Avid Bioservices Inc (CDMO)

[Fire Fox]

... but more importantly, articles like the one this morning that talks about "other" pharmas tryint to develop some other immune associated cancer drug further shows the effectiveness and safety of Bavi.

There will be much fanfare at ASCO about PD-1 and PD-L1. These mabs block the downstream "off-switch" for killer T-cells but do nothing to block the "off-switch" for upstream PS, which is a much more important and far-reaching immune response off-switch. By increasing the number of killer T-cells, PD-1 causes greater tumor remission, but does nothing to enhance the body's "innate immunity" to the cancer or viral pathogens.

The key to understanding Bavi's advantages over PD-1 and PD-L1 can be seen in the Abstract from the AACR poster that got so much attention this year on how Bavi reactivates tumor immunity. Here are the two key statements from the Abstract of the Company's AACR poster in early April:

"Antibody treatment reduced the presence of myeloid-derived suppressor cells (MDSCs) in the tumors and caused macrophages to repolarize from the immunosuprressive, proangiogenic M2-like state into a tumoricidal M1-like state. ... Thus, PS-targeting antibodies appear to reactivate innate immunity in tumors which could hold tumor development in check."

www.peregrineinc.com/images/stories/pdfs/yi_2013.pdf

Unless you block PS, the tumor environment will keep producing MDSCs, which in turn produce the M2-like state, which includes the "off-switch" for killer T-cells. Because PD-1 and PD-L1 impact a down-stream off-switch, you will have to keep using more of it because it never stops the source of the problem, which is the M2-like state caused by MDSC.

By contrast, Bavi blocks a very upstream immune suppression switch, which induces an M1-like state where there is no need to block the T-cell off switch because this off-switch never develops.

PD-1 and PD-L1 don't produce an M1-like state. All they do is block an off-switch that results from the M2-like state.

Moreover, and perhaps more important, the AACR Abstract points out that Bavi (or 2aG4 which is the mouse version of Bavi) caused the MDSC "to differentiate into M1-like macrophages and DCs." DCs are Dentritic Cells. These are the cells that trigger our innate immune system to recognize the cancer and viral cells as foreign pathogens which need to be destroyed.

PD-1 and PD-L1 do nothing to enhance the innate immune system's ability to recognize the tumor as a pathogen and thereby "hold tumor development in check" (see last sentence of AACR Abstract).

PD-1 and PD-L1 work by brining more firemen (i.e. killer T-cells) to the fire but do nothing to block the source of the flames and the body's ability to recognize that flame as a pathogen next time it appears.