Replies to post #205717 on Avid Bioservices Inc (CDMO)

[cjgaddy]

PPHM’s Dr.Jeff.Hutchins 3-25-15 Oral at Immune-Checkpoint-Inhibitors Forum/Boston. “Pioneers such as Merck, BMS, Genentech, Novartis, EMD Serono, and Amgen will unveil the very latest exciting industry intelligence leaving you bursting with insights, ideas and solutions.” Peregrine is 1 of 7 Sponsors.

Mar24-26 2015: “Immune Checkpoint Inhibitors: Validate Novel Pathways, Discover Predictive Biomarkers, Optimize Clinical Strategy”, Boston
“"This conference will be the 1st to exclusively explore the current state & future of ICI in drug development. Designed with Merck, BMS, Genentech, Novartis, EMD Serono, and Amgen, this industry forum will crack the roadblocks limiting further progress in the field. Building on the foundations of pioneering academic research this conference will focus uniquely on the challenges for drug developers.”
http://immune-checkpoint.com Agenda: http://immune-checkpoint.com/what/agenda
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3-25-15 11:30am ORAL Pres: Jeff Hutchins, PhD, VP/Preclin-Res., Peregrine Pharm.
“Expansion & Activation of T-cells via the Targeting of the Immunosuppressive Ligand Phosphatidylserine: Combination Strategy with Other Checkpoint Inhibitors”




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Bavi MOA: Video (3:34) added ~3-2014 http://vimeo.com/87116642 "Bavituximab: A Novel Immunotherapy Candidate Targeting an Upstream Immune Checkpoint to Fight Cancer"
Bavi MOA: Video (1:33) on Bavi’s Immunotherapeutic MOA added to Youtube on 3-27-14

BAVI MOA 2-9-15: PPHM/VP Dr. Bruce Freimark’s presentation at KEYSTONE "Tumor Immunology Meeting", Banff/CN – PR & Slides: http://tinyurl.com/q6cx4w6
BAVI MOA 12-12-14 San Antomio Breast Cancer Symposium, Dr. Bruce Freimark, Bavi+anti-PD-1 vs. Breast Cancer http://tinyurl.com/p5ng6vs
BAVI MOA 11-2014 SITC’14: 3 posters on preclin. Bavi+aCTLA4/aPD1 combo data (Hutchins Freimark Brekken Huang etal) http://tinyurl.com/pchzr6h
BAVI MOA 8-28-14: Italy’s Dr. Federico Cappuzzo, Bavi/NSCLC profile article (DovePress OpenAccess, 7pgs) - http://tinyurl.com/n3oa7bc
BAVI MOA 8-11-14: PPHM/VP Dr. Jeff Hutchins’ presentation at ImVacS "Immunotherapies & Vaccine Summit", Boston - PR: http://tinyurl.com/lpjy3u7 ; PDF(31 Slides): http://tinyurl.com/oueldme
...MLV’s Dr. George Zavoico’s 8-27-14 report on Dr. Jeff Hutchins’ 8-11-14 ImVacS/Boston Bavi MOA presentation: http://tinyurl.com/l3tw63c
BAVI MOA 5-28-14: Dr. Rolf Brekken’s 47min CRI “Cancer Immunotherapy” webinar about Bavituximab as an Upstream/Global Immune Checkpoint Inhibitor – REPLAY: http://tinyurl.com/lxgftyx
. . .CRI=Cancer Research Institute (NYC – Supported by BMS): http://www.cancerresearch.org - Facebook: http://tinyurl.com/pbmhb2z , https://twitter.com/CancerResearch
. . .CRI launches “Answer to Cancer” (cancer immunotherapy) website http://www.theanswertocancer.org
. . .8-12-14: CRI adds Youtube links to the 5-28-14 CRI Immunotherapy webinar, incl. Dr. Brekken's talk "about Bavi and how it works against lung, liver, and other kinds of cancers" http://tinyurl.com/ps5h6h8
BAVI MOA 3-25-14: Dr. Rolf Brekken’s 40min talk at NYAS Lung Cancer Symposium http://tinyurl.com/lq9stnk (45 Slides)
. . .Dr.Brekken’s talk: “Antibody-mediated Inhibition of PS - A Novel Strategy for Immune Checkpoint Blockade” (the 5 speakers: Jessica Donington, Roy Herbst, Balazs Halmos, Suresh Ramalingam, Rolf Brekken)
12-10-13: With recent scientific insights highlighting bavi’s immunostimulatory moa, these additions to PPHM’s SAB: Dimitry Gabrilovich, Scott Antonia, David Carbone**, Hakan Mellstedt http://tinyurl.com/mw776mk
......**A/o 9-2014, Dr. David Carbone (PPHM SAB/KOL) is President-Elect of IASLC https://www.iaslc.org/about-us/board
BAVI MOA: 12-2013 Bavi’s Immunotherapeutic MOA overviewed by UTSW’s Brekken/Huang in Pan European Networks Jrnl. http://tinyurl.com/lnb46pq
BAVI MOA 11-9-13: Annual SITC (WashDC) – 2 posters about Bavi’s Immunostimulatory MOA http://tinyurl.com/mjaweu5
...“We are actively working towards initiating a clinical trial in the coming months to further investigate the potential synergistic effects of bavituximab and an approved [anti-CTLA-4] immunotherapy in patients with Melanoma."
10-28-13 IASLC/Sydney: “Immune Checkpoints in the Tumor Environment: Novel Targets & the Clinical Promise of Combined Immunotherapies” http://tinyurl.com/mjaweu5
…Symposium speakers: Scott J. Antonia/MD-PhD(H.Lee Moffitt CC), Dmitry I. Gabrilovich/MD-PhD(Wistar Inst), Rolf A. Brekken/PhD(UTSW), David E. Gerber/MD(UTSW)
BAVI MOA: 8-19-13 Data Supporting Bavituximab’s Immunotherapy MOA Published in “Cancer Immunology Research” (AACR) - http://tinyurl.com/mhjftka (PDF)
…“PS-Targeting Antibody Induces M1 Macrophage Polarization & Promotes Myeloid-Derived Suppressor Cell Differentiation” (Thorpe etal)
BAVI MOA: 8-13-13 PPHM/VP Dr. Jeff Hutchins’ Presentation on the Downstream Immunostimulatory Effects/Moa of PS-targeting antibodies (like Bavi) at CHI’s “Immunotherapies Congress”/Boston http://tinyurl.com/m6h2tvt
BAVI MOA: 10-12-12 NMB article on how Bavi "Induces Innate & Specific Anti-tumor Responses" http://tinyurl.com/cw9odb8
BAVI MOA: 5-1-12 Dr. Phil Thorpe's 46min talk at NYAS PS-Targeting Symposium http://tinyurl.com/9792gl5
. . .Symposium title: "Phosphatidylserine (PS) Asymmetry - Therapeutic Apps. in Cancer & Infectious Disease Symposium"
. . .Replays of 5 speakers: Alan Schroit, Chris Reutlingsperger, David Ucker, Ari Helenius, Philip Thorpe

[cjgaddy]

CEO S.King’s 3-9-15 ROTH/DanaPT Talk (40 Slides/24mins)

Mar8-11 2015: “Roth’s 27th Annual OC Growth Stock Conf.”, DanaPT, CA
http://www.roth.com/main/Page.aspx?PageID=7207

CEO Steven King’s 24 min. Presentation – Roth/DanaPT CA
3-9-2015 10amPT WEBCAST Replay: http://ir.peregrineinc.com/events.cfm
Direct Replay: http://wsw.com/webcast/roth29/pphm







































































Slide37/S.King(17:57): “We have a wholly-owned subsidiary, Avid Bioservices, which is a profitable business. In fact, if you look at the revenues generated from Avid, they more or less cover our overall G&A, so as we go out and raise capital, more of that goes directly to fund R&D efforts, which of course lead to the big increases in evaluation in the future. We’ve had nice growth over the last several years, and, again, we are in the process of expanding this facility. This is be a state-of-the-art facility, driven by both client interest as well as the work going on at Peregrine with Bavi and other compounds in development. This more than doubles our overall mfg. capacity, so creating a lot of addl. revenue-generating potential as well as preparing us for Bavi commercialization in the future. And this can be very important, because if you look at the recent news from the immune-oncology space, probably the biggest news came out of Bristol-Meyers was their PD-1 compound, and with the compound they had interim data looks; they stopped the trial based on positive results from that interim data look, and as little as 3 mos. later they’ve already now received FDA approval. So, it shows how quickly in this space that compounds can move. Part of this is having clinical data, and part of it is being in a position to mfg. the drug, so it’s a big benefit having this type asset that generates revenues and also prepares us for that success.”








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Roth Capital /Joe Pantginis - init. 7-15-10 Buy/PT=$10, CURR: Buy/$5 http://www.roth.com
. . .Universe (click link bottom right): http://roth.bluematrix.com/docs/pdf/BLUE.pdf
. . .12-11-14: Roth maintains PPHM PT=$5 ("we believe visibility from the broadening bavi profile & partnering potential should drive the stock in ‘15") http://tinyurl.com/k95gxum
. . .9-10-14: Roth maintains PPHM PT=$5 ("broadening bavituximab profile & partnering potential should drive the stock") http://tinyurl.com/qgkqm75
. . .7-15-14: Roth maintains PPHM PT=$5 ("remains encouraged by progress in FY14") http://tinyurl.com/nwacgev
. . .6-28-13: Roth lowers PPHM PT 7=>$5 (following PPHM's 6-27-13 press release)
. . .6-3-13: Roth raises PPHM PT 4=>$7 ("ASCOdata+FDA_ph3 agreement & visibility should represent the final potential triggers to conclude a partnership deal.") http://tinyurl.com/kkvddt2
. . .1-14-13: Roth raises PPHM PT 2.70=>$4.00 ("partnering discussions have new found life") http://tinyurl.com/a9t29lb
. . .1-7-13: Roth ups Neutral to BUY, PT 1.25=>$2.70 (after 2nd-Line NSCLC Review Upd) http://tinyurl.com/bfj7mva
. . .12-11-12: Roth ups PT $.70=>$1.25 after Cotara Ph3 design approval & 12-10-12/10Q-CC.
. . .9-24-12: Roth cuts PT $9=>$.70 after PPHM PR about 2nd-Line NSCLC trial data problems.
. . .9-10-12: Roth ups PT $5=>$9 ("highly encouraged by 2ndLine NSCLC clinical data") http://tinyurl.com/9blrqk7
. . .8-15-12: Roth adds PPHM to focus list as a Top Biotech Pick: http://tinyurl.com/9rx5bps
. . .5-21-12: Roth ups PT $3.30=>$5 ("impressed by the strong 2ndLine NSCLC clinical data") http://tinyurl.com/cnghzyv

[cjgaddy]

AACR’15(Apr19-21), Peregrine’s 3 Abstracts: “PS targeting can override PS-mediated immunosuppression, reactivate innate tumor immunity, and evoke adaptive antitumor immunity”…

Apr18-22 2015: AACR 106th Annual Meeting, Phily http://www.aacr.org/2015
Abstracts: http://www.abstractsonline.com/plan/start.aspx
PEREGRINE’s Posters:
• Abstract #274(Apr19): “Bavituximab Modulates Tumor Microenvironment and Activates CD8+ Tumor Infiltrating Lymphocytes in a Patient-Derived 3D Ex-Vivo System of Lung Cancer”
• Abstract #252(Apr19): “Antibody-Mediated Phosphatidylserine Blockade Significantly Enhances the Efficacy Of Immune Checkpoint Blockades in K1735 & B16 Mouse Melanoma Models” [Bavi+Ipilimumab(BMS’s Yervoy)]
• Abstract #4289(Apr21): “Targeting of Phosphatidylserine by Monoclonal Antibodies Enhances the Activity of Immune Checkpoint Inhibitors in Breast Tumors”

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.

Sun. Apr 19, 2015, 1-5pm, Abstract#252, Session: IMMUNE CHECKPOINTS
“Antibody-Mediated Phosphatidylserine Blockade Significantly Enhances the Efficacy of Immune Checkpoint Blockades in K1735 & B16 Mouse Melanoma Models”
Bruce Freimark 1, Jian Gong 1, Dan Ye 2, Rolf Brekken 2, Shen Yin 1, Jeff Hutchins 1, Van Nguyen 1, Chris Hughes 3, Xianming Huang 2
1=Peregrine Pharm.; 2=UTSW-MC/Dallas; 3=Univ. of Calif/Irvine
ABSTRACT: Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane and becomes exposed abundantly on tumor endothelial cells, tumor-secreted microvesicles, and tumor cells in response to chemo- and radiotherapy. Extensive studies have shown that PS is a global immune checkpoint and major contributor to tumor immunosuppression, which promotes the expansion of immunosuppressive cells, such MDSC & M2 macrophages, inhibits DCs maturation, while stimulates them to secrete immunosuppressive mediators. We have shown that PS targeting can override PS-mediated immunosuppression, reactivate innate tumor immunity, and evoke adaptive antitumor immunity. In the present study, we assessed the antitumor effect of the combination of PS blockade and anti-CTLA-4 or anti-PD-1 antibodies in B16 & K1735 melanoma models. Both combinations showed significantly superior tumor growth inhibition over single treatment, with many mice achieving complete tumor regression. Flow cytometry analysis showed that the combination treatment had significantly greater total and functional tumor-infiltrating CD8+ T, more IL-2- and IFNy-producing splenic T cells, and lower number of splenic MDSCs than did single treatment. In addition, the ratio of M2 to M1 in the tumor was significantly lower in the combination treatment than that in single treatment. Finally, no toxicity was observed in any of the treatment groups following multiple treatment doses. These data suggest that combination of PS blockade with immune checkpoint blockade promotes strong, localized, enhanced therapeutic efficacy without the side-effects of systemic immune activation and represents a promising combinatorial strategy for cancer immunotherapy. A chimeric PS-targeting antibody, bavituximab, is being used in combination with chemotherapy to treat patients with solid tumors in multiple late-stage clinical trials. These data support our Phase I IST evaluation of our PS-targeting antibody bavituximab in combination with ipilimumab in advanced melanoma patients.
NOTES:
Ipilimumab=BMS’s Yervoy (anti-CTLA-4) http://www.yervoy.com ]
O. PPHM’s 6th IST Trial: Bavi+Ipilimumab(Yervoy) vs. Adv.Melanoma (Ph1b, random, open-label, 2arms, n=24)
Protocol (UTSW): http://www.clinicaltrials.gov/ct2/show/NCT01984255 (PI: Dr. Arthur Frankel - see "Researching for Cures"

)
UTSW's listing: http://www.utsouthwestern.edu/research/fact/detail.html?studyid=STU%20102013-007
...4-23-14: Bavi+Yervoy IST trial initiated: http://tinyurl.com/km7krcm

Tue. Apr 21, 2015, 1-5pm, Abstract#4289, Session: NOVEL IMMUNOMODULATORS
”Targeting of Phosphatidylserine by Monoclonal Antibodies Enhances the Activity of Immune Checkpoint Inhibitors in Breast Tumors”
Jian Gong, Shen Yin, Van Nguyen, Jeff Hutchins, Bruce D. Freimark - Peregrine Pharm.
ABSTRACT: Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane that becomes exposed on tumor vascular endothelial cells (ECs) and tumor cells. PS exposure becomes enhanced in response to chemotherapy, irradiation, and oxidative stresses in the tumor microenvironment. PS exposure in tumors promotes an immunosuppressive microenvironment which includes the recruitment of myeloid derived suppressor cells (MDSCs), immature dendritic cells and M2-like macrophages, as well as, the production of anti-inflammatory cytokines. Binding of PS targeting antibodies on tumor endothelial cells, tumor cells and their secreted microparticles triggers an Fc-FcR mediated pro-inflammatory cellular and cytokine response that reverses the immunosuppressive PS meditated checkpoint, thereby enhancing anti-tumor immunity. A chimeric PS-targeting antibody, bavituximab, is being used in combination with chemotherapy to treat patients with solid tumors in multiple late-stage clinical trials. Using breast tumors in immune competent mice, we demonstrate PS targeting antibodies enhance the anti-tumor activity of combination therapies including anti-PD-1 antibodies. Tumor growth inhibition correlates with statistically significant increases in the infiltration of CD8+ T cells and a reduction of myeloid-derived suppressor cells (MDSCs). The combination of these mechanisms promotes strong, localized, anti-tumor responses without the side-effects of systemic immune activation.

[TampaTradr]

That’s not a slide, that is a CJG post.

You are incorrect and he is not.