KNOXVILLE, TN, -- Provectus (OTCQB: PVCT) today announced that the United States Patent and Trademark Office (USPTO) has allowed US patent (USP) application 15/804,357 for the combination of intratumoral 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. Intratumoral injection of oncolytic immunotherapy PV-10 can yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells.1-5 Drug development of PV-10 includes cutaneous melanoma and cancers of the liver, such as hepatocellular carcinoma, metastatic neuroendocrine tumors, and metastatic uveal melanoma, in both monotherapy and combination therapy settings.
This prospective new patent is the third continuation of USP 9,107,887, Provectus' first and foundational cancer combination therapy patent granted by the USPTO in 2015. It is also related to USP 9,808,524 and USP 9,839,688, which are also continuations and the Company's second and third cancer combination therapy patents granted by the USPTO in 2017. Pfizer, Inc. (Pfizer) is a co-assignee on all four awarded and allowed patents. No formal or informal agreement exists between Provectus and Pfizer regarding potential or possible patent economics.
Dominic Rodrigues, Vice Chair of the Company's Board of Directors, said, "This fourth addition to Provectus' cancer combination patent family represents our continued efforts to increase the potential commercial value of investigational cancer immunotherapy PV-10. We are grateful to Pfizer for their acquiescence as we pursue further patent protection of PV-10 as well as combinations of PV-10 with checkpoint inhibitor drugs."
Mr. Rodrigues added, "This pending new patent reinforces our clinical development strategy for combining PV-10 with checkpoint inhibitor drugs. From a cancer combination therapy perspective, global anti-PD-1 and anti-PD-L1 agents are essentially clinically interchangeable, in our view, and have no notable differences except pricing. We also believe that patients suffering from certain tumor types, like non-T cell inflamed and low tumor mutation burden ones, may benefit from the combination of PV-10, an anti-CTLA-4 drug, and an anti-PD-(L)1 drug."
PV-10 causes acute oncolytic destruction of injected tumors, releasing damage 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. T cell function can be further augmented by combining PV-10 with immune checkpoint inhibition.
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 cancers like neuroblastoma5, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.
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's active pharmaceutical ingredient is rose bengal disodium (RB) (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein disodium salt), a small molecule halogenated xanthene. 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 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 identify and control these substances is in accordance with International Conference on Harmonisation (ICH) guidelines for the manufacturing of active pharmaceutical ingredient that is suitable for clinical trial and commercial pharmaceutical use. USPs include 8,530,675 (awarded in 2013), 9,273,022 (2016) and 9,422,260 (2017), with expirations ranging from 2030 to 2031.
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, www.clinicaltrials.gov. For additional information about Provectus, please visit the Company's website at www.provectusbio.com.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Kenilworth, New Jersey, U.S.A.
OPDIVO® and YERVOY® are registered trademark of Bristol-Myers Squibb, New York, New York, 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," "would," "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.
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 our Annual Report on Form 10-K for the year ended December 31, 2018).
Provectus Biopharmaceuticals, Inc.
Heather Raines, CPA
Chief Financial Officer