Tuesday, November 11, 2014 8:31:54 AM
SITC’14 (Nov7-8): PPHM’s 4 Posters: Bavi+Sorafenib/LIVER/UTSW/Yopp “correlative studies” data ("translational data showing immune changes"), and 3 AntiPS+AntiPD1/Melanoma+Breast preclin’s indicating PS-targeting Mabs “enhance the activity of immune checkpoint inhibitors”. Freimark, Hutchins, Yopp, Shan, Brekken CW.Hughes(UC-Irvine), Menander, King, D.Gabrilovich(Wistar/KOL), etal…
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2014 Meeting: http://www.eventscribe.com/2014/sitc
SUMMARY – these 4 posters presented – details below, incl. images of the posters themselves:
• 11-8-14/P214: “Correlative studies of a Phase II study of Bavituximab & Sorafenib in Patients with Advanced Hepatocellular Carcinoma” (Yopp Kallinteris Shan Menander Hutchins King Gabrilovich Brekken Huang)
• 11-7-14/P266: “Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-CTLA-4 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment” (Freimark Hutchins CW-Hughes Brekken Huang)
• 11-8-14/P205: “Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor a-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment” (Freimark Hutchins CW-Hughes Brekken Xianming Huang)
• 11-8-14/P206: ”Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor a-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Breast Tumor Microenvironment” (Gong, Yin, VanNguyen, Hutchins, Freimark)
DETAIL (Nov7 & Nov10 PR’s below):
= = = = = = = = = =11-2014/SITC POSTERS Source=PeregrineInc.com:
11-8-14/SITC: “Correlative studies of a Phase II study of Bavituximab & Sorafenib in Patients with Advanced Hepatocellular Carcinoma”
Adam Yopp 1, Nikoletta L. Kallinteris 2, Joe Shan 2, Kerstin Menander 2, Shen Yin 2, Jeff Hutchins 2 , Steve King 2, Xiaowei Xu 3, Dmitry Gabrilovich 4, Brekken 1,5, Xianming Huang 5 [1=UTSW, 2=PPHM, 3=UPENN, 4=Wistar, 5=UTSW]
VIEW POSTER (Jrnl=P214) http://www.peregrineinc.com/images/stories/pdfs/sitc_2014_h_nk_pphm_1240.pdf
• Nikoletta Kallinteris’ comments: "These translational data align very well with previous preclin. data that define bavituximab's immunotherapy-based moa and show that the combination of bavituximab & sorafenib can potentiate an anti-tumor response in patients with advanced HCC. Another interesting observation is that the increase in PD-1 positive T-cells observed in several patients from this trial provides rationale for the potential of bavituximab to increase the number of subjects who may respond to PD-1 targeted treatments.”
• Dimitry I. Gabrilovich’s (KOL/Wistar) comments: “The correlative studies from these liver cancer patients provide further support for the hypothesis that bavituximab can positively regulate immune cells in tumors and thus may provide a new and exciting possibility for therapeutic manipulation of the tumor microenvironment.”
= = = = = = = = = = = = =
H. 1st Investigator-Sponsored (IST) Ph.I/II Trial (Bavi+Sorafenib vs. Liver Cancer/HCC, open-label)
...Note: Sorafenib = Onyx/Bayer's Nexavar - see http://www.nexavar.com
Protocol: http://clinicaltrials.gov/ct2/show/NCT01264705 UTSW: http://tinyurl.com/mwdc2ql (5 sites: 3/UTSW, Parkland-Hosp, Dallas/VA, PI=Dr. Adam Yopp)
...4-4-12 AACR'12: Dr. Adam Yopp, "promising safety profile to-date" http://tinyurl.com/7yrwqm7 (see #5591)
...Feb'12-Sep’14 10+ times: CEO Steve King hints of future ex-US partner-driven Bavi+Sorafenib/LIVER trial in Asia: http://tinyurl.com/nkaxtcc
......Articles & Data describe Liver Cancer challenges in Asian populations: http://tinyurl.com/7z7o8j9 & http://tinyurl.com/7z99cy4
...12-1-10: PPHM's 1st IST (Liver Cancer) initiated at UTSW, ~56 patients - http://tinyurl.com/3xd3e6c
…Per S.King, 5-18-10/R&R, "We've had a lot of interest in running clinical trials with the compound from investigators who have either had prior experience with the drug or would like to study the drug in various settings. Potential IST indications include all the major solid tumor types. Of particular interest is Liver Cancer, in which we have a natural tie-in with our HCV program, Ovarian Cancer and Pancreatic Cancer, also very nicely supported by the prior data."
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11-7-14/SITC: “Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-CTLA-4 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment”
Bruce Freimark 1, Jian Gong 1, Shen Yin 1, Van Nguyen 1, Jeff Hutchins 1, Chris Hughes 2, Rolf A. Brekken 3, and Xianming Huang 3 [1=PPHM, 2=UC/Irvine, 3=UTSW]
VIEW-POSTER (Jrnl=P266) http://www.peregrineinc.com/images/stories/pdfs/sitc_2014_m_ctla4_bf_pphm_1961.pdf
• Dr. Bruce Freimark’s comments (11-7-14 PPHM PR): "These statistically significant data show that the combination of a PS targeting antibody and the immune checkpoint inhibitor, anti-CTLA-4, achieved a superior tumor immune response over anti-CTLA-4 alone. It is gratifying to see the immunostimulatory mechanism of action of PS-targeting antibodies that our colleagues at UTSW published utilizing tumor zenograft models is robustly translating to our immune competent models of melanoma in mice; particularly when it comes to lowering the levels of MDSCs and M2 macrophages in the tumor microenvironment. These data further support the mechanism of action of bavituximab and strengthen the pre-clinical rationale for an ongoing Phase Ib evaluation of bavituximab in combination with the approved CTLA-4 inhibitor Yervoy in patients with advanced melanoma; highlighting our belief that the combination of upstream & downstream checkpoint inhibitors could improve overall response rates."
.
.
= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =
11-8-14/SITC: “Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor a-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment”
Bruce Freimark 1, Jian Gong 1, Shen Yin 1, Van Nguyen 1, Jeff Hutchins 1, Chris Hughes 2, Rolf A. Brekken 3, Xianming Huang 3 [1=PPHM, 2=UC/Irvine, 3=UTSW]
VIEW POSTER (Jrnl=P205) http://www.peregrineinc.com/images/stories/pdfs/sitc_2014_m_pd1_bf_pphm_1076.pdf
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= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =
11-8-14/SITC: ”Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor a-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Breast Tumor Microenvironment”
Jian Gong, Shen Yin, Van Nguyen, Jeff Hutchins, Bruce Freimark [Peregrine]
VIEW POSTER (Jrnl=P206) http://www.peregrineinc.com/images/stories/pdfs/sitc_2014_b_pd1_bf_pphm_4936.pdf
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11-10-14/MON. PR: Phase II Clinical Data Presented at SITC Annual Meeting Support Immunotherapeutic Mechanism of Action of Peregrine Pharmaceuticals' Bavituximab in Liver Cancer
• Combination of Bavituximab and Sorafenib in Patients With Advanced Liver Cancer Resulted in Increased Cytotoxic T-cell Activation and Other Immune Responses Within Tumors Which Positively Correlated With Patient Outcome
• Additional Presentations Demonstrate Bavituximab Combined With Anti-CTLA-4 Treatments Increased Tumor-Fighting Immune Cells and Reduced Immune-Suppression Resulting in Statistically Significant Anti-Tumor Activity in Preclinical Models of Breast Cancer and Melanoma
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=881691
TUSTIN, 11/10/14: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM) (NASDAQ: PPHMP), today announced the presentation of clinical and preclinical data related to the company's immuno-oncology development program and its lead investigational immunotherapy drug candidate bavituximab at the Society for Immunotherapy of Cancer's (SITC) 29th Annual Meeting and Associated Programs [ http://www.eventscribe.com/2014/sitc ]. This conference was held November 6-9, 2014 at the Gaylord National Hotel and Convention Center in National Harbor, Maryland. The translational clinical presentation titled: "Correlative Studies of a Phase II Clinical Study of Bavituximab and Sorafenib in Patients with Advanced Hepatocellular Carcinoma (HCC)" was presented Saturday.
"The correlative studies from these liver cancer patients provide further support for the hypothesis that bavituximab can positively regulate immune cells in tumors and thus may provide a new and exciting possibility for therapeutic manipulation of the tumor microenvironment," said Dimitry I. Gabrilovich, M.D., Ph.D., a collaborator on the studies and a Christopher M. Davis Professor in Cancer Research and Program Leader, Translational Tumor Immunology at The Wistar Institute in Philadelphia, Pennsylvania.
Data from this translational sub-study consisting of six patients show that half of the patients evaluated 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, suggesting the possibility of a clinically meaningful anti-tumor immune response. Three of the six patients evaluated had increased infiltration of CD8 T-cells into the tumor microenvironment which correlated with a prolonged time to disease progression. In addition, these responding patients 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.
"These translational data align very well with previous preclinical data that define bavituximab's immunotherapy-based mechanism of action and show that the combination of bavituximab and sorafenib can potentiate an anti-tumor response in patients with advanced HCC," said Nikoletta Lea Kallinteris, M.Sc., CCRP, senior scientist, translational research at Peregrine Pharmaceuticals. "Another interesting observation is that the increase in PD-1 positive T-cells observed in several patients from this trial provides rationale for the potential of bavituximab to increase the number of subjects who may respond to PD-1 targeted treatments.”
Peregrine is actively working to further explore the potential of bavituximab in this and other indications as we look forward to the presentation of full clinical outcome data from this Phase II clinical trial by its lead investigator, Adam Yopp, M.D., assistant professor of surgery at the University of Texas Southwestern Medical Center in Dallas, Texas at a future medical conference. More information on this trial can be found at www.ClinicalTrials.gov using Identifier NCT01264705. [ http://clinicaltrials.gov/ct2/show/NCT01264705 ]
In addition to this translational clinical data, two additional preclinical data presentations were made at the Saturday poster session of the SITC annual meeting.
A poster titled, "Antibody-mediated Blockade of Phosphatidylserine (PS) Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Breast Tumor Microenvironment" was presented by Bruce Freimark, Ph.D., director, preclinical research, oncology at Peregrine Pharmaceuticals. Data show that the combination of the phosphatidylserine (PS)-targeting antibody ch1N11, the preclinical equivalent to bavituximab, and an anti-PD-1 antibody demonstrated statistically significant (p=0.036) tumor growth inhibition in mice bearing EMT-6 breast tumors compared to anti-PD-1 alone. Further, researchers using fluorescence-activated cell sorting (FACS) found that T cell infiltration of the tumor was significantly increased in tumors of mice treated with the combination of ch1N11 and anti-PD-1 compared to single agent treatments alone. Lastly, data show that the combination treatment resulted in a significant reduction in MDSCs, whose presence plays a dominant role in suppressing the immune system associated with tumor progression in animal models.
The second pre-clinical presentation titled, "Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment" was presented by Xianming Huang, Ph.D., assistant professor, Hamon Center for Therapeutic Oncology, Pharmacology, Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center, Dallas, Texas. Dr. Huang reviewed data showing that the PS-targeting antibody ch1N11, the preclinical equivalent to bavituximab, significantly enhances tumor growth inhibition of anti-PD-1 in the B16 model of melanoma as well as showing the suppression of outgrowth of tumors resistant to anti-PD-1 therapy. Researchers also show that the combination of ch1N11 and anti-PD-1 produced significantly greater T cell infiltration in both tumor models compared to single agents as well as an increased percentage of splenic T cells producing IL-2 and IFNg, factors associated with immune activation, in the K1735 tumor model. Data further show a significant reduction in MDSCs in the combination group when compared to single agents alone. Lastly, the combination of ch1N11 and an anti-PD-1 produced significantly decreased levels of M2 immunosuppressive macrophages in tumors of K1735 bearing animals compared to control treated animals.
The links to all of these posters can be found from the front page of the company's website at: www.peregrineinc.com.
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. Additional information about Peregrine can be found at http://www.peregrineinc.com .
Safe Harbor *snip*
Contact: Christopher Keenan, Peregrine Pharmaceuticals, Inc., (800) 987-8256,
info@peregrineinc.com
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11-7-14/FRI. PR: Data to Be Presented at the SITC Annual Meeting Support Synergy of PS-Targeting and Anti-CTLA-4 Immunotherapies to Enhance Anti-Tumor Treatments in Melanoma
• Combining PS-Targeting and Anti-CTLA-4 Antibodies Results in Statistically Significant Improvement in Anti-Tumor Activity as Compared to Anti-CTLA-4 Treatment Alone; Data Support Ability of PS-Targeting Antibodies to Decrease Immunosuppressive MDSCs and M2 Macrophages Which Potentiates Anti-CTLA-4 Anti-Tumor Effects
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=881452
TUSTIN CA, 11/7/14: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM) (NASDAQ: PPHMP), today announced the first of four presentations of clinical and preclinical data related to the company's immuno-oncology development program and its lead investigational immunotherapy drug candidate bavituximab. Data from today's presentation show that the combination of a phosphatidylserine (PS)-targeting antibody equivalent to bavituximab and an antibody targeting the immune checkpoint CTLA-4 yielded statistically significant anti-tumor effects as compared to the anti-CTLA-4 antibody alone. In addition, this combination decreased levels of Arg1, a molecule predominantly expressed by myeloid derived suppressor cells (MDSC) and M2 macrophages; two key cell types that contribute to immunosupressive activity in animal models of melanoma. This presentation will be made at the Society for Immunotherapy of Cancer's (SITC) 29th Annual Meeting and Associated Programs being held November 6-9, 2014 at the Gaylord National Hotel and Convention Center in National Harbor, Maryland.
The poster titled: "Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-CTLA-4 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment" will be presented in a poster session on Friday, November 7, 2014 by Bruce Freimark, Ph.D., Director, Preclinical Research, Oncology at Peregrine Pharmaceuticals. Dr. Freimark's presentation will review preclinical data demonstrating that animals treated with the PS-targeting antibody ch1N11, the preclinical equivalent to bavituximab, in combination with anti-CTLA-4 in melanoma models demonstrated statistically significant (p=0.0019) delayed tumor growth and suppression compared to anti-CTLA-4 alone. New data presented today show the expression of Arg1 is decreased in K1735 tumors treated with ch1N11 alone or in combination with anti-CTLA-4 compared with anti-CTLA4 or control antibody. In addition, using immunohistochemistry, the ratio of CD8/CD3 T cells is increased in tumors from animals administered the combination of ch1N11 and anti-CTLA-4 compared to tumors from animals administered control antibodies.
Dr. Freimark said: "These statistically significant data show that the combination of a PS targeting antibody and the immune checkpoint inhibitor, anti-CTLA-4, achieved a superior tumor immune response over anti-CTLA-4 alone. It is gratifying to see the immunostimulatory mechanism of action of PS-targeting antibodies that our colleagues at UT Southwestern published utilizing tumor zenograft models is robustly translating to our immune competent models of melanoma in mice; particularly when it comes to lowering the levels of MDSCs and M2 macrophages in the tumor microenvironment. These data further support the mechanism of action of bavituximab and strengthen the pre-clinical rationale for an ongoing Phase Ib evaluation of bavituximab in combination with the approved CTLA-4 inhibitor Yervoy® in patients with advanced melanoma; highlighting our belief that the combination of upstream and downstream checkpoint inhibitors could improve overall response rates."
Peregrine today also announced that the following poster presentations will be made during sessions tomorrow, Saturday, November 8, 2014.
Title: Correlative Studies of a Phase II Clinical Study of Bavituximab & Sorafenib in Patients with Advanced Hepatocellular Carcinoma
Presenter: Nikoletta Lea Kallinteris, M.Sc., CCRP, senior scientist, translational research at Peregrine Pharmaceuticals, Inc.
Poster No.: P236
Title: Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor a-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Breast Tumor Microenvironment
Presenter: Bruce Freimark, Ph.D., director, preclinical research, oncology at Peregrine Pharmaceuticals, Inc.
Poster No.: P228
Title: Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment
Presenter: Xianming Huang, Ph.D., assistant professor, Hamon Center for Therapeutic Oncology, Pharmacology, Simmons Comprehensive Cancer Center Univ. of Texas Southwestern Medical Center, Dallas, Texas.
Poster No.: P226
In addition to these poster presentations, Peregrine will be hosting conference attendees at Booth #117 located in Prince George's Exhibition Hall C. The link to today's poster can be found from the front page of the company's website at: http://www.peregrineinc.com.
ABOUT PEREGRINE PHARMACEUTICALS, INC. (*snip* – see 11-10-14 PR)
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2014 Meeting: http://www.eventscribe.com/2014/sitc
SUMMARY – these 4 posters presented – details below, incl. images of the posters themselves:
• 11-8-14/P214: “Correlative studies of a Phase II study of Bavituximab & Sorafenib in Patients with Advanced Hepatocellular Carcinoma” (Yopp Kallinteris Shan Menander Hutchins King Gabrilovich Brekken Huang)
• 11-7-14/P266: “Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-CTLA-4 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment” (Freimark Hutchins CW-Hughes Brekken Huang)
• 11-8-14/P205: “Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor a-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment” (Freimark Hutchins CW-Hughes Brekken Xianming Huang)
• 11-8-14/P206: ”Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor a-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Breast Tumor Microenvironment” (Gong, Yin, VanNguyen, Hutchins, Freimark)
DETAIL (Nov7 & Nov10 PR’s below):
= = = = = = = = = =11-2014/SITC POSTERS Source=PeregrineInc.com:
11-8-14/SITC: “Correlative studies of a Phase II study of Bavituximab & Sorafenib in Patients with Advanced Hepatocellular Carcinoma”
Adam Yopp 1, Nikoletta L. Kallinteris 2, Joe Shan 2, Kerstin Menander 2, Shen Yin 2, Jeff Hutchins 2 , Steve King 2, Xiaowei Xu 3, Dmitry Gabrilovich 4, Brekken 1,5, Xianming Huang 5 [1=UTSW, 2=PPHM, 3=UPENN, 4=Wistar, 5=UTSW]
VIEW POSTER (Jrnl=P214) http://www.peregrineinc.com/images/stories/pdfs/sitc_2014_h_nk_pphm_1240.pdf
• Nikoletta Kallinteris’ comments: "These translational data align very well with previous preclin. data that define bavituximab's immunotherapy-based moa and show that the combination of bavituximab & sorafenib can potentiate an anti-tumor response in patients with advanced HCC. Another interesting observation is that the increase in PD-1 positive T-cells observed in several patients from this trial provides rationale for the potential of bavituximab to increase the number of subjects who may respond to PD-1 targeted treatments.”
• Dimitry I. Gabrilovich’s (KOL/Wistar) comments: “The correlative studies from these liver cancer patients provide further support for the hypothesis that bavituximab can positively regulate immune cells in tumors and thus may provide a new and exciting possibility for therapeutic manipulation of the tumor microenvironment.”
= = = = = = = = = = = = =
H. 1st Investigator-Sponsored (IST) Ph.I/II Trial (Bavi+Sorafenib vs. Liver Cancer/HCC, open-label)
...Note: Sorafenib = Onyx/Bayer's Nexavar - see http://www.nexavar.com
Protocol: http://clinicaltrials.gov/ct2/show/NCT01264705 UTSW: http://tinyurl.com/mwdc2ql (5 sites: 3/UTSW, Parkland-Hosp, Dallas/VA, PI=Dr. Adam Yopp)
...4-4-12 AACR'12: Dr. Adam Yopp, "promising safety profile to-date" http://tinyurl.com/7yrwqm7 (see #5591)
...Feb'12-Sep’14 10+ times: CEO Steve King hints of future ex-US partner-driven Bavi+Sorafenib/LIVER trial in Asia: http://tinyurl.com/nkaxtcc
......Articles & Data describe Liver Cancer challenges in Asian populations: http://tinyurl.com/7z7o8j9 & http://tinyurl.com/7z99cy4
...12-1-10: PPHM's 1st IST (Liver Cancer) initiated at UTSW, ~56 patients - http://tinyurl.com/3xd3e6c
…Per S.King, 5-18-10/R&R, "We've had a lot of interest in running clinical trials with the compound from investigators who have either had prior experience with the drug or would like to study the drug in various settings. Potential IST indications include all the major solid tumor types. Of particular interest is Liver Cancer, in which we have a natural tie-in with our HCV program, Ovarian Cancer and Pancreatic Cancer, also very nicely supported by the prior data."
.
.
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11-7-14/SITC: “Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-CTLA-4 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment”
Bruce Freimark 1, Jian Gong 1, Shen Yin 1, Van Nguyen 1, Jeff Hutchins 1, Chris Hughes 2, Rolf A. Brekken 3, and Xianming Huang 3 [1=PPHM, 2=UC/Irvine, 3=UTSW]
VIEW-POSTER (Jrnl=P266) http://www.peregrineinc.com/images/stories/pdfs/sitc_2014_m_ctla4_bf_pphm_1961.pdf
• Dr. Bruce Freimark’s comments (11-7-14 PPHM PR): "These statistically significant data show that the combination of a PS targeting antibody and the immune checkpoint inhibitor, anti-CTLA-4, achieved a superior tumor immune response over anti-CTLA-4 alone. It is gratifying to see the immunostimulatory mechanism of action of PS-targeting antibodies that our colleagues at UTSW published utilizing tumor zenograft models is robustly translating to our immune competent models of melanoma in mice; particularly when it comes to lowering the levels of MDSCs and M2 macrophages in the tumor microenvironment. These data further support the mechanism of action of bavituximab and strengthen the pre-clinical rationale for an ongoing Phase Ib evaluation of bavituximab in combination with the approved CTLA-4 inhibitor Yervoy in patients with advanced melanoma; highlighting our belief that the combination of upstream & downstream checkpoint inhibitors could improve overall response rates."
.
.
= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =
11-8-14/SITC: “Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor a-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment”
Bruce Freimark 1, Jian Gong 1, Shen Yin 1, Van Nguyen 1, Jeff Hutchins 1, Chris Hughes 2, Rolf A. Brekken 3, Xianming Huang 3 [1=PPHM, 2=UC/Irvine, 3=UTSW]
VIEW POSTER (Jrnl=P205) http://www.peregrineinc.com/images/stories/pdfs/sitc_2014_m_pd1_bf_pphm_1076.pdf
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= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =
11-8-14/SITC: ”Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor a-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Breast Tumor Microenvironment”
Jian Gong, Shen Yin, Van Nguyen, Jeff Hutchins, Bruce Freimark [Peregrine]
VIEW POSTER (Jrnl=P206) http://www.peregrineinc.com/images/stories/pdfs/sitc_2014_b_pd1_bf_pphm_4936.pdf
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11-10-14/MON. PR: Phase II Clinical Data Presented at SITC Annual Meeting Support Immunotherapeutic Mechanism of Action of Peregrine Pharmaceuticals' Bavituximab in Liver Cancer
• Combination of Bavituximab and Sorafenib in Patients With Advanced Liver Cancer Resulted in Increased Cytotoxic T-cell Activation and Other Immune Responses Within Tumors Which Positively Correlated With Patient Outcome
• Additional Presentations Demonstrate Bavituximab Combined With Anti-CTLA-4 Treatments Increased Tumor-Fighting Immune Cells and Reduced Immune-Suppression Resulting in Statistically Significant Anti-Tumor Activity in Preclinical Models of Breast Cancer and Melanoma
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=881691
TUSTIN, 11/10/14: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM) (NASDAQ: PPHMP), today announced the presentation of clinical and preclinical data related to the company's immuno-oncology development program and its lead investigational immunotherapy drug candidate bavituximab at the Society for Immunotherapy of Cancer's (SITC) 29th Annual Meeting and Associated Programs [ http://www.eventscribe.com/2014/sitc ]. This conference was held November 6-9, 2014 at the Gaylord National Hotel and Convention Center in National Harbor, Maryland. The translational clinical presentation titled: "Correlative Studies of a Phase II Clinical Study of Bavituximab and Sorafenib in Patients with Advanced Hepatocellular Carcinoma (HCC)" was presented Saturday.
"The correlative studies from these liver cancer patients provide further support for the hypothesis that bavituximab can positively regulate immune cells in tumors and thus may provide a new and exciting possibility for therapeutic manipulation of the tumor microenvironment," said Dimitry I. Gabrilovich, M.D., Ph.D., a collaborator on the studies and a Christopher M. Davis Professor in Cancer Research and Program Leader, Translational Tumor Immunology at The Wistar Institute in Philadelphia, Pennsylvania.
Data from this translational sub-study consisting of six patients show that half of the patients evaluated 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, suggesting the possibility of a clinically meaningful anti-tumor immune response. Three of the six patients evaluated had increased infiltration of CD8 T-cells into the tumor microenvironment which correlated with a prolonged time to disease progression. In addition, these responding patients 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.
"These translational data align very well with previous preclinical data that define bavituximab's immunotherapy-based mechanism of action and show that the combination of bavituximab and sorafenib can potentiate an anti-tumor response in patients with advanced HCC," said Nikoletta Lea Kallinteris, M.Sc., CCRP, senior scientist, translational research at Peregrine Pharmaceuticals. "Another interesting observation is that the increase in PD-1 positive T-cells observed in several patients from this trial provides rationale for the potential of bavituximab to increase the number of subjects who may respond to PD-1 targeted treatments.”
Peregrine is actively working to further explore the potential of bavituximab in this and other indications as we look forward to the presentation of full clinical outcome data from this Phase II clinical trial by its lead investigator, Adam Yopp, M.D., assistant professor of surgery at the University of Texas Southwestern Medical Center in Dallas, Texas at a future medical conference. More information on this trial can be found at www.ClinicalTrials.gov using Identifier NCT01264705. [ http://clinicaltrials.gov/ct2/show/NCT01264705 ]
In addition to this translational clinical data, two additional preclinical data presentations were made at the Saturday poster session of the SITC annual meeting.
A poster titled, "Antibody-mediated Blockade of Phosphatidylserine (PS) Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Breast Tumor Microenvironment" was presented by Bruce Freimark, Ph.D., director, preclinical research, oncology at Peregrine Pharmaceuticals. Data show that the combination of the phosphatidylserine (PS)-targeting antibody ch1N11, the preclinical equivalent to bavituximab, and an anti-PD-1 antibody demonstrated statistically significant (p=0.036) tumor growth inhibition in mice bearing EMT-6 breast tumors compared to anti-PD-1 alone. Further, researchers using fluorescence-activated cell sorting (FACS) found that T cell infiltration of the tumor was significantly increased in tumors of mice treated with the combination of ch1N11 and anti-PD-1 compared to single agent treatments alone. Lastly, data show that the combination treatment resulted in a significant reduction in MDSCs, whose presence plays a dominant role in suppressing the immune system associated with tumor progression in animal models.
The second pre-clinical presentation titled, "Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment" was presented by Xianming Huang, Ph.D., assistant professor, Hamon Center for Therapeutic Oncology, Pharmacology, Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center, Dallas, Texas. Dr. Huang reviewed data showing that the PS-targeting antibody ch1N11, the preclinical equivalent to bavituximab, significantly enhances tumor growth inhibition of anti-PD-1 in the B16 model of melanoma as well as showing the suppression of outgrowth of tumors resistant to anti-PD-1 therapy. Researchers also show that the combination of ch1N11 and anti-PD-1 produced significantly greater T cell infiltration in both tumor models compared to single agents as well as an increased percentage of splenic T cells producing IL-2 and IFNg, factors associated with immune activation, in the K1735 tumor model. Data further show a significant reduction in MDSCs in the combination group when compared to single agents alone. Lastly, the combination of ch1N11 and an anti-PD-1 produced significantly decreased levels of M2 immunosuppressive macrophages in tumors of K1735 bearing animals compared to control treated animals.
The links to all of these posters can be found from the front page of the company's website at: www.peregrineinc.com.
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. Additional information about Peregrine can be found at http://www.peregrineinc.com .
Safe Harbor *snip*
Contact: Christopher Keenan, Peregrine Pharmaceuticals, Inc., (800) 987-8256,
info@peregrineinc.com
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11-7-14/FRI. PR: Data to Be Presented at the SITC Annual Meeting Support Synergy of PS-Targeting and Anti-CTLA-4 Immunotherapies to Enhance Anti-Tumor Treatments in Melanoma
• Combining PS-Targeting and Anti-CTLA-4 Antibodies Results in Statistically Significant Improvement in Anti-Tumor Activity as Compared to Anti-CTLA-4 Treatment Alone; Data Support Ability of PS-Targeting Antibodies to Decrease Immunosuppressive MDSCs and M2 Macrophages Which Potentiates Anti-CTLA-4 Anti-Tumor Effects
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=881452
TUSTIN CA, 11/7/14: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM) (NASDAQ: PPHMP), today announced the first of four presentations of clinical and preclinical data related to the company's immuno-oncology development program and its lead investigational immunotherapy drug candidate bavituximab. Data from today's presentation show that the combination of a phosphatidylserine (PS)-targeting antibody equivalent to bavituximab and an antibody targeting the immune checkpoint CTLA-4 yielded statistically significant anti-tumor effects as compared to the anti-CTLA-4 antibody alone. In addition, this combination decreased levels of Arg1, a molecule predominantly expressed by myeloid derived suppressor cells (MDSC) and M2 macrophages; two key cell types that contribute to immunosupressive activity in animal models of melanoma. This presentation will be made at the Society for Immunotherapy of Cancer's (SITC) 29th Annual Meeting and Associated Programs being held November 6-9, 2014 at the Gaylord National Hotel and Convention Center in National Harbor, Maryland.
The poster titled: "Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-CTLA-4 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment" will be presented in a poster session on Friday, November 7, 2014 by Bruce Freimark, Ph.D., Director, Preclinical Research, Oncology at Peregrine Pharmaceuticals. Dr. Freimark's presentation will review preclinical data demonstrating that animals treated with the PS-targeting antibody ch1N11, the preclinical equivalent to bavituximab, in combination with anti-CTLA-4 in melanoma models demonstrated statistically significant (p=0.0019) delayed tumor growth and suppression compared to anti-CTLA-4 alone. New data presented today show the expression of Arg1 is decreased in K1735 tumors treated with ch1N11 alone or in combination with anti-CTLA-4 compared with anti-CTLA4 or control antibody. In addition, using immunohistochemistry, the ratio of CD8/CD3 T cells is increased in tumors from animals administered the combination of ch1N11 and anti-CTLA-4 compared to tumors from animals administered control antibodies.
Dr. Freimark said: "These statistically significant data show that the combination of a PS targeting antibody and the immune checkpoint inhibitor, anti-CTLA-4, achieved a superior tumor immune response over anti-CTLA-4 alone. It is gratifying to see the immunostimulatory mechanism of action of PS-targeting antibodies that our colleagues at UT Southwestern published utilizing tumor zenograft models is robustly translating to our immune competent models of melanoma in mice; particularly when it comes to lowering the levels of MDSCs and M2 macrophages in the tumor microenvironment. These data further support the mechanism of action of bavituximab and strengthen the pre-clinical rationale for an ongoing Phase Ib evaluation of bavituximab in combination with the approved CTLA-4 inhibitor Yervoy® in patients with advanced melanoma; highlighting our belief that the combination of upstream and downstream checkpoint inhibitors could improve overall response rates."
Peregrine today also announced that the following poster presentations will be made during sessions tomorrow, Saturday, November 8, 2014.
Title: Correlative Studies of a Phase II Clinical Study of Bavituximab & Sorafenib in Patients with Advanced Hepatocellular Carcinoma
Presenter: Nikoletta Lea Kallinteris, M.Sc., CCRP, senior scientist, translational research at Peregrine Pharmaceuticals, Inc.
Poster No.: P236
Title: Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor a-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Breast Tumor Microenvironment
Presenter: Bruce Freimark, Ph.D., director, preclinical research, oncology at Peregrine Pharmaceuticals, Inc.
Poster No.: P228
Title: Antibody-mediated Blockade of Phosphatidylserine Enhances the Anti-tumor Activity of Immune Checkpoint Inhibitor anti-PD-1 by Affecting Myeloid Derived Suppressor Cells (MDSC) and Lymphocyte Populations in a Melanoma Tumor Microenvironment
Presenter: Xianming Huang, Ph.D., assistant professor, Hamon Center for Therapeutic Oncology, Pharmacology, Simmons Comprehensive Cancer Center Univ. of Texas Southwestern Medical Center, Dallas, Texas.
Poster No.: P226
In addition to these poster presentations, Peregrine will be hosting conference attendees at Booth #117 located in Prince George's Exhibition Hall C. The link to today's poster can be found from the front page of the company's website at: http://www.peregrineinc.com.
ABOUT PEREGRINE PHARMACEUTICALS, INC. (*snip* – see 11-10-14 PR)
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