@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: Moffitt's PV-10 Human MOA Trial

A simple summary of Moffitt's PV-10 human MOA trial from the cancer center's website.

$PVCT: Immunology Data on PV-10 to Be Presented at the #AACR Annual Meeting

In today's PR, Craig said: "The researchers at Moffitt are providing valuable insights into how PV-10 harnesses the immune system in specific response to the injected tumor. Although the study being presented was done in murine models of melanoma and breast cancer, the currently open clinical trial at Moffitt is designed to investigate this mechanism in melanoma patients. We are pleased to enhance our understanding of intralesional PV-10 and its potential to produce a systemic benefit in cancer patients."

$PVCT #AACR2013: Combination of PV-10 immuno-chemoablation and systemic anti-CTLA-4 antibody therapy in murine models of #melanoma

Presentation Title: Combination of PV-10 immuno-chemoablation and systemic anti-CTLA-4 antibody therapy in murine models of melanoma

Abstract Body: Rose bengal disodium (PV-10) is an investigational small molecule ablative agent currently entering pivotal phase 3 clinical testing as a monotherapy for locoregional control of cutaneous metastatic melanoma. Upon intralesional (IL) administration, PV-10 localizes to the injected tumor tissues while clearing rapidly from healthy tissue. Tumor infiltration with PV-10 leads to rapid necrosis of the injected lesion, with complete resolution common within 2-8 weeks. In phase 2 testing in 80 patients with Stage IIIB-IV(M1c) melanoma, IL PV-10 elicited an objective response in injected tumors in 51% of patients (CR:25%, PR:26%) after 1-4 treatment cycles. In addition to this direct ablative effect on injected tumors, some patients achieved an objective response in their monitored untreated tumors (CR:26%, PR:7% in 42 subjects with monitored untreated lesions) in an apparent immune-mediated bystander response that highly correlated with successful ablation of their injected tumors. Treatment was generally well tolerated, with adverse events confined mainly to the injection site and no grade 4 or 5 adverse events associated with use of PV-10. Recent nonclinical testing in the B16-F10 murine melanoma tumor line has confirmed that PV-10 ablation induces tumor-specific immunity, resulting in marked suppression of synchronous lung metastases upon ablation of a flank tumor and tumor-specific IFN-γ production. In this study we assess potential benefit of combination of PV-10 immuno-chemoablation with the hamster anti-murine CTLA-4 antibody 9H10 in bilateral flank and lung metastasis models (B16-F10 melanoma in C57BL/6 mice). Results from these models will be reported and could support clinical development of combination therapy in advanced melanoma patients, such as stage IV patients with substantial tumor burden in locations inaccessible to PV-10 injection. The rapid reduction in tumor burden and tumor specific immunologic stimulation provided by PV-10 may complement the immune stimulation of anti-CTLA-4 antibodies such as ipilimumab without increased toxicity.

$PVCT -- @MoffittNews #AACR2013: Intralesional injection with PV-10 induces a systemic anti-tumor immune response in murine models of #breast #cancer and #melanoma

Presentation Title: Intralesional injection with PV-10 induces a systemic anti-tumor immune response in murine models of breast cancer and melanoma

Abstract Body: PV-10 is a 10% solution of Rose Bengal that is currently being examined as a novel cancer therapeutic. In melanoma patients, intralesional injection (IL) of PV-10 has led to regression of injected lesions as well as distant metastases. In this study, we examined the efficacy and potential immune mechanism of PV-10 treatment in murine models of breast cancer and melanoma. In BALB/c mice bearing MT-901 breast cancer, injection of PV-10 led to regression of injected and untreated contralateral subcutaneous lesions (p<0.05 compared to IL-PBS-treated mice). A significant increase in survival was observed in mice treated with PV-10. To examine immune response, MT901-specific IFN-gamma production and cytotoxicity were measured in splenocytes collected from mice treated with IL-PBS or IL-PV-10. MT901-bearing mice treated with IL-PV-10 demonstrated enhanced IFN-gamma production (992 ± 453 pg/ml) compared to splenocytes from PBS-treated mice (174 ± 105, p<0.05). In addition, a significant increase in lysis of MT-901 cells by T cells after PV-10 treatment was observed (p<0.01 compared to PBS-treated mice). No lysis of irrelevant CT-26 cells was detected. In a murine model of melanoma, B16-F10 cells were injected into C57BL/6 mice to establish one subcutaneous tumor and multiple lung lesions. Treatment of the subcutaneous lesion with a single injection of IL-PV-10 led to regression of the injected lesion as well as distant B16 melanoma lung metastases. In B16-bearing mice, treatment with IL-PV-10 led to the induction of T cells that produced IFN-gamma in response to B16 tumors but not irrelevant tumor (p<0.05) and demonstrated specific lysis of B16 (p<0.01 compared to T cells isolated from PBS-treated mice). In total, these studies support the induction of tumor-specific T cell-mediated immunity after single treatment with IL-PV-10 in multiple histologic subtypes. The immune mechanism of PV-10 ablation in cutaneous melanoma patients is currently under investigation at our institution.

$PVCT -- @MoffittNews #AACR2013: Intralesional injection with PV-10 induces a systemic anti-tumor immune response in murine models of #breast #cancer and #melanoma

A Moffitt poster presentation at AACR in April: Intralesional injection with PV-10 induces a systemic anti-tumor immune response in murine models of breast cancer and melanoma

Author Block: Shari A. Pilon-Thomas, Amy Weber, Krithika Kodumudi, Lisa Kuhn, Paul Toomey, Amod Sarnaik. Lee Moffitt Cancer Ctr. & Res. Inst., Tampa, FL; University of South Florida, Tampa, FL

$PVCT: Proposed MOA & Tumor Immunity (#BIOCEO13 Presentation?)

The company's website presentation was updated to include the two slides below. I wonder if Peter will be using this version today?

$PVCT: @Moffitt Recruiting For Its $PVCT/PV-10 Human Immunological MOA Study

Source link here.

$PVCT @ #JPM13: Immunotherapeutic Potential

The conversation with Big Pharma has changed considerably after SSO in March 2012. Big Pharma and Big Biotech eyes are on Moffitt's pre-clinical and clinical work. Discussion of immunotherapeutic compound potential at the conference was prominent.

Provectus News today listed the attention the company's January 8 press release about the Moffitt human trial has garnered thus far:

• Pharmaceutical Business Review
• Medical News Today
• News-Medical.net
• Therapeutics Daily
• Kate's Foundation
• BioSpace
• BioPortfolio
• I4U News
• Topix

Sign up for Provectus News here.

$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.

$PVCT: Moffitt's Human Clinical Trial for Immunologic MOA Characterization

Moffitt (responsible party) posted its human PV-10 clinical trial on ClinicalTrials.gov. Provectus has not yet issued a PR related to this work due in large part to, I think, the Moffitt personnel-derived quotes for the PR not yet being approved by the cancer research center's administration. Once approved, the PR should then be issued (perhaps later this week).

This human trial work is the highly anticipated follow-up to Moffitt's second set of murine model work (the first set of results was presented at SSO in March 2012), the results of which also are highly anticipated and to be presented at a very high profile conference later this year. I think some of the results of this human work also could make their way into the same conference presentation(s) of the aforementioned second set of murine work results.

Recall the conclusions of Craig et al.'s poster at SITC (below) in October.

As an aside, based on a very recent reading of several data points, I could be (probably am) off in my speculation of when the SPA might arrive. It is very possible management may finally be done with the refinements of the trial design, various associated parameters, features and facets, and related discussions with the FDA. If the SPA does not arrive in January, I would next expect February in order for the MM Phase 3 trial to commence prior to quarter (Q1) end.

$PVCT: Detection of Immune Cell Infiltration Into Melanomas Treated by PV-10, a Feasibility Study

Clinical trial site link here.

Primary outcome:

Secondary outcome:

$PVCT: January Effect

Before Big Pharma pays billions of dollars for Provectus, value-increasing steps obviously have to drive the company's market capitalization much higher from where it is now (such as to at least above $1 billion). The market cap could get there in January through some combination or permutation of:

• The SPA arrival;

• A regional geographic oncology deal (a "mini-oncology" deal) for China. Signed, but perhaps not closed;

• Visibility into Moffitt's forthcoming mouse and human immunologic MOA characterization work;

• A dermatology deal. Alternatively, we might learn more about the status of the license process: information about PH-10's immunologic MOA characterization, how this MOA work factors into questions about the lack of PH-10 toxicity, the end-of-Phase-2 meeting, and the Phase 3 trial design; and

• Another mini-oncology deal. Such a transaction might be another regional geographic deal, some form of equity investment in Provectus by Big Pharma or an "interesting" license-related/oriented transaction.

$PVCT: Blog Reader Question

I really appreciate your posts. Please keep them coming. One issue that I am having with the continued lack of any licensing agreement or income, is if perhaps PVCT is pricing itself unrealistically? I have seen this happen to companies before, when they think they know what their product is worth, but no one else is willing to pay so much for it, and they just go on and on without ever signing anything. They go to their graves secure in the knowledge that no one has taken unfair advantage of them, but without ever cashing in their product which does have genuine value. You wrote that " license interest and discussions are heating up." If this is so, then what I am fearing is not a problem.

Great comments and question, and thank you.

I have had prior experience with management or [particularly] founding teams being unrealistic: about technology, the product, valuation, and other issues. It is frustrating as an investor and shareholder to see intransigence, derived from lack of realism or pragmatism (or both), overtake what started out as a great investment opportunity.

My interactions with Provectus management have not caused me to question their realism as it relates to valuation. Craig and Peter will tell you, quickly, often and repeatedly, they routinely seek out counsel in this area, and enjoy the benefit of several very experienced counselors.

While Craig strikes and has always struck me as fundamentally understanding the value of what the team has innovated, he does not seem to be ideological about valuation. While the check will have to be very large, I do not think him a person desirous of extracting every last dollar from a/the would-be acquirer.

That said, I am struck by management's perspective about the potential impact on valuation of PV-10's immunologic potential. Repeating a portion of a post of mine from a couple of days ago:

The conclusions of the forthcoming immunologic mechanism of action characterization work by Moffitt Cancer Center could be profound. Will Moffitt researchers make full-throated statements regarding PV-10's immunologic potential?

$PVCT: Immunologic Potential, and thus Value

"The holy grail for cancer would be to trigger the body's own immune system to fight off the cancer so that you somehow stimulate the anti-bodies in a way that that happens." Fareed Zakaria, CNN GPS, from a December 9, 2012 interview with Dr. Ronald DePinho, President, M.D. Anderson Cancer Center

The progression of PV-10 & Provectus potential value

Click figure to enlarge it.

My expectation (above) most certainly is a very lofty one.

The conclusions of the forthcoming immunologic mechanism of action characterization work by Moffitt Cancer Center could be profound. Will Moffitt researchers make full-throated statements regarding PV-10's immunologic potential?

PV-10: A robust (strong), durable (long-lasting), portable (vaccine-like) immune-mediated response.

$PVCT: If Not China, Then What?

In a prior post, I illustrated the then current snapshot of the horserace.

There may be a second geographic region in play (Australia?, India?*). My take on a comparison of license or deal headline numbers is below:

If the company wanted to hold onto oncology longer, a cost breakdown of the contemplated pivotal, key and other trials appears to be:

A China deal (or whatever possible combination of outlying geographic deals) that net a $25-50MM upfront payment goes a long way to providing the necessary funding for Provectus to make even more clinical trial progress.

Could dermatology nose out oncology at the finish line? Sure.

Recall the path Provectus traveled with PV-10 and oncology: clinical trials and regulatory discussions, followed by immunologic mechanism of action characterization work by a world-class institution. The early spadework to demonstrate efficacy, safety and multi-indication viability was followed and enhanced by Moffitt's past and future murine model results (not including, yet, human immunologic work). And while shareholders wished for Big/International Pharma to snap to attention (i.e., license PV-10) because of outstanding early-phase trial results, it now appears the immunology work already presented by Moffitt at SSO and Craig at SITC, followed by forthcoming work to be presented by Moffitt, is accelerating license interest and discussions of both regional and global natures.

Could PH-10 be following a similar path?

The "hang-up" with PV-10 appeared to have been with Big Pharma folks being unable to wrap their heads around how well PV-10 worked. They needed help to understand something they had never seen before. They appear to understand now, or at least are getting closer. As such, license interest and discussions are heating up.

It is not unreasonable to analogize PV-10's path to PH-10's, and thus potentially explain the delay in getting to a dermatology license or sale transaction. Perhaps immunologic mechanism of action characterization work is being done on PH-10 by a world-class institution to complete the understanding of prospective dermatology licensees before they fully commit to jumping into the pool. I think this immunology mechanism of action work is being at The Rockefeller University (the Laboratory for Investigative Dermatology?).

Once this PH-10 immunologic mechanism of action characterization work is completed and provided to prospective partners (I do not know when the work was started and when it and the subsequent analysis was or will be completed), and assuming this knowledge concludes their thinking, dermatology might well beat oncology to the finish line.

In this horse race, however, the more horses that cross the finish line -- Provectus licenses deals -- the better.

* I suspect PV-10's extremely low cost structure, and thus tremendous pricing flexibility, helps facilitate country discussions without fear or risk of patent loss (or too much of it).

$PVCT.OB: The First Anniversary of This Blog

I wrote my first blog post on November 16, 2011. At the time of that post: "The share price is $0.88. 14,700 shares have traded." Today, it closed at approximately $0.53, down about 40%, and traded about 54,000 shares.

Click on the figure to enlarge it.

In the past 12 months, Provectus' notable PRs included:

• October 29, 2012: Provectus Presents Nonclinical Data on Antitumor Immune Response to PV-10 Immuno-Chemoablation (very key),
• October 17, 2012: Provectus Pharmaceuticals Terminates Proposed Convertible Preferred Stock Offering (the failed IPO),
• October 2, 2012: Provectus Pharmaceuticals Presents Final Phase 2 Melanoma Data at ESMO 2012 (key),
• September 28, 2012: Provectus Pharmaceuticals' Patent Application Published for Combining Local and Systemic Therapies for Enhanced Treatment of Cancer (the joint Pfizer-Provectus patent app),
• September 27, 2012: Provectus Expands Protocol for Phase 1 Liver Cancer Study (important),
• June 26, 2012: Provectus Pharmaceuticals Presents Final Phase 2 on PV-10 At 2nd European Post-Chicago Melanoma Meeting 2012 on June 22, 2012 (visibility),
• May 30, 2012: Doug Ulman, National Cancer Survivorship Advocate, Joins Provectus Pharmaceuticals' Corporate Advisory Board (a great get),
• May 14, 2012: Provectus Pharmaceuticals Forms Independent Board to Meet Corporate Governance Requirements (an important corporate governance advance),
• April 10, 2012: Phase 2 Data on Provectus's PV-10 to Be Presented at the HemOnc Today - Melanoma and Cutaneous Malignancies Conference on April 13, 2012 (visibility),
• March 26, 2012: Intralesional PV-10 Treatment Leads to the Induction of Anti-Tumor Immunity  (very key),
• March 23, 2012: Mechanism of Action Data On PV-10 Demonstrates Therapy Induces Immunologic Response (very key),
• March 19, 2012: Provectus Announces Top Line Phase 2 Data For PH-10 in Its First Randomized Controlled Psoriasis Study (important), and
• January 18, 2012: Provectus Receives Guidance From FDA On Pathway to Approval for Phase 3 Trial of PV-10 For Metastatic Melanoma (important regulatory step).

As for the blog itself, readership has steadily grown.

Click on the figure to enlarge it.

Thank you for visiting and reading!

$PVCT.OB: When Does PV-10 Fail?

"Put enough water onto the fire, and it goes out."

The compassionate use program, where doctors have significantly more flexibility than in the clinical trials to treat and re-treat patients revealed much to Provectus management about what the drug can truly accomplish when it enables the body's own immune system to cure cancer in a patient (and how to better design the pivotal MM Phase 3 trial). Put enough water onto the fire, and it goes out. Regularly treat the patient with enough PV-10 and, over time, the cancer goes away.

Constrained by treatment. As such, some trial failures of PV-10 are not actually failures. Some "failures" occur out of necessity because of the design of the trials. In both the dermatology and oncology studies, management was inhibited by the trial design per regulatory compliance. In the MM Phase 1 and 2 trials, principal investigators were only allowed to inject a few tumors. Nevertheless, you have to be impressed by how well the bystander effect worked given the trial constraints hamstringing the treatment approach. Injecting all accessible tumors with PV-10, of course, would be best. The impact of this is to (a) lower the tumor burden and, thus, the load the patient's immune system has to overcome, and (b) address tumor heterogeneity. Tumors are heterogeneous; that is, they are not all the same antigenically (i.e., what they present to the immune system). So, if the antigens the immune system needs to see are on in one tumor and not another, it is vital to inject PV-10 into as many tumors as possible.

Constrained by time of reporting. Some patients were fine at, say, week XXX; however, the trial design required observation at week X (XXX > X). Efficacy at week XXX, even if higher or better, goes unreported. The patient was listed as a failure.

Constrained by physician implementation. The trial design prevented tumors from being injected more than once: A doctor missed a tumor. There was no ability to retreat to correct the miss. The patient was listed as a failure.

Constrained by patient behavior. It is rumored a PV-10 trial patient flew from the U.S. to Australia in order to participate in the MM Phase 2 trial. His tumors were injected, and they went away. Apparently, it also is rumored that he broke his promise to stay and be observed, and returned home to the U.S. The patient was listed as a failure.

Our immune system can be overwhelmed. As with an infection, doctors use antibiotics to slow it down until the immune system itself can clear it away and cure the patient. If the host cannot help, there is no cure.

Provectus treats cancer like an infectious disease.

Thus, in the case of very late stage disease or very heavy tumor burden disease, more PV-10 is applied at the outset, the drug is applied again and again (i.e., re-treat or throw more water onto the fire), or PV-10 is combined with radiotherapy, chemotherapy or other immunotherapies to stimulate the immune system, reduce the burden and "hold the infection in place" and, eventually, allow the patient's immune system to takeover and finish the task of healing the body.

Failure? Perhaps not so much.

$PVCT.OB Blog Reader Question

I read an old interview (2010) with Craig Dees where he explained the novelty of their
approach in targeting the tumor as opposed to just using a systemic agent that is
(hopefully) more active on the tumor than on the healthy cells. What I was not clear on
is: is this a new philosophic approach, or is it expressed in chemistry? Do they have
some chemical delivery system that is being used to deliver Rose Bengal to the
tumors? Is the novelty of their approach that they are looking for something to target
the tumors directly as opposed to the approach used up to now?

Craig frames Provectus' approach to treating cancer in the following way: the harder you punch the immune system, the greater the response. He references a lecture by a veterinary virologist Carl Olson who showed a picture of a cow with a basketball-sized papilloma hanging from its stomach. The professor said (paraphrasing): "Cut that off aseptically and cleanly, and it will grow back every time. Tear it off, make it bleed, kick dirt into the wound, and it will never come back." Shock the heck out of the immune system with tissue destruction (wake it up), break tolerance and encourage a large-scale release of tumor antigens into the system so they can be seen in context.

Dirt, in the story above, like a vaccine adjuvant, riles up the immune system causing it to attack. Much of what Provectus is doing is treating cancer like an infectious disease, and recruiting immune system help. There's another explanation, besides "PV-10 did not work," for non- or poorly responsive injected lesions and bystander lesions that responded poorly or did not respond at all. PV-10's mechanism of immune response is an autophagy-induced, systemwide antitumor one.

Sufficiently inject the lesion (or tumor); induce autophagy and shrink or eliminate the lesion; and, induce the immune system, via the antigens released from successfully treating the injected lesion(s), to successfully treat bystander lesions and remote cancerous locations. In other words, effectively punch the target lesion enough so the immune system can more effectively punch cancer around the patient's body enough. Proper action. Beneficial reaction.

Rather than a new philosophic approach, Craig views Provectus' work as the creation of a new paradigm. See The Structure of Scientific Revolutions by Thomas S. Kuhn. "Kuhn argued for an episodic model in which periods of such conceptual continuity in normal science were interrupted by periods of revolutionary science."

People have tried the intra-tumoral route with little or no success. Some approached getting the immune system to act in the manner described above by Dr. Olson. Still others discovered tumor-killing autophagy induced specific, system-wide, antitumor immunity.

Why did others fail to do it well? In Provectus' view, other drugs killed cancers through toxicity rather than tumor tissue specificity, and thus had poor efficacy and problematic side effects. The drugs killed normal tissue, leaked out and systemically poisoned patients, preventing the proper and effective stimulation of the immune system.

PV-10 kills by autophagy and is very much focused only on diseased tissue. According to the company, stimulation of help by the host's anti-tumor defenses appears to be mediated by T-cells and direct actions on antigen-presenting cells. Management thus believes the approach to treating cancer with PV-10 is a new paradigm: Treat cancer like it is an infectious disease. Of course, don't use systemic poisons. Ultimately, however, components of Provectus's approach include pieces of other knowledge assembled to form a whole new approach: A therapy that functions.

$PVCT.OB: Trying to See Provectus' Forest For Its Trees

The SPA: The path to the SPA, from an investor perspective, like mine, has been an interesting and informative one. It also has been a difficult and impatient one. You may recall I linked to this article about pursuing an SPA: Special Protocol Assessment, a Blessing or a Bane? The author's take home messages certainly resonate:

• "Make sure you really need an SPA. It may take longer to obtain one than you think."
• "If you choose to pursue an SPA, be unambiguous in the questions you ask and meticulous in your filing. Be realistic about the timing."
• "Be prepared to explain your reasoning to investors and board members."

You probably have heard different versions, views and reasons of when the SPA will, might or could arrive. From:

• A "final" re-submission sometime in September or October [early- to mid-November], to
• Within 6 weeks or by December 15 [now through mid-December], to
• Foreshadowing by the October 2 PR's specifics regarding the trial design [mid-November], to
• Using math for the September 19 PR first indicating the MM Phase 3 trial would commence in late 2012 or early 2013 [mid-November through at least early-January].

You may recall A, which I blogged here, that ended in the January 18 PR; B, the 45-day count after the end of March and best case Q2; and C, base case Q3. I see A as demonstrating the potential upturn in the share price when the SPA arrives, B as the markets taking a wait-and-see attitude, and C as more increasing skepticism about the SPA rather than simply a commentary on timing.

The person on the management team who has had and continues to have the best perspective on SPA timing is Eric. Management had to waive off their base case Q3 expectations using their September 19 PR. The October 2 PR clearly was intended to affirm the SPA was on its way (using trial design specs and quotes by Eric), but no one knows exactly when the SPA will arrive including, I think, Eric.

"It's not a matter of if, it is a matter of when, and we are much closer to the end than we are to the beginning."

Your and my best bet is to keep an eye out for the SPA over the next few weeks, but do not be surprised if it arrives in December (maybe or possibly) or January (I highly doubt). When it does arrive, those who doubt the potential for the SPA to move the share price, thinking it has been priced into the share price (which I think is incorrect) might be surprised.

License deals. Management reminds us they currently are pursuing PH-10 and PV-10 geographic deals, which they think can happen at any time. They remain very confident one or more of these will happen.

More Moffitt data. The October 29 PR (more specifically, the poster included with the PR) noted more Moffitt data is expected in 2013 (the AACR annual meeting). Management is trying to get some information out about Moffitt's ground-breaking results sooner. Moffitt's Phase 1 MOIA human trial to elucidate the bystander effect should begin in November. Turnaround should be swift (i.e., a few months if that).

Surprises? Perhaps, including certain publications in play and other potential surprises, but we will have to wait and see.