Here’s why PPHM is expecting accelerated approval in the upcoming NSCLC registration trial.
Let’s go back to some basic science about Bavi’s MOA in destroying tumor vessels. To understand why the Company is expecting great tumor response rates (i.e. shrinkage) even in these refractory 2nd line patients, you have to understand Bavi’s original MOA. Probably the best explanation of this MOA is seen in the old Thorpe video that is still on PPHM website here: http://www.peregrineinc.com/index.php?option=com_content&task=view&id=29&Itemid=45
What you need to hear again is Dr. Thorpe’s 2 minute fireside chat on Bavi’s MOA that starts 1 minute into the video. He emphasizes that PS targets the tumor vessels not the tumor cells. Thus it makes no difference to Bavi whether the tumor cells have become resistant to chemo. What makes Bavi effective is the ability of chemotherapy and radiation to upregulate (i.e. increase) exposed PS on the surface of tumor vessels but not on the surface of other vessels.
As SK said in his 1-13-10 presentation last week, the increase in exposed PS on the tumor vessels happens just the same whether the tumor cells have become refractory to the chemo treatment or not. Here’s the quote from the presentation last week:
“Perhaps why we’re most excited about this is this drug is an ideal combination with chemotherapy, and we think it has an excellent potential in the treatment of refractory disease. ... And, it’s simple because chemotherapy & radiation actually up-regulate our target on tumor blood vessels, increasing the effectiveness. Secondly, even in refractory disease or chemo-resistant tumors, the chemotherapy and radiation are still are able to up-regulate the [PS] target on vessels and we still get the same increased benefit from the therapy.”
Note in the above text how SK twice emphasized that he was talking about the increase in exposed PS on tumor vessels.
If you watch Thorpe’s video again on the PPHM website, you will see that Bavi’s primary anti-cancer MOA works like this: One end of the Bavi MAb sticks to the PS. The other end of the Bavi MAb is called the FC Receptor and is wagging in the breeze as various white cells in the blood supply float buy. These white cells (in particular Macrophage and Natural Killer Cells) stick to the FC Receptor on Bavi and immediately cause a cytotoxic reaction that “attacks and destroys the tumor blood vessels” (Thorpe’s words in the video). Vessel destruction means the tumor cells don’t get the oxygen and nutrients they need and this lack of oxygen quickly destroys the whole tumor.
If you understand these basic principles of Bavi’s original MOA, it becomes easy to understand why SK is willing to stick his neck out and predict that Bavi will reduce tumor size “just the same” in refractory 2nd line tumors as in 1st line tumors. Yes, in refractory tumors the chemo no longer has the same ability to kill tumor cells, but SK confirmed last week some great news: chemo does have the same ability to increase (upregulate) exposed PS on tumor vessel walls in both refractory and non-refractory tumors.Therefore Bavi is expected to work roughly the same – i.e. “we still get the same increased benefit” -- in both refractory and non-refractory tumors.
Herein lies our path to accelerated approval. :) :)
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