November 1, 2012

$PVCT.OB: Blog Reader Questions

Would a repeat of the study with HCC and melanoma cell lines make sense using pancreatic and breast cancer cell lines? If so, would that be significant to Big Pharma when these 4 studies are viewed collectively?
I think there are some technical challenges, especially with breast cancer. Cancers have to be Major Histocompatibility Complex-matched to the host. Cancer, including mouse cancer, should immediately be killed by the immune system. That is why organ transplants have to be matched as closely as possible. Anti-tumor immunity does not reason. It kills what is not identical to the host.

I do not know of mouse breast cancers lines that would match an immuno-competent host. I think Provectus already has successfully treated naturally occurring breast cancers in mice, and killed human breast cancers produced in mice deficient of anti-tumor immunity (nude mice). I recall Craig showing these pictures in past presentations. I think naturally occurring breast cancer has been treated in dogs. Breast and prostate cancer markets are very hard to penetrate except in very late stage disease, which makes success expensive for Provectus to pursue and achieve in small markets at this tine. Target markets like liver cancer are more accessible.

I think management some pancreatic cancer data in mouse models, ablating pancreatic cancer tumors and again observing the bystander effect. Running more mechanism variants in animal models probably would not add value. One real problem with pancreatic cancer is diagnostic, as it often is very widespread when detected. The immune system can be overwhelmed. For now, it is an open question, and one only answered by trials, as to the value for the company for this disease. A combinational therapy approach probably would have the highest chance of success.

As I previously wrote, I think other types of cancer tumors also have been studied by Moffitt. Mechanism of action is not required for FDA licensure, only safety and efficacy. To secure permission to run trials in humans, Provectus has to demonstrate to regulatory authorities that PV-10 appears safe and has potential benefit, not how it works. The company has run most of its studies with that goal in mind. Other goals have included hoping to improve efficacy or expanding into new indication markets.

As for adding value to Big Pharma, the greatest additional value would be demonstrating safety and efficacy in humans. The vast majority of the melanoma market is not very late stage disease. In the melanoma studies, the majority of the market is lies between early stage 4 and earlier, which is where the MM Phase 3 trial was designed to target. A small percentage of the market is very late stage disease.

Part of Provectus' recent presentation at the SITC 27th Annual Meeting clearly was directed at expanding into the very late stage disease market area by using a combined therapy treatment protocol. I think management believes it is the right thing to do for ethical reasons even though it could gain little in market size.

Work with models should be expanded to and published data should be available for other chemo- and immunotherapy agents (e.g., anti-CTLA 4). The goal would be to demonstrate safety and efficacy in these models with the subsequent goal of asking regulatory authorities for permission to test the combined protocols in humans.

A similar path has been followed in expanding the liver studies in people for late stage disease or disease with heavy tumor burden that might be overwhelming the human immune system. Provectus should have data on the combined therapy (PV-10 + sorafenib) in mice and permission to test the combined therapy in humans, which I think would start as soon as the trial site is able to begin the study.

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