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Provectus Announces PV-10's Assessment for Drug-Drug Interaction Potential is Subject of Article Published by Xenobiotica

PVCT, BIOGY

Provectus Biopharmaceuticals, Inc. (OTCQB:PVCT) (http://www.pvct.com), a development-stage oncology and dermatology biopharmaceutical company, and XenoTech, a preclinical CRO and pioneer in collaborative research surrounding in vitro drug metabolism and pharmacokinetics (DMPK) services, today announced that an article describing a study to determine the potential of rose bengal disodium to cause drug-drug interactions has been published by Xenobiotica, a peer-reviewed scientific journal that publishes comprehensive research papers on pharmacokinetics (the study of distribution, metabolism, disposition and excretion of drugs). The published research indicated that the risk of PV-10 causing clinically relevant drug-drug interactions is likely minimal. PV-10, a 10% solution of rose bengal that is currently under clinical investigation as a novel cancer therapeutic, is designed to selectively target and destroy cancer cells without harming surrounding healthy tissue, minimizing the potential for systemic side effects.

The study was undertaken prior to initiation of the now ongoing testing of PV-10 plus sorafenib (cohort 2) in a clinical trial of PV-10 intralesional injection in hepatocellular carcinoma patients taking a stable dose of sorafenib (ClinicalTrials.gov Identifier: NCT00986661). Sorafenib is a competitive inhibitor of cytochrome P450 (CYP) drug metabolism enzymes and is reliant on the UDP-glucuronosyltransferase (UGT) pathway for efficient clearance. CYP and UGT enzymes help to biotransform small lipophilic drugs like sorafenib into water-soluble excretable metabolites.

Provectus researchers collaborated with XenoTech’s experts to design the appropriate in vitro experiments necessary to assess the risk for potential liability when rose bengal is co-administered with other drugs in humans. Rose bengal, known for inducing singlet oxygen on exposure to light, can cause erroneous results in conventional in vitro test systems. These assay artifacts were shown to be test system dependent in DMPK studies. XenoTech scientists successfully tailored experiments to ascertain CYP and UGT inhibition potential in more appropriate model systems.

The lead author, Faraz Kazmi, a Senior Scientist at XenoTech said, “The FDA guidance for industry on drug-drug interactions requires an in vitro assessment of the potential liability for a new drug to engender drug-drug interactions. These experiments are important because they provide the basis for safe, rational clinical trial design and are important determinants toward the ultimate goal, which is patient safety.”

Dr. Craig Dees, PhD, CEO of Provectus said, "We were thrilled to collaborate with XenoTech on these important studies that not only support the PV-10 plus sorafenib study, but also have implications for treating melanoma patients. Provectus has been fortunate to work with many CROs with innovative scientists, but Xenotech stands out for their focus on the unique scientific problem as demonstrated in their rapid, expert assay development, suitable for publication in a peer reviewed journal.” Dr. Dees continued, “As we discuss our clinical results with regulatory authorities, we continue to be intensely committed to building all sections of the prescribing information for a future package insert for PV-10.”

Jason Neat, COO of XenoTech said, “We are very pleased with the expertise shown by our scientists. Rose bengal presented a unique challenge, but we rose up to meet that challenge and showed what XenoTech as a company is all about. Our customers get rapid results, but they also receive the context to be assured that those results will be meaningful in their development programs.”

The paper, titledIn vitro inhibition of human liver cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes by rose bengal: system-dependent effects on inhibitory potential,” was authored by Faraz Kazmi, Lois J. Haupt, Jennifer R. Horkman, Brian D. Smith and David B. Buckley from XenoTech, Eric A. Wachter, and Jamie M. Singer of Provectus.

About XenoTech

XenoTech is a Contract Research Organization with unparalleled experience and expertise in evaluating drug candidates as substrates, inhibitors and inducers of cytochrome P450, UGT and other drug metabolizing enzymes and drug transporters. The company offers a variety of in vitro contract studies for drug candidate evaluation, as well as an extensive selection of products for drug metabolism research. XenoTech’s product selection includes a wide-range of high quality standard reagents, from subcellular fractions and hepatocytes to recombinant enzymes, substrates and metabolites. The company can also prepare and deliver custom-designed products and services in response to client requests. XenoTech is based in Lenexa, Kansas, USA and has approximately 100 employees. For additional information, please refer to the company’s website at http://www.xenotechllc.com or call +1 (913) 438-7450.

About Provectus Biopharmaceuticals, Inc.

Provectus Biopharmaceuticals specializes in developing oncology and dermatology therapies. Its novel oncology drug PV-10 is designed to selectively target and destroy cancer cells without harming surrounding healthy tissue, significantly reducing potential for systemic side effects. Its oncology focus is on melanoma, breast cancer and cancers of the liver. The Company has received orphan drug designations from the FDA for its melanoma and hepatocellular carcinoma indications. Its dermatological drug PH-10 also targets abnormal or diseased cells, with the current focus on psoriasis and atopic dermatitis. Provectus has recently completed Phase 2 trials of PV-10 as a therapy for metastatic melanoma, and of PH-10 as a topical treatment for atopic dermatitis and psoriasis. Information about these and the Company's other 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.pvct.com or contact Porter, LeVay & Rose, Inc.

FORWARD-LOOKING STATEMENTS: The forward-looking statements contained herein are subject to certain risks and uncertainties that could cause actual results to differ materially from those reflected in the forward-looking statements. Readers are cautioned not to place undue reliance on these forward-looking statements, which reflect management's analysis only as of the date hereof. The company undertakes no obligation to publicly revise these forward-looking statements to reflect events or circumstances that arise after the date thereof.



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