Exploratory Data Analyses of Intralesional PV-10 Clinical Phase 2 Study Results Presented at ECC 201


Exploratory Data Analyses of Intralesional PV-10 Clinical Phase 2 Study Results Presented at ECC 2013 Demonstrate Effective Locoregional Disease Control and Support Systemic Immunologic Activity in Refractory Metastatic Melanoma

Blistering Adverse Event is Strong Predictor of Locoregional Disease Control

KNOXVILLE, Tenn.--(BUSINESS WIRE)-- Provectus Pharmaceuticals, Inc. (OTCQB:PVCT) (http://www.pvct.com), a development-stage oncology and dermatology biopharmaceutical company, presented detailed findings of several exploratory analyses of data from its completed Phase 2 study of intralesional PV-10 in metastatic melanoma during the Poster Session on "Melanoma and Skin Cancer" on Monday, September 30 at the European Cancer Congress 2013 (ECCO 17- ESMO-38 - ESTRO 32) in Amsterdam, The Netherlands.

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 potential for systemic side effects.

Sanjiv S. Agarwala, MD, Principal Investigator for the Phase 2 trial of PV-10, and Chief of Medical Oncology and Hematology at St. Luke's Hospital and Health Network in Bethlehem, PA, presented the poster which was based on Abstract No. 3.755, entitled, "Locoregional Disease Control in Metastatic Melanoma: Exploratory Analyses From Phase 2 Testing of Intralesional Rose Bengal," authored by S.S. Agarwala, J.F. Thompson, B.M. Smithers, M.I. Ross, B.J. Coventry, D.R. Minor, C.R. Scoggins, J. M. Singer and E.A. Wachter.

The international, multicenter, Phase 2 study examined the effect of up to 4 treatment cycles of intralesional (IL) PV-10 in 80 subjects with AJCC Stage IIIB-IV melanoma. All subjects had locally advanced disease refractory to a median of 6 previous interventions. Intralesional PV-10 tumor ablation provided, after a median of 2 treatment cycles, rapid locoregional disease control. A high rate of response in untreated bystander lesions and transient cutaneous locoregional blistering were consistent with the novel tumor-specific immune mediated mechanism of action of PV-10.

In the phase 2 study, up to 10 cutaneous or subcutaneous target lesions and up to 10 additional non-target lesions received intralesional PV-10 at day 0 and could be reinjected as necessary at weeks 8, 12 and 16 if tumor tissue remained. Up to 2 additional cutaneous or subcutaneous lesions were left untreated to assess bystander response. The primary endpoint in the single arm trial was best overall response rate (BORR) judged by modified RECIST in each subject's up to 10 target lesions.

Results showed that for all subjects, BORR was 51% (26% CR, 25% PR) with the amount of tumor burden accessible to PV-10 injection prognostic for outcome. In the majority of subjects (68%) the lesions treated with PV-10, together with the up to two untreated bystander lesions, constituted all disease present, and these subjects achieved a BORR of 63%. In subjects where all disease was treated (35% of subjects) BORR further increased to 71% (with 50% achieving CR).

Additional new data analyses explored response rates relative to locoregional blistering, a specific reaction observed in 40% of subjects. This phenomenon generally occurred within seven days of PV-10 injection but with no clear pattern of incidence, and typically resolved within four weeks. Appearance of this potentially immune-mediated effect was strongly predictive of outcome. Subjects who developed blisters had 66% BORR (44% CR) vs. 42% (15% CR) for those not developing blisters. The correlation between occurrence of blisters and locoregional disease control was even stronger: among subjects with blisters, 91% achieved stable disease or better vs. 54% of subjects without blisters.

The poster presentation highlighted mounting clinical and non-clinical evidence that PV-10 induces systemic immunologic activity. The clinical evidence includes: the inverse relationship of response to untreated tumor burden; the potential immune related adverse event of locoregional blistering; the strong correlation between objective response (OR) of target lesions and regression of untreated bystander lesions; and regression or stasis of untreated visceral disease in Stage IV subjects with OR of their injected target lesions. Non-clinical evidence cited by the researchers in support of systemic immunologic activity includes: synergy of PV-10 with anti-CTLA-4 therapy (presented at the AACR Annual Meeting 2013); and regression of synchronous flank and visceral tumors and adoptive transfer of immunity via T cells (PloS One 8, e68561, 2013).

The poster can be viewed by clicking on the following link: http://www.pvct.com/publications/Provectus-ECCO-2013.pdf

The well-controlled trial demonstrated, via the self-evident ablative effect, that intralesional PV-10 provides a viable strategy to maintain long-term locoregional control of melanoma in patients whose cutaneous and subcutaneous melanoma has recurred. Additionally, the mounting evidence of induction of a tumor-specific immunologic effect, secondary to the PV-10 ablative effect, indicates that treatment with PV-10 has the potential to delay, reverse or prevent progression to life-threatening visceral disease. In addition to the 80 participants in the study, the researchers noted that over 90 additional melanoma patients have been treated with PV-10 under expanded access.

Dr. Craig Dees, PhD, CEO of Provectus, stated, "The researchers concluded that PV-10 has a unique immuno-chemoablative profile that offers significant potential due to several important attributes. First, its safety and efficacy compare favorably with existing and emerging therapies. Second, its safety profile makes it an attractive candidate as a combination strategy for treatment of advanced disease. And finally, it provides a powerful combination of rapid reduction of tumor burden with induction of tumor-specific immune response that can achieve rapid disease control in refractory patients with locally advanced melanoma."

Dr. Dees continued, "Melanoma patients and their caregivers experience profound discouragement upon recurrence of the serious skin manifestations of this disease. The investigators on this study describe the effect of PV-10 as 'rapid, durable response' but as the photographs have documented, many of the PV-10 treated tumors almost appear to have never been present. PV-10 was only injected intermittently, when tumors were present during the first 16 weeks of the study, in stark contrast to typical clinical studies where treatment is given until either resistance is engendered or patients experience unacceptable toxicity. We are gratified that response to PV-10 was demonstrated consistently across all study centers, with minimal intervention in patients refractory to multiple prior treatments. PV-10's unique mechanism of action, alone or in combination with existing or emerging therapy, has the potential to shift the paradigm in oncology, where an intermittent intervention can dramatically reduce disease burden and may prod the immune system into preventing or arresting the formation of life threatening metastases."

About ECCO

As founding members of ECCO - the European CanCer Organisation, ESMO, ESTRO, ESSO, EACR, EONS and SIOPE, have joined together again to form a powerful combination of seven senior organisations endorsing multidisciplinarity as the way forward to best improve the prevention, diagnosis, treatment and care of cancer patients.

This renowned biennial series of multidisciplinary European Cancer Congresses are recognized as the premier cancer meetings in Europe. The 17th ECCO - 38th ESMO - 32nd ESTRO European Cancer Congress, held in Amsterdam from September 27 to October 1, 2013, brought together all partner organisations in their efforts to continue positioning multidisciplinarity as the way forward to best improve the prevention, diagnosis, treatment and care of cancer patients. The recognized multidisciplinary setting of the Congress provided ideal surroundings for participants to leverage knowledge, promote education and build awareness about oncology - placing the patient at the heart of all our efforts and discussions.

About Provectus Pharmaceuticals, Inc.

Provectus Pharmaceuticals 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.

Provectus Pharmaceuticals, Inc.
Peter R. Culpepper, CFO, COO
866-594-5999 #30
Porter, LeVay & Rose, Inc.
Marlon Nurse, DM, SVP - Investor Relations
Bill Gordon - Media Relations

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The article Exploratory Data Analyses of Intralesional PV-10 Clinical Phase 2 Study Results Presented at ECC 2013 Demonstrate Effective Locoregional Disease Control and Support Systemic Immunologic Activity in Refractory Metastatic Melanoma originally appeared on Fool.com.

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