Hypothesis: Intralesional PV10 induces systemic immunity in humans

Provectus issued a press release today and made an associated 8-K filing (that included another item) regarding Moffitt Cancer Center's Dr. Vernon Sondak, MD's presentation in Munich, Germany, Provectus Biopharmaceuticals' Data on PV-10 as Treatment for Melanoma Presented at 5th European Post-Chicago Melanoma / Skin Cancer Meeting. The company made Dr. Sondak's presentation available; the link is here.

I believe the key takeaway comes from the 19th slide in the deck, which clearly and simply states [what I think is] the ultimate goal of Moffitt's research work on PV-10: to prove or disprove the hypothesis that intralesional PV10 induces systemic immunity in humans [for melanoma].

Click to enlarge. Slide no. 19. New 2015 slide (v. 2014)

The other slide of note [to me], and that I was struck by, was the presentation's final slide (of "The Moffitt PV-10 Team").

Click to enlarge. Slide no. 21. New 2015 slide (v. 2014)

Below I compare Sondak's 2014 presentation to his 2015 one, which in the early going are ostensibly the same. A shareholder who attended last year's presentation sent me pictures of it.

Disclosures

Click to enlarge. 2014

Click to enlarge. 2015: Slide no. 2

Potential Applications

Click to enlarge. 2014

Click to enlarge. 2014

Click to enlarge. 2015: Slide no. 3

Click to enlarge. 2015: Slide no. 4

Properties of the Ideal Agent

Click to enlarge. 2014

Click to enlarge. 2015: Slide no. 5

New in 2015: Sondak included a "history of" slide, which speaks to Rose Bengal lying around in plain sight of Big Pharma for about 75 years before Provectus' cofounders "re-discovered" it, and the drug substance/drug product's safety and specificity (i.e., Pharmacology).

Click to enlarge. 2015: Slide no. 6

Properties of PV-10

Click to enlarge. 2014 

Click to enlarge. 2014

Click to enlarge. 2015: Slide no. 7

Click to enlarge. 2015: Slide no. 8

Click to enlarge. 2015: Slide no. 9

New in 2015: A picture of Melanoma Institute Australia and the University of Sydney's Dr./Prof. John Thompson, MD with PV-10 (Rose Bengal) on his face?

Click to enlarge. 2015: Slide no. 10 

Click to enlarge. 2014

Click to enlarge. 2014

Click to enlarge. 2014

Click to enlarge. 2014

Click to enlarge. 2015: Slide no. 12

Click to enlarge. 2015: Slide no. 13

Click to enlarge. 2015: Slide no. 11

Click to enlarge. 2015: Slide no. 14

New in 2015: Summary/overview slides of Moffitt's work to assess systemic immunity from intralesional therapy, in mice and humans (noting whether and where such work was or was not published in a peer-reviewed journal).

Click to enlarge. 2015: Slide no. 15

Click to enlarge. 2015: Slide no. 16

Click to enlarge. 2015: Slide no. 17

Click to enlarge. 2015: Slide no. 18

Click to enlarge. 2015: Slide no. 19. Notable, as discussed above

Conclusions

Click to enlarge. 2014

Click to enlarge. 2015: Slide no. 20

Final Slide

Sondak's final June 2014 presentation slide was telling, given the FDA's May 2014 denial of Provectus' application for breakthrough therapy designation for PV-10 (in locally advanced cutaneous melanoma), and that he made that presentation well before the Agency's April 2015's advisory committees overwhelming vote in favor of Amgen's talimogene laherparepvec ("T-Vec") having an overall favorable benefit-risk profile for the treatment of injectable regionally or distantly metastatic melanoma (for the latter, see blog post The first guy through the wall).

Click to enlarge. 2014

In June 2015, however, there are smiling faces:

Click to enlarge. 2015: Slide no. 21

Recall Eric said on Provectus' May 7th 1Q15 conference call:

"We really can't speculate on the direct implications of the T-VEC decision other than to say that clearly the regulatory environment is continuing to change what the agency identified deficiencies in the T-VEC package. And this may come as significant review questions when the agency finalizes the review of potential decision to approve or not approve the BLA, the application for approval for that my logic may have relevance for us going forward. That being said, the end points that were used for the T-VEC pivotal study were different than the ones that we used in Phase 2 study. And more importantly, the T-VEC Phase 3 study, pivotal study was larger, so have more patients than we have in the Phase 2 study. I would speculate that we can see that what was clearly very strong headwinds a year ago are maybe abating here in Washington and that presumably bodes well for future success with PV-10." {Underlined emphasis is mine}

N.B. Provectus did not make Dr. Sondak's 2014 presentation at the 4th European Post-Chicago Melanoma / Skin Cancer Meeting available last year. For whatever reason (e.g., perhaps Eric is more comfortable and confident now than he was then*), Provectus' Chief Technology Officer Dr. Eric Wachter, PhD appears to have allowed the company's Chief Operating Officer/Chief Financial Officer Peter Culepper to press release the 2015 presentation.

* If true and in the absence of more explanation directly from him on this, then my reaction is that such feeling(s) is(are) are disrespectful to Provectus shareholders and representative of an intellectually inconsistent sub-process.

@MoffittNews' PR of its work (study) on $PVCT's PV-10 trending of Twitter

Click to enlarge figure.

Moffitt Cancer Center's PR from yesterday -- Single Injection May Revolutionize Melanoma Treatment, Moffitt Study Shows -- is trending on Twitter. A screen shot of a recent portion of it is on the left (click the picture to enlarge it). You also can observe it yourself by searching for "Moffitt" and "cancer" and looking at "All" Tweets (this link should do this for you, but it may not).

Several news and web sites have picked up Moffitt's PR thus far; however, I'm more interested in how the PR and story, brief as it currently is (since the only available information for most folks is from the PR), is circulating within and across social media.

At the moment, while the story is trending, it has not yet reached so-called biotech Twitter pros, such as those mentioned in Xconomy's Luke Timmerman's article Who Should Biotech Pros Follow on Twitter? An Update for 2013, and other more recognized names.

As a reminder, the blog is on Twitter here: @PVCTinvestor. Please follow!


Moffitt's PR, in my view, was very compelling, if not astounding. Among other things:

• The use of a single treatment (i.e., injection) of PV-10, which is not [I think] to say one injection, but rather one treatment cycle, which may or should comprise multiple injections and several vials of PV-10 (i.e., a treatment cycle) [Updated: I erred. Moffitt meant a single injection. Multiple injections are required when the initial one is applied incorrectly, or when the target tumor requires more PV-10 because of tumor volume and thus additional injections of drug],
• "Revolutionize:" 1. change (something) radically or fundamentally, "this fabulous new theory will revolutionize the whole of science," synonyms: transform, alter dramatically, shake up, turn upside down, restructure, reorganize, transmute, metamorphose, and
• The mention of boosting the immune response in the blood stream, which I believe is a focus area of Moffitt (but more on that item in a subsequent post).

It will take time for the PR to circulate on social media and elsewhere, and requires follow-up from Moffitt to further broaden and deepen the story, message and narrative. There is no mention of Provectus, as there should not be from an institution focused on translational research.

This story only has begun. There is much more Moffitt has done by way of pre-clinical and clinical studies (e.g., on PV-10, on combinations of PV-10 with other agents, on other indications, etc.). While some of these results no doubt have been provided to the FDA, Moffitt will, in its self-interest, present and promote their findings and the implications and ramifications of such, over time.

As a result, I do not think there will be any immediate impact on share price. The market primarily is focused on regulatory clarity.

But, one could well think PV-10's, and thus Provectus', legitimacy has been established. The FDA, then, follows. From there the share price naturally will react.

$PVCT: Provectus Pharmaceuticals Announces H. Lee Moffitt Cancer Center Initiates Phase 1 Study of PV-10 to Elucidate Bystander Effect

Provectus issued a PR today to announce the Moffitt human trial and immunological MOA characterization work.

Dr. Sarnaik's quote, below and approved by the cancer & research center, highlights two key points.

First, verifying through this human work the second set of Moffitt murine results, which [as I wrote yesterday] are highly anticipated and will be presented at a very high profile conference later this year, is both important and, I think, highly likely. To garner the use of "verifying" from Moffitt in the quote also is important.

Second, the notion of PV-10 making cancer treatment more effective in combination with other therapies also is important (very, actually); particularly for late stage patients (a group not targeted by Provectus' current registration pathway for PV-10, which is to facilitate the treatment of Stage III and early-Stage IV patients) and those with heavy tumor burden.

Craig's quote, below, highlights the same key point about PV-10 therapy combinations.

He clearly is speaking to big Pharma. Foote et al.'s initial and ongoing work combining PV-10 and radiotherapy are showing dramatic improvement for patients with much later stage disease (Stage IV) and heavy tumor burden. Craig et al.'s SITC-published work provided additional data demonstrating the use of PV-10 in combination with systemic chemotherapy (Fluorouracil or 5-FU, and trademarked as Efudex).

I have to think Big Pharma was very excited by Craig's study (the data for which, again, was shown at SITC) showing the improvement of chemotherapy when combined with PV-10 and, specifically, the improvement of 5-FU, another "dirt cheap" drug (see the table to the right, and this link from 2004 regarding the cost of 5-FU).

It is growing clearer PV-10 can be used first (before surgery), second, last and everywhere in between for cancer patient treatment. Showing further effectiveness in combination for late stage disease patients and those with heavy tumor burden adds to eventual PV-10 treatment decision tree.