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Release – Tonix Pharmaceuticals Initiates Enrollment in Phase 2 ‘UPLIFT’ Study of TNX-601 ER (Tianeptine Hemioxalate Extended-Release Tablets) for the Treatment of Major Depressive Disorder (MDD)

Posted on March 16, 2023March 16, 2023 by [email protected]

March 16, 2023 7:00am EDTDownload as PDF

Results from Planned Interim Analysis Expected Fourth Quarter 2023

Approximately 21 Million Adults in U.S. Suffer From a Major Depressive Episode Each Year

TNX-601 ER is a Once-Daily Tablet that is Bioequivalent to Three-Times-Daily Tianeptine Sodium Immediate Release (IR) that has been available in Europe, Asia and Latin America for More than Three Decades

Tianeptine IR is Associated with Low Incidences of Sexual Dysfunction, Sleep Disruption, Sedation, Weight Gain, and Cognitive Impairment Compared with Traditional Monoaminergic Antidepressants

TNX-601 ER is a New Chemical Entity in the U.S. and Represents a Potential Innovative Approach to Addressing Depression: Restoration of Neuroplasticity and Neurogenesis Rather than Modulation of Neurotransmitter Levels and Activity

CHATHAM, N.J., March 16, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that the first participant was enrolled in the Phase 2 ‘UPLIFT’ study of TNX-601 ER¹ (tianeptine hemioxalate extended-release tablets) for the treatment of major depressive disorder (MDD). The double-blind, placebo-controlled registrational-quality study has a target enrollment of 300 participants at approximately 30 sites across the U.S. Results from a planned interim analysis are expected to be released in the fourth quarter of 2023.

The proprietary once-daily formulation of TNX-601 ER was designed to be bioequivalent to the three-times-a-day formulation of tianeptine sodium (amorphous) immediate release (IR) tablets. IR tianeptine sodium has been available in Europe and many countries in Asia and Latin America for the treatment of MDD for more than three decades since being first marketed in France in 1989. No tianeptine-containing product has been approved by the U.S. Food and Drug Administration (FDA).

“Despite the availability of several classes of MDD treatments in the U.S. that directly modulate neurotransmitters and their synaptic receptors, there remains an unmet need for novel approaches,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “In animal studies, TNX-601 ER has a unique mechanism of action that restores brain neuroplasticity by exerting biological effects on neurons and glial cells that increase arborization of dendrites in critical hippocampal circuits.² In animal models, tianeptine also reverses stress-induced impairments in synaptic glutamate neurotransmission, and it restores hippocampal neurogenesis.²”

Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals said, “After a decade of development of our proprietary once-daily tianeptine formulation, it is very gratifying to enter the next stage of clinical testing required to make TNX-601 ER available to those suffering from MDD in the U.S. TNX-601 ER not only has the potential to relieve depressive symptoms, but also to improve the quality of life and resiliency for the millions of MDD sufferers. The short and long-term safety of tianeptine sodium IR has been well-established based on its clinical use outside the US.”

Dr. Sullivan added, “The efficacy of tianeptine sodium IR has repeatedly been shown to be comparable with that of either selective serotonin reuptake inhibitor (SSRI) or tricyclic antidepressants^3,4 while being associated with a lower incidence of sexual dysfunction, derangement of sleep architecture, sedation, weight gain, or cognitive impairment.^5-7 Given tianeptine’s metabolic pathway, which is independent of the hepatic cytochrome P450 system, we believe that TNX-601 ER has a reduced risk of drug-drug interactions compared to antidepressants marketed in the U.S.⁷

“MDD is a seriously disabling condition that is also often associated with suicidal behavior. Extensive animal studies have taught us that tianeptine restores the stress-induced deficits in neuroplasticity and neurogenesis. The dramatic impact of tianeptine on a brain experiencing many types of stress is best illustrated by the effects it has in restoring dendritic arborization and spine synapse remodeling of pyramidal neurons in the CA3 region of hippocampus, as well as new neuron formation and their microglia-mediated integration into neuronal networks of the hippocampal formation. With an estimated 21 million individuals suffering from a major depressive episode each year in the U.S., it’s exciting to move beyond neurotransmitter modulation and begin an era where MDD may be treated by enhancing a resilient biological phenotype of neurons and glial cells under stress.”

¹TNX-601 ER is in the Phase 2 stage of development and is not approved for any indication
²McEwen, B. S., et al. Mol. Psychiatry 2010, 15 (3), 237–249.
³Jeon, H. J., et al. .J. Clin. Psychopharmacol. 2014, 34 (2), 218–225.
⁴Emsley, R., et al. J. Clin. Psychiatry 2018, 79 (4)
⁵Bonierbale M, et al. Curr Med Res Opin 2003, 19(2):114-124.
⁶Costa e Silva, J. A., et al. Neuropsychobiology 1997, 35 (1), 24–29.
⁷Wagstaff, A. J. et al. CNS Drugs 2001, 15 (3), 231–259.

About the Phase 2 UPLIFT Study

The Phase 2 UPLIFT study, TNX-TI-M201, is a double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-601 ER taken by mouth once-daily for 6 weeks for the treatment of MDD. It is a parallel design study with two arms, a TNX-601 ER 39.4 mg arm and a placebo arm. A total of 300 participants will be randomized in a 1:1 ratio into the two arms across approximately 30 U.S. sites, enrolling adult patients 18-65 years old with a DSM-5 diagnosis of depression and a duration for the current major depressive episode (MDE) of at least 12 weeks. The primary efficacy endpoint is mean change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6. Key secondary efficacy endpoints include the Clinical Global Impression of Severity Scale (CGI-S) and the Sheehan Disability Scale (SDS). An interim analysis is expected to be completed after the first 50% of enrolled patients have completed the study for the purpose of potential sample size re-estimation, currently anticipated in the fourth quarter of 2023. A 24-week open-label extension study, TNX-TI-M202, is planned to receive patients completing the UPLIFT study.

For more information, see ClinicalTrials.gov Identifier: NCT05686408

About Major Depressive Disorder (Depression)

According to the National Institute of Mental Health, an estimated 21 million adults in the U.S. in 2020 experienced at least one major depressive episode¹, with highest prevalence among individuals aged 18-25 at a rate of 17.0%. Depression is a condition characterized by symptoms such as a depressed mood or loss of interest or pleasure in daily activities most of the time for two weeks or more, accompanied by appetite changes, sleep disturbances, motor restlessness or retardation, loss of energy, feelings of worthlessness or excessive guilt, poor concentration, and suicidal thoughts and behavior. These symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. The majority of people who suffer from depression do not respond adequately to initial antidepressant therapy.² The current FDA approved drugs for long term monotherapy treatment of MDD include selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and Auvelity® (dextromethorphan HBr-bupropion HCl). Dextromethorphan is a direct antagonist of the NMDA-type glutamate receptor.

¹Data Courtesy of SAMHSA on Past Year Prevalence of Major Depressive Episode Among U.S. Adults (2020). Retrieved from http://www.nimh.nih.gov/health/statistics/major-depression.shtml
²Rush AJ, et al. (2007) Am J. Psychiatry 163:11, pp. 1905-1917 (STAR*D Study).

About TNX-601 ER

TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a novel oral formulation of tianeptine hemioxalate designed for once-daily daytime dosing in development as a candidate for the treatment for MDD, posttraumatic stress disorder, and neurocognitive dysfunction associated with corticosteroid use. Tianeptine sodium (amorphous) immediate release (dosed 3 times daily) was first marketed for depression in France in 1989 and has been available for decades in Europe, Russia, Asia, and Latin America for the treatment of depression. Tianeptine sodium has an established safety profile from decades of use in these jurisdictions. Currently there is no tianeptine-containing product approved in the U.S. and no extended-release tianeptine product approved in any jurisdiction. Tonix discovered a novel oxalate salt of tianeptine that may provide improved stability, consistency, and manufacturability compared to known salt forms of tianeptine. Tianeptine is believed to work in depression as an indirect modulator of the glutamatergic system, without direct binding NMDA, AMPA or kainate receptors. Tianeptine reverses stress induced increases in AMPA receptor trafficking, restores hippocampal long-term potentiation and neurogenesis, and reverses the negative neuroplastic changes from stress and corticosteroid exposure. In contrast with the modulation of neurotransmitter levels and activity at synaptic receptors like traditional antidepressants, in animal models tianeptine restores dendritic arborization of pyramidal neurons in the CA3 region of hippocampus and in the dentate gyrus region promotes new neuron formation and integration into hippocampal networks.¹ Tianeptine’s enhancement of neuroplasticity in animal models of stress implies a mechanism of action involving indirect glutamatergic modulation, which makes TNX-601 ER’s properties distinct from traditional monoaminergic antidepressants in the U.S. and contributes to its potential for clinical indications beyond MDD and stress disorders. Tianeptine and its MC5 metabolite are also weak mu-opioid receptor (MOR) agonists that present a potential abuse liability if illicitly misused in large quantities (typically abused at 8-80 times the therapeutic dose on a daily basis²). In patients who were prescribed tianeptine for depression, the French Transparency Committee found an incidence of misuse of approximately 1 case per 1,000 patients treated³ suggesting low abuse liability when used at the antidepressant dose in patients prescribed tianeptine for depression. Clinical trials have shown that cessation of a therapeutic course of tianeptine does not appear to result in dependence or withdrawal symptoms following 6-weeks^4-8, 3-months⁹, or 12-months¹⁰ of treatment. The ER formulation of TNX-601 includes several potentially abuse deterrent ingredients include gel forming polymers which impede extraction. In addition, the tablet’s hardness makes it difficult to crush, cut or grind to fine particle size, which potentially hinders efforts to misuse by insufflation or intravenous routes. Tianeptine’s reported pro-cognitive and anxiolytic effects as well as its ability to attenuate the neuropathological effects of excessive stress responses suggest that it may also be used to treat posttraumatic stress disorder (PTSD), and neurocognitive dysfunction associated with corticosteroid use. TNX-601 ER is expected to have patent protection through 2037.

¹McEwen, B. S., et al. Mol. Psychiatry 2010, 15 (3), 237–249.
²Lauhan, R., et al. Psychosomatics 2018, 59 (6), 547–53.
³Haute Authorite de Sante; Transparency Committee Opinion. Stablon 12.5 Mg, Coated Tablet, Re- Assessment of Actual Benefit at the Request of the Transparency Committee. December 5, 2012.
⁴Emsley, R., et al. J. Clin. Psychiatry 2018, 79 (4)
⁵Bonierbale M, et al. Curr Med Res Opin 2003, 19(2):114-124.
⁶Guelfi, J. D., et al. Neuropsychobiology 1989, 22 (1), 41–48.
⁷Invernizzi, G. et al., Neuropsychobiology 1994, 30 (2–3), 85–93.
⁸Lepine, J. P., et al. Hum. Psychopharmacol. 2001, 16 (3), 219–227.
⁹Guelfi, J. D. et al., Neuropsychobiology 1992, 25 (3), 140–148.
¹⁰Lôo, H. et al., Br. J. Psychiatry. Suppl. 1992, No. 15, 61–65.

About Tonix Pharmaceuticals Holding Corp.*

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition, for which a Phase 2 study was initiated in the third quarter of 2022. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is currently enrolling with interim data expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation of tianeptine being developed as a treatment for major depressive disorder (MDD), is also currently enrolling with interim data expected in the fourth quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the second quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes 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 and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the second quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox, for which a Phase 1 study is expected to be initiated in the second half of 2023. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease portfolio also includes TNX-3900, a class of broad-spectrum small molecule oral antivirals.

*All of Tonix’s product candidates are investigational new drugs or biologics and have not been approved for any indication.

This press release and further information about Tonix can be found at www.tonixpharma.com.

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; 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 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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
[email protected]
(862) 904-8182

Olipriya Das, Ph.D. (media)
Russo Partners
[email protected]
(646) 942-5588

Peter Vozzo (investors)
ICR Westwicke
[email protected]
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Released March 16, 2023

Onconova Therapeutics (ONTX) – Two Narazaciclib Studies To Be Presented At AACR Meeting

Posted on March 16, 2023March 16, 2023 by [email protected]

Thursday, March 16, 2023

Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation. Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in two Phase 1 dose-escalation and expansion studies. These trials are currently underway in the United States and China. Onconova’s product candidate rigosertib is being studied in an investigator-sponsored study program, including in a dose-escalation and expansion Phase 1/2a investigator-sponsored study with oral rigosertib in combination with nivolumab for patients with KRAS+ non-small cell lung cancer.

Robert LeBoyer, Vice President, Research Analyst, Life Sciences , Noble Capital Markets, Inc.

Refer to the full report for the price target, fundamental analysis, and rating.

Narazaciclib Data To Be Presented. Onconova announced two narazaciclib studies have been accepted for poster presentations at the American Association for Cancer Research (AACR) meeting to be held April 14-19, 2023. The abstracts for the presentations include preclinical data on narazaciclib targets and activity that show it to have greater potency and/or broader activity than approved drugs in the CDK4/6 inhibitor category.

Models In Mantle Cell Lymphoma. The first study tested narazaciclib alone and in combination with ibrutinib (Imbruvica, AbbVie) in preclinical models of mantle cell lymphoma. Narazaciclib was tested as a single-agent in both ibrutinib-resistant and ibrutinib-sensitive cell lines and showed significant anti-tumor activity. Next, the combination of narazaciclib with ibrutinib was found to synergistic compared with either drug alone in both resistant and sensitive cell lines. The study also tested narazaciclib against approved CDK4/6 inhibitors in mantle cell lymphoma cell lines and found it to be superior to palbociclib (Ibrance, Pfizer) and ribociclib (Kisqali, Novartis) and similar to abemaciclib (Verzenio, Lilly).

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This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).

*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.

Release – Onconova Therapeutics Announces Upcoming Poster Presentations at The Aacr Annual Meeting

Posted on March 15, 2023March 15, 2023 by [email protected]

Research News and Market Data on ONXT

Mar 15, 2023

PDF Version

NEWTOWN, Pa., March 15, 2023 (GLOBE NEWSWIRE) — Onconova Therapeutics, Inc. (NASDAQ: ONTX), (“Onconova”), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, today announced the publication of two abstracts that have been accepted for poster presentations at the American Association for Cancer Research (AACR) Annual Meeting, which is taking place at the Orange County Convention Center in Orlando, Florida from April 14 – 19, 2023.

The full texts of the published abstracts can be found on the AACR Annual Meeting website. The corresponding posters will be presented during the “Cyclin-dependent Kinases and Cyclin-dependent Kinase Inhibitors” poster session, which is taking place from 9:00 a.m. – 12:30 p.m. ET on April 19, 2023. Additional information on the posters is shown below.

Poster Title: Synergistic activity of the CDK4/6 antagonist narazaciclib (ON123300) with irreversible BTK inhibition in ibrutinib-resistant mantle cell lymphoma

Abstract Number: 5974

This poster will describe studies evaluating narazaciclib in preclinical models of mantle cell lymphoma (MCL). Results from these studies demonstrated narazaciclib’s single-agent antitumor activity in MCL cell lines independent of their sensitivity to ibrutinib, which is a Bruton’s tyrosine kinase inhibitor (BTKi) approved by the U.S. Food and Drug Administration (FDA) for the treatment of MCL. When combining narazaciclib with ibrutinib, synergistic increases in antitumor activity against both BTKi-resistant and BTKi-sensitive MCL cell lines were observed.

Additional analyses showed that narazaciclib’s antitumor activity against the evaluated MCL cell lines was superior to that of the FDA-approved CDK 4/6 inhibitors palbociclib and ribociclib, and similar to that of the FDA-approved CDK 4/6 inhibitor abemaciclib. Treatment with narazaciclib also led to tumor growth inhibition without detectable toxicity in a chicken embryo chorioallantoic membrane (CAM) xenograft model of MCL.

Poster Title: Differential targets engaged by narazaciclib in comparison to the approved CDK4/6 inhibitors contribute to enhanced inhibition of tumor cell growth

Abstract Number: 5987

This poster will describe cell-based, in vitro, and bioinformatic analyses comparing narazaciclib and palbociclib. Results from a cell-based murine mammary carcinoma model showed a stronger induction of programmed cell death with narazaciclib compared to palbociclib. In vitro and cell-based analyses revealed multiple targets that are engaged by narazaciclib but not by palbociclib. These targets included BUB1, the overexpression of which is correlated with poor survival in triple negative breast cancer. The results of additional cell-based assays that will be described in the poster suggest that narazaciclib may promote antitumor immunity and show that combining narazaciclib with autophagy inhibitors sensitizes breast cancer cells to cell death.

About Onconova Therapeutics, Inc.

Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in two separate and complementary Phase 1 dose escalation and expansion studies. These trials are currently underway in the United States and China. Based on preclinical and clinical studies of CDK 4/6 inhibitors, Onconova is also planning a combination trial of narazaciclib with estrogen blockade in advanced endometrial cancer, as well as its clinical study in additional indications.

Onconova’s product candidate rigosertib is being studied in multiple investigator-sponsored studies, including a dose-escalation and expansion Phase 1/2a study of oral rigosertib in combination with nivolumab in patients with KRAS+ non-small cell lung cancer, and a Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa.

For more information, please visit www.onconova.com.

Forward-Looking Statements

Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, and involve risks and uncertainties. These statements relate to Onconova’s expectations regarding its clinical development and trials, its product candidates, its business and financial position. Onconova has attempted to identify forward-looking statements by terminology including “believes,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” “preliminary,” “encouraging,” “approximately” or other words that convey uncertainty of future events or outcomes. Although Onconova believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including the success and timing of Onconova’s clinical trials, investigator-initiated trials and regulatory agency and institutional review board approvals of protocols, Onconova’s collaborations, market conditions and those discussed under the heading “Risk Factors” in Onconova’s most recent Annual Report on Form 10-K and quarterly reports on Form 10-Q. Any forward-looking statements contained in this release speak only as of its date. Onconova undertakes no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.

Company Contact:
Mark Guerin
Onconova Therapeutics, Inc.
267-759-3680
[email protected]
https://www.onconova.com/contact/

Investor Contact:
Bruce Mackle
LifeSci Advisors, LLC
646-889-1200
[email protected]

Tonix Pharmaceuticals (TNXP) – FY2023 Reported – Clinical Milestones Expected In 2Q23

Posted on March 14, 2023March 14, 2023 by [email protected]

Tuesday, March 14, 2023

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics and diagnostics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of immunology, rare disease, infectious disease, and central nervous system (CNS) product candidates. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-15001 which is a humanized monoclonal antibody targeting CD40-ligand being developed for the prevention of allograft and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the second half of 2022. Tonix’s rare disease portfolio includes TNX-29002 for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan-Drug Designation by the FDA. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox called TNX-8013, next-generation vaccines to prevent COVID-19, and an antiviral to treat COVID-19. Tonix’s lead vaccine candidates for COVID-19 are TNX-1840 and TNX-18504, which are live virus vaccines based on Tonix’s recombinant pox vaccine (RPV) platform. TNX-35005 (sangivamycin, i.v. solution) is a small molecule antiviral drug to treat acute COVID-19 and is in the pre-IND stage of development. TNX-102 SL6, (cyclobenzaprine HCl sublingual tablets), is a small molecule drug being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix expects to initiate a Phase 2 study in Long COVID in the second quarter of 2022. The Company’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL, is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022. Finally, TNX-13007 is a biologic designed to treat cocaine intoxication that is expected to start a Phase 2 trial in the second quarter of 2022. TNX-1300 has been granted Breakthrough Therapy Designation by the FDA.

Robert LeBoyer, Vice President, Research Analyst, Life Sciences , Noble Capital Markets, Inc.

Refer to the full report for the price target, fundamental analysis, and rating.

Tonix Reported FY2022 and Gave Clinical Milestone Updates. Tonix reported a loss of $34.1 million or ($0.56) per share for 4Q22 and $116.9 million or $(3.27) per share for FY2022. The company reaffirmed its guidance for a 2Q23 announcement of interim analysis for TNX102 SL in the Phase 3 RESILIANT trial testing in fibromyalgia. The full analysis is expected in 4Q23, one of several clinical milestones expected in 2023. Tonix had $120.2 million in cash on December 31.

Interim Analysis Expected For Phase 3 in Fibromyalgia. The RESILIANT Phase 3 trial is a double-blind, placebo-controlled study for fibromyalgia. It reached the 50% patient milestone in December 2022, with the interim analysis results expected in 2Q23. If successful, the RESILIANT trial could lead to an NDA filing for product approval.

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Release – Schwazze’s New Mexico Retail Banner, R.Greenleaf, Launches New Ecommerce Customer Experience

Posted on March 13, 2023March 13, 2023 by [email protected]

Research News and Market Data on SHWZ

March 13, 2023

PDF Version

NEO: SHWZ
OTCQX: SHWZ

R.Greenleaf Paves Way for Direct Commerce Relationship with Customers,
Provides Seamless, Time-Saving Shopping Experience

DENVER, March 13, 2023 /PRNewswire/ – Schwazze, (NEO: SHWZ) (OTCQX: SHWZ) (“Schwazze” or the “Company”), announces the launch of a new ecommerce shop site for R.Greenleaf, its New-Mexico based retail banner with 17 locations throughout the state. This new shopping experience, available at http://rgreenleaf.com, allows customers to ‘skip the line and order online’ by ordering ahead to reserve product and picking up in store. Customers can create an account on the new shop site to access prior orders and receive special offers while also enrolling in R.Greenleaf’s customer loyalty program, Gratify.

“We are excited to bring the convenience of ecommerce shopping to all of our R.Greenleaf locations. Our enhanced online shopping experience allows us to deliver our brands, product assortment and dedicated service to customers in all of our neighborhoods as we continue to expand throughout the state,” said Ken Diehl, Division President – New Mexico.

R.Greenleaf, offering a wide variety of quality products serviced by top-notch, knowledgeable staff, has grown from 10 locations to now 17 since Schwazze’s acquisition nearly one year ago. All locations serve the needs of medical patients as well as recreational consumers.

Since April 2020, Schwazze has acquired, announced the planned acquisition of, or opened 44 cannabis dispensaries as well as seven cultivation facilities and two manufacturing assets in Colorado and New Mexico. In May 2021, Schwazze announced its BioSciences division and in August 2021 it commenced home delivery services in Colorado.

About Schwazze

Schwazze (NEO: SHWZ) (OTCQX: SHWZ) is building a premier vertically integrated regional cannabis company with assets in Colorado and New Mexico and will continue to take its operating system to other states where it can develop a differentiated regional leadership position. Schwazze is the parent company of a portfolio of leading cannabis businesses and brands spanning seed to sale. The Company is committed to unlocking the full potential of the cannabis plant to improve the human condition. Schwazze is anchored by a high-performance culture that combines customer-centric thinking and data science to test, measure, and drive decisions and outcomes. The Company’s leadership team has deep expertise in retailing, wholesaling, and building consumer brands at Fortune 500 companies as well as in the cannabis sector. Schwazze is passionate about making a difference in our communities, promoting diversity and inclusion, and doing our part to incorporate climate-conscious best practices.

Medicine Man Technologies, Inc. was Schwazze’s former operating trade name. The corporate entity continues to be named Medicine Man Technologies, Inc. Schwazze derives its name from the pruning technique of a cannabis plant to enhance plant structure and promote healthy growth.

Forward-Looking Statements

This press release contains “forward-looking statements.” Such statements may be preceded by the words “plan,” “will,” “may,” “continue,” “predicts,” or similar words. Forward-looking statements are not guarantees of future events or performance, are based on certain assumptions, and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company’s control and cannot be predicted or quantified. Consequently, actual events and results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) our inability to manufacture our products and product candidates on a commercial scale on our own or in collaboration with third parties; (ii) difficulties in obtaining financing on commercially reasonable terms; (iii) changes in the size and nature of our competition; (iv) loss of one or more key executives or scientists; (v) difficulties in securing regulatory approval to market our products and product candidates; (vi) our ability to successfully execute our growth strategy in Colorado and outside the state, (vii) our ability to consummate the acquisition described in this press release or to identify and consummate future acquisitions that meet our criteria, (viii) our ability to successfully integrate acquired businesses, including the acquisition described in this press release, and realize synergies therefrom, (ix) the ongoing COVID-19 pandemic, * the timing and extent of governmental stimulus programs, and (xi) the uncertainty in the application of federal, state and local laws to our business, and any changes in such laws. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company’s filings with the Securities and Exchange Commission (SEC), including the Company’s Annual Report on Form 10-K and its Quarterly Reports on Form 10-Q. Investors and security holders are urged to read these documents free of charge on the SEC’s website at http://www.sec.gov. The Company assumes no obligation to publicly update or revise its forward-looking statements as a result of new information, future events or otherwise except as required by law.

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SOURCE Schwazze

Investors: Joanne Jobin, Investor Relations, [email protected], 647.964.0292; Media: Julie Suntrup, Schwazze, Vice President | Corporate Marketing & Brands, [email protected], 303.371.0387

Release – Tonix Pharmaceuticals Reports Fourth Quarter and Full Year 2022 Financial Results and Operational Highlights

Posted on March 13, 2023March 13, 2023 by [email protected]

Research News and Market Data on TNXP

March 13, 2023 7:00am EDT

Related Documents

Interim Analysis of Registration-Enabling Phase 3 Fibromyalgia Trial of TNX-102 SL Expected Second Quarter 2023; Topline Data Expected Fourth Quarter 2023

Potentially Pivotal Phase 2 Trials of TNX-1900 in Chronic Migraine and TNX-601 ER in Depression Scheduled for Interim Analyses in Fourth Quarter 2023

Potentially Pivotal Phase 2 Fibromyalgia-Type Long COVID Study Enrolling

Cash and Cash Equivalents Totaled Approximately $120.2 Million at December 31, 2022

CHATHAM, N.J., March 13, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced financial results for the fourth quarter and full year ended December 31, 2022, and provided an overview of recent operational highlights.

“Our clinical activity is at a high point in the Company’s history, and we believe it is setting the stage for a year of significant accomplishments across an expanded portfolio of novel pharmaceutical candidates designed to serve major unmet medical needs,” said Seth Lederman, M.D., Chief Executive Officer of Tonix.

“We are pleased with the progress of our current Phase 3 program in fibromyalgia, and we are looking forward to the results of a planned interim analysis due next quarter, followed by topline results in the fourth quarter of this year. If successful, we believe it will be the second and final adequate and well-controlled efficacy trial required for filing a New Drug Application (NDA) for approval by the U.S. Food and Drug Administration (FDA)”, he added. “Moreover, we believe we have satisfied all the other clinical and non-clinical requirements for an NDA.”

Dr. Lederman added, “Patients and caregivers alike report widespread dissatisfaction with the three currently approved drugs for fibromyalgia – Lyrica^®, Cymbalta^®, and Savella^®, and generic pregabalin and duloxetine – switching back and forth between them, and too often taking off-label products, including addictive opiates. Fibromyalgia affects between six and 12 million adults in the U.S. according to the American Pain Association, and there hasn’t been a new FDA drug approval in the category in more than a dozen years.”

Dr Lederman continued, “Our recently expanded late-stage clinical programs include four potentially pivotal Phase 2 trials. Two are currently enrolling, one in Long COVID and the other in chronic migraine. The two others – one in depression and the other in cocaine intoxication – are due to start enrolling. We expect to initiate enrollment in the depression study by the end of March, followed by the cocaine intoxication study in the second quarter of this year.”

“In summary”, he concluded, “these programs, together with several others in earlier development, represent a diverse portfolio of programs with multiple opportunities for value creation in 2023 and beyond.”

Recent Highlights—Key Product Candidates*

Central Nervous System (CNS) Pipeline

TNX-102 SL (cyclobenzaprine HCl sublingual tablet): small molecule for the management of fibromyalgia (FM)

The first 50% of participants were randomized on December 19, 2022, in the RESILIENT study, a double-blind, randomized, placebo-controlled, potentially pivotal confirmatory Phase 3 study of TNX-102 SL for the management of fibromyalgia. Results from a planned interim analysis are expected in the second quarter of 2023, with topline results expected in the fourth quarter of 2023. A positive topline outcome, together with results from the previous positive Phase 3 RELIEF study, would support submission of an NDA.

TNX-102 SL for the treatment of Fibromyalgia-Type Long COVID, also known as Post-Acute Sequelae of COVID-19 (PASC)

Enrollment continues in the PREVAIL study, a potentially pivotal Phase 2 study of TNX-102 SL for fibromyalgia-type Long COVID.
During a February 2023 virtual event co-hosted by BIO and Solve M.E. titled, “Long COVID: What Will it Take to Accelerate Therapeutic Progress?”, the Company presented its analysis that the majority of Long COVID patients present with a constellation of symptoms called nociplastic pain that overlap with fibromyalgia, and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and that fibromyalgia-type Long COVID appears to be one of several chronic overlapping pain conditions (COPCs) that are related by sharing the neurological process called central sensitization.

TNX-1900 (intranasal potentiated oxytocin): small peptide for migraine, craniofacial pain, insulin resistance and related disorders, and obesity-associated binge eating disorder

In February 2023, Tonix announced that enrollment began in the potentially pivotal Phase 2 PREVENTION study of TNX-1900 for the prevention of migraine headache in chronic migraineurs. The double-blind, placebo-controlled study has a target enrollment of 300 participants at approximately 25 sites across the U.S. Results from a planned interim analysis after the first 50% of enrolled patients have completed the study are expected in the fourth quarter of 2023.
In January 2023, data from clinical and nonclinical studies were presented at the 16^th Annual Headache Cooperative of the Pacific (HCOP) Winter Conference by collaborator Professor David Yeomans. The oral presentation titled, “Primary vs Secondary Sex Hormones and Migraine,” includes research sponsored by and licensed by Tonix. Preliminary results from a positron emission tomography (PET) study in humans showed that intranasal application of a radioisotope of magnesium-potentiated oxytocin is delivered to the trigeminal ganglia which have known roles in migraine headaches. In addition, preliminary results of data collected from isolated human trigeminal ganglia neurons in vitro show co-expression of oxytocin receptors and calcitonin gene-related peptide (CGRP), which are believed to represent the first observation of oxytocin receptors in human trigeminal ganglia. Furthermore, the presentation highlights data which suggest a sex difference in oxytocin potency.
Tonix announced data from an in vitro study describing the impact of oxytocin on isolated human sensory neurons, presented by collaborator Professor David Yeomans at Neuroscience 2022, the annual meeting of the Society for Neuroscience. The poster, titled “In Vitro Impact of Oxytocin on Human Sensory Neurons,” is the first to show that oxytocin receptors are present on human sensory neurons and that inflammation drives expression of oxytocin receptors on these neurons. The results of this study are consistent with data from animal models and provide support for the use of oxytocin for the treatment of pain.
An investigator-initiated Phase 2 study of TNX-1900 in obesity-associated binge eating disorder is expected to start enrolling in the second quarter of 2023 directed by principal investigator Professor Elizabeth Lawson at the Massachusetts General Hospital, a teaching hospital of Harvard Medical School.

TNX-601 ER (tianeptine hemioxalate extended-release tablets): a once-daily orally-administered small molecule for the treatment of major depressive disorder (MDD), Posttraumatic Stress Disorder (PTSD), and neurocognitive dysfunction associated with corticosteroid use.

Enrollment is expected to initiate in the first quarter of 2023 in the potentially pivotal Phase 2 ‘UPLIFT’ Study for the treatment of MDD. Results from planned interim analysis after the first 50% of enrolled patients have completed the study are expected fourth quarter 2023.
TNX-601 ER represents a novel approach to treating depression in the U.S., since the active ingredient tianeptine induces a neuroprotective and resilient phenotype in both neurons and microglia under conditions of stress. In contrast, antidepressants that are marketed in the U.S. act by modulating neurotransmitter levels or receptor binding in the synapse. The Phase 2 UPLIFT study is a double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-601 ER taken orally once-daily for 6 weeks to treat MDD. It is a parallel design study with two arms, a TNX-601 ER 39.4 mg arm and a placebo arm. A total of 300 participants will be randomized in a 1:1 ratio into the two arms across approximately 30 U.S. sites, enrolling adult patients 18-65 years old with a DSM-5 diagnosis of depression and a duration for the current major depressive episode (MDE) of at least 12 weeks. The primary efficacy endpoint is mean change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6. Key secondary efficacy endpoints include the Clinical Global Impression of Severity Scale (CGI-S) and the Sheehan Disability Scale (SDS).

TNX-1300 (recombinant double mutant cocaine esterase): biologic for life-threatening cocaine intoxication

Tonix expects to initiate a new, potentially pivotal, Phase 2 clinical study of TNX-1300 for the treatment of cocaine intoxication in the second quarter of 2023, pending agreement with the FDA on trial design.
As previously mentioned, in 2022, Tonix received a Cooperative Agreement grant from the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), to support development of TNX-1300.
TNX-1300 has been granted Breakthrough Therapy designation by the FDA.

Rare Disease Pipeline

TNX-2900 (intranasal potentiated oxytocin): small peptide for the treatment of Prader-Willi syndrome (PWS)

TNX-2900 has been granted Orphan Drug designation from the FDA for the treatment of PWS.
As previously mentioned, in 2022, Tonix delivered a presentation titled, “TNX-2900 (Intranasal Oxytocin + Magnesium) in Development for the Treatment of Hyperphagia in Adolescents and Young Adults with Prader-Willi Syndrome” at the World Orphan Drug Congress USA.

Immunology Pipeline

TNX-1500 (anti-CD40L monoclonal antibody): third generation anti-CD40L monoclonal antibody for prophylaxis of organ transplant rejection and treatment of autoimmune disorders.

A First-in-Human Phase 1 study is expected to start in the second quarter of 2023 of TNX-1500 for prophylaxis of organ rejection in adult patients receiving a kidney transplant.
In February 2023, Tonix announced a research agreement with the University of Maryland, Baltimore, to study and assess the role of TNX-1500 in the prevention of heart xenograft rejection. The genetically engineered pig donors will be provided by the Revivicor Division of United Therapeutics Corporation. Preclinical xenotransplantation studies are expected to support an IND application.
Tonix announced a research agreement with Boston Children’s Hospital to study TNX-1500 for the prevention of graft-versus-host diseases (GvHD) after hematopoietic stem cell transplantation (HCT) in animals. HCT from unrelated donors is a component of the treatment protocol for several hematologic malignancies, but GvHD complicates treatment and limits the success of engraftment after HCT.

Infectious Disease Pipeline

TNX-801 (live horsepox virus vaccine for percutaneous administration): vaccine to protect against smallpox and mpox designed as a single-administration vaccine to elicit T cell immunity

A Phase 1 study in is expected to start in the second half of 2023.
Tonix presented a development update from the Company’s TNX-801 vaccine program in an oral presentation at the World Vaccine and Immunotherapy Congress on December 1, 2022. The oral presentation titled, “Live Virus Smallpox and Monkeypox Vaccine,” describes the history of live virus vaccines and rationale for the development of the Company’s Recombinant Pox Virus (RPV) platform, including TNX-801 to protect against mpox and smallpox. Non-human primates vaccinated with TNX-801 were fully protected with sterilizing immunity from a lethal challenge with intra-tracheal monkeypox.
A publication describing the activity of TNX-801 to protect non-human primates against a lethal challenge with intra-tracheal monkeypox was published in the peer-reviewed journal, Viruses (Noyce RS, et al. “Single Dose of Recombinant Chimeric Horsepox Virus (TNX-801) Vaccination Protects Macaques from Lethal Monkeypox Challenge.” Viruses. 2023 Jan 26;15(2):356. doi: 10.3390/v15020356. PMID: 36851570; PMCID: PMC9965234.)

*All of Tonix’s product candidates are investigational new drugs or biologics and none have been approved for any indication.

Recent Highlights—Corporate and Other

In February 2023, Tonix announced the appointment of R. Newcomb Stillwell to its Board of Directors, effective March 15, 2023. Mr. Stillwell is a retired partner at Ropes & Gray LLP, an international law firm, where he devoted approximately 38 years.
In February 2023, Tonix announced that it has exercised an option to obtain an exclusive license from Columbia University for the development of a portfolio of fully human (TNX-3600) and murine (TNX-4100) monoclonal antibodies for the treatment or prophylaxis of SARS-CoV-2 infection. The licensed monoclonal antibodies were developed as part of a research collaboration and option agreement between Tonix and Columbia University, originally announced in 2020.
In February 2023, Tonix announced the acquisition of a preclinical portfolio of next-generation antiviral technology assets from Healion Bio, Inc. (Healion). Healion’s drug portfolio includes a class of broad-spectrum small molecule oral antiviral drug candidates including TNX-3900, formerly known as HB-121, which are cathepsin protease inhibitors, some of which have activity in vitro against SARS-CoV-2.
On January 26, 2023, data from Tonix’s research collaboration with The University of Alberta were presented by Tom Hobman, Ph.D., Professor of Cell Biology, University of Alberta, during a presentation at the 2^nd Wnt/β-catenin Targeted Drug Development Conference. The oral presentation titled, “Targeting the Wnt/β-catenin pathway as a broad-spectrum antiviral strategy,” includes research sponsored by Tonix Pharmaceuticals focused on the development and testing of Wnt/β-catenin signaling pathway inhibitors as broad-spectrum antivirals against SARS-CoV-2 and other emerging viruses.
In January 2023, Tonix announced the publication of a paper entitled, “Development of a rapid image-based high-content imaging screening assay to evaluate therapeutic antibodies against the monkeypox virus,” in the journal Antiviral Research. The publication describes the development and optimization of two high-content image-based assays that were employed to screen for potential therapeutic antibodies against the monkeypox virus using surrogate poxviruses such as vaccinia virus. The article highlights Tonix’s TNX-3400 platform, which includes antibodies to potentially prevent or treat mpox and smallpox. These data represent the first wave of research and development conducted at the Company’s Infectious Disease R&D Center (RDC) in Frederick, Md. (Kota KP, et al., “Development of a rapid image-based high-content imaging screening assay to evaluate therapeutic antibodies against the monkeypox virus.” Antiviral Res. 2023 Feb;210:105513. doi: 10.1016/j.antiviral.2022.105513. Epub 2022 Dec 30. PMID: 36592670; PMCID: PMC9803393.)
In January 2023, Tonix announced the appointment of Zeil Rosenberg, M.D., M.P.H. as its new Executive Vice President, Medical.
Tonix announced data from its fully human anti-SARS-CoV-2 monoclonal antibody platform in an oral presentation at the World Antiviral Congress 2022. The presentation titled, “Platform for Generating Fully Human anti-SARS-CoV-2 Spike Therapeutic Monoclonal Antibodies” highlights the need for a broad array of monoclonal antibodies which can be scaled up quickly and potentially combined with other monoclonal antibodies to treat or prevent COVID-19. The platform is part of a broader research collaboration and option agreement with scientists at Columbia University designed to fill in important gaps in understanding the detailed immune responses to COVID-19, and to provide a foundation upon which to target vaccines and therapeutics to appropriate individuals by precision medicine.
In December 2022, Tonix announced that it has obtained an exclusive license from Curia Global, Inc., a leading contract research, development and manufacturing organization, for the development of three humanized murine monoclonal antibodies for the treatment or prophylaxis of SARS-CoV-2 infection, the cause of COVID-19. Immunocompromised individuals, including organ transplant recipients, are at increased risk of severe COVID-19 and poor clinical outcomes. SARS-CoV-2 has mutated to evade the existing FDA Emergency Use Authorization (EUA)-approved therapeutic monoclonal antibodies.

Recent Highlights—Financial

As of December 31, 2022, Tonix had $120.2 million of cash and cash equivalents, compared to $178.7 million as of December 31, 2021. Net proceeds from financing activities were approximately $87.8 million for full year 2022, compared to $212.5 million for the full year 2021.

Since January 1, 2023, the Company repurchased 15,700,269 shares of common stock under a $12.5 million share purchase program at prices ranging from $0.44 to $1.38 for a gross aggregate cost of approximately $12.5 million.

In January 2023, the Board of Directors approved a new $12.5 million share repurchase program. Since January 1, 2023, the Company repurchased 1,000,000 shares of common stock under this share repurchase program at $1.14 for a gross aggregate cost of $1.1 million.

Cash used in operations was approximately $98.1 million for the full year 2022, compared to $75.6 million for the full year 2021. The increase in cash outlays was primarily due to an increase in research and development (R&D) and general and administrative (G&A) activities, described below.

Cash used by investing activities for the years ended December 31, 2022, and 2021 was approximately $48.1 million and $35.3 million, respectively, related to the purchase of property and equipment.

Fourth Quarter 2022 Financial Results

R&D expenses for the fourth quarter 2022 were $24.7 million, compared to $22.3 million for the same period in 2021. The increase is predominately due to increased employee-related, facility and laboratory expenses. We expect R&D expenses to increase during 2023 as we move our clinical development programs forward and invests in our development pipeline.

G&A expenses for the fourth quarter 2022 were $8.1 million, compared to $7.3 million for the same period in 2021. The increase is primarily due to increased employee-related and financial reporting expenses.

Net loss available to common stockholders was $34.1 million, or $0.56 per share, basic and diluted, for the fourth quarter 2022, compared to net loss of $29.6 million, or $2.08 per share, basic and diluted, for the same period in 2021. The basic and diluted weighted average common shares outstanding for the fourth quarter 2022 was 61,379,692 compared to 14,230,897 shares for the same period in 2021.

Full Year 2022 Financial Results

R&D expenses for the full year 2022 were $81.9 million, compared to $68.8 million for the same period in 2021. The increase is predominately due to increased employee-related, facility and laboratory expenses. We expect R&D expenses to increase during 2023 as we move our clinical development programs forward and invest in our development pipeline.

G&A expenses for the full year 2022 were $30.2 million, compared to $23.5 million for the same period in 2021. The increase is primarily due to increased employee-related and financial reporting expenses.

Net loss available to common stockholders was $116.9 million, or $3.27 per share, basic and diluted, for the full year 2022, compared to net loss of $92.3 million, or $8.10 per share, basic and diluted, for the same period in 2021. The basic and diluted weighted average common shares outstanding for full year 2022 was 35,739,057 compared to 11,387,308 shares for the same period in 2021.

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is being studied in a potential pivotal Phase 2 study that initiated enrollment in the first quarter of 2023 and for which interim data is expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the second quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes 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 and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the second quarter of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and mpox, TNX-801; a next-generation vaccine to prevent COVID-19, TNX-1850; a platform to make fully human and murine monoclonal antibodies to treat COVID-19, TNX-3600 and TNX-4100, respectively; and humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800; and a class of broad-spectrum small molecule oral antivirals, TNX-3900. TNX-801, Tonix’s vaccine in development to prevent smallpox and mpox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in the second half of 2023.

*All of Tonix’s product candidates are investigational new drugs or biologics and have not been approved for any indication.

This press release and further information about Tonix can be found at www.tonixpharma.com.

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; delays and uncertainties caused by the global COVID-19 pandemic and social and economic unrest; 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 as filed with the Securities and Exchange Commission (the “SEC”) 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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
[email protected]
(862) 904-8182

Olipriya Das, Ph.D. (media)
Russo Partners
[email protected]
(646) 942-5588

Peter Vozzo (investors)
ICR Westwicke
[email protected]
(443) 213-0505

Biotech Announcement Sends Stock Up 258%

Posted on March 13, 2023March 13, 2023 by [email protected]

The Power of Small Companies Highlighted in Today’s Biopharma Announcements

Business headlines surrounding Silicon Valley Bank and its customers may take some time to fade from the front page. In the meantime, looking past them, there are some positive news and developments. Two news items involve announcements by biotech/pharmaceutical companies this week. One is a deal you don’t have to dig too deep to find, Pfizer (PFE), the pharmaceutical behemoth, is looking to acquire Seagen (SGEN) for $43 billion. The second is a smaller deal and has been crowded off many newsfeeds. Provention Bio (PRVB) is expected to be purchased by Sanofi (SNY) a large French-based pharmaceutical company.

Seagen shares increased 17% in the first hour of trading after the Pfizer announcement, shares of Provention were up 258% the same morning after the Sanofi announcement. Below is a chart of the month-to-date performance of the two that are to be acquired.

The Power of Flying Below the Radar

Seagen is a borderline household name and has been a known acquisition target for some time. Just last July, Merck offered 40 billion for the company, this known interest in the company has kept the price elevated. Shifting the focus on the power of smaller, less talked about companies, they often have more potential for larger gains because they are less known. And while the numbers ($43 billion vs $2.9 billion) don’t make for compelling headlines, the numbers in the graph above demonstrate the impact can be far more compelling to investors.

The Provention Bio Deal

Sanofi and Provention Bio, a U.S.-based, publicly traded biopharmaceutical company focused on preventing autoimmune diseases, including type 1 diabetes (T1D), entered into an agreement for Sanofi to acquire Provention Bio, Inc., for $25.00 per share in cash.

Under the terms of the agreement, Sanofi will begin a cash tender offer to acquire all outstanding shares of Provention Bio.

The actual completion of the tender is subject to standard conditions, including the tendering of a number of shares of Provention Bio, Inc. common stock that, together with shares already owned by Sanofi or its affiliates, represents at least a majority of the outstanding shares of Provention Bio, Inc. common stock.

If the tender offer is successfully completed, then a wholly owned subsidiary of Sanofi will merge with and into Provention Bio, Inc., and all of the outstanding Provention shares that are not tendered in the offer will be converted into the right to receive the same $25.00 per share in cash offered to Provention Bio, Inc. shareholders as part of the offer. Sanofi plans to fund the transaction with available cash. Subject to the satisfaction or waiver of customary closing conditions, Sanofi expects to complete the acquisition in the second quarter of 2023.

Worth Noting

The largest pharmaceutical companies developed huge cash “war chests” during the pandemic era. While they are prudent and tactical when deciding to grow through acquisition, the earnings on much of their cash stockpiles relative to inflation may be erosive to the pool’s purchasing power. Additionally, many small pharmaceutical and biotech companies that are developing tomorrow’s next wonder drugs are short the cash they need to drive their R&D to the finish line, and then to market. It’s presumed these companies are quietly being reviewed for a possible fit by big pharma. Big pharma’s current patents are also being eroded by time as each day they approach patent expiration. This is added incentive for these large companies to be actively looking for future merger and acquisition targets.

Smaller companies, for their part want their progress and potential more known. It is only through being known, and the more broadly the better, that investors of all types understand the work they do and the potential along with the risk they hold. These companies often hire the service of impartial, highly credible equity analysts to provide details of the pipeline and the successes and challenges of the company. This company-sponsored research provides investors with a third-party window into the company. The window is, at times, as basic as the idea that investors need to know enough about the existence of a small company to want to own shares. Greater investor interest typically increases liquidity which could help the company continue moving forward and developing its products.

Channelchek houses quality company-sponsored research. For Life Sciences company-sponsored research covered by FINRA licensed Sr. Analyst Robert LeBoyer visit this link. For Healthcare Services Sr. Analyst Gregory Aurand visit this link.

Paul Hoffman

Managing Editor, Channelchek

Release – Onconova Therapeutics to Provide Corporate Update And Announce Fourth Quarter And Full Year 2022 Financial Results On March 16, 2023

Posted on March 10, 2023March 10, 2023 by [email protected]

Research News and Market Data on ONTX

Mar 09, 2023

PDF Version

Company to host conference call and webcast at 4:30 p.m. ET on Thursday, March 16, 2023

NEWTOWN, Pa., March 09, 2023 (GLOBE NEWSWIRE) — Onconova Therapeutics, Inc. (NASDAQ: ONTX), (“Onconova”), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, today announced that the Company intends to release its fourth quarter and full year 2022 financial results on Thursday, March 16, 2023. Management plans to host a conference call and live webcast at 4:30 p.m. ET on the same day to discuss these results and provide an update on its pipeline programs.

Conference Call and Webcast Information

Interested parties who wish to participate in the conference call may do so by dialing (800) 715-9871 for domestic and (646) 307-1963 for international callers and using conference ID 3097517.

Those interested in listening to the conference call via the internet may do so by visiting the investors and media page on the Company’s website at www.onconova.com and clicking on the webcast link. In addition to the live webcast, a replay will be available on the Onconova website for 90 days following the call.

About Onconova Therapeutics, Inc.

For more information, please visit www.onconova.com.

Forward Looking Statements

Company Contact:
Mark Guerin
Onconova Therapeutics, Inc.
267-759-3680
[email protected]
https://www.onconova.com/contact/

Investor Contact:
Bruce Mackle
LifeSci Advisors, LLC
646-889-1200
[email protected]

Release – MustGrow Reports Growth of Global Patent Portfolio

Posted on March 8, 2023March 8, 2023 by [email protected]

Research News and Market Data on MGROF

Mustard-derived intellectual property portfolio has significantly advanced in quantity and scope.
Patents have been filed across six continents.
Patent portfolio has grown from 23 to 84 in three year period.

SASKATOON, Saskatchewan, Canada, Mar. 8, 2023 – MustGrow Biologics Corp. (TSXV: MGRO) (OTC: MGROF) (FRA: 0C0) (the “Company” or “MustGrow”), is pleased to report on the growth of its intellectual property portfolio (the “IP Portfolio”) in both quantity and scope, particularly with respect to the Company’s patents.

“The growth of our IP Portfolio enhances the potential commercial value of MustGrow’s organic mustard-derived crop protection and food preservation technologies through potential product sales, licensing fees and royalities, and/or other commercial transactions – all of which would contribute to driving shareholder value,” remarked Corey Giasson, MustGrow’s President & CEO.

MustGrow’s global IP Portfolio has grown from 23 to 84 total patents issued and pending over the last three years. Of the 84 total patents, 62 have been issued, an increase from 18 issued patents three years ago. The IP Portfolio also includes trade secrets and protects MustGrow’s mustard-derived technology across six continents, including various composition, production process, and end-use applications. The IP Portfolio covers MustGrow’s three key areas of focus: pre-plant soil fumigation, postharvest food preservation, and bioherbicide.

Since 2021, MustGrow has been developing its biologic technologies with four global partners – Janssen PMP, Bayer, Sumitomo Corporation, and NexusBioAg – and retains the ability to commercialize all of its partnership-generated data and discoveries. These arrangements have allowed MustGrow to substantially accelerate technology development and potential future commercialization. MustGrow continues to innovate in biological crop protection and food preservation with the breadth and depth of its IP Portfolio, driven by laboratory, greenhouse, and field trials.

———

About MustGrow

MustGrow is an agriculture biotech company developing organic biopesticides and bioherbicides by harnessing the natural defense mechanism of the mustard plant to protect the global food supply from diseases, insect pests, and weeds. MustGrow and its leading global partners – Janssen PMP (pharmaceutical division of Johnson & Johnson), Bayer, Sumitomo Corporation, and Univar Solutions’ NexusBioAg – are developing mustard-based organic solutions to potentially replace harmful synthetic chemicals. Over 150 independent tests have been completed, validating MustGrow’s safe and effective approach to crop and food protection. Pending regulatory approval, MustGrow’s patented technology could be applied through injection, standard drip or spray equipment, improving functionality and performance features. Now a platform technology, MustGrow and its global partners are pursuing applications in several different industries from preplant soil treatment and weed control, to postharvest disease control and food preservation. MustGrow has approximately 49.7 million basic common shares issued and outstanding and 55.6 million shares fully diluted. For further details, please visit www.mustgrow.ca.

ON BEHALF OF THE BOARD

“Corey Giasson”

Director & CEO
Phone: +1-306-668-2652
[email protected]

MustGrow Forward-Looking Statements

Certain statements included in this news release constitute “forward-looking statements” which involve known and unknown risks, uncertainties and other factors that may affect the results, performance or achievements of MustGrow.

Generally, forward-looking information can be identified by the use of forward-looking terminology such as “plans”, “expects”, “is expected”, “budget”, “estimates”, “intends”, “anticipates” or “does not anticipate”, or “believes”, or variations of such words and phrases or statements that certain actions, events or results “may”, “could”, “would”, “might”, “occur” or “be achieved”. Examples of forward-looking statements in this news release include, among others, statements MustGrow makes regarding: (i) enhancements to potential commercial value of its organic mustard-derived crop protection and food preservation technologies through potential product sales, licensing fees and royalities, and/or other commercial transactions; and (ii) the potential outcomes stemming from the Company’s efforts with respect to its IP Portfolio to continue driving shareholder value.

Forward-looking statements are subject to a number of risks and uncertainties that may cause the actual results of MustGrow to differ materially from those discussed in such forward-looking statements, and even if such actual results are realized or substantially realized, there can be no assurance that they will have the expected consequences to, or effects on, MustGrow. Important factors that could cause MustGrow’s actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, the following: (i) the preferences and choices of agricultural regulators with respect to product approval timelines; (ii) the ability of MustGrow’s partners to meet obligations under their respective agreements; and (iii) other risks described in more detail in MustGrow’s Annual Information Form for the year ended December 31, 2021 and other continuous disclosure documents filed by MustGrow with the applicable securities regulatory authorities which are available at www.sedar.com. Readers are referred to such documents for more detailed information about MustGrow, which is subject to the qualifications, assumptions and notes set forth therein.

This release does not constitute an offer for sale of, nor a solicitation for offers to buy, any securities in the United States.

Neither the TSXV, nor their Regulation Services Provider (as that term is defined in the policies of the TSXV), nor the OTC Markets has approved the contents of this release or accepts responsibility for the adequacy or accuracy of this release.

Onconova Therapeutics (ONTX) – Additional Rigosertib Mechanism of Action Data Presented

Posted on March 8, 2023March 8, 2023 by [email protected]

Wednesday, March 08, 2023

Robert LeBoyer, Vice President, Research Analyst, Life Sciences , Noble Capital Markets, Inc.

Refer to the full report for the price target, fundamental analysis, and rating.

New Data Shows Mechanisms of Inflammation and Cell Death. Onconova presented new preclinical data on the mechanisms of action for Rigosertib, its cell-signal inhibitor for cancer. The poster presentation at the AACR Special Conference for Targeting RAS included new data showing additional targets and mechanisms of action. We believe the presentation expands on the previous mechanism of action data and differentiates rigosertib from other KRAS drugs.

Data Shows Effects On Early and Late In Cancer Pathways. Rigosertib was shown to activate early targets which then trigger inhibition of the RAS/RAF pathway, as well as inflammation and interruption of cell division. Rigosertib also activates the inflammasome NLRP3, increasing levels of the pro-inflammatory cytokines IL1beta and IL-18. This inflammatory response supports the combination of Rigosertib with a checkpoint inhibitor, currently in clinical trials.

Get the Full Report

This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).

What to Look for in a Biotech Stock

Posted on March 8, 2023March 8, 2023 by [email protected]

Steps to Discover Which Biotech Stocks May Get Hot

The biotech sector is in and of itself exciting. A company developing an idea that can improve human lives, decrease suffering, or even prevent death, by nature, could be a more rewarding endeavor than investing in a company that, by comparison, does little to make a big difference. If, at the same time, the opportunity to return the investor a multiple over returns available elsewhere in the market, then the motivation to allocate a portion of investment capital increases dramatically. But how does an investor gauge a company in the biotech sector and evaluate its chance of survival and likelihood of success?

As with much of investing, sure things don’t often provide a good return. And adding risk doesn’t necessarily equate to added return. The higher perceived risk of a sector such as biotech needs to be offset by research. Filtering stocks through a selection process is key, so the probability of picking those that survive and thrive is higher than average.

I spoke with Robert LeBoyer, the Senior Life Sciences Analyst at Noble Capital Markets, and asked him to list factors to improve the likelihood of choosing a successful biotech company. His knowledge and enthusiasm for the sector caused me to want to share what I learned.

Differentiation

Companies developing a drug that is different than all that came before for what it proposes to treat or prevent stand a good chance of getting funding to make it through the different phases of study. With a development time of 3-5 years, it is best if there is a clear unmet need for the therapy or no current therapies at all.

Investors should determine if there are treatments presently and ask whether the drug or treatment mechanism is a significant improvement over any current product. Also is the field crowded or will it soon be crowded with alternatives to what a company may bring to market? LeBoyer recommended asking where there is an improvement. He gave the example of many cholesterol-lowering drugs, which he said all target the same enzyme. A company with a drug that similarly targets that enzyme may not be worth exploring. Learning of a company that has a different mechanism of action, one which shows promise of greater efficacy, or, reduced cost, or fewer side effects may be worth exploring further.

As an example of a company that had met these criteria some years back, Gilead received approval for a once-daily tablet to treat hepatitis C. Prior to this, the only treatment options involved a year-long regimen of weekly interferon injections and ribavirin tablets. The side effects were depression, nausea, flu-like symptoms, and a reduction in some blood cells. The cost of the injections and treatments could cost a health insurer $1 million over the life of the patient. The Gilead treatment, which has a price tag of $93,000, is mathematically more cost-effective. The therapy which Gilead got approved in the U.S. in 2013 was a better treatment than what existed, and even better tolerated by patients. The stock went from $20 to $120 in about a years time after approval.

Development

Clinical development was another attribute brought up by Noble’s analyst. With even the best proof of concept or early-stage trial success, assessing the chance that clinical stage trials may fail for pipeline candidates is difficult. This is why a company with a diverse pipeline with a number of products being developed or in later stages of clinical trials, increases the probability of successful biotech investment. Many companies easily pass stage one trials and even stage two, but don’t get past the final hurdle. LeBoyer shared with me a story of a company he now covers that had a vaccine for Covid-19 early on. The human clinical trials, however, were not done in the U.S., but were instead the result of trials on persons mostly of similar lineage. The FDA required a sampling comparable to the diversification of heritage or gene pool in the U.S.

Obtaining a basic understanding of the FDA side of development is important for anyone making decisions on biotech stocks.

The drug approval process in the U.S. involves multi-layered (Step One through Step Four) with each representing an important milestone on the path to full approval so the product can be brought to market or meet rejection along the path.

Step One is the development phase, Step Two is research, Step Three is Clinical Trials, and Step Four is FDA Approval.

Knowing where companies stands in the FDA step process can help an investor assess the likelihood of approval. Many products, can get to the last step and not be approved, but those just starting out on Step One are a greater risk both in the time it will take and the chance for something to not be to the FDA’s liking.

Finances

Biotech companies, by and large burn through cash in their research, development and trial periods. Understanding how long the cash on hand and other available sources can last before they need to raise more cash, then comparing this with how close to an expected finish line they are, could help an investor steer away from a company that may have a product in the pipeline that meets other key elements investors should look at, but unfortunately, funds may stand in the way of success.

Robert LeBoyer explained that the current high-interest rate environment, coupled with depressed stock prices, makes this particularly important now. For those companies that can borrow, the cost of money is now far more expensive than it had been in the last decade and a half. And issuing more shares, essentially selling more of the company, dilutes the value of shares currently held. It could become a tricky situation that stockholders or those deciding to become a stockholder should monitor

Take Away

Are there companies with a pipeline that includes drugs that meet a large unmet need (as one example, Alzheimer’s), or can attack a disease like cancer in a unique way that would be embraced by the medical community and patients? “Unicorn” companies do exist, but finding them, assessing them, and doing it before a louder investment buzz occurs takes some digging. A solid place to start digging is under the biotech company section on Channelchek. Available by clicking here, here investors are exposed to many opportunities and the underlying data, the latest news, and of course, thorough company descriptions.

Biotech companies covered by analyst Robert LeBoyer, along with his current research are available here. Channelchek will be highlighting interesting biotechs in future articles and discussing their work and status against the criteria presented above. Join Channelchek to receive emails and gain free access to these articles, video presentations, updated research reports, and news of company roadshows. Visit Rob LeBoyers coverage list here.

Paul Hoffman

Managing Editor, Channelchek

Release – Tonix Pharmaceuticals Announces Results from a Preclinical Study of Murine TNX-1700 Presented in a Poster at the Keystone Symposia, “Cancer Immunotherapy: Mechanisms of Response Versus Resistance”

Posted on March 7, 2023March 7, 2023 by [email protected]

Research News and Market Data on TNXP

March 07, 2023 7:00am EST

Murine TNX-1700 (mTNX-1700) Enhances Anti-Tumor Activity of PD-1 Blockade in Mouse Models of Colorectal Cancer

TNX-1700 is in Development as Monotherapy and in Combination with Anti-PD-1 Checkpoint Inhibitor Therapy for Colorectal and Gastric Cancers

In Animal Models of Colorectal Cancer, mTNX-1700 Treatment Leads to the Activation of Cancer-Killing CD8⁺ T Cells and Limits Immune Evasion by Cancer Cells

CHATHAM, N.J., March 07, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that preclinical results of mTNX-1700 (recombinant murine TFF2-murine serum albumin, or MSA, fusion protein) were presented in a poster at the Keystone Symposia, “Cancer Immunotherapy: Mechanisms of Response Versus Resistance” on March 6, 2023, at the Fairmont Banff Springs Conference Center in Banff, Alberta, Canada. The poster can be found on the Scientific Presentations page of Tonix’s website.

The poster, titled “TFF2-MSA Suppresses Tumor Growth and Increases Survival in an anti-PD-1 Treated MC38 Colorectal Cancer Model by Targeting MDSCs,” includes data from preclinical studies which evaluated the ability of mTNX-1700 to treat colorectal cancer as monotherapy or in combination with anti-PD-1 in mouse models. TNX-1700 targets myeloid-derived suppressor cells (MDSCs) which interfere with the immune response to cancer by suppressing the CD8⁺ T cell response and creating a toxic tumor microenvironment. The data show that mTNX-1700 and anti-PD-1 monotherapy each were able to evoke anti-tumor immunity in the MC38 model of colorectal cancer, and that mTNX-1700 augmented the anti-tumor efficacy of anti-PD-1 therapy in two different colorectal cancer models. Tonix is developing TNX-1700 (recombinant human TFF2-human serum albumin or HSA) for the treatment of colon and gastric cancers.

“Anti-PD-1 treatment has revolutionized the treatment of other cancers and is known as immuno-oncology,” said Seth Lederman, M.D., Chief Executive Officer of Tonix. “Colorectal cancer is notoriously unresponsive to anti-PD-1 treatment. Much research has been focused on trying to turn anti-PD-1 unresponsive tumors into anti-PD-1 responsive tumors.”

Bruce Daugherty, Ph.D., Executive Vice President, Research of Tonix, the presenter and lead author of the study added, “we believe that the data from these preclinical studies demonstrate that mTNX-1700 treatment augmented the response of two different models of colorectal tumors. In addition, it was shown that mTNX-1700 inhibits the MDSCs which contribute to the toxic element of the tumor microenvironment. Together these findings support the idea that whether a tumor is anti-PD1 non-responsive or responsive may relate to the tumor microenvironment rather than the tumor itself. We are excited to start additional work to learn if TNX-1700 therapy modifies the toxic tumor microenvironment in humans and will make colorectal cancer responsive to anti-PD-1 therapy.”

About Trefoil Factor 2 (TFF2)
Human TFF2 is a secreted protein, encoded by the TFF2 gene in humans, that is expressed in gastrointestinal mucosa where it functions to protect and repair mucosa. TFF2 is also expressed at low levels in splenic immune cells and is now appreciated to have intravascular roles in the spleen and in the tumor microenvironment. In gastric cancer, TFF2 is epigenetically silenced, and TFF2 is suggested to be protective against cancer development through several mechanisms. Tonix is developing TNX-1700 (rTFF2-HSA) for the treatment of gastric and colon cancers under a license from Columbia University. Columbia was granted patent claims, which, excluding possible patent term extensions, is expected to provide U.S. market exclusivity until April 2, 2033^1,2. The inventor at Columbia is Dr. Timothy Wang, who is an expert in the molecular mechanisms of carcinogenesis whose research has focused on the carcinogenic role of inflammation in modulating stem cell functions. Dr. Wang demonstrated that knocking out the mTFF2 gene in mice leads to faster tumor growth and that overexpression of TFF2 markedly suppresses tumor growth by curtailing the homing, differentiation, and expansion of MDSCs to allow activation of cancer-killing CD8⁺ T cells³. He went on to show that a novel engineered form of recombinant murine TFF2 (mTFF2-CTP) had an extended half-life in vivo and was able to suppress MDSCs and tumor growth in an animal model of colorectal cancer. Later, he showed in gastric cancer models that suppressing MDSCs using chemotherapy enhances the effectiveness of anti-PD1 therapy and significantly reduces tumor growth.⁴ Dr. Wang proposed the concept of employing rTFF2 in combination with other therapies in cancer prevention and early treatment. Dr. Wang presented data at the American Association for Cancer Research (AACR) conference as a collaboration between Tonix and Columbia University in 2020⁵ that includes data from a preclinical study which investigated the role of PD-L1 in colorectal tumorigenesis and evaluated the utility of targeting myeloid-derived suppressor cells (MDSCs) in combination with PD-1 blockade in mouse models of colorectal cancer. The data show that anti-PD-1 monotherapy was unable to evoke anti-tumor immunity in this model of colorectal cancer, but mTFF2-CTP augmented the efficacy of anti-PD-1 therapy. Anti-PD-1 in combination with TFF2-CTP showed greater anti-tumor activity in PD-L1-overexpressing mice.

¹Tonix 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 :: Tonix Pharmaceuticals Holding Corp. (TNXP)
²The U.S. Patent and Trademark Office issued U.S. Patent No. 11,167,010 on November 9, 2021.
³Dubeykovskaya ZA et al, Nat Commun 2016
⁴Kim W et al, Gastroenterology 2021
⁵Tonix Pharmaceuticals Announces Results from Preclinical Study of TNX-1700 Presented in a Poster at AACR Virtual Annual Meeting 2020 :: Tonix Pharmaceuticals Holding Corp. (TNXP)

Tonix Pharmaceuticals Holding Corp.^*

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the second quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is being studied in a potential pivotal Phase 2 study that initiated enrollment in the first quarter of 2023 and for which interim data is expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes 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 and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the second quarter of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801; a next-generation vaccine to prevent COVID-19, TNX-1850; a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600; humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800; and a class of broad-spectrum small molecule oral antivirals, TNX-3900. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in the second half of 2023.

^*All of Tonix’s product candidates are investigational new drugs or biologics and have not been approved for any indication.

This press release and further information about Tonix can be found at www.tonixpharma.com.

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; 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, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, 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.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
[email protected]
(862) 904-8182

Olipriya Das, Ph.D. (media)
Russo Partners
[email protected]
(646) 942-5588

Peter Vozzo (investors)
ICR Westwicke
[email protected]
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Released March 7, 2023

CBD – What We Know, What We Don’t, and What We Will

Posted on March 7, 2023March 7, 2023 by [email protected]

Here’s What Science Now Says about CBD’s Health Benefits

Over the last five years, an often forgotten piece of U.S. federal legislation – the Agriculture Improvement Act of 2018, also known as the 2018 Farm Bill – has ushered in an explosion of interest in the medical potential of cannabis-derived cannabidiol, or CBD.

After decades of debate, the bill made it legal for farmers to grow industrial hemp, a plant rich in CBD. Hemp itself has tremendous value as a cash crop; it’s used to produce biofuel, textiles and animal feed. But the CBD extracted from the hemp plant also has numerous medicinal properties, with the potential to benefit millions through the treatment of seizure disorders, pain or anxiety.

Prior to the bill’s passage, the resistance to legalizing hemp was due to its association with marijuana, its biological cousin. Though hemp and marijuana belong to the same species of plant, Cannabis sativa, they each have a unique chemistry, with very different characteristics and effects. Marijuana possesses tetrahydrocannabinol, or THC, the chemical that produces the characteristic high that is associated with cannabis. Hemp, on the other hand, is a strain of the cannabis plant that contains virtually no THC, and neither it nor the CBD derived from it can produce a high sensation.

This article was republished with permission from The Conversation, a news site dedicated to sharing ideas from academic experts. It represents the research-based findings and thoughts of Kent E Vrana, Professor and Chair of Pharmacology, Penn State.

As a professor and chair of the department of pharmacology at Penn State, I have been following research developments with CBD closely and have seen some promising evidence for its role in treating a broad range of medical conditions.

While there is growing evidence that CBD can help with certain conditions, caution is needed. Rigorous scientific studies are limited, so it is important that the marketing of CBD products does not get out ahead of the research and of robust evidence.

Unpacking the Hype Behind CBD

The primary concern about CBD marketing is that the scientific community is not sure of the best form of CBD to use. CBD can be produced as either a pure compound or a complex mixture of molecules from hemp that constitute CBD oil. CBD can also be formulated as a topical cream or lotion, or as a gummy, capsule or tincture.

Guidance, backed by clinical research, is needed on the best dose and delivery form of CBD for each medical condition. That research is still in progress.

But in the meantime, the siren’s call of the marketplace has sounded and created an environment in which CBD is often hyped as a cure-all – an elixir for insomnia, anxiety, neuropathic pain, cancer and heart disease.

Sadly, there is precious little rigorous scientific evidence to support many of these claims, and much of the existing research has been performed in animal models.

CBD is simply not a panacea for all that ails you.

Childhood Seizure Disorders

Here’s one thing that is known: Based on rigorous trials with hundreds of patients, CBD has been shown to be a proven safe and effective drug for seizure disorders, particularly in children.

In 2018, the U.S. Food and Drug Administration granted regulatory approval for the use of a purified CBD product sold under the brand name Epidiolex for the treatment of Lennox-Gastaut and Dravet syndromes in children.

These two rare syndromes, appearing early in life, produce large numbers of frequent seizures that are resistant to traditional epilepsy treatments. CBD delivered as an oral solution as Epidiolex, however, can produce a significant reduction – greater than 25% – in the frequency of seizures in these children, with 5% of the patients becoming seizure-free.

More than 200 Scientific Trials

CBD is what pharmacologists call a promiscuous drug. That means it could be effective for treating a number of medical conditions. In broad strokes, CBD affects more than one process in the body – a term called polypharmacology – and so could benefit more than one medical condition.

As of early 2023, there are 202 ongoing or completed scientific trials examining the effectiveness of CBD in humans on such diverse disorders as chronic pain, substance use disorders, anxiety and arthritis.

In particular, CBD appears to be an anti-inflammatory agent and analgesic, similar to the functions of aspirin. This means it might be helpful for treating people suffering with inflammatory pain, like arthritis, or headaches and body aches.

CBD also holds potential for use in cancer therapy, although it has not been approved by the FDA for this purpose.

The potential for CBD in the context of cancer is twofold:

First, there is evidence that it can directly kill cancer cells, enhancing the ability of traditional therapies to treat the disease. This is not to say that CBD will replace those traditional therapies; the data is not that compelling.

Second, because of its ability to reduce pain and perhaps anxiety, the addition of CBD to a treatment plan may reduce side effects and increase the quality of life for people with cancer.

The Risks of Unregulated CBD

While prescription CBD is safe when used as directed, other forms of the molecule come with risks. This is especially true for CBD oils. The over-the-counter CBD oil industry is unregulated and not necessarily safe, in that there are no regulatory requirements for monitoring what is in a product.

What’s more, rigorous science does not support the unsubstantiated marketing claims made by many CBD products.

In a 2018 commentary, the author describes the results of his own study, which was published in Dutch (in 2017). His team obtained samples of CBD products from patients and analyzed their content. Virtually none of the 21 samples contained the advertised quantity of CBD; indeed, 13 had little to no CBD at all and many contained significant levels of THC, the compound in marijuana that leads to a high – and that was not supposed to have been present.

In fact, studies have shown that there is little control of the contaminants that may be present in over-the-counter products. The FDA has issued scores of warning letters to companies that market unapproved drugs containing CBD. In spite of the marketing of CBD oils as all-natural, plant-derived products, consumers should be aware of the risks of unknown compounds in their products or unintended interactions with their prescription drugs.

Regulatory guidelines for CBD are sorely lacking. Most recently, in January 2023, the FDA concluded that the existing framework is “not appropriate for CBD” and said it would work with Congress to chart a way forward. In a statement, the agency said that “a new regulatory pathway for CBD is needed that balances individuals’ desire for access to CBD products with the regulatory oversight needed to manage risks.”

As a natural product, CBD is still acting as a drug – much like aspirin, acetaminophen or even a cancer chemotherapy. Health care providers simply need to better understand the risks or benefits.

CBD may interact with the body in ways that are unintended. CBD is eliminated from the body by the same liver enzymes that remove a variety of drugs such as blood thinners, antidepressants and organ transplant drugs. Adding CBD oil to your medication list without consulting a physician could be risky and could interfere with prescription medications.

In an effort to help prevent these unwanted interactions, my colleague Dr. Paul Kocis, a clinical pharmacist, and I have created a free online application called the CANNabinoid Drug Interaction Resource. It identifies how CBD could potentially interact with other prescription medications. And we urge all people to disclose both over-the-counter CBD or recreational or medical marijuana use to their health care providers to prevent undesirable drug interactions.

In the end, I believe that CBD will prove to have a place in people’s medicine cabinets – but not until the medical community has established the right form to take and the right dosage for a given medical condition.