PV-10® Abstract Previously Accepted for Presentation at Terminated American Association for Cancer Research (AACR) Annual Meeting 2020
KNOXVILLE, TN, March 17, 2020 (GLOBE NEWSWIRE) -- Provectus (OTCQB: PVCT) today said that data from ongoing research into investigational lysosomal-targeting cancer immunotherapy PV-10 (rose bengal disodium) for the treatment of solid tumor and blood cancers had been accepted for presentation at the now terminated AACR Annual Meeting 2020, which was originally scheduled to be held April 24-29 in San Diego, California. Intratumoral injection with PV-10 yields immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells.1-4
The details of the previously accepted abstract were:
- Title: Association of heat shock proteins as chaperone for STING: A potential link in a key immune activation mechanism revealed by the novel anti-cancer agent PV-10
- Abstract Control Number: 8165
- Session Category: Clinical Research
- Session Title: Inflammation, Immunity, and Cancer/Modifiers of the Tumor Microenvironment 1
- Poster Board Number: 6
- Permanent Abstract Number: 5393
This work was led by Aru Narendran, MD, PhD and his team of researchers at the Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC) Laboratory for Pre-Clinical and Drug Discovery Studies at the University of Calgary (Canada).
On March 10th, , the AACR Annual Meeting 2020 was terminated based on their evaluation of currently available information related to the novel coronavirus (COVID-19) outbreak and a rescheduled meeting is being planned for later this year.
About PV-10
PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver (including metastatic neuroendocrine tumors and metastatic uveal melanoma). PV-10 is also undergoing preclinical study for pediatric solid tumor cancers (like neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma) and pediatric blood cancers (like leukemia).5,6
Tumor Cell Lysosomes as the Seminal Drug Target
Lysosomes are the central organelles for intracellular degradation of biological materials, and nearly all types of eukaryotic cells have them. Discovered by Christian de Duve, MD in 1955, lysosomes are linked to several biological processes, including cell death and immune response. In 1959, de Duve described them as ‘suicide bags’ because their rupture causes cell death and tissue autolysis. for discovering and characterizing lysosomes, which are also linked to each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.
Building on the Discovery, Exploration, and Characterization of Lysosomes
Cancer cells, particularly advanced cancer cells, are very dependent on effective lysosomal functioning.7 Cancer progression and metastasis are associated with lysosomal compartment changes8,9, which are closely correlated with (among other things) invasive growth, angiogenesis, and drug resistance10.
PV-10 selectively accumulates in the lysosomes of cancer cells upon contact, disrupts them, and causes them to die. The physicochemical properties of lysosomes trap PV-10. A lumenal pH of 4.5 to 5.0 is ideal for the conversion of the hydrophilic RB salt into the hydrophobic (lipophilic) lactone version. Provectus1,11, external collaborators5, and other researchers12-14 have independently shown that PV-10 (RB) triggers each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.
Cancer Cell Autolytic Death via PV-10: PV-10 inducing autolytic cell death, or death by self-digestion, in Hepa1-6 murine HCC cells (ethidium homodimer [ED-1] stains DNA, but is excluded from intact nuclei; lysosensor green [LSG] stains intact lysosomes; the video is provided in 30-second frames; the event has a duration of approximately one hour). Exposure to PV-10 triggers the disruption of lysosomes, followed by nucleus failure and autolytic cell death. Identical responses have been shown by the Company in HTB-133 human breast carcinoma (which ; this event has a duration of approximately two hours) and H69Ar human multidrug-resistant small cell lung carcinoma. Cancer cell autolytic cell death was reproduced by research collaborators from POETIC using relapsed and refractory human pediatric neuroblastoma cells .5
Immune Signaling Pathways: PV-10 causes acute oncolytic destruction of injected tumors (i.e., cell death), mediating several identified immune signaling pathways studied to date, such as the release of danger-associated molecular pattern molecules (DAMPs) and tumor antigens that initiate an immunologic cascade where local response by the innate immune system facilitates systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. Other mediated immune signaling pathways that have been identified include poly-ADP ribose polymerase (PARP) cleavage and, now, stimulator of interferon genes (STING), which plays an important role in innate immunity. PV-10 is the first cancer drug that may facilitate multiple, complementary, immune system signaling pathways.15
Orphan Drug Designations (ODDs)
ODD status has been granted to PV-10 by the U.S. Food and Drug Administration for the treatments of , , , and .
Drug Product
Rose bengal disodium (RB) (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein disodium salt) is a small molecule halogenated xanthene and PV-10’s active pharmaceutical ingredient. PV-10 drug product is a formulation of 10% w/v RB in 0.9% saline, supplied in single-use glass vials containing 5 mL (to deliver) of solution, and administered without dilution to solid tumors via intratumoral injection.
Intellectual Property (IP)
Provectus’ IP includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the process by which pharmaceutical grade RB and related xanthenes are produced, reducing the formation of previously unknown transhalogenated impurities that exist in commercial grade RB in uncontrolled amounts. The requirement to control these impurities is in accordance with International Conference on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are , , and , with expirations ranging from 2030 to 2031.
The Company's IP also includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the combination of PV-10 and systemic immunomodulatory therapy (e.g., anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents) for the treatment of a range of solid tumor cancers. US patent numbers are , , , and , with expirations ranging from 2032 to 2035.
About Provectus
Provectus Biopharmaceuticals, Inc. (Provectus or the Company) is a clinical-stage biotechnology company developing a new class of drugs based on an entirely- and wholly-owned family of chemical small molecules called halogenated xanthenes. Information about the Company’s clinical trials can be found at the NIH registry, . For additional information about Provectus, please visit the Company's website at .
References
1. Wachter et al. . Proceedings of SPIE 4620, 143, 2002.
2. Liu et al. . Oncotarget 7, 37893, 2016.
3. Qin et al. . Cell Death and Disease 8, e2584, 2017.
4. Liu et al. . PLoS One 13, e0196033, 2018.
5. Swift et al. . OncoTargets and Therapy 12, 1293, 2019.
6. Swift et al. . 2018 ASCO Annual Meeting, J Clin Oncol 36, 2018 (suppl; abstr 10557).
7. Piao et al. . Annals of the New York Academy of Sciences. 2016; 1371(1): 45.
8. Nishimura et al. . Pathology Oncology Research. 1998; 4(4): 283.
9. Gocheva et al. . Genes & Development. 2006; 20(5): 543.
10. Fehrenbacher et al. . Cancer Research. 2005; 65 (8): 2993.
11. Wachter et al. . Proceedings of SPIE 4622, 112, 2002.
12. Koevary. . International Journal of Physiology, Pathophysiology and Pharmacology 4(2), 99, 2012.
13. Zamani et al. . Journal of Immunotoxicology, 11(4), 367, 2014.
14. Luciana et al. . Cancer Biology & Therapy, 10:10, 1048, 2010.
15. Panzarini et al. . Cell Death & Disease 2, 169, 2011.
Trademarks
PV-10® is a registered trademark of Provectus, Knoxville, Tennessee, U.S.A.
FORWARD-LOOKING STATEMENTS: This release contains forward-looking statements as defined under U.S. federal securities laws. These statements reflect management's current knowledge, assumptions, beliefs, estimates, and expectations and express management's current views of future performance, results, and trends and may be identified by their use of terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “will,” and other similar terms. Forward-looking statements are subject to a number of risks and uncertainties that could cause our actual results to materially differ from those described in the forward-looking statements. Readers should not place undue reliance on forward-looking statements. Such statements are made as of the date hereof, and we undertake no obligation to update such statements after this date. No claims with respect to PV-10, Provectus’ investigational drug for oncology, or PH-10, the Company’s investigational drug for dermatology, are intended regarding safety or efficacy in the context of any forward-looking statements made in this press release.
Risks and uncertainties that could cause our actual results to materially differ from those described in forward-looking statements include those discussed in our filings with the Securities and Exchange Commission (including those described in Item 1A of ).
###
Contact:
Provectus Biopharmaceuticals, Inc.
Heather Raines, CPA
Chief Financial Officer
Phone: (866) 594-5999
