July 5, 2015

The Ever Expanding Clinical Value Proposition of PV-10


Agnostic:[1],[2],[3] “Compatible” with all disease presentations; i.e., PV-10 ablates any tumor tissue on which it has been tested

Pharmacokinetics:[1],[4] Comparable and consistent

Compare the pharmacokinetics portion of Provectus' 2015 ESMO GI liver poster with that of the company's ASCO 2015 melanoma poster:

Liver Cancer, 2015 ESMO GI
Click to enlarge.
Click to enlarge.
Melanoma, 2010 ASCO
Click to enlarge.

Primary Ablative Mechanism of Action:[5] Ablation in 1-2 hours. Kills cancer tumors into which it is injected by selectively passing through cell membranes and accumulating in lysosomes to force cell death with no biochemical action or effect

Secondary Immunologic Activation Mechanism of Action:[6] Immunomodulation in 1-2 weeks. Cell death resulting from local tumor treatment (injection) attracts tumor-specific T cells and causes an up-regulating immune effect, which leads to a systemic, tumor-specific immune response in untreated (“bystander”) tumors and distant disease

Use:[7] Simple to store, handle, and use and reuse

Safety:[2],[7],[8] Modest, local, transient toxicity that is predominantly confined to the injection site, and minimal-to-no systemic toxicity

Local Efficacy:[1],[2],[7] Rapid, durable, complete tumor destruction, and induction of antigen release in injected lesions

Tissue Sparing:[7] Prompt, complete healing of injected lesion sites after tumor destruction

Systemic Efficacy:[6],[7],[9] Reliable, reproducible induction of regional and system immune effects capable of destroying, regardless of prior treatments, (i) occult tumor cells, (ii) “bystander” lesions and (iii) distant metastatic lesions

Multi-indication Viability:[1],[6],[9],[10] More than 240 treated cancer patients have been treated:12 in a Phase 1 recurrent breast cancer study, at least 13 in a Phase 1 hepatocellular carcinoma & metastatic liver cancer study, 20 in a Phase 1 melanoma study, 80 in a Phase 2 melanoma study, at least 100 patients treated as of 2013 year-end in a compassionate use program, and at least 10 in an investigator-initiated study of PV-10 chemoablation followed by radiotherapy. Independent third-party preclinical work has been carried out on breast cancer, melanoma and colon cancer.

Orthogonal:[11],[12] Low risk of clinically relevant drug-drug interactions

Independently Reproduced:[6],[9],[13] Apoptosis, Tissue and cell selectivity, Clinically relevant local-regional and systemic effects, Tumor-specific immunity, T cells, Immune-mediated response, Multi-indication viability

[1] Goldfarb et al., Ann Oncol (2015) 26 (suppl 4): iv33.
[2] Thompson, Agarwala et al., Phase 2 Study of Intralesional PV-10 in Refractory Metastatic Melanoma, Annals of Surgical Oncology (2014)
[3] Sarnaik et al., J Clin Oncol 32:5s, 2014 (suppl; abstr 9028)
[4] Agarwala et al., J Clin Oncol 28:15s, 2010 (suppl; abstr 8534)
[5] Wachter et al., SPIE Proceedings 2002; 4620: 143-147.
[6] Toomey et al., PLoS1 2013, 8: e68561.
[7] Sondak, Moffitt Cancer Center, 4th European Post-Chicago Melanoma/Skin Cancer Meeting (2014)
[8] Rose Bengal, PV-10’s active pharmaceutical ingredient, has an established FDA safety profile for prior human use as an intravenous hepatic diagnostic (Robengatope®) and topical ophthalmic diagnostic (Rosettes® and Minims®)
[9] Pardiwala et al., Intralesional Injection of Rose Bengal Induces an Anti-tumor Immune Response and Potent Tumor Regressions in a Murine Model of Colon Cancer, Annals of Surgical Oncology, Volume 22, Supplement 1, February 2015
[10] Provectus website, page: Clinical Trials and Compassionate Use/PV-10 for Melanoma
[11] Kazmi et al., Xenobiotica. 2014 Jul;44(7):606-14
[12] Pilon-Thomas et al., Journal for ImmunoTherapy of Cancer 2014, 2(Suppl 3):P120
[13] Illustrative examples: Zamani Taghizadeh Rabe et al., Rose Bengal suppresses gastric cancer cell proliferation via apoptosis and inhibits nitric oxide formation in macrophages, Journal of Immunotoxicology (2014); Tan et al., Novel use of Rose Bengal (PV-10) in two cases of refractory scalp sarcoma, ANZ Journal of Surgery (2013); Koevary, Selective toxicity of rose bengal to ovarian cancer cells in vitro, International Journal of Physiology, Pathophysiology and Pharmacology (2012)

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