March 6, 2013

$PVCT #AACR2013 Thoughts...

Two summary thoughts from today's release of the AACR abstracts, one by Moffitt and one by Provectus, follow.

The first one derives from the second to last sentence of Moffitt's abstract: "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."

"Multiple histologic subtypes," an extremely comprehensive statement, refers to all cancer indications tested by Moffitt: breast, melanoma, ... Tumor specific immunity was achieved in multiple indications.

Chemoablation via PV-10 ablation causes antigenization, and antigenization causes immunization.

Wachter et al.
The second thought comes from the last sentence of the company's abstract"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."

You will recall I wrote earlier:
The crux of the matter is that PV-10, as a local agent, needs to show systemic potential for life science investors, Big Pharma and the FDA to view the drug as clinically relevant. This is the local agent "burden of proof." There must be systemic potential to be relevant for treating cancer after surgery, where cancer is viewed by definition as a systemic disease. PV-10 is an drug with tremendous local efficacy and before unseen systemic benefit (even more so than systemic agents). 
But PV-10 still is a local agent. 
The mindset of the industry -- medical oncologists and hematologist-oncologists, but not surgeons -- is that a local agent has to be combined with a systemic agent to be relevant.  The industry does not yet realize how much of an impact PV-10 will be just as a local agent. All it can currently understand is that PV-10 works, and harnesses the immune system in novel manner. It is obvious to industry PV-10 will get even better systemic results when combined with other agents, or, other agents will get better results when combined with PV-10.
"PV-10 may complement the immune stimulation of anti-CTLA-4 antibodies...without increased toxicity:" Provectus further elucidates the concept of PV-10 orthogonality to systemic therapies; in this case, systemic immunotherapy in the form of anti-CTLA4 agents like Bristol Myers' ipilimumab (Yervoy) in murine model work. Ipilimumab gets better results when combined with PV-10, with no increased toxicity.

Orthogonality: In geometry, two lines (vectors) are orthogonal if they are perpendicular; that is, they form a right angle. Our three dimensions -- the x-, y- and z-axes -- are orthogonal because each is at right angles with the others: non-overlapping, uncorrelated, or independent of each other. In computer science, orthogonality is "a system design property which guarantees that modifying the technical effect produced by a component of a system neither creates nor propagates side effects to other components of the system." (Source: Wikipedia).

Previously, the company demonstrated orthogonality (in pre-clinical work that led up to the upcoming human trial) with systemic chemotherapy agent sorafenib (in the case of liver cancer/HCC). Sorafenib gets better results when combined with PV-10, with no increased toxicity.

Later, Provectus provided results of orthogonality with [inexpensive] systemic chemotherapy agent 5-fluorouracil ("5-FU") in murine model work. 5-FU gets better results when combined with PV-10, with no increased toxicity.

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