$PVCT.OB Presents Final Phase 2 Melanoma Data At ESMO 2012

Provectus issued a PR yesterday describing final MM Phase 2 data, providing a copy of the ESMO 2012 poster and describing design parameters of the pivotal MM Phase 3 trial for which the company is seeking an SPA from the FDA.

Phase 2 data. The final MM data was first presented by Dr. Agarwala in Munich on June 22 at At 2nd European Post-Chicago Melanoma Meeting 2012. See the PR here. There some slight differences from the data presented in Vienna on October 1 that may be gleaned from comparing the two PRs. These appear negligible or immaterial:

• An Objective Response Rate of 51% (v. 50% in Munich) in subjects' target lesions (25% Complete Response and 26% Partial Response [v. 25%]);
• 69% disease control (v. 70%) in these lesions (combined Complete, Partial and Stable Response subjects); and
• Stage III subjects experienced a substantially higher target lesion response rate (60% OR [v. 58%] and 79% [v. 81%] disease control) versus Stage IV subjects (22% and 33%, respectively);
• Analysis of temporal data showed that Stage III subjects also experienced significantly greater mean Progression Free Survival (PFS) of at least 9.7 [v. 9.6] months, versus 3.1 months for Stage IV subjects (median PFS for Stage III subjects was not reached during the 12-month study interval).

What appeared new (in contrast to the Munich presentation was overall survival.

Overall, the Phase 2 data was very strong, particularly for Stage III subjects, who will be the patient population for the Phase 3 trial. It was striking to net out those subjects experiencing early progression prior to the week 8 assessment who were then classified as non‐evaluable (NEV): 66% OR -- two-thirds of subjects -- and 88% disease control -- nearly 9 in 10 subjects, assuming my process and math is correct. The PFS curve is very similar when netting out NEV, although it does improve.

What is even more striking is the expectation the Phase 3 trial will improve further -- Phase 2 bested Phase 1, and now Phase 3 is expected to best Phase 2 -- since Phase 3 investigators will be able to treat all lesions.

The finalization of this data bodes well for its long-awaited publication in The Lancet in 2012.

ESMO poster. The poster itself had a few other useful nuggets. First, the Australian combination therapy study of intralesional PV-10 plus radiotherapy by Foote et al. had enrolled 7 patients as of July. The recent rumor of a double digit number of patients enrolled in the trial makes sense.

Second, the start of the human MOA study by Moffitt was imminent as of the submission of the poster.

Phase 3 trial design. I had thought Dr. Agarwala's Munich presentation had contained the final design. I was incorrect. I am led to believe there is no more negotiating or discussion with the FDA on the trial design, which makes sense. The Vienna PR goes into great detail about the design parameters, as contrasted with the Munich PR, which did not mention any meaningful aspect of the trial design.

The second quote attributed to Eric in the trial design section of the PR is telling. In particular: "This study is designed to demonstrate delay or avoidance of progression of melanoma from a locoregional disease to a life-threatening systemic stage." PV-10 treats disease so well, there will be much less Stage IV disease. Melanoma will not spread to visceral organs because the drug would have stopped it before it does.

There would appear to be no doubt the Phase 3 trial will hit is primary endpoint of PFS. If Provectus hits the same PFS in Phase 3 as the company did in Phase 2, the endpoint is reached. The contemplated hazard ratio dictates almost 6 months PFS for PV-10 versus just less than 3 months for DTIC/TMZ.

The 4-week clinical response assessment (in addition to the 12-week full response assessment) is interesting new design parameter. It is an excellent way for Provectus to measure how effective PV-10 is versus DTIC/TMZ as the study progresses (i.e., a very clear picture of trial success as early as 1Q13 or 2Q13).

$PVCT.OB: Didn't See That Coming

I have been blogging a lot this month. There has been a lot about which to write. Month-over-month blog readership is up 30-60% across all major metrics (e.g., visits +46%, unique visitors +31%, pageviews +57%, average visit duration +41%, etc.). There will be as much or more to write about next month.

I think this there is an outcome much of the market currently does not see coming. I wrote yesterday about the market confusion regarding the PVCTP "IPO" and the current depression of the share price. At this point in time the market is about expectations. And those expectations, unfortunately, are not high going into ESMO 2012 and October.

We await regulatory clarity of the path to approval of PV-10 for metastatic melanoma (i.e., the SPA PR). We know the company requires money to conduct pivotal, key and other trial work (e.g., MM Phase 3, expanded liver Phase 1, liver Phase 2/3, pancreas Phase 1, psoriasis Phase 3, etc.). $15-30MM certainly substantially or fully covers this work. The market is unsure of the timing of the SPA PR. It also thinks the company will incur substantial dilution to achieve this fund raising.

What happens to market expectations of the company and common stock share price if the SPA PR is followed by a license deal announcement, whether dermatology or geographic-specific oncology, that provides most or all of the money above? This outcome causes a complete and utter upside surprise to the market, given what it thinks right now. The share price should blow upward because Provectus not only would have exceeded expectations but destroyed them through a non-dilutive "financing" event.

Below is my current take of the horse race of financing and "financing" options to secure monies for more trial work. I hope to update this more frequently as facts change and events transpire.

$PVCT.OB/$PFE's Patent Application Published For Combining Local And Systemic Therapies For Enhanced Treatment Of Cancer

Provectus issued a PR today for its joint patent application with Pfizer. The patent application was first revealed a week ago.

In a break from historical practice, management issued a PR for a patent application rather than only for an issued patent. While not wanting to hype this achievement (since a patent application has a way to go before it is finalized [if at all]), Provectus nevertheless clearly wanted to highlight another aspect of its growing relationship with Pfizer.

Having made venture capital investments in hi tech start-up companies (mostly information technology ones, but some life sciences companies) on behalf of a corporation, I understand the situation Provectus faced. I have no doubt management dutifully asked the folks at Pfizer's Specialty Care and Oncology business unit for permission to include the Big Pharma company's name in today's PR. The Pfizer BU asked Pfizer's corporate legal department, which subsequently said no (an answer that was not going to change).

As a corporate VC, I knew the tangible and intangible value to the investee from having our parent company's name in the investee's PR announcing the investment round (and our investment). On the other hand, our corporate legal department was fearful of misrepresenting the nature of the relationship between the corporation and the investee company, no matter how minuscule the potential or actual risk. It was one thing to say the corporation's wholly owned but separately governed and functioning subsidiary invested in a start-up company. It was another thing to imply any kind or sniff of "partnership" that did not yet exist between the corporation, howerver, and the investee.

While it may be disappointing to shareholders the relationship with Pfizer was not more broadly broadcast, more of it should become evident over time. For example, we may learn more about it coming out of ESMO next week. Alternatively, if PVCTP ultimately is used, we may learn Pfizer is the lead investor, or one of two lead investors (PFE + another Big Pharma company, PFE + a life sciences investor/fund).

$PVCT.OB At ESMO 2012

Provectus reminded us in a PR today the company will report final efficacy data from the metastatic melanoma Phase 2 trial at ESMO 2012, noting the conference abstract.

Monthly volume, from when I last commented on the topic (on September 14), remains robust (there's that word again) relative to prior months. Today's volume was no exception. Click to enlarge.

It looks like the month-over-month traded volume of the stock (look at, below, Projected Monthly Total Volume, which is divided by 10 so it fits the left-hand Y-axis) still is going to double in September. Click to enlarge. "Monthly Average Volume" (below) means the average daily volume for the days of the month.

It was very clear from today's trading action that at least one investor substantially initiated a position or added to their position in Provectus stock.

From the rumor mill: On the topic of combination therapies, a double digit number of patients have been enrolled in the PV-10 + radiotherapy treatment study being run by in Australia by Foote et al. Prior work indicated, albeit in a very small number of patients, this combination produced spectacular results in very late stage patients with heavy tumor burden. PV-10-induced immunity initially overwhelmed by heavy tumor burden requires a little assistance to reach full potential. Just like in the situation of the immune system fighting infection, antibiotics just give it (the immune system) a little help. Ultimately, innate immunity cures.