Replies to post #216148 on Avid Bioservices Inc (CDMO)

[harry crumb]

Very promising data here. Pphm could be a blockbuster in due time!

[Protector]

So far for "ONLY PPHM SAYS IT !"

Notice how PPHM sells the I-O space: "the company's Immuno-Oncology Development Program". They mention it several times and clearly established it as a specific leg of activities.

Secondly it is no longer PPHM/Avid/UTSW and the KOLs (Key opinion leaders) saying Bavi works, and it is no longer at the generic terminology of PS-Targetting without mentioning the name Bavituximab either.

As of this AACR we can start a list, to be extended the coming period, with other sources:

researchers from Moffitt Cancer Center
researchers from Nilogen Oncosystems

said Sigrid M. Volko, Ph.D., CLP the lead investigator on the study and President and Chief Executive Officer of Nilogen Oncosystems.

This is a NEW episode starting and possible the FIRST fall-out of the 24+ collaborations.

What is probably COMPLETELY NEW for us is the "BAVI-Alone" activity. It is surprising because we kind of had discarded that as a possibility. We have operated under the assumption that the Cancer itself doesn't exposed the needed damage/PS-exposure ratio for the immune system to detect it while Bavi suppressed the limited amount of PS that exposed. But there seem to be OTHER things that go on that now come to the surface. That is the advantage of ex vivo over in vivo, you can do more things to measures and you have better control of the environment and the changes.

But while the above is surprising, the real good news is in the tail! The CONSISTENCY between all these observations ranging from these new ones over our Liver biopsy results up to our SUNRISE PIII clinical trial.

I am looking forward to the next results of things that PPHM does with other collaborators and get the word out by other parties then just PPHM. If the Judge dismisses the CA I think we may see fireworks in that area and that we'll start our slow climb up.

[cjgaddy]

Piper Jaffray 4-20-15 PPHM Company Note

”Bavi – Not Just Another IO Candidate”

CHARLES C. DUNCAN, PhD, Sr. Research Analyst, Piper Jaffray & Co.
http://www.piperjaffray.com/3col.aspx?id=103

= = = = = = = = = = = = =
Data Presented at AACR Demonstrate Peregrine Pharmaceuticals' Bavituximab Induces Immune Activation in PD-L1 Negative NSCLC Tumors
• Bavituximab Alone and in Combination with Docetaxel Elicit a Tumor-Specific Immune Response in PD-L1 Negative Tumors Extracted from NSCLC Patients
• Immune Modulating Results Consistent with Previously Conducted Translational Studies in Liver Cancer
• Presented Data Further Support Clinical Studies Evaluating the Effectiveness of Bavituximab Immunotherapy Combinations in Patients with PD-L1 Negative Tumors
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=907312

Sun. Apr 19, 2015, 1-5pm, Abstract#274, Session: TUMOR MICROENVIRONMENT/INNATE IMMUNE ACTIVATORS
”Bavituximab Modulates Tumor Microenvironment and Activates CD8+ tumor Infiltrating Lymphocytes in a Patient-derived 3D Ex Vivo System of Lung Cancer”
Soner Altiok 1, Melanie Mediavilla-Valera 2, Jenny Kreahling 2, David Noyes 2, Tiffany N. Razabdouski 2, Nikoletta L. Kallinteris 3, Joseph Shan 3, Scott Antonia 2
1=Nilogen Oncosystems, Tampa, FL; 2=Moffitt CC/Tampa; 3=Peregrine Pharm.
ABSTRACT: Bavituximab is a monoclonal antibody directed against the membrane phospholipid phosphatidylserine exposed on the outer leaflet of tumor and vascular endothelial cells of the tumor microenvironment. Bavituximab modulates the tumor microenvironment by blocking PS-mediated immune suppression and activating cytotoxic T lymphocyte anti-tumor responses.
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. Tissue was 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-gamma in culture media as a surrogate of TIL activation.
Preliminary results indicate the combination of bavituximab & docetaxel can induce TIL activation as demonstrated by a significant increase in IFN-gamma secretion when compared to tumors treated with control or either agent alone. Flow cytometry analysis revealed that this effect was associated with low PD-1 expression on CD8 cells, but did not correlate with other known immune-modulating receptors.
This lung patient derived ex-vivo approach indicates that bavituximab in combination with docetaxel 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 low PD1 expression as a potential prognostic biomarker of positive response to bavituximab treatment.

POSTER #274 PDF: http://www.peregrineinc.com/images/stories/pdfs/aacr_2015_lung.pdf