Thursday, April 23, 2015 10:24:14 AM
AACR’15 (3 Abstracts, 2 PR’s): Bavi Clinical TransData/Lung & PreClinData/Melanoma/Breast – Moffitt/S.Antonia, UTSW, Univ. of Calif/Irvine, Peregrine
AACR2015 PR #1 4-20-15:
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
TUSTIN, April 20, 2015: Peregrine Pharmaceuticals, Inc. (Nasdaq:PPHM) (Nasdaq:PPHMP) today announced the presentation of data from clinical translational studies of the company's phosphatidylserine (PS)-targeting immunotherapy bavituximab. Initial data from a pilot study of clinical translational ex vivo cultures show that bavituximab, both alone and with docetaxel, elicits evidence of a tumor-specific immune response in patients with human adenocarcinoma of the lung and that bavituximab exhibits an impact on tumors with negative PD-L1 expression. These data were presented yesterday, Sunday, April 19th, in a poster presentation at the 106th Annual Meeting of the American Association for Cancer Research (AACR) being held in Philadelphia, Pennsylvania from April 18-22, 2015. Bavituximab is currently being evaluated in second-line non-small cell lung cancer (NSCLC) as part of the SUNRISE pivotal Phase III clinical trial.
"Our translational findings of a cytokine profile that reflects an immune response following either bavituximab single-agent or combination treatment are encouraging. Furthermore, these preliminary translational data show that tumors with negative PD-L1 expression and low levels of PD-1 expression on CD8+ tumor infiltrating T cells showed immune response to bavituximab treatment ex vivo," said Sigrid M. Volko, Ph.D., CLP the lead investigator on the study and President & CEO of Nilogen Oncosystems [=Moffit Startup: http://otmc.moffitt.org/startups.aspx ]. "It is an exciting time for the field of immunotherapy and the data we have been generating support that bavituximab has the potential to activate a tumor specific immune response in patients with PD-L1 negative tumors that generally do not respond as well to PD-1 or PD-L1 inhibitors."
In a poster [ AACR’15 Abstract #274] titled: "Bavituximab Modulates Tumor Microenvironment and Activates CD8+ Tumor Infiltrating Lymphocytes in a Patient-derived 3D ex vivo System of Lung Cancer," researchers from Moffitt Cancer Center [Dr. Scott Antonia et al], Nilogen Oncosystems, and Peregrine present initial data from a pilot translation study analyzing tumor tissue from 6 lung cancer patients to evaluate the immunomodulatory effects of bavituximab in a human ex vivo model of NSCLC. Researchers generated 3D tumor microspheres from tumor tissues produced at the time of surgical resection. These microspheres were treated ex vivo for 36 hours with bavituximab, bavituximab and docetaxel, or controls in the presence of Interleukin-2 (IL-2), a cytokine that regulates the activities of white blood cells that are responsible for immunity. Data show that bavituximab as a single agent or in combination with docetaxel induces lymphocyte activation in tumors as demonstrated by a significant increase in interferon-gamma (IFNy), TNF-alpha, and GM-CSF secretion when compared to tumors treated with IL-2 control. Researchers also concluded that the immune response to treatment with bavituximab correlates with negative PD-L1 expression in the resected tumor tissue and low PD-1 expression on CD8+ tumor infiltrates thus serving as a potential prognostic biomarker of positive response to bavituximab treatment.
"These data are exciting as the immune responses seen in this translational lung cancer study mirror what we saw in translational data from a liver cancer clinical trial and is perfectly aligned with what has been seen preclinically to date. It was also encouraging to see how well these data further support our ongoing Phase III SUNRISE trial in that the combination of bavituximab and docetaxel induces immune activity," said Joseph Shan, MPH, VP of Clinical and Regulatory Affairs at Peregrine. "These data are playing a key role in advancing the clinical portion of an Immuno-Oncology Development Program which has been built upon a growing body of favorable data supporting the potential combination of bavituximab and checkpoint inhibitors. Specifically, these data show that activating the immune system in this negative PD-L1 patient population provides a strong rational for combining bavituximab with inhibitors of the PD-1/PD-L1 pathway. We look forward to detailing our plans for additional immuno-oncology combination clinical trials in the near future."
Liver Cancer Translational Data
In November, clinical translational data from the company's Immuno-Oncology Development Program were presented assessing changes in immune response pre- and post-treatment in 6 patients participating in a Phase II IST evaluating bavituximab in combination with sorafenib in advanced hepatocellular carcinoma. Data from this translational sub-study of patients, show that half of the patients had an increase in tumor fighting immune cells following one cycle of treatment, similar to what has been shown for PS-targeting antibodies in multiple preclinical cancer models. In addition, the increase in immune response was associated with patients that remained on study treatment for longer time periods, consistent with an immunotherapeutic mechanism and suggest the possibility of a clinically meaningful anti-tumor immune response. Immune responding patients also had increased infiltration of CD8 T-cells in the tumor microenvironment which correlated with a prolonged time to disease progression. In addition, these immune responders expressed lower levels of PD-1, an established marker of T cell activation and disease outcome, prior to the initiation of therapy, followed by a measurable rise.
A link to this presentation is located on the front page of Peregrine's website at http://www.peregrineinc.com .
http://www.peregrineinc.com/publications/posters-and-presentations.html
POSTER #274 PDF: http://www.peregrineinc.com/images/stories/pdfs/aacr_2015_lung.pdf
…ABOUT BAVITUXIMAB & ABOUT PEREGRINE: see PR#2 below.
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AACR2015 PR #2 4-21-15:
Preclinical Data Presented at AACR Demonstrate Synergistic Anti-Tumor Effects of Peregrine Pharmaceuticals' Phosphatidylserine (PS)-Targeting Antibodies With Immune Checkpoint Inhibitors in Models of Melanoma and Breast Cancer
• Combination Treatment Reduces Tumor Immune System Blockade and Enhances Tumor Specific Immune Responses
• Studies Reveal Significant Increases in Tumor-Infiltrating CD8+ T Cells and Immune-Activating Cytokines while Decreasing Tumor-Promoting Macrophages and Myeloid Cells
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=907609
TUSTIN, April 21, 2015: Peregrine Pharmaceuticals, Inc. (Nasdaq:PPHM) (Nasdaq:PPHMP) today announced the presentation of data from preclinical studies demonstrating the combination of phosphatidylserine (PS) blockade with anti-PD-1 or anti-CTLA-4 immune checkpoint inhibitors promoted strong, localized and enhanced efficacy in models of melanoma and breast cancer. These data were presented at the 106th Annual Meeting of the American Association for Cancer Research (AACR) being held in Philadelphia, Pennsylvania from April 18-22, 2015. Peregrine's lead PS-blocking antibody, bavituximab, is currently being evaluated in second-line non-small cell lung cancer (NSCLC) in a Phase III clinical trial named Sunrise.
"The data presented this week at AACR showed in much greater detail the collective ability of PS and PD-1 blockade to change the immune response in melanoma and breast cancer models," said Jeff T. Hutchins, Ph.D., VP of Preclinical Research at Peregrine. "These data showed that blocking PS resulted in a decrease in immune-blocking cell types such as myeloid-derived suppressor cells and M2 macrophages while increasing the number of activated T-cells that are able to specifically recognize and kill tumor cells which set the stage for anti-PD-1 therapy that keeps the immune response going. The result were synergistic anti-tumor effects in established melanoma and breast cancers. The consistency of the data generated from pre-clinical experiments, and, more recently, in clinical translational studies is impressive. When taken together with the additional lung cancer translational data presented Sunday, we are obtaining a clearer picture as to the potential of bavituximab in different immuno-oncology combinations. We look forward to presenting additional supporting data over the coming months."
In a poster [ AACR’15 Abstract #252] titled: "Antibody-mediated Phosphatidylserine Blockade Significantly Enhances the Efficacy of Immune Checkpoint Blockades in K1735 & B16 Mouse Melanoma Models," researchers from Peregrine, UT Southwestern Medical Center and the University of California at Irvine presented data assessing the antitumor effect of the combination of PS blockade and anti-CTLA-4 or anti-PD-1 antibodies in preclinical models of melanoma. Both combinations showed significantly superior tumor growth inhibition over single treatment, with many subjects achieving complete tumor regressions. The combination treatment showed significantly greater total and functional tumor-infiltrating CD8+ T, more IL-2- and interferon gamma (IFN?)-producing splenic T cells, and lower number of splenic myeloid derived suppressor cells myeloid-derived suppressor cells (MDSCs) than did single treatment. In addition, the ratio of M2 to M1 macrophages 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.
In a poster [ AACR’15 Abstract #4289] titled: "Targeting of Phosphatidylserine by Monoclonal Antibodies Enhances the Activity of Immune Checkpoint Inhibitors in Breast Tumors," Peregrine researchers presented data demonstrating that PS blockade enhances the anti-tumor activity of combination therapies including anti-PD-1 antibodies in an immune competent model of breast cancer. 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 and localized anti-tumor responses without the side-effects of systemic immune activation.
Copies of these presentations can be found on the front page of Peregrine's website at http://www.peregrineinc.com .
POSTER #252 PDF: http://www.peregrineinc.com/images/stories/pdfs/aacr_2015_melanoma.pdf
POSTER #4289 PDF:
http://www.peregrineinc.com/images/stories/pdfs/gong_2015_aacr_p.pdf
About Bavituximab: A Targeted Investigational Immunotherapy
Scientific research has shown that tumors evade immune detection due partly to the expression of phosphatidylserine, or PS, a highly immunosuppressive molecule. Peregrine's immuno-oncology development program has developed bavituximab, an investigational monoclonal antibody that targets and binds to PS, blocking its immunosuppressive effects while activating tumor fighting immune cells, thus enabling the immune system with the ability to better recognize and fight cancer. Bavituximab's immune-stimulatory mechanism-of-action data is the subject of a manuscript published in the October 2013 issue of the American Association for Cancer Research (AACR) peer-reviewed journal, Cancer Immunology Research [8-19-13: http://tinyurl.com/mhjftka PDF]. Bavituximab is currently being evaluated in several solid tumor indications, including non-small cell lung cancer (the SUNRISE Phase III trial), breast cancer, liver cancer, rectal cancer and advanced melanoma. In January 2014, bavituximab received Fast Track designation by the U.S. Food and Drug Administration (FDA) for the potential second-line treatment of patients with non-small cell lung cancer.
About Peregrine Pharmaceuticals, Inc.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a pipeline of novel drug candidates in clinical trials for the treatment and diagnosis of cancer. The company's lead immunotherapy candidate, bavituximab, is in Phase III development for the treatment of second-line non-small lung cancer (the "SUNRISE trial") along with several investigator-sponsored trials evaluating other treatment combinations and additional oncology indications. The company is also advancing a molecular imaging agent, 124I-PGN650, in an exploratory clinical trial for the imaging of multiple solid tumor types. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. (http://www.avidbio.com ), which provides development and biomanufacturing services for both Peregrine and third-party customers. For more information, please visit http://www.peregrineinc.com.
Safe Harbor *snip*
CONTACT: Christopher Keenan, Peregrine Pharmaceuticals, Inc., (800) 987-8256, info@peregrineinc.com
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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.
POSTER #274 PDF: http://www.peregrineinc.com/images/stories/pdfs/aacr_2015_lung.pdf
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.
POSTER #252 PDF: http://www.peregrineinc.com/images/stories/pdfs/aacr_2015_melanoma.pdf
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" http://youtu.be/0zLAxjFny5Q )
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.
POSTER #4289 PDF: http://www.peregrineinc.com/images/stories/pdfs/gong_2015_aacr_p.pdf
= = = = = = = = = =PIPER JAFFRAY 4-20-15 COMPANY NOTE:
”Bavi – Not Just Another IO Candidate”
= = = = = = = = = =ROTH CAPITAL 4-20-15 UPDATE:
”Positive on PPHM Following Bavituximab AACR’15 Presentation”
Roth Capital affirmed Peregrine Pharma (Nasdaq: PPHM) at Buy with a price target of $5 after the company announced the presentation of data from clinical translational studies of the company's phosphatidylserine (PS)-targeting immunotherapy bavituximab. Peregrine said that initial data from a pilot study of clinical translational ex vivo cultures show that bavituximab, both alone and with docetaxel, elicits evidence of a tumor-specific immune response in patients with human adenocarcinoma of the lung and that bavituximab exhibits an impact on tumors with negative PD-L1 expression.
Analyst Joseph Pantginis commented, ”We generally do not write on preclinical data, however we believe these data continue to represent important incremental steps in defining bavituximab's immunotherapy mechanism of action. In the lung model, immune response to treatment correlates with negative PD-L1 expression and low PD-1 expression on CD8+ tumor cells, which could represent a prognostic biomarker. We believe these data represent the closest ex-vivo model of the patient population being assessed in the ongoing Phase III SUNRISE study in 2nd-line NSCLC. Nilogen’s drug discovery platform is described in the figure below. Over the next 12-mos, we expect to see an increase in visibility on the shares based on 1) completion of enrollment into the Phase III SUNRISE study, 2) incremental data updates from earlier clinical studies, and 3) increasing visibility for bavituximab's mechanism of action within the immuno-oncology landscape. The ~600 patient SUNRISE study in 2nd-line NSCLC is expected to complete enrollment by the end of 2015…”
http://www.streetinsider.com/Analyst+Comments/Roth+Capital+Remains+Positive+on+Peregrine+Pharma+%28PPHM%29+Following+Bavituximab+Presentation/10471273.html
http://www.roth.com – Universe: http://roth.bluematrix.com/docs/pdf/BLUE.pdf
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Bavituximab MOA & Clinical Data: http://www.peregrineinc.com/pipeline/bavituximab-oncology.html
...Bavi Publications: http://www.peregrineinc.com/publications/publications.html
...Bavi Posters & Presentations: http://www.peregrineinc.com/publications/posters-and-presentations.html
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 https://www.youtube.com/watch?v=Esewl35JD8s
BAVI MOA 3-25-15: PPHM/VP Dr. Jeff Hutchins’ presentation at "Immune Checkpoint Inhibitors Conf.", Boston - PDF(34 Slides): http://tinyurl.com/ooxkhq7
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
BAVI MOA: 5-26-11 Dr.Thorpe's keynoter at Recombinant-Mabs/Barcelona http://tinyurl.com/3klpodc & http://tinyurl.com/3m33h33
AACR2015 PR #1 4-20-15:
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
TUSTIN, April 20, 2015: Peregrine Pharmaceuticals, Inc. (Nasdaq:PPHM) (Nasdaq:PPHMP) today announced the presentation of data from clinical translational studies of the company's phosphatidylserine (PS)-targeting immunotherapy bavituximab. Initial data from a pilot study of clinical translational ex vivo cultures show that bavituximab, both alone and with docetaxel, elicits evidence of a tumor-specific immune response in patients with human adenocarcinoma of the lung and that bavituximab exhibits an impact on tumors with negative PD-L1 expression. These data were presented yesterday, Sunday, April 19th, in a poster presentation at the 106th Annual Meeting of the American Association for Cancer Research (AACR) being held in Philadelphia, Pennsylvania from April 18-22, 2015. Bavituximab is currently being evaluated in second-line non-small cell lung cancer (NSCLC) as part of the SUNRISE pivotal Phase III clinical trial.
"Our translational findings of a cytokine profile that reflects an immune response following either bavituximab single-agent or combination treatment are encouraging. Furthermore, these preliminary translational data show that tumors with negative PD-L1 expression and low levels of PD-1 expression on CD8+ tumor infiltrating T cells showed immune response to bavituximab treatment ex vivo," said Sigrid M. Volko, Ph.D., CLP the lead investigator on the study and President & CEO of Nilogen Oncosystems [=Moffit Startup: http://otmc.moffitt.org/startups.aspx ]. "It is an exciting time for the field of immunotherapy and the data we have been generating support that bavituximab has the potential to activate a tumor specific immune response in patients with PD-L1 negative tumors that generally do not respond as well to PD-1 or PD-L1 inhibitors."
In a poster [ AACR’15 Abstract #274] titled: "Bavituximab Modulates Tumor Microenvironment and Activates CD8+ Tumor Infiltrating Lymphocytes in a Patient-derived 3D ex vivo System of Lung Cancer," researchers from Moffitt Cancer Center [Dr. Scott Antonia et al], Nilogen Oncosystems, and Peregrine present initial data from a pilot translation study analyzing tumor tissue from 6 lung cancer patients to evaluate the immunomodulatory effects of bavituximab in a human ex vivo model of NSCLC. Researchers generated 3D tumor microspheres from tumor tissues produced at the time of surgical resection. These microspheres were treated ex vivo for 36 hours with bavituximab, bavituximab and docetaxel, or controls in the presence of Interleukin-2 (IL-2), a cytokine that regulates the activities of white blood cells that are responsible for immunity. Data show that bavituximab as a single agent or in combination with docetaxel induces lymphocyte activation in tumors as demonstrated by a significant increase in interferon-gamma (IFNy), TNF-alpha, and GM-CSF secretion when compared to tumors treated with IL-2 control. Researchers also concluded that the immune response to treatment with bavituximab correlates with negative PD-L1 expression in the resected tumor tissue and low PD-1 expression on CD8+ tumor infiltrates thus serving as a potential prognostic biomarker of positive response to bavituximab treatment.
"These data are exciting as the immune responses seen in this translational lung cancer study mirror what we saw in translational data from a liver cancer clinical trial and is perfectly aligned with what has been seen preclinically to date. It was also encouraging to see how well these data further support our ongoing Phase III SUNRISE trial in that the combination of bavituximab and docetaxel induces immune activity," said Joseph Shan, MPH, VP of Clinical and Regulatory Affairs at Peregrine. "These data are playing a key role in advancing the clinical portion of an Immuno-Oncology Development Program which has been built upon a growing body of favorable data supporting the potential combination of bavituximab and checkpoint inhibitors. Specifically, these data show that activating the immune system in this negative PD-L1 patient population provides a strong rational for combining bavituximab with inhibitors of the PD-1/PD-L1 pathway. We look forward to detailing our plans for additional immuno-oncology combination clinical trials in the near future."
Liver Cancer Translational Data
In November, clinical translational data from the company's Immuno-Oncology Development Program were presented assessing changes in immune response pre- and post-treatment in 6 patients participating in a Phase II IST evaluating bavituximab in combination with sorafenib in advanced hepatocellular carcinoma. Data from this translational sub-study of patients, show that half of the patients had an increase in tumor fighting immune cells following one cycle of treatment, similar to what has been shown for PS-targeting antibodies in multiple preclinical cancer models. In addition, the increase in immune response was associated with patients that remained on study treatment for longer time periods, consistent with an immunotherapeutic mechanism and suggest the possibility of a clinically meaningful anti-tumor immune response. Immune responding patients also had increased infiltration of CD8 T-cells in the tumor microenvironment which correlated with a prolonged time to disease progression. In addition, these immune responders expressed lower levels of PD-1, an established marker of T cell activation and disease outcome, prior to the initiation of therapy, followed by a measurable rise.
A link to this presentation is located on the front page of Peregrine's website at http://www.peregrineinc.com .
http://www.peregrineinc.com/publications/posters-and-presentations.html
POSTER #274 PDF: http://www.peregrineinc.com/images/stories/pdfs/aacr_2015_lung.pdf
…ABOUT BAVITUXIMAB & ABOUT PEREGRINE: see PR#2 below.
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AACR2015 PR #2 4-21-15:
Preclinical Data Presented at AACR Demonstrate Synergistic Anti-Tumor Effects of Peregrine Pharmaceuticals' Phosphatidylserine (PS)-Targeting Antibodies With Immune Checkpoint Inhibitors in Models of Melanoma and Breast Cancer
• Combination Treatment Reduces Tumor Immune System Blockade and Enhances Tumor Specific Immune Responses
• Studies Reveal Significant Increases in Tumor-Infiltrating CD8+ T Cells and Immune-Activating Cytokines while Decreasing Tumor-Promoting Macrophages and Myeloid Cells
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=907609
TUSTIN, April 21, 2015: Peregrine Pharmaceuticals, Inc. (Nasdaq:PPHM) (Nasdaq:PPHMP) today announced the presentation of data from preclinical studies demonstrating the combination of phosphatidylserine (PS) blockade with anti-PD-1 or anti-CTLA-4 immune checkpoint inhibitors promoted strong, localized and enhanced efficacy in models of melanoma and breast cancer. These data were presented at the 106th Annual Meeting of the American Association for Cancer Research (AACR) being held in Philadelphia, Pennsylvania from April 18-22, 2015. Peregrine's lead PS-blocking antibody, bavituximab, is currently being evaluated in second-line non-small cell lung cancer (NSCLC) in a Phase III clinical trial named Sunrise.
"The data presented this week at AACR showed in much greater detail the collective ability of PS and PD-1 blockade to change the immune response in melanoma and breast cancer models," said Jeff T. Hutchins, Ph.D., VP of Preclinical Research at Peregrine. "These data showed that blocking PS resulted in a decrease in immune-blocking cell types such as myeloid-derived suppressor cells and M2 macrophages while increasing the number of activated T-cells that are able to specifically recognize and kill tumor cells which set the stage for anti-PD-1 therapy that keeps the immune response going. The result were synergistic anti-tumor effects in established melanoma and breast cancers. The consistency of the data generated from pre-clinical experiments, and, more recently, in clinical translational studies is impressive. When taken together with the additional lung cancer translational data presented Sunday, we are obtaining a clearer picture as to the potential of bavituximab in different immuno-oncology combinations. We look forward to presenting additional supporting data over the coming months."
In a poster [ AACR’15 Abstract #252] titled: "Antibody-mediated Phosphatidylserine Blockade Significantly Enhances the Efficacy of Immune Checkpoint Blockades in K1735 & B16 Mouse Melanoma Models," researchers from Peregrine, UT Southwestern Medical Center and the University of California at Irvine presented data assessing the antitumor effect of the combination of PS blockade and anti-CTLA-4 or anti-PD-1 antibodies in preclinical models of melanoma. Both combinations showed significantly superior tumor growth inhibition over single treatment, with many subjects achieving complete tumor regressions. The combination treatment showed significantly greater total and functional tumor-infiltrating CD8+ T, more IL-2- and interferon gamma (IFN?)-producing splenic T cells, and lower number of splenic myeloid derived suppressor cells myeloid-derived suppressor cells (MDSCs) than did single treatment. In addition, the ratio of M2 to M1 macrophages 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.
In a poster [ AACR’15 Abstract #4289] titled: "Targeting of Phosphatidylserine by Monoclonal Antibodies Enhances the Activity of Immune Checkpoint Inhibitors in Breast Tumors," Peregrine researchers presented data demonstrating that PS blockade enhances the anti-tumor activity of combination therapies including anti-PD-1 antibodies in an immune competent model of breast cancer. 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 and localized anti-tumor responses without the side-effects of systemic immune activation.
Copies of these presentations can be found on the front page of Peregrine's website at http://www.peregrineinc.com .
POSTER #252 PDF: http://www.peregrineinc.com/images/stories/pdfs/aacr_2015_melanoma.pdf
POSTER #4289 PDF:
http://www.peregrineinc.com/images/stories/pdfs/gong_2015_aacr_p.pdf
About Bavituximab: A Targeted Investigational Immunotherapy
Scientific research has shown that tumors evade immune detection due partly to the expression of phosphatidylserine, or PS, a highly immunosuppressive molecule. Peregrine's immuno-oncology development program has developed bavituximab, an investigational monoclonal antibody that targets and binds to PS, blocking its immunosuppressive effects while activating tumor fighting immune cells, thus enabling the immune system with the ability to better recognize and fight cancer. Bavituximab's immune-stimulatory mechanism-of-action data is the subject of a manuscript published in the October 2013 issue of the American Association for Cancer Research (AACR) peer-reviewed journal, Cancer Immunology Research [8-19-13: http://tinyurl.com/mhjftka PDF]. Bavituximab is currently being evaluated in several solid tumor indications, including non-small cell lung cancer (the SUNRISE Phase III trial), breast cancer, liver cancer, rectal cancer and advanced melanoma. In January 2014, bavituximab received Fast Track designation by the U.S. Food and Drug Administration (FDA) for the potential second-line treatment of patients with non-small cell lung cancer.
About Peregrine Pharmaceuticals, Inc.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a pipeline of novel drug candidates in clinical trials for the treatment and diagnosis of cancer. The company's lead immunotherapy candidate, bavituximab, is in Phase III development for the treatment of second-line non-small lung cancer (the "SUNRISE trial") along with several investigator-sponsored trials evaluating other treatment combinations and additional oncology indications. The company is also advancing a molecular imaging agent, 124I-PGN650, in an exploratory clinical trial for the imaging of multiple solid tumor types. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. (http://www.avidbio.com ), which provides development and biomanufacturing services for both Peregrine and third-party customers. For more information, please visit http://www.peregrineinc.com.
Safe Harbor *snip*
CONTACT: Christopher Keenan, Peregrine Pharmaceuticals, Inc., (800) 987-8256, info@peregrineinc.com
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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.
POSTER #274 PDF: http://www.peregrineinc.com/images/stories/pdfs/aacr_2015_lung.pdf
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.
POSTER #252 PDF: http://www.peregrineinc.com/images/stories/pdfs/aacr_2015_melanoma.pdf
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" http://youtu.be/0zLAxjFny5Q )
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.
POSTER #4289 PDF: http://www.peregrineinc.com/images/stories/pdfs/gong_2015_aacr_p.pdf
= = = = = = = = = =PIPER JAFFRAY 4-20-15 COMPANY NOTE:
”Bavi – Not Just Another IO Candidate”
= = = = = = = = = =ROTH CAPITAL 4-20-15 UPDATE:
”Positive on PPHM Following Bavituximab AACR’15 Presentation”
Roth Capital affirmed Peregrine Pharma (Nasdaq: PPHM) at Buy with a price target of $5 after the company announced the presentation of data from clinical translational studies of the company's phosphatidylserine (PS)-targeting immunotherapy bavituximab. Peregrine said that initial data from a pilot study of clinical translational ex vivo cultures show that bavituximab, both alone and with docetaxel, elicits evidence of a tumor-specific immune response in patients with human adenocarcinoma of the lung and that bavituximab exhibits an impact on tumors with negative PD-L1 expression.
Analyst Joseph Pantginis commented, ”We generally do not write on preclinical data, however we believe these data continue to represent important incremental steps in defining bavituximab's immunotherapy mechanism of action. In the lung model, immune response to treatment correlates with negative PD-L1 expression and low PD-1 expression on CD8+ tumor cells, which could represent a prognostic biomarker. We believe these data represent the closest ex-vivo model of the patient population being assessed in the ongoing Phase III SUNRISE study in 2nd-line NSCLC. Nilogen’s drug discovery platform is described in the figure below. Over the next 12-mos, we expect to see an increase in visibility on the shares based on 1) completion of enrollment into the Phase III SUNRISE study, 2) incremental data updates from earlier clinical studies, and 3) increasing visibility for bavituximab's mechanism of action within the immuno-oncology landscape. The ~600 patient SUNRISE study in 2nd-line NSCLC is expected to complete enrollment by the end of 2015…”
http://www.streetinsider.com/Analyst+Comments/Roth+Capital+Remains+Positive+on+Peregrine+Pharma+%28PPHM%29+Following+Bavituximab+Presentation/10471273.html
http://www.roth.com – Universe: http://roth.bluematrix.com/docs/pdf/BLUE.pdf
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Bavituximab MOA & Clinical Data: http://www.peregrineinc.com/pipeline/bavituximab-oncology.html
...Bavi Publications: http://www.peregrineinc.com/publications/publications.html
...Bavi Posters & Presentations: http://www.peregrineinc.com/publications/posters-and-presentations.html
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 https://www.youtube.com/watch?v=Esewl35JD8s
BAVI MOA 3-25-15: PPHM/VP Dr. Jeff Hutchins’ presentation at "Immune Checkpoint Inhibitors Conf.", Boston - PDF(34 Slides): http://tinyurl.com/ooxkhq7
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
BAVI MOA: 5-26-11 Dr.Thorpe's keynoter at Recombinant-Mabs/Barcelona http://tinyurl.com/3klpodc & http://tinyurl.com/3m33h33
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