Broad-spectrum Host- directed Therapeutics: CD45 Inhibitor as Antiviral
July 2024
NASDAQ: TNXP
Version P0576 July 15, 2024 (Doc 1476)
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Tonix Awarded $34M Contract from DTRA/DoD
DTRA contract is expected to advance development of Tonix's broad-spectrum oral antiviral program (TNX-4200) for medical countermeasures
• Other Transaction Agreement (OTA) with a potential for up to $34 million over five years
Objective: Develop an orally available small molecule that reduces CD45 enzymatic activity, with broad-spectrum protection against a range of viral families through the completion of Phase 1 clinical evaluation
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© 2024 Tonix Pharmaceuticals Holding Corp.
DoD Moves Beyond "One Drug, One Bug" Approach1,2
- The US Department of Defense (DoD) is moving beyond the traditional "one drug, one bug" approach to antivirals, and embracing the "one drug, multiple bugs" approach to protect against viral illness in warfighters
- The Defense Threat Reduction Agency (DTRA) is a division of the DoD that supports research to protect the warfighter
- DoD/DTRA collaborate with commercial partners to translate fundamental discoveries into products
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1Vergun, D. DOD News. January 10, 2023. DoD aims to shield warfighters from novel biological agents. https://www.defense.gov/News/News-Stories/Article/Article/3261095/dod-aims-to-shield-warfighters-from-novel-biological-agents
2US Department of Defense, Chemical and Biological Defense Program, "Approach for Research, Development and Acquisition of Medical Countermeasure and Test Products, Dec. 2022.4https://media.defense.gov/2023/Jan/10/2003142624/-1/-1/0/APPROACH-RDA-MCM-TEST-PRODUCTS.PDF
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Broad-spectrum Host Directed Antiviral Drug Development vs Virus-specific Approaches
Conventional Approach | Broad Spectrum Antivirals1 |
Single Virus Family | Broad Spectrum | ||||
Virus-Targeted2 | Virus-Targeted | Host-Targeted | |||
Drug | Virus | Drug | Virus | Drug | Virus |
Biktarvy® | HIV | Veklury® | COVID | Intron-A® | Hep-C |
tenofovir/ | Remdesivir | SARS-CoV-2 | Pegasys® | ||
emtricitabine | interferon-alpha | ||||
Sovaldi® | Hep-C | Paxlovid® | COVID | ||
Sofosbuvir | nirmatrelvir | SARS-CoV-2 | |||
/ritonavir | |||||
Valtrex® | Herpes simplex | Ribavirin | Hep-C, RSV | ||
Valacyclovir | and varicella | ||||
Arestvy® | Smallpox | Tembexa® | Smallpox | ||
Tecovirimat | brincidofovir | ||||
Tamiflu® | Influenza | ||||
oseltamivir | |||||
Host-targetedbroad-spectrum antivirals is a new and emerging category
1Bekerman E, and Einav, S. Science. 2015 348(6232):282-3. doi: 10.1126/science.aaa3778.
2Examples: not a complete list
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Enhancing Viral Immunity Has the Potential to Protect Against Viral Diseases
Too Little
Immune Suppression
Humira (adalimumab)
Enbrel (etanercept)
Rituxan (Rituximab)
Dupixent (dupilumab)
Keytruda (pembrolizumab)
Opdivo (nivolumab)
Intron A (interferon alpha -2a)
Pegasys (interferon alpha -2a)
Spectrum of Immunity
Therapeutic Zone
Tone down the | Rev up the |
immune system | immune system |
to treat: | to treat: |
Autoimmunity examples: | Cancer examples: |
Humira® | Keytruda® |
Enbrel® | Opdivo® |
Rituxan® | Viral disease examples: |
Allergy examples: | Intron A® |
Dupixent® | Pegasys® |
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Too Much
Autoimmunity
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Enhancing Viral Immunity by Inhibiting CD45 Phosphatase
- CD45 is a transmembrane protein tyrosine phosphatase (PTPase) expressed on most hematopoietic cells, including T lymphocytes
- CD45 regulates receptor signaling pathways, particularly T cell activation
- It dephosphorylates the negative regulatory tyrosine kinases (e.g., lck and src)
- Decreased levels of CD45 enhance antiviral1 and antibacterial immunity in animals2
- Oral small-molecule inhibitors of CD45 have the potential to enhance antiviral immunity3-5
Goal: Develop an orally available small molecule that reduces
CD45 enzymatic activity
CD45 modulating host-directed antivirals would be an entirely new class of medicines
1Panchal RG, et al., Cell Host Microbe. 2009 6(2):162-73. doi: 10.1016/j.chom.2009.07.003. PMID: 19683682.
2Panchal RG, et al. J Biol Chem. 2009 284(19):12874-85. doi: 10.1074/jbc.M809633200
3Miski M, et al. Bioorg Med Chem Lett. 1995 5(14):1519-22. doi: 10.1016/0960-894X(95)00250-W.
4Hamaguchi T, et al. Bioorg Med Chem Lett. 2000 10(23):2657-60. doi: 10.1016/s0960-894x(00)00539-4. PMID: 11128645.
5Carr G, et al. Methods. 2014. 65(2):229-38, doi: 10.1016/j.ymeth.2013.09.007.
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Kinases Enhance and Phosphatases Modulate Immune Responses
Kinasesenhance | CD45 phosphatase |
immune responses | modulates |
immune responses |
Kinasesadd phosphate "P" to | CD45 phosphatase |
removes phosphate "P" | |
signaling molecules | |
From signaling molecules | |
Panchal RG, et al., .J Biol Chem. 2009 May 8;284(19):12874-85. doi: 10.1074/jbc.M809633200. Epub 2009 Mar 6.PMID: 19269962
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Phosphatase Inhibitors Decrease Enzymatic Activity of CD45 and Potentially Enhance Viral Immunity
CD45 phosphatase
Kinasesenhance immune responses
Panchal RG, et al. J Biol Chem. 2009 284(19):12874-85. doi: 10.1074/jbc.M809633200.© 2024 Tonix Pharmaceuticals Holding Corp.
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TNX-4200: Orally Available CD45 Antagonists
- Tonix is exploiting regenerative AI and computational biology to identify modulators of CD45 expression and inhibitors of CD45 function to develop candidate broad- spectrum antiviral drugs1
Goal: broad spectrum antivirals
CD45 modulating host-directed antivirals would be an entirely new class of medicines
- Drugs that strengthen the body's immunity and protect against viral illness are called "host-directed" antivirals2,3
1Panchal RG, et al. J Biol Chem. 2009 284(19):12874-85. doi: 10.1074/jbc.M809633200
2Radoshitzky SR, et al., PLoS Pathog. 2016 Mar 31;12(3):e1005466. doi: 10.1371/journal.ppat.1005466. eCollection 2016 PMID: 27031835
3Loureiro ME, et al., PLoS Pathog. 2018 Jul 12;14(7):e1007125. doi: 10.1371/journal.ppat.1007125. eCollection 2018 Jul.PMID: 30001425
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Tonix Pharmaceuticals Holding Corp. published this content on 15 July 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 16 July 2024 16:41:05 UTC.