Avid Bioservices Inc (CDMO)

[eb0783]

Let’s not be short sighted because there may be a much bigger picture here than “A” biomarker or "The" biomarker. I remind us of the poster from the 2015 AACR which showed results from measuring many immune checkpoint proteins and many cytokines. (albeit from only 6 patients but confirming preclinical results) They all increased or decreased in varying amounts when Bavi was added to the mix. Rather than a single musical note (“A” biomarker) we may be seeing a chord, a movement, or a full symphony displaying the results of Bavituximab. Dr Thorpe may turn out to be our Beethoven.

“In this study, we tested the immunomodulatory effect of bavituximab using a proprietary 3D ex vivo tumor microsphere technology. Upon obtaining informed consent, fresh tumor tissue from lung cancer patients were collected at the time of surgical resection. Tissues were processed for characterization of the tumor microenvironment and potential immunosuppressive mechanisms such as expression of PD-1, CTLA4, LAG3, TIM3, BTLA, and Adenosine A2AR. 3D tumor microspheres were prepared and cells were treated ex vivo with f(ab)’2 version of bavituximab, bavituximab, docetaxel, and a combination of bavituximab and docetaxel for 36 hours within the 3D tumor microsphere simulating an intact tumor microenvironment made up of tumor infiltrating lymphocytes (TIL) and myeloid cells. At the end of the treatment, TILs were analyzed by flow cytometry for cell activation and changes in CD4, CD8 and Treg (CD25+/CD127-) subpopulations. A multiplex human cytokine assay was used to simultaneously analyze the differential secretion of cytokines, including human IFN-? in culture media as a surrogate of TIL activation.

Preliminary results indicate that bavituximab as a single agent, or combination of bavituximab and docetaxel can induce TIL activation as demonstrated by a significant increase in IFN-? secretion when compared to tumors treated with IL-2 control or docetaxel alone. Flow cytometry analysis revealed that this effect was associated with negative PD-L1 expression on tumor cells and low PD-1 expression on CD8 cells at baseline, but did not correlate with other known immune-modulating receptors. Results from six patients are presented.

This lung patient derived ex-vivo approach indicates that bavituximab single agent, or combination treatment can elicit a tumor specific immune response in human adenocarcinoma of the lung. This effect involves, at least in part, activation of CD8+ TIL and increased inflammatory cytokine production by lymphoid and myeloid cells. In addition, we have observed negative baseline expression of PD-L1 on tumors and low PD1 expression on CD8 cells as potential prognostic biomarkers of immune response to bavituximab treatment. Furthermore, these data suggest that the interruption of the PD-1/PD-L1 axis may enhance the bavituximab activity in lung cancer.”