Tarvy, re: “Evolution has favored pathogenesis that resembles apoptosis.” (JBM) - that was nicely explained from a Bavi-viewpoint by S.King yesterday at Wedbush, as he discussed Slide7...
CEO Steven King’s 29 min. Presentation – Wedbush/NYC 8-15-2012 Aug15, 2012 - Wedbush Life Sciences Mgt. Access Conf., NYC REPLAY direct link: http://wsw.com/webcast/wedbush21/pphm
SK/S7: “A very novel MOA - it turns out that PS is not simply a marker of disease, but is actually involved in controlling the immune response to disease. By blocking that immunosuppressive signal, we actually allow the immune system to turn on and fight the disease. The concept is, Phosphatidylserine (PS) itself is a normal component of cellular membranes, present in every cell of the body, only very-tightly regulated to internal side of the cell. So, essentially, if you inject PS-finding agents, such as is done in our Imaging pgm, the agents simply float around and eventually clear the body if there’s no sign of disease. What our scientists discovered, is that as cancer develops, you get a very unique environment, you have poor blood flow, reactive oxygen species, hypoxia – as a result of all these insults, the mechanisms that keep PS inside of cells become disrupted, and the PS becomes exposed on the outside of the cell. It turns out that this exposed PS in the tumor microenvironment is very important in controlling the immune response. The only normal time which you have PS exposure is when cells undergo normal programmed cell death, or apoptosis. So, as cells die, you see the same phenomenon of PS becoming expressed or exposed on the outside of the cell. What happens then is, as the immune system is undergoing its daily routine of removing dead & dying cells, those macrophages & dendritic cells, whose responsibility it is to remove the cells, interact with the dead & dying cells, and actually have a PS-receptor on their surface. As the exposed PS binds to the receptor on the immune cells, it actually sends specific signals to down-regulate the immune response, because when you’re removing dead & dying cells you don’t need a robust immune response, obviously. It turns out that cancer, as well as a number of other diseases, have taken advantage of this fact, and by simply causing PS-exposure during the tumor microenvironment, you now do not get an adequate immune-response to the disease, allowing the tumors to outgrow the poor immune-response that’s being given. Bavituximab is injected, it goes to the site of the disease, so it accumulates on the PS inside the tumor environment, blocks the PS that’s exposed in that environment, and now those immune cells - you can actually detect a significant change in there phenotypes, as they go from a non-inflammatory to a pro-inflammatory state and really begin the fight the disease. And over time, you see development of a full adaptive immune response. As at fully adaptive immune response happens, you then have this full immune response, which includes ADCC, mediated by the antibody itself, normal cell-killing, mediated by the antibody, as well as activation and down-stream effects of the immune response.”