On September 24, 2019 Provectus (OTCQB: PVCT) reported that data from an ongoing clinical trial of lysosomal-targeting cancer immunotherapy PV-10 in combination with checkpoint inhibition for the treatment of advanced cutaneous melanoma (NCT02557321) will be presented on two poster presentations at the SMR 2019 Congress (the Society for Melanoma Research annual meeting), held in Salt Lake City, Utah from November 20-23, 2019 (Press release, Provectus Biopharmaceuticals, SEP 24, 2019, View Source [SID1234539748]). The accepted abstracts are:
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"Results from a checkpoint inhibition-naive cohort of patients in a phase 1b study of PV-10 and anti-PD-1 in advanced melanoma" (the study’s main cohort), and
"Initial results from a phase 1b study of PV-10 and anti-PD-1 in melanoma refractory to checkpoint inhibition" (the study’s first expansion cohort).
Intralesional (aka intratumoral) injection with PV-10 can yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells.1-4
About PV-10
Better drugging of the druggable and effective drugging of the undruggable starts with the cancer cell and continues with the activation of the immune system in the tumor microenvironment (TME). PV-10 may unlock any TME because it is the first lysosomal-targeting cancer drug. Nearly all types of eukaryotic cells, both diseased and normal, contain lysosomes, which are the central organelles for intracellular degradation of biological materials (e.g., the ‘stomach’ of the cell, the ‘recycle bin’ of the cell, the ‘trash bin,’ etc.).
Provectus has shown that PV-10 selectively accumulates in the lysosomes of only cancer cells upon contact, disrupts them, and causes the cancer cells to die1,5, a mechanism that has been reproduced by external collaborators6. Provectus, external collaborators, and independent researchers have further shown that PV-10 treatment (RB application) can trigger each of the three major and distinct lysosomal cell death pathways of apoptosis, autophagy, and necrosis, and do so in a disease-dependent manner.2,3,6-9
PV-10 causes acute oncolytic destruction of injected tumors (i.e., cell death), mediating several identified immune signaling pathways to date, such as the release of danger-associated molecular patterns (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 a third pathway currently being investigated that plays an important role in innate immunity. PV-10 is the first cancer drug that may facilitate multiple, temporally-distinct, immune system signaling pathways.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), and preclinical study for pediatric solid tumor cancers (like neuroblastoma5, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma) and pediatric blood cancers (like leukemia).
Orphan drug designation status has been granted to PV-10 by the U.S. Food and Drug Administration for the treatments of metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.
PV-10 is an injectable formulation of rose bengal disodium (RB) (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein disodium salt), which is a small molecule halogenated xanthene and PV-10’s active pharmaceutical ingredient. PV-10 drug product is a bright rose red solution containing 10% w/v RB in 0.9% saline for injection, which is supplied in single-use glass vials containing 5 mL (to deliver) of solution and administered without dilution to solid tumors via intratumoral injection.
Provectus’ intellectual property (IP) includes a family of US and international 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 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.
The Company’s IP also includes a family of US and international 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 9,107,887, 9,808,524, and 9,839,688, and a US patent application number is 15/804,357 (allowed, but not yet awarded), with expirations ranging from 2032 to 2035.