The Usual Suspect[s]

Verbal: Who is Keyser Soze? He is supposed to be Turkish. Some say his father was German. Nobody believed he was real. Nobody ever saw him or knew anybody that ever worked directly for him, but to hear Kobayashi tell it, anybody could have worked for Soze. You never knew. That was his power. The greatest trick the Devil ever pulled was convincing the world he didn't exist. And like that, poof. He's gone.

When I learned of Dr. Eagle's addition to the corporate advisory board, it was eminently clear [when combining this announcement with my historical due diligence] that Pfizer was the leader in the clubhouse to acquire the company once the necessary and several boxes were suitably checked. Not that J&J, Novartis and Roche (and, to a lesser extent, GSK) won't have a say, but there are too many indications that PV-10 will soon become a strategic priority at Pfizer.

With BMS having the most high profile anti-CTLA-4 compound, and Pfizer's anti-CTLA-4 fail, it seemed strange there had been no progress by Pfizer in this regard. People previously have noted that the difference between the two compounds is small: Both are fully human monoclonal CTLA-4-directed antibodies; however, while ipilimumab is an immunoglobulin (Ig)G1 isotype, tremelimumab is an IgG2 isotype. Some commentators point to tremelimumab's failure in melanoma Phase 3 trials simply as the result of the dosing, scheduling and trial design. Different and better dosing, scheduling and trial designs could lead to successful outcomes.

Then, in October 2011, MedImmune licensed tremelimumab from Pfizer. Was this the end of Pfizer's efforts for this family of compound? Yet, under the terms of the agreement, while MedImmune would assume global development rights, Pfizer retained the rights to use tremelimumab with specified types of combination therapies. Since ipilimumab's coming out party, combination therapies, such as with vemurafenib (and others), are being suggested to optimize its utilization.

Combination therapies, in my view, relate to novel approaches combined together, such as radiotherapy and PV-10, rather than comparators, such as sorafenib and PV-10. The former represents the frontier of further beating cancer senseless, while the latter relates to the regulatory approval process (if management had not made a calculated risk-based decision to pursue accelerated approval for MM that with the benefit of hindsight turned out to be wrong, we would have seen an RCT completed by now).

I asked management about the MedImmune transaction, as it was well known that Pfizer had, for some time, discussed out-licensing tremelimumab with several parties:

• Did Pfizer approach you to license tremelimumab? No comment.
• Have you discussed combination therapies with Pfizer, such as tremelimumab and PV-10? No comment.

As you know from Provectus' IP strategy, the company aggressively has patented or applied for patents on:

• Rose bengal structurally and as an active pharmaceutical ingredient;
• The manner in which rose bengal is biopharmaceutical delivered; and
• Combined use. The first evidence of this relates to the combination of radiotherapy and PV-10 dating well before the Australian team's successful outcome was first revealed.

Investigators and scientists obviously believe it is too early to make declarative judgements on the ipilimumab's ultimate efficacy as well as how to effectively combine it with other treatments for the ultimate benefit of patients. That simply is the nature of science and research.

But, if management had the forethought to address the future in its IP and patenting strategy, is there something to Pfizer retaining the rights to use tremelimumab with specified types of combination therapies? This certainly bears watching.