Avid Bioservices Inc (CDMO)

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Aug2015 NatureReviews article by Dana-Farber/Harvard Oncologists profiles Bavi in 20pg article, “Combination Cancer Immunotherapy & New Immunomodulatory Targets”

Nature Reviews Drug Discovery (series: Cancer Immunotherapy)
Aug. 2015 (Pub. online: 7-31-15)
“Combination Cancer Immunotherapy & New Immunomodulatory Targets”
KATHLEEN M. MAHONEY, Paul D. Rennert, Gordon J. Freeman
Dana–Farber Cancer Institute, Harvard Medical School, Dept of Medical Oncology, Boston
http://www.nature.com/nrd/journal/v14/n8/abs/nrd4591.html
PDF: http://www.sugarconebiotech.com/wp/wp-content/uploads/2015/07/nrd4591-1.pdf
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Interesting last sentence by Dr. Mahoney:
Pg19: “Bavituximab might also be beneficial when paired with a targeted therapy such as the VEGFR2-specific antibody ramucirumab (Cyramzain, developed by Eli Lilly & Co.), which has reported positive Phase III trial data as 2nd-Line therapy in combination with docetaxel for NSCLC.
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Note: On 12-12-14, the FDA approved Eli Lilly’s ramucirumab (trade name Cyramzain) combination with docetaxel, for treatment of metastatic NSCLC with disease progression on or after platinum-containing chemotherapy.
http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm444496.htm

TEXT OF ARTICLE (pg.18-19):
Phosphatidylserine: Phosphatidylserine is a membrane marker exposed during the process of programmed cell death or apoptosis and serves as an ‘eat me’ signal for phagocytes. Phosphatidylserine is also expressed on rapidly dividing cells, notably proliferating lymphocytes, tumor cells and the tumor vasculature. Profligate tumor cell proliferation leads to the death of large numbers of cells. Because apoptosis is a controlled mechanism of cell death it does not normally trigger immune activation, and therefore phosphatidylserine expression on tumor cells does not induce an antitumor immune response. Indeed, tumor cells may further evade infiltrating immune cells via binding of phosphatidylserine to TIM3 expressed on T cells.
The phosphatidylserine-specific antibody bavituximab (developed by Peregrine Pharmaceuticals) acts by dimerizing soluble B2-glycoprotein 1, converting it from a low to a high avidity binder of phosphatidylserine 182. This allows an antitumor immune response to develop, possibly by coating the tumor cells with antibody or by converting apoptotic cell death to a more immunostimulatory type of cell death. A Phase II trial of bavituximab in advanced NSCLC yielded positive results on progression-free survival and, more importantly, improved overall survival from less than 6 mos. to 12 mos. 183, leading the FDA to grant a Fast Track Designation for bavituximab as a 2nd-Line therapy. A Phase III trial of bavituximab as a second-line therapy for advanced NSCLC is underway [ http://www.clinicaltrials.gov/ct2/show/NCT01999673 ]. Recent presentations showed synergy of phosphatidylserine-specific antibody treatment with CTLA4-specific and PD1-specificantibodies in mouse models, through effects on MDSC and lymphocyte activity 184,185.
Bavituximab might also be beneficial when paired with a targeted therapy such as the VEGFR2-specific antibody ramucirumab (Cyramzain, developed by Eli Lilly & Co.), which has reported positive Phase III trial data as 2nd-Line therapy in combination with docetaxel for NSCLC 186.