On October 24, 2019 Provectus (OTCQB: PVCT) reported that data from an ongoing clinical trial of lysosomal-targeting, cancer immunotherapy PV-10 (rose bengal disodium) as a single-agent and in combination with standard of care checkpoint inhibition for the treatment of uveal melanoma metastatic to the liver (NCT00986661, single-center expansion cohort) will be presented on two poster presentations at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress 2019, held in Geneva, Switzerland from December 11-14, 2019 (Press release, Provectus Biopharmaceuticals, OCT 24, 2019, View Source [SID1234542496]). The accepted abstracts are:
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"A phase 1 study of percutaneous oncolytic rose bengal disodium for metastatic uveal melanoma patients with hepatic metastases – a single-center cohort summary," and
"Response Assessment of Metastatic Uveal Melanoma Treated with Rose Bengal Disodium."
PV-10 is administered percutaneously when targeting primary or metastatic tumors of the liver, such as hepatocellular carcinoma, metastatic colorectal cancer, metastatic neuroendocrine tumors, and metastatic uveal melanoma. 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
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 does 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.