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Provectus Biopharmaceuticals’ PV-10 Data Show Exceptional Complete Response Rates in Refractory Melanoma Patients

Source: Market Watch, May 2014

Study Examines Complete Response and Induced Immune Response That May Produce “Bystander Effect” Seen in PatientsData Will Be Featured in Two Highlighted Poster Presentations at the American Society of Clinical Oncology (ASCO) Annual Meeting, McCormick Place in Chicago, IL, June 2, 2014

A development-stage oncology and dermatology biopharmaceutical company, announced today that data on its investigational agent PV-10 for intralesional (IL) treatment of locally advanced cutaneous melanoma will be featured in two presentations in the Poster Highlights Session, Melanoma/Skin Cancers, on June 2, 2014 during the American Society of Clinical Oncology (ASCO) annual meeting to be held at McCormick Place, Chicago, IL. These presentations show that IL PV-10 (a) can potentially offer cancer patients control of their cutaneous symptoms and (b) elicit a systemic anti-tumor immune response that may lead to response of uninjected lesions (the “bystander effect” that has been observed in prior clinical studies of PV-10).

The first highlighted poster, presented by Sanjiv S. Agarwala, MD, of the St. Luke’s Cancer Center, based upon abstract #132320 (permanent ID 9027), is entitled “Efficacy of intralesional rose bengal in patients receiving injection in all existing melanoma in phase II study PV-10-MM-02.”

The second highlighted poster, presented by Amod Sarnaik, MD, of Moffitt Cancer Center, based upon abstract #132288 (permanent ID 9028), is entitled “Assessment of immune and clinical efficacy after intralesional PV-10 in injected and uninjected metastatic melanoma lesions.”

Dr. Agarwala and co-authors from 7 prominent melanoma centers in the United States and Australia studied the safety and efficacy of IL PV-10 in an 80 patient international, multicenter, single arm phase 2 trial. A subgroup analysis of 28 patients with all existing melanoma lesions injected and an additional 26 patients with only 1-2 uninjected bystander lesions showed that these patients experienced an exceptionally high rate of response. The best overall response rate (BORR) in the 28-patient “all treated” subgroup was 71% (confidence interval of 51-87%), with 50% complete response (CI 31-69%). Among the 54 patients in both of these subgroups (i.e., patients who had all of their disease monitored in the study), CR (Complete Response) was achieved in 232 of 363 injected lesions (64% CR). Furthermore, CR was achieved in 121 lesions after a single injection of PV-10; 84 lesions required 2 injections to achieve CR; 22 lesions required 3 injections; and 5 lesions required all four allowed 4 injections.

Dr. Agarwala said, “The high rate of symptom control in refractory patients with disease limited to the skin, manifested in CR of all monitored disease after minimal intervention, is the basis for a pending breakthrough therapy designation application for PV-10. Although the primary ablative effect is responsible for CR in injected lesions, durability of response and bystander response observed in this study implicate an immunologic mechanism of action secondary to ablation.”

In the Moffitt poster, Dr. Sarnaik and co-authors report interim results of a pilot clinical trial designed to investigate the immunologic basis of this bystander response. In this single institution translational study, a target lesion and a bystander were biopsied prior to treatment of the target lesion with PV-10. Both lesions were then resected within 7-14 days of target lesion injection and compared to pre-treatment biopsies. Peripheral blood was also collected pre-treatment, at the time of resection and at day 28. The researchers note “treatment with IL PV-10 led to pCR (pathologic complete response) in the post-treatment biopsies of both PV-10 injected and uninjected study lesions in 4 of the 8 patients, and all 8 exhibited at least partial regression of the injected lesion.” The abstract continues, “six of the 8 patients had metastatic disease refractory to previous ipilimumab, anti-PD-1 and/or vemurafenib therapy.” Based on T cells isolated from the peripheral blood of the patients, the authors conclude that, “IL PV-10 treatment can lead to systemic anti-melanoma immunity and pCR in injected and uninjected lesions including treatment-refractory tumors.”

Craig Dees, PhD, CEO of Provectus said, “Taken together, these posters indicate that, with minimal intervention, PV-10 can rapidly eliminate refractory cutaneous melanoma lesions. IL PV-10 is also associated with an increase in important circulating immune cells specific to the injected lesion, potentially explaining the high rate of bystander lesion regression seen in our clinical trials of PV-10 in locally advanced melanoma patients.

Dees continued, “The duration of response and the bystander response reported in the phase 2 trial was beyond the scope of simple tumor ablation. Last year Moffitt published data from mice showing increased anti-tumor T cell responses, and this year at ASCO they have bridged that nonclinical finding to the same phenomenon in man. It is unprecedented for a small molecule ablative agent to have this kind of immune system activity detectable in peripheral blood of patients. The 1-2 punch from PV-10 (rapidly reducing tumor burden and producing immune system stimulation) is presumably the underlying driver of these durable complete responses in patients with cutaneous melanoma.”

Provectus submitted an application in March 2014 to the FDA for breakthrough therapy designation for PV-10 based on the results from its phase 2 clinical study related to metastatic melanoma and is researching efficacy of PV-10 for other indications, including liver and breast cancers.

About Moffitt Cancer Center

Located in Tampa, Moffitt is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers , a distinction that recognizes Moffitt’s excellence in research, its contributions to clinical trials, prevention and cancer control. Moffitt is the No. 1 cancer hospital in Florida and has been listed in U.S. News & World Report as one of “America’s Best Hospitals” for cancer since 1999. With more than 4,200 employees, Moffitt has an economic impact on the state of nearly $2 billion. For more information, visit , and follow the Moffitt momentum on Facebook , Twitter and YouTube .

About St. Luke’s University Health Network

St. Luke’s University Health Network is a nationally recognized, regional, integrated network of non-profit hospitals, physicians and other health-related organizations providing care in Lehigh, Northampton, Carbon, Schuylkill, Bucks, Montgomery, Berks and Monroe counties in Pennsylvania, and in Warren County, New Jersey. St. Luke’s provides cancer services throughout its network, providing care to approximately 2,400 patients each year. St. Luke’s has three comprehensive outpatient cancer centers in Allentown, Bethlehem and Easton (Anderson Campus), and also provides cancer services in Quakertown, Coaldale and Warren County, NJ.

St. Luke’s Cancer Center is staffed by a team of fellowship-trained cancer experts specializing in surgical oncology, medical oncology, radiation oncology, gynecologic oncology, thoracic surgery, urologic surgery and neurosurgical oncology. The Center emphasizes patient satisfaction and treats all types of cancer, including: abdominal, bones and joints, brain and spine, breast, colon and rectum, cancer of the digestive system, gynecologic, head and neck, liver, lung/thoracic, lymphoma/leukemia, melanoma, prostate, thyroid/endocrine system and urinary. The Center offers advanced programs for melanoma, lung, breast, brain and spine, prostate, gynecological and gastrointestinal cancers.

About Provectus Biopharmaceuticals, Inc.

Provectus Biopharmaceuticals specializes in developing oncology and dermatology therapies. Its novel oncology drug PV-10, (a formulation of the small molecule ablative agent rose bengal disodium) 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, . For additional information about Provectus please visit the Company’s website at or contact Porter, LeVay & Rose, Inc.

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