formulation of oxytocin. In August 2020, Tonix presented preclinical results of TNX-1900 from its study investigating the efficacy of intranasal oxytocin in relieving pain and associated depressive behavior following traumatic brain injury at the American Academy of Neurology’s first-ever Sports Concussion Conference.[12] The research was sponsored by Trigemina, Inc.

In January 2021, Tonix acquired an exclusive license to University of Geneva’s technology for oxytocin-based treatments for treating insulin resistance, diabetes, and obesity from privately held Katana Pharmaceuticals, Inc.[13] This license allowed Tonix to expand its intranasal potentiated oxytocin development program, TNX-1900, into cardiometabolic syndromes.

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.[14] Other symptoms include tiredness to a degree that normal activities are affected, sleep problems and troubles with memory.[15] Some people also report restless legs syndrome, bowel or bladder problems, numbness and tingling and sensitivity to noise, lights or temperature.[15] Fibromyalgia is frequently associated with depression, anxiety and posttraumatic stress disorder.[14] Other types of chronic pain are also frequently present.[14]

In November 2019 Tonix announced the initiation of the Phase 3 study of TNX-102 SL for the management of fibromyalgia with interim analysis expected in September 2020 and topline data in the first quarter of 2021.[16] In January 2020, Tonix reported it has finished the essential fed-fasting and dose proportionality tests in support of a NDA.

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.[17] The enrollment of this study was completed in July 2020.[18] 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.[19]

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.[20] RALLY is the Company's second of two Phase 3 studies of TNX-102 SL.

In early December 2020, Tonix 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.[21]

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.[22][23] 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.[22] These symptoms last for more than a month after the event.[22] Young children are less likely to show distress, but instead may express their memories through play.[22] A person with PTSD is at a higher risk of suicide and intentional self-harm.[24][25]

Tonix continued work on TNX-102 SL in PTSD; the IND for that use had been accepted in 2014[26] and in December 2016 after the Phase IIa trial was done, TNX-102 was granted Breakthrough Therapy designation by the FDA in December 2017[27] which was rescinded in January 2019, but then restored in March 2019.[28] 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".[29] 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.[30][31]

Covid19

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.[32] The disease has since spread worldwide, leading to an ongoing pandemic.[33] 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.[34] 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.[35]

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.[36] 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.[37] 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.[38] 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 the third week of 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.[39] 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.[40] 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 of 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.[41]

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.[42] 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.[43] TNX-2100 comprises three different mixtures of synthetic peptides (TNX-2110, -2120, and -2130).

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.[44][45][46] The research was published in 2018.[47] In December 2020, Tonix announced that independent researchers reported 99.7% colinear identity between a circa 1860 U.S. smallpox vaccine and horsepox virus.[48] Tonix’s TNX-801 is a horsepox-based live virus vaccine being developed as a potential vaccine to prevent smallpox and monkeypox.[49] 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.[50] 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).[51]

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.[52][53] TNX-1300 (formerly known as RBP-8000) is being developed under an Investigational New Drug application (IND) for the treatment of cocaine intoxication.[54] 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.[55] The gene encoding CocE was identified and the protein was extensively characterized.[56][57][58] 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.[58] 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.[54] 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.[59] 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.[60]

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.[61]

Prader-Willi Syndrome

The company also announced that they have licensed technology from the French National Institute of Health and Medical Research (Inserm) to treat the rare genetic disorder Prader-Willi Syndrome.[62] TNX-2900 (intranasal potentiated oxytocin) will be investigated for its ability to address feeding behavior issues in patients.

References

  1. ^ "What's special about Tonix Pharma and Southern Research's COVID-19 vac". www.thepharmaletter.com. Retrieved 2020-07-08.
  2. ^ rebecca.fiedler@theeagle.com, REBECCA FIEDLER. "College Station-based developers to manufacture clinical trial doses of COVID-19 vaccine". The Eagle. Retrieved 2020-07-08.
  3. ^ a b "Tonix Pharmaceuticals Holding Corp. Form S-1/A". SEC Edgar. August 8, 2013.
  4. ^ "TONIX Pharmaceuticals Elects Ernest Mario, PhD, to its Board of Directors". www.tonixpharma.com. Retrieved 2021-03-28.
  5. ^ "Covid vaccine company to build research facility in Dartmouth". Dartmouth. Retrieved 2021-03-28. {{cite web}}: Check |url= value (help)
  6. ^ "Tonix Pharmaceuticals Plans Vaccine Development and Manufacturing Facility in Hamilton". Sterling CRE Advisors. 2020-12-23. Retrieved 2021-03-28.
  7. ^ "Tonix Pharmaceuticals $70M; Plans To Develop COVID-19 Skin Test". finance.yahoo.com. Retrieved 2021-03-28.
  8. ^ "Tonix Pharmaceuticals Holdings Corp. Prices $70M Common Stock Offering Priced At-The-Market Under Nasdaq Rules". BioSpace. Retrieved 2021-03-28.
  9. ^ "Tonix Pharmaceuticals Announces Licensing Agreement with Columbia University for the Development of Recombinant Trefoil Family Factor 2 (rTFF2), or TNX-1700, for the Treatment of Gastric and Pancreatic Cancers". www.tonixpharma.com. Retrieved 2020-07-08.
  10. ^ "Tonix Pharmaceuticals Announces that Results from Preclinical Studies of TNX-1700 Will be Presented in a Poster at the AACR Virtual Annual Meeting 2020". AP NEWS. 2020-06-17. Retrieved 2020-07-08.
  11. ^ "Tonix Pharmaceuticals Posted Results from Pharmacokinetic Analyses of TNX-102 SL and TNX-601 CR in Advance of Virtual Poster Presentations at the American Society of Clinical Psychopharmacology". www.tonixpharma.com. Retrieved 2020-07-08.
  12. ^ "Abstracts". www.aan.com. Retrieved 2021-03-28.
  13. ^ "Tonix deal sets up use of intranasal drug in diabetes, obesity". FiercePharma. Retrieved 2021-03-28.
  14. ^ a b c Ngian, Gene-Siew; Guymer, Emma K.; Littlejohn, Geoffrey O. (2011). "The use of opioids in fibromyalgia". International Journal of Rheumatic Diseases. 14 (1): 6–11. doi:10.1111/j.1756-185X.2010.01567.x. ISSN 1756-185X. PMID 21303476. S2CID 29000267.
  15. ^ a b Clauw, Daniel J. (2014-04-16). "Fibromyalgia: A Clinical Review". JAMA. 311 (15): 1547–1555. doi:10.1001/jama.2014.3266. ISSN 0098-7484. PMID 24737367.
  16. ^ "Tonix Pharmaceuticals Announces Initiation of the Phase 3 RELIEF Study of TNX-102 SL for the Management of Fibromyalgia". www.tonixpharma.com. Retrieved 2020-07-08.
  17. ^ Corp, Tonix Pharmaceuticals Holding (2020-09-29). "Tonix Pharmaceuticals Announces Plan to Complete the Phase 3 RELIEF Study of TNX-102 SL for Management of Fibromyalgia with Currently Enrolled Participants Based on Results of Interim Analysis". GlobeNewswire News Room. Retrieved 2021-03-28.
  18. ^ PhD, Steve Bryson. "Bedtime Fibromyalgia Therapy TNX-102 SL Sees Faster Trial Enrollment". Retrieved 2021-03-28.
  19. ^ "Tonix Pharmaceuticals Achieves 50 Percent Enrollment in Phase 3 RELIEF Study of TNX-102 SL (Cyclobenzaprine HCl Sublingual Tablets) for Management of Fibromyalgia". BioSpace. Retrieved 2021-03-28.
  20. ^ Tonix Pharmaceuticals, Inc. (2021-03-17). "A Phase 3, Double-Blind, Randomized, Multicenter, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of TNX-102 SL Taken Daily At Bedtime In Patients With Fibromyalgia". {{cite journal}}: Cite journal requires |journal= (help)
  21. ^ Figueiredo, Marta. "TNX-102 Found to Lessen Pain, Sleep Problems, Fatigue in Fibromyalgia". Retrieved 2021-03-28.
  22. ^ a b c d Diagnostic and statistical manual of mental disorders : DSM-5. Internet Archive. Arlington, VA : American Psychiatric Association. 2013. ISBN 978-0-89042-554-1.{{cite book}}: CS1 maint: others (link)
  23. ^ "Post-traumatic stress disorder (PTSD) - Symptoms and causes". Mayo Clinic. Retrieved 2021-03-15.
  24. ^ Bisson, Jonathan I; Cosgrove, Sarah; Lewis, Catrin; Roberts, Neil P (2015-11-26). "Post-traumatic stress disorder". The BMJ. 351: h6161. doi:10.1136/bmj.h6161. ISSN 0959-8138. PMC 4663500. PMID 26611143.
  25. ^ Panagioti, Maria; Gooding, Patricia A.; Triantafyllou, Kalliopi; Tarrier, Nicholas (2015-04-01). "Suicidality and posttraumatic stress disorder (PTSD) in adolescents: a systematic review and meta-analysis". Social Psychiatry and Psychiatric Epidemiology. 50 (4): 525–537. doi:10.1007/s00127-014-0978-x. ISSN 1433-9285. PMID 25398198. S2CID 23314414.
  26. ^ Baum S (Jun 23, 2014). "Tonix Pharmaceuticals developing treatment for underserved PTSD patients". MedCity News.
  27. ^ Keshavan M (20 December 2016). "Can a muscle relaxant ease symptoms of PTSD?". STAT.
  28. ^ "Tonix Pharmaceuticals Announces that Breakthrough Therapy Designation Remains in Effect for Tonmya® for the Treatment of Posttraumatic Stress Disorder". www.tonixpharma.com. Retrieved 2020-07-08.
  29. ^ "Safety and Efficacy Study of TNX-102 SL in Patients With Military-related PTSD (HONOR)". ClinicalTrials.gov. 2018-09-17. Retrieved 2020-06-18.
  30. ^ "Cyclobenzaprine very low dose - Tonix Pharmaceuticals". AdisInsight. Retrieved 16 August 2017.
  31. ^ "10-K annual SEC report of Tonix Pharmaceuticals". Tonix Pharmaceuticals. 2020-03-24. Retrieved 2020-06-18. In PTSD, we are completing the Phase 3 RECOVERY trial and expect to report topline results in the second quarter of 2020, however, we cannot predict whether the global COVID-19 pandemic will impact the timing of topline results. Moreover, the RECOVERY study is unlikely to show an effect of TNX-102 SL, because at a pre-planned interim analysis in February of 2020, an Independent Data Monitoring Committee, or IDMC, reported that the drug effect, if any, was below the pre-specified criteria for futility, based on the results of the first 50% of enrolled participants. Based on the IDMC's recommendation to stop the study, the RECOVERY study stopped enrolling new patients in February 2020.
  32. ^ York, Jeremy Page in Beijing, Drew Hinshaw in Warsaw and Betsy McKay in New (2021-02-26). "In Hunt for Covid-19 Origin, Patient Zero Points to Second Wuhan Market". Wall Street Journal. ISSN 0099-9660. Retrieved 2021-03-19.{{cite news}}: CS1 maint: multiple names: authors list (link)
  33. ^ Zimmer, Carl (2021-02-26). "Opinion | The Secret Life of a Coronavirus". The New York Times. ISSN 0362-4331. Retrieved 2021-03-19.
  34. ^ "224-year-old Smallpox Treatment Modified for COVID-19 Candidate Vaccine". Technology Networks. Retrieved 2020-07-08.
  35. ^ Oliver, Bill (2020-06-02). "B/CS Biocorridor Manufacturer Is Selected To Produce A Possible Coronavirus Vaccine". WTAW | 1620AM & 94.5FM. Retrieved 2020-07-08.
  36. ^ Philippidis, Alex (2020-07-27). "Tonix Pharmaceuticals and Columbia University". GEN - Genetic Engineering and Biotechnology News. Retrieved 2021-03-28.
  37. ^ Avisol Capital Partners (October 28, 2020). "Tonix Provides Updates For Fibromyalgia, And Other News: The Good, Bad And Ugly Of Biopharma". Seeking Alpha.{{cite news}}: CS1 maint: url-status (link)
  38. ^ "University signs research agreement for COVID-19 vaccine candidate | Kansas State University | News and Communications Services". www.k-state.edu. Retrieved 2021-03-28.
  39. ^ Corp, Tonix Pharmaceuticals Holding (2020-09-17). "Tonix Pharmaceuticals to Host Live Webinar: Antibody vs. T Cell Immunity: Is a Single Vaccine Enough to Stop COVID-19?". GlobeNewswire News Room. Retrieved 2021-03-28.
  40. ^ "Tonix Pharmaceuticals Enrolls First Patient in COV-LOGIC, an Observational Study to Assess Antibody and T Cell Responses to SARS-CoV-2, the Virus that Causes COVID-19Results from COV-LOGIC Study Expected in First Half of 2021". BioSpace. Retrieved 2021-03-28.
  41. ^ McCluskey, Ashlee (2020-11-25). "Southern Research and Tonix Pharmaceuticals COVID-19 Vaccine Research Update". Southern Research. Retrieved 2021-03-28.
  42. ^ "Tonix Pharma to develop a test to measure COVID-19 exposure and T cell immunity (NASDAQ:TNXP)". SeekingAlpha. Retrieved 2021-03-28.
  43. ^ February 10, Patrick LaveryPublished; 2021. "NJ pharma firm preps skin test to gauge COVID exposure, immunity". New Jersey 101.5. Retrieved 2021-03-28. {{cite web}}: |last2= has numeric name (help)CS1 maint: numeric names: authors list (link)
  44. ^ Kupferschmidt K (6 July 2017). "How Canadian researchers reconstituted an extinct poxvirus for $100,000 using mail-order DNA". Science. doi:10.1126/science.aan7069.
  45. ^ Achenbach J, Sun LH (July 7, 2017). "Scientists synthesize smallpox cousin in ominous breakthrough". Washington Post.
  46. ^ "Research programme: smallpox vaccines - Tonix Pharmaceuticals/University of Alberta". AdisInsight. Retrieved 16 August 2017.
  47. ^ Noyce RS, Lederman S, Evans DH (January 19, 2018). "Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments". PLOS ONE. 13 (1): e0188453. Bibcode:2018PLoSO..1388453N. doi:10.1371/journal.pone.0188453. PMC 5774680. PMID 29351298.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  48. ^ Brinkmann, Annika; Souza, Aline R. V.; Esparza, José; Nitsche, Andreas; Damaso, Clarissa R. (2020-12-04). "Re-assembly of nineteenth-century smallpox vaccine genomes reveals the contemporaneous use of horsepox and horsepox-related viruses in the USA". Genome Biology. 21 (1): 286. doi:10.1186/s13059-020-02202-0. ISSN 1474-760X. PMC 7716468. PMID 33272280.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  49. ^ "Vaccine Genome Researchers Report 99.7% Colinear Identity Between a U.S. Civil War Era Smallpox Vaccine and Horsepox Virus". www.tonixpharma.com. Retrieved 2021-03-23.
  50. ^ Littrell, Jill (2014-01-02). Understanding and Treating Alcoholism: Volume I: An Empirically Based Clinician's Handbook for the Treatment of Alcoholism:volume Ii: Biological, Psychological, and Social Aspects of Alcohol Consumption and Abuse. Psychology Press. ISBN 978-1-317-78314-5.
  51. ^ Hudson, Kate (2020-08-13). "FDA Grants Clearance of IND for TNX-102 SL from Tonix Pharmaceuticals Holding Corp (NASDAQ:TNXP) To Treat Alcohol Use Disorder (AUD)". BioPharmaJournal. Retrieved 2021-03-28.
  52. ^ Collins T (2018), "Kicking against the pricks", How Football Began, Routledge, pp. 65–74, doi:10.4324/9781315177212-10, ISBN 9781315177212
  53. ^ "Tonix boosts pipeline with Columbia University-developed cocaine intoxication drug". FierceBiotech. Retrieved 2019-05-28.
  54. ^ a b Nasser AF, Fudala PJ, Zheng B, Liu Y, Heidbreder C (2014). "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". Journal of Addictive Diseases. 33 (4): 289–302. doi:10.1080/10550887.2014.969603. PMID 25299069. S2CID 8417112.
  55. ^ Bresler MM, Rosser SJ, Basran A, Bruce NC (March 2000). "Gene cloning and nucleotide sequencing and properties of a cocaine esterase from Rhodococcus sp. strain MB1". Applied and Environmental Microbiology. 66 (3): 904–8. doi:10.1128/aem.66.3.904-908.2000. PMC 91920. PMID 10698749.
  56. ^ Larsen NA, Turner JM, Stevens J, Rosser SJ, Basran A, Lerner RA, Bruce NC, Wilson IA (January 2002). "Crystal structure of a bacterial cocaine esterase". Nature Structural Biology. 9 (1): 17–21. doi:10.1038/nsb742. PMID 11742345. S2CID 847034.
  57. ^ Turner JM, Larsen NA, Basran A, Barbas CF, Bruce NC, Wilson IA, Lerner RA (October 2002). "Biochemical characterization and structural analysis of a highly proficient cocaine esterase". Biochemistry. 41 (41): 12297–307. doi:10.1021/bi026131p. PMID 12369817.
  58. ^ a b Gao D, Narasimhan DL, Macdonald J, Brim R, Ko MC, Landry DW, Woods JH, Sunahara RK, Zhan CG (February 2009). "Thermostable variants of cocaine esterase for long-time protection against cocaine toxicity". Molecular Pharmacology. 75 (2): 318–23. doi:10.1124/mol.108.049486. PMC 2684895. PMID 18987161.
  59. ^ "News briefing: Marius submits NDA for oral hypogonadism therapy; Celltrion's billionaire founder steps down". Endpoints News. Retrieved 2021-03-28.
  60. ^ Corp, Tonix Pharmaceuticals Holding (2019-08-21). "Tonix Pharmaceuticals and Massachusetts General Hospital Enter into Research Collaboration to Develop Tonix's Third Generation Anti-CD154 Monoclonal Antibody, TNX-1500, for the Treatment and Prevention of Organ Transplant Rejection". GlobeNewswire News Room. Retrieved 2021-03-28.
  61. ^ PhD, Marta Figueiredo. "Tonix Files for Patent for TNX-1500 for MS, Other Autoimmune Diseases". Retrieved 2021-03-28.
  62. ^ "Tonix Pharma Shares Rally After In-Licensing Of Technology For A Rare Genetic Eating Disorder". finance.yahoo.com. Retrieved 2021-03-28.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Tonix_Pharmaceuticals&oldid=1022280113"