More Drugs to Help BRAF Melanoma Patients

Two new GSK oral oncology treatments, BRAF-inhibitor Tafinlar® (dabrafenib) capsules and the first MEK-inhibitor Mekinist™ (trametinib) tablets, approved by FDA as single-agent therapies.

Glaxo Wins FDA Approval for Two Targeted Skin Cancer Drugs "The Food and Drug Administration today approved Tafinlar and Mekinist for patients with melanoma, the most dangerous form of skin cancer, that has spread or can’t be surgically removed. The drugs are aimed at patients who have certain gene mutations that need to be detected using a diagnostic test made by Marcy L’Etoile, France-based BioMerieux (BIM), which the FDA also cleared."

"Tafinlar may produce $279 million in sales in 2016 while Mekinist may generate $343 million, according to the average of eight analysts’ estimates compiled by Bloomberg."

A relatively small, unmet need marginally less unmet: BRAF, unresectable, very late stage. A small addressable market still desperately in need of better solutions than these two drugs.

dabrafenib (TAFINLAR)

Daiichi Sankyo: A Dark Horse Challenger to Big Pharma Buying $PVCT

Earlier this month I identified visits from Daiichi Sankyo in Tokyo spending many, many hours on the blog. Later, I confirmed visits from Daiichi's U.S. headquarters in Parsippany, New Jersey. I think Daiichi Sankyo is interested in a multi-faceted relationship with Provectus.

Plexxikon reported interim analysis of its MM Phase 3 trial for vemurafenib (Zelboraf) in January 2011. In February, the following month, the company announced it was being acquired by Daiichi Sankyo. When a corporate approaches a target, the dance generally begins with an introduction typically 3 to 6 months or more before an acquisition, if achieved, is announced. By this math, Daiichi may have begun speaking with Plexxikon around mid-2010. Plexxikon treated the Phase 3 trial's first patient in January 2010.

Daiichi, one could argue, acted aggressively. "Just a few months after Daiichi Sankyo Co. Ltd. purchased biotech Plexxikon Inc. of Berkeley, Calif., for nearly $1 billion, the Japanese pharmaceutical company is reaping the benefits. A drug developed by Plexxikon and now owned by Daiichi, vemurafenib, was approved for treating metastatic melanoma by the U.S. Food and Drug Administration, the company said Wednesday." (Source here)

Think about it. Daichii approaches Provectus before Moffitt's data has been presented at AACR in April. Before Provectus' contemplated pivotal MM Phase 3 trial is finalized -- where "finalization" means the receipt of the SPA -- and well before enrollment is commenced. That should come as no surprise because PV-10 is far superior to vemurafenib (Zelboraf) and has more multi-indication potential already (whereas vemurafenib did not).

Daiichi has the balance sheet to pay what Provectus desires. In 2008 Daiichi announced that it would pay up to $4.6 billion for a controlling stake in Ranbaxy Laboratories, one of the largest manufacturers of drugs in India; this deal valued all of Ranbaxy at $8.5 billion (a 31% premium to its stock market capitalization prior to the announcement).

Daiichi also has a Japanese cultural approach to M&A that might force Pfizer's hand. That is, it could push Pfizer to act because it has to act to protect an asset (Provectus) it values but heretofore has no impetus to acquire.

"Global studies of M&A point out that once executives dive into the transaction process, they often become so invested in the deal that they cannot pull out even when necessary. In most markets today, however, common wisdom prevails that being able to walk away is a hallmark of M&A sophistication. That notion is rare among Japanese practitioners of outbound M&A." (Source here)

"The demands of Japanese-style consensus building, requiring the hard-won agreement of many parties, make abandoning a deal particularly hard. The potential loss of face in such a decision makes participants reluctant to suggest it, even if the logic of proceeding is undermined by new information."

Daichii was agressive in acquiring Plexxikon, paying more for the company than anyone else offered or was willing to pay. From all accounts, the acquisition is or eventually should be accretive.

If Daiichi executives set their mind to licensing PV-10 (or PH-10) or acquiring Provectus, then Big Pharma (including, in particular, Pfizer) might lose the asset to the Japanese if they're not willing to counter bid.

$PVCT: Daiichi Sankyo

It appears Daiichi Sankyo is interested in Provectus (based on some very specific information I unearthed that leads me to speculate this). It is not yet clear whether such interest is limited to Japan (and possibly India, through its ownership in Ranbaxy), or whether the Japanese global pharmaceutical company's interest extends to a global license of PV-10.

In February 2011, Daiichi Sankyo announced its acquisition of Plexxikon for $805 million up-front and near-term milestone payments associated with the approval of PLX4032 (vemurafenib, now Zelboraf) for up to an additional $130 million. The deal closed in April.

Other acquisitions include Zepharma (2006), the OTC drugs unit of Astellas Pharma, a majority stake in Indian generic drug maker Ranbaxy (2008) valued at ~$4.6 billion, and U3 Pharma (2008) for the company's anti-HER3 antibody. (See Wikipedia)

@MoffittNews' Dr. Jeffrey S. Weber, MD, PhD -- $PVCT KOL

Moffitt's Dr. Amod Sarnaik, MD said, in Provectus' January 8, 2013 PR, "We look forward to verifying the promising pre-clinical data from our ongoing work in this translational study. These results should help elucidate the immunologic basis of the 'bystander effect' noted in previous clinical studies of PV-10 and help optimize PV-10 treatment, particularly in combination with other therapies."

On the bio page of Dr. Jeffrey Weber, MD, PhD, the director of the Donald A. Adam Comprehensive Melanoma Research Center at Moffitt Cancer Center, you will read "As a tumor immunologist & immunotherapist, I focus on translational clinical trials including development of novel trials in melanoma based on my lab work."

What does a translational study in cancer research mean? A translational study turns knowledge from the laboratory into a treatment for patients.

Such is the gravity of what Moffitt should say.

According to the October 2002 paper from the immediately prior link, "[T]he concept of translational research addresses what would be an efficient and orderly way of applying the advanced understanding and technology of the field of biology to cancer treatment. The essence of translational research lies in coming to understand the biological features of a cancer so as to translate molecular biological evidence into clinical anticancer strategies. In other words, "translational research" can simply be defined as the process of determining a treatment solely on the basis of molecular biological characteristics."

The paper goes on to say: "There has been much debate over many years as to the best approach to stimulate immunity against tumors. Previously, researchers involved in immunotherapy ground up tumors and simply gave them back to the patients they were removed from or to other patients. This is not really translational research. At present, there is an understanding that the tumor antigens can be isolated and grouped as to which are more or less likely to provoke an immune response by collaborating with HLA antigens. Knowledgeof this resulted from an understanding of the biology of how antigens are processed. We can now define which peptides in which the antigens have a likelihood of inducing a response when they are presented either as cells or with dendritic cells or in other ways. It can be said that to merely give tumor vaccines without consideration of immune response is not translational. But it is translational to have a selection of antigens based on our understanding of how the immune system operates and which antigens are likely to be or actually are expressed in a tumor, because we are incorporating the biology into the clinical trial design."

Dr. Weber was instrumental in the approval of Vemurafenib (now Zelboraf), saying in April 2012 the success of Vemurafenib represented "the single most dramatic improvement in the treatment of melanoma in 20 years."

According to more of his Moffitt biographic information, Dr. Weber is charged with "...bringing together basic scientists, clinical and translational investigators and prevention/epidemiology scientists in an integrated overall melanoma research effort that rapidly brings new drugs and ideas to the clinic."

"He works extensively with [Dr.] Vernon Sondak...[and] has an extensive history of conducting translational and investigator-initiated clinical trials."

"Dr. Weber’s research interests lie in the monitoring and characterization of T cell responses to vaccination in cancer patients, and in the establishment of in vitro models to facilitate the understanding of how immune modulating antibodies amplify T cell responses in patients. He is also interested in the mechanisms by which achieving autoimmunity induces regression of cancer."

Such is the gravitas of Moffitt's Dr. Weber.