AI
Thursday, April 11, 2013 8:59:33 AM
AACR/2013: Peregrine’s 3 preclin Posters (immune stimulating moa of Bavi, anti-tumor & imaging potential of other PS-targeting constructs)…
Apr6-10 2013: “AACR 104th Annual Meeting 2013”, WashDC
http://www.aacr.org/AACR2013
3 Peregrine Baci/AntiPS Abstracts:
#1244/Apr8 – “PS-Targeting Antibody Reactivates Tumor Immunity & Destroys Tumor Vasculature In Mice” [UTSW]
#2850/Apr9 – “Predicting Anti-Tumor Responses to PS-Targeting Antibodies Using Tumor Imaging” [PPHM, UCI]
#4326/Apr9 – “PS-Targeting ‘Betabodies’ for the Treatment of Cancer” [UTSW]
Peregrine’s Anti-PS Mabs:
• PGN635 is Fully-Human Bavituximab=1N11=AT004 (B2GPI-depen.) – see http://tinyurl.com/cparur & http://tinyurl.com/6ql5nf
• PGN632 is the Duke-PPHM-HIV candidate=11.31=AT005 (B2GPI-indep.) – see http://tinyurl.com/7x4l3k5 & http://tinyurl.com/cxkcb4
• PGN650 is a human F(ab’)2 fragment that targets PS expression (1st ref’d in AACR’13 #2452) – see http://tinyurl.com/76nqqkm . 124I-PGN650 is Peregrine’s PS-Imaging candidate, whose IND clinical filing was announced 4-3-12.
Note: PGN632 (Duke/HIV preclin’s) binds to PS indep. of B2-glycoprotein I (B2GPI), unlike Bavi & FH-Bavituximab(PGN635) which depend on B2GPI as a binding intermediary.
AACR’13 DETAILS & ABSTRACT BODIES & PRESS RELEASE COMMENTS…
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4-8-13/Mon Poster #1244: “Phosphatidylserine-Targeting Antibody Reactivates Tumor Immunity & Destroys Tumor Vasculature In Mice”
Yi Yin, Xianming Huang, Dan Ye, Philip Thorpe - UTSW-MC/Dallas
Session: Cytokines, Modification of the Tumor Microenvironment, and Intervention
ABSTRACT:
The immunosuppressive lipid, phosphatidylserine (PS), becomes exposed on tumor blood vessels and tumor cells responding to therapy. The exposed PS contributes to the immunosuppressed tumor microenvironment. Bavituximab is a phosphatidylserine (PS)-targeting antibody that is being combined with chemotherapy in clinical trials in cancer patients. Here, we tested the hypothesis that innate immunity against cancer can be elicited by combining chemotherapy with a monoclonal antibody that indirectly binds exposed phosphatidylserine (PS). We used a murine version of bavituximab, 2aG4, plus docetaxel to treat prostate tumors in mice. Combination treatment markedly retarded tumor growth, prolonged survival times and delayed progression to androgen-independent disease. Antibody treatment reduced the presence of myeloid-derived suppressor cells (MDSCs) in the tumors and caused macrophages to repolarize from the immunosuppressive, proangiogenic M2-like state into a tumoricidal M1-like state. The reactivated macrophages destroyed antibody-coated tumor vasculature and tumor cells. Addition of 2aG4 to MDSCs in vitro caused them to differentiate into M1-like macrophages and DCs. Thus, PS-targeting antibodies appear to reactivate innate immunity in tumors resulting in tumor growth inhibition.
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PPHM 4-10-13 PRESS RELEASE COMMENTS RE: #1244:
”Additional data presented from a series of preclinical studies(3) demonstrate that PS-targeting antibodies mediate immuno-stimulatory changes in tumors resulting in an increase of tumor-fighting (M1) macrophages, immune cells strongly associated with survival benefits in patients with NSCLC(1). Peregrine recently reported promising data from a randomized, double-blind, placebo-controlled Phase II second-line NSCLC clinical trial demonstrating a 60% improvement in median overall survival (OS) in patients receiving 3 mg/kg bavituximab plus docetaxel compared to the control arm. The company plans to meet with the U.S. FDA in the 2nd Qtr of calendar year 2013 with the goal of initiating a Phase III trial by calendar year-end.”
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=755519
PDF of AACR’13 Poster #1244:
http://www.peregrineinc.com/images/stories/pdfs/yi_2013.pdf
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4-9-13/Tue Poster #2850: “Predicting Anti-Tumor Responses to Phosphatidylserine-Targeting Antibodies Using Tumor Imaging”
Jian Gong 1, Richard Archer 1, Van Nguyen 1, Christopher C.W. Hughes 2, Jeff Hutchins 1, Bruce Freimark 1
1 Peregrine Pharmaceuticals; 2 Univ. of California/ Irvine
Session: Immune Therapeutics & Monoclonal Antibodies 1
ABSTRACT:
Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane and becomes exposed on tumor vascular endothelial cells and tumor cells in response to chemotherapy, irradiation and oxidative stresses in the tumor microenvironment. Binding of antibodies targeting PS on the tumor endothelial cells and tumors induces the recruitment of immune cells and engages the immune system to destroy tumor vasculature. The antibodies also enhance anti-tumor immunity by blocking the immunosuppressive action of PS. A chimeric PS-targeting antibody, bavituximab, is being used in combination with chemotherapy to treat patients with solid tumors in Phase II trials. Fully human antibody PGN635 binds PS through the interaction of beta-2-glycoprotein 1 (B2GP1) in the same manner as bavituximab. Using human PC-3 prostate tumor xenografts in SCID mice, we demonstrate that targeting of PS in tumors by PGN635 is enhanced by chemotherapy. Combination of PGN635 with docetaxel inhibited tumor growth compared to the control IgG plus docetaxel group (p<0.05). Near-infrared optical imaging of PS in tumors with PGN650, an F(ab')2 antibody fragment of PGN635, showed tumor growth inhibition in mice treated with docetaxel correlates with PS expression levels in the tumors. Maximal uptake of the PS imaging was observed when chemotherapy was given 24 hours before the imaging probe.
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PPHM 4-10-13 PRESS RELEASE COMMENTS RE: #2850:
Data presented from imaging studies(2) demonstrate that the chemotherapeutic drug docetaxel, a commonly prescribed second-line treatment for patients with advanced NSCLC, increases the exposure of bavituximab's target molecule, phosphatidylserine (PS), on tumor blood vessel cells and tumor cells. Results also showed that PS exposure in tumors is correlated with tumor burden and response to docetaxel treatment, supporting exposed PS as a promising biomarker of cancer and response to therapy. Peregrine's PS-targeting imaging agent I-124-PGN650 is currently being evaluated in a clinical trial [ http://clinicaltrials.gov/ct2/show/NCT01632696 ] to assess its safety and potential to image multiple tumor types in patients with cancer.”
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=755519
PDF of AACR’13 Poster #2850:
http://www.peregrineinc.com/images/stories/pdfs/jian_2013.pdf
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4-9-13/Tue Poster #4326: “Phosphatidylserine-Targeting ‘Betabodies’ for the Treatment of Cancer”
Xianming Huang 1, Dan Ye 1, Troy Luster 2, E. Sally Ward 1, Philip Thorpe1
1 UTSW-MC/Dallas; 2 Human Genome Science, Maryland, MD
Session: Antibody Therapeutics & Novel Delivery Technologies
ABSTRACT:
Bavituximab is a chimeric monoclonal antibody that is being combined with chemotherapy to treat patients with lung or pancreatic cancer in randomized Phase II clinical trials. Bavituximab targets the immunosuppressive lipid, phosphatidylserine (PS), which becomes exposed on the outer membrane surface of tumor blood vessels and tumor cells in tumors responding to therapy. The antibody acts by destroying tumor vasculature and by reactivating tumor immunity. Here, we generated new PS-targeting therapeutics by fusing domains of the PS-binding plasma protein, mouse B2-glycoprotein I (B2GP1), to the Fc region of mouse IgG2a. Such ‘betabodies’ potentially have the following advantages: they bind directly to PS, and do not require a cofactor protein (B2GP1) for binding; they can be made fully human; they are smaller in size (100 KDa); and they have slower blood clearance rates. A construct was generated that bound strongly to PS-expressing cells and plates, localized to tumor vascular endothelium in vivo, and had a B-phase blood half-life of approximately 5 days after intravenous injection into mice as compared with one day for a murine version of bavituximab, 2aG4. Betabodies could potentially be the next generation of PS-targeting cancer therapeutics.
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PPHM 4-10-13 PRESS RELEASE COMMENTS RE: #4326:
” Researchers also presented details of new PS-binding constructs(4). Termed "betabodies," the molecules consist of the PS-binding domain of the serum protein B2-glycoprotein I (B2GPI), fused to the constant region of an antibody. Betabodies bind to PS directly, are smaller in size and have a longer serum half-life than natural antibodies. Early studies indicate that betabodies hold potential as next-generation PS-binding agents that have the potential to be used for a broad number of applications including antibody-drug conjugates and next generation therapeutics for oncology and infectious diseases."
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=755519
PDF of AACR’13 Poster #4326:
http://www.peregrineinc.com/images/stories/pdfs/xianming_2013.pdf
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PR 4-10-13: Data Presented at AACR Annual Meeting Support Targeted Immune Reactivation Mechanism and Potential of Peregrine's Bavituximab in Solid Tumor Therapy
• Imaging Studies Show Docetaxel Strongly Upregulates Bavituximab's PS Target in Tumors, Further Supporting Lead Clinical Indication in Second Line Non-Small Cell Lung Cancer
• Preclinical Studies Support Potential of Bavituximab to Induce Cancer-Fighting Changes in Immune Response to Tumors That Have Been Associated With Prolonged Survival in Lung Cancer Patients
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=755519
TUSTIN, CA 4/10/13: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a biopharmaceutical company developing first-in-class monoclonal antibodies focused on the treatment and diagnosis of cancer, today highlighted data presented at the Annual Meeting of the American Association for Cancer Research (AACR). Data was presented this week from preclinical studies investigating the immune-stimulating mechanism of action of Peregrine's lead phosphatidylserine (PS)-targeting oncology clinical candidate bavituximab and the anti-tumor and imaging potential of other PS-targeting molecules. Bavituximab is currently being evaluated in several oncology clinical trials including the lead indication of second-line non-small cell lung cancer (NSCLC), which is anticipated to advance into a pivotal Phase III trial later this year.
"These studies yield important insights into the fundamental role that exposed PS plays in tumor immune evasion, and further support our lead clinical candidate bavituximab's ability to reactivate tumor immunity. This is now clearly evidenced by several specific measurements of both the immune-stimulating and anti-tumor mechanisms mediated by PS-targeting antibodies as well as imaging studies demonstrating that tumor growth inhibition is correlated with PS expression levels in tumors," said Jeff T. Hutchins, Ph.D., VP of Preclinical Research at Peregrine Pharmaceuticals. "Included in these presentations was a compelling finding of a pronounced antibody-mediated increase in tumor-fighting immune cells that is independently correlated with an impressive survival benefit in patients with NSCLC based on a published retrospective study of clinical data(1). When taken together, these results support PS as a promising oncology drug target and provide additional rationale for the impressive Phase II survival data we have seen in bavituximab's lead indication of second-line NSCLC."
Data presented from imaging studies(2) demonstrate that the chemotherapeutic drug docetaxel, a commonly prescribed second-line treatment for patients with advanced NSCLC, increases the exposure of bavituximab's target molecule, phosphatidylserine (PS), on tumor blood vessel cells and tumor cells. Results also showed that PS exposure in tumors is correlated with tumor burden and response to docetaxel treatment, supporting exposed PS as a promising biomarker of cancer and response to therapy. Peregrine's PS-targeting imaging agent I-124-PGN650 is currently being evaluated in a clinical trial to assess its safety and potential to image multiple tumor types in patients with cancer.
Additional data presented from a series of preclinical studies(3) demonstrate that PS-targeting antibodies mediate immuno-stimulatory changes in tumors resulting in an increase of tumor-fighting (M1) macrophages, immune cells strongly associated with survival benefits in patients with NSCLC(1). Peregrine recently reported promising data from a randomized, double-blind, placebo-controlled Phase II second-line NSCLC clinical trial demonstrating a 60% improvement in median overall survival (OS) in patients receiving 3 mg/kg bavituximab plus docetaxel compared to the control arm. The company plans to meet with the U.S. Food and Drug Administration (FDA) in the second quarter of calendar year 2013 with the goal of initiating a Phase III trial by calendar year-end.
Researchers also presented details of new PS-binding constructs(4). Termed "betabodies," the molecules consist of the PS-binding domain of the serum protein B2-glycoprotein I (B2GPI), fused to the constant region of an antibody. Betabodies bind to PS directly, are smaller in size and have a longer serum half-life than natural antibodies. Early studies indicate that betabodies hold potential as next-generation PS-binding agents that have the potential to be used for a broad number of applications including antibody-drug conjugates and next generation therapeutics for oncology and infectious diseases.
(1) ”The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time” Ma et al. BMC Cancer 2010, 10:112. Open access research article: http://www.biomedcentral.com/content/pdf/1471-2407-10-112.pdf
PRESENTATION DETAILS:
(2) Jian Gong(1), Richard Archer(1), Van Nguyen(1), Christopher C.W. Hughes(2), Jeff Hutchins(1), Bruce Freimark(1). 1. Peregrine Pharmaceuticals, Inc., Tustin, CA; 2. University of California, Irvine, Irvine, CA.
“Predicting Anti-Tumor Responses to Phosphatidylserine Targeting Antibodies Using Tumor Imaging”
In Proceedings of the 104th Annual Meeting of the American Association for Cancer Research (AACR); 2013 Apr 6-10; Washington, D.C. Abstract 2850
[ PDF of AACR’13 Poster #2850: http://www.peregrineinc.com/images/stories/pdfs/jian_2013.pdf ]
(3) Yi Yin, Xianming Huang, Dan Ye, Philip Thorpe. UT Southwestern Medical Ctr., Dallas, TX
“Phosphatidylserine-Targeting Antibody Reactivates Tumor Immunity and Destroys Tumor Vasculature in Mice”
In Proceedings of the 104th Annual Meeting of the American Association for Cancer Research (AACR); 2013 Apr 6-10; Washington, D.C. Abstract 1244
[ PDF of AACR’13 Poster #1244:
http://www.peregrineinc.com/images/stories/pdfs/yi_2013.pdf ]
(4) Xianming Huang(1), Dan Ye(1), Troy Luster(2), E. Sally Ward(1), Philip Thorpe(1). 1. UT Southwestern Medical Ctr., Dallas, TX; 2. Human Genome Science, Maryland
”Phosphatidylserine-Targeting 'Betabodies' for the Treatment of Cancer”
In Proceedings of the 104th Annual Meeting of the American Association for Cancer Research (AACR); 2013 Apr 6-10; Washington, D.C. Abstract 4326
[ PDF of AACR’13 Poster #4326:
http://www.peregrineinc.com/images/stories/pdfs/xianming_2013.pdf ]
Copies [PDF’s] of the AACR posters are available at Peregrine's website at http://www.peregrineinc.com/technology/bavituximab-oncology/recent-data.html
ABOUT BAVITUXIMAB
Bavituximab is a first-in-class phosphatidylserine (PS)-targeting monoclonal antibody that represents a new approach to treating cancer. Bavituximab is the lead drug candidate from the company's PS technology platform and is currently being tested in eight clinical trials, including three randomized Phase II trials in front-line and second-line non-small cell lung cancer and front-line pancreatic cancer, and five investigator-sponsored trials (ISTs) in additional oncology indications. PS is a highly immunosuppressive molecule usually located inside the membrane of healthy cells, but "flips" and becomes exposed on the outside of cells that line tumor blood vessels, creating a specific target for anti-cancer treatments. PS-targeting antibodies target and bind to PS and block this immunosuppressive signal, thereby enabling the immune system to recognize and fight the tumor.
ABOUT PEREGRINE PHARMACEUTICALS, INC.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials focused on the treatment and diagnosis of cancer. The company is pursuing multiple clinical programs in cancer with its lead product candidate bavituximab and novel brain cancer agent Cotara®. 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 or Jay Carlson
Peregrine Pharmaceuticals, Inc. (800) 987-8256
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Snapshots of Peregrine’s AACR’13 Posters – from http://www.peregrineinc.com/technology/bavituximab-oncology/recent-data.html
AACR’13 4-8-13/Mon Poster #1244: “Phosphatidylserine-Targeting Antibody Reactivates Tumor Immunity & Destroys Tumor Vasculature In Mice”
Yi Yin, Xianming Huang, Dan Ye, Philip Thorpe - UTSW-MC/Dallas
Session: Cytokines, Modification of the Tumor Microenvironment, and Intervention
AACR’13 4-9-13/Tue Poster #2850: “Predicting Anti-Tumor Responses to Phosphatidylserine-Targeting Antibodies Using Tumor Imaging”
Jian Gong 1, Richard Archer 1, Van Nguyen 1, Christopher C.W. Hughes 2, Jeff Hutchins 1, Bruce Freimark 1
1 Peregrine Pharmaceuticals; 2 Univ. of California/ Irvine
Session: Immune Therapeutics & Monoclonal Antibodies 1
AACR’13 4-9-13/Tue Poster #4326: “Phosphatidylserine-Targeting ‘Betabodies’ for the Treatment of Cancer”
Xianming Huang 1, Dan Ye 1, Troy Luster 2, E. Sally Ward 1, Philip Thorpe1
1 UTSW-MC/Dallas; 2 Human Genome Science, Maryland, MD
Session: Antibody Therapeutics & Novel Delivery Technologies
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“In Memoriam
Philip E. Thorpe, Ph.D.
1951-2013
Founder, scientist, and friend”
http://www.peregrineinc.com
“Phil will be sorely missed as a colleague and friend. At Peregrine, each of us is pursuing Phil's dream of bringing important drugs to patients who need them based on his basic research. We are more motivated than ever to see this dream through.”
Apr6-10 2013: “AACR 104th Annual Meeting 2013”, WashDC
http://www.aacr.org/AACR2013
3 Peregrine Baci/AntiPS Abstracts:
#1244/Apr8 – “PS-Targeting Antibody Reactivates Tumor Immunity & Destroys Tumor Vasculature In Mice” [UTSW]
#2850/Apr9 – “Predicting Anti-Tumor Responses to PS-Targeting Antibodies Using Tumor Imaging” [PPHM, UCI]
#4326/Apr9 – “PS-Targeting ‘Betabodies’ for the Treatment of Cancer” [UTSW]
Peregrine’s Anti-PS Mabs:
• PGN635 is Fully-Human Bavituximab=1N11=AT004 (B2GPI-depen.) – see http://tinyurl.com/cparur & http://tinyurl.com/6ql5nf
• PGN632 is the Duke-PPHM-HIV candidate=11.31=AT005 (B2GPI-indep.) – see http://tinyurl.com/7x4l3k5 & http://tinyurl.com/cxkcb4
• PGN650 is a human F(ab’)2 fragment that targets PS expression (1st ref’d in AACR’13 #2452) – see http://tinyurl.com/76nqqkm . 124I-PGN650 is Peregrine’s PS-Imaging candidate, whose IND clinical filing was announced 4-3-12.
Note: PGN632 (Duke/HIV preclin’s) binds to PS indep. of B2-glycoprotein I (B2GPI), unlike Bavi & FH-Bavituximab(PGN635) which depend on B2GPI as a binding intermediary.
AACR’13 DETAILS & ABSTRACT BODIES & PRESS RELEASE COMMENTS…
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4-8-13/Mon Poster #1244: “Phosphatidylserine-Targeting Antibody Reactivates Tumor Immunity & Destroys Tumor Vasculature In Mice”
Yi Yin, Xianming Huang, Dan Ye, Philip Thorpe - UTSW-MC/Dallas
Session: Cytokines, Modification of the Tumor Microenvironment, and Intervention
ABSTRACT:
The immunosuppressive lipid, phosphatidylserine (PS), becomes exposed on tumor blood vessels and tumor cells responding to therapy. The exposed PS contributes to the immunosuppressed tumor microenvironment. Bavituximab is a phosphatidylserine (PS)-targeting antibody that is being combined with chemotherapy in clinical trials in cancer patients. Here, we tested the hypothesis that innate immunity against cancer can be elicited by combining chemotherapy with a monoclonal antibody that indirectly binds exposed phosphatidylserine (PS). We used a murine version of bavituximab, 2aG4, plus docetaxel to treat prostate tumors in mice. Combination treatment markedly retarded tumor growth, prolonged survival times and delayed progression to androgen-independent disease. Antibody treatment reduced the presence of myeloid-derived suppressor cells (MDSCs) in the tumors and caused macrophages to repolarize from the immunosuppressive, proangiogenic M2-like state into a tumoricidal M1-like state. The reactivated macrophages destroyed antibody-coated tumor vasculature and tumor cells. Addition of 2aG4 to MDSCs in vitro caused them to differentiate into M1-like macrophages and DCs. Thus, PS-targeting antibodies appear to reactivate innate immunity in tumors resulting in tumor growth inhibition.
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PPHM 4-10-13 PRESS RELEASE COMMENTS RE: #1244:
”Additional data presented from a series of preclinical studies(3) demonstrate that PS-targeting antibodies mediate immuno-stimulatory changes in tumors resulting in an increase of tumor-fighting (M1) macrophages, immune cells strongly associated with survival benefits in patients with NSCLC(1). Peregrine recently reported promising data from a randomized, double-blind, placebo-controlled Phase II second-line NSCLC clinical trial demonstrating a 60% improvement in median overall survival (OS) in patients receiving 3 mg/kg bavituximab plus docetaxel compared to the control arm. The company plans to meet with the U.S. FDA in the 2nd Qtr of calendar year 2013 with the goal of initiating a Phase III trial by calendar year-end.”
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=755519
PDF of AACR’13 Poster #1244:
http://www.peregrineinc.com/images/stories/pdfs/yi_2013.pdf
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4-9-13/Tue Poster #2850: “Predicting Anti-Tumor Responses to Phosphatidylserine-Targeting Antibodies Using Tumor Imaging”
Jian Gong 1, Richard Archer 1, Van Nguyen 1, Christopher C.W. Hughes 2, Jeff Hutchins 1, Bruce Freimark 1
1 Peregrine Pharmaceuticals; 2 Univ. of California/ Irvine
Session: Immune Therapeutics & Monoclonal Antibodies 1
ABSTRACT:
Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane and becomes exposed on tumor vascular endothelial cells and tumor cells in response to chemotherapy, irradiation and oxidative stresses in the tumor microenvironment. Binding of antibodies targeting PS on the tumor endothelial cells and tumors induces the recruitment of immune cells and engages the immune system to destroy tumor vasculature. The antibodies also enhance anti-tumor immunity by blocking the immunosuppressive action of PS. A chimeric PS-targeting antibody, bavituximab, is being used in combination with chemotherapy to treat patients with solid tumors in Phase II trials. Fully human antibody PGN635 binds PS through the interaction of beta-2-glycoprotein 1 (B2GP1) in the same manner as bavituximab. Using human PC-3 prostate tumor xenografts in SCID mice, we demonstrate that targeting of PS in tumors by PGN635 is enhanced by chemotherapy. Combination of PGN635 with docetaxel inhibited tumor growth compared to the control IgG plus docetaxel group (p<0.05). Near-infrared optical imaging of PS in tumors with PGN650, an F(ab')2 antibody fragment of PGN635, showed tumor growth inhibition in mice treated with docetaxel correlates with PS expression levels in the tumors. Maximal uptake of the PS imaging was observed when chemotherapy was given 24 hours before the imaging probe.
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PPHM 4-10-13 PRESS RELEASE COMMENTS RE: #2850:
Data presented from imaging studies(2) demonstrate that the chemotherapeutic drug docetaxel, a commonly prescribed second-line treatment for patients with advanced NSCLC, increases the exposure of bavituximab's target molecule, phosphatidylserine (PS), on tumor blood vessel cells and tumor cells. Results also showed that PS exposure in tumors is correlated with tumor burden and response to docetaxel treatment, supporting exposed PS as a promising biomarker of cancer and response to therapy. Peregrine's PS-targeting imaging agent I-124-PGN650 is currently being evaluated in a clinical trial [ http://clinicaltrials.gov/ct2/show/NCT01632696 ] to assess its safety and potential to image multiple tumor types in patients with cancer.”
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=755519
PDF of AACR’13 Poster #2850:
http://www.peregrineinc.com/images/stories/pdfs/jian_2013.pdf
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4-9-13/Tue Poster #4326: “Phosphatidylserine-Targeting ‘Betabodies’ for the Treatment of Cancer”
Xianming Huang 1, Dan Ye 1, Troy Luster 2, E. Sally Ward 1, Philip Thorpe1
1 UTSW-MC/Dallas; 2 Human Genome Science, Maryland, MD
Session: Antibody Therapeutics & Novel Delivery Technologies
ABSTRACT:
Bavituximab is a chimeric monoclonal antibody that is being combined with chemotherapy to treat patients with lung or pancreatic cancer in randomized Phase II clinical trials. Bavituximab targets the immunosuppressive lipid, phosphatidylserine (PS), which becomes exposed on the outer membrane surface of tumor blood vessels and tumor cells in tumors responding to therapy. The antibody acts by destroying tumor vasculature and by reactivating tumor immunity. Here, we generated new PS-targeting therapeutics by fusing domains of the PS-binding plasma protein, mouse B2-glycoprotein I (B2GP1), to the Fc region of mouse IgG2a. Such ‘betabodies’ potentially have the following advantages: they bind directly to PS, and do not require a cofactor protein (B2GP1) for binding; they can be made fully human; they are smaller in size (100 KDa); and they have slower blood clearance rates. A construct was generated that bound strongly to PS-expressing cells and plates, localized to tumor vascular endothelium in vivo, and had a B-phase blood half-life of approximately 5 days after intravenous injection into mice as compared with one day for a murine version of bavituximab, 2aG4. Betabodies could potentially be the next generation of PS-targeting cancer therapeutics.
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PPHM 4-10-13 PRESS RELEASE COMMENTS RE: #4326:
” Researchers also presented details of new PS-binding constructs(4). Termed "betabodies," the molecules consist of the PS-binding domain of the serum protein B2-glycoprotein I (B2GPI), fused to the constant region of an antibody. Betabodies bind to PS directly, are smaller in size and have a longer serum half-life than natural antibodies. Early studies indicate that betabodies hold potential as next-generation PS-binding agents that have the potential to be used for a broad number of applications including antibody-drug conjugates and next generation therapeutics for oncology and infectious diseases."
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=755519
PDF of AACR’13 Poster #4326:
http://www.peregrineinc.com/images/stories/pdfs/xianming_2013.pdf
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PR 4-10-13: Data Presented at AACR Annual Meeting Support Targeted Immune Reactivation Mechanism and Potential of Peregrine's Bavituximab in Solid Tumor Therapy
• Imaging Studies Show Docetaxel Strongly Upregulates Bavituximab's PS Target in Tumors, Further Supporting Lead Clinical Indication in Second Line Non-Small Cell Lung Cancer
• Preclinical Studies Support Potential of Bavituximab to Induce Cancer-Fighting Changes in Immune Response to Tumors That Have Been Associated With Prolonged Survival in Lung Cancer Patients
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=755519
TUSTIN, CA 4/10/13: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a biopharmaceutical company developing first-in-class monoclonal antibodies focused on the treatment and diagnosis of cancer, today highlighted data presented at the Annual Meeting of the American Association for Cancer Research (AACR). Data was presented this week from preclinical studies investigating the immune-stimulating mechanism of action of Peregrine's lead phosphatidylserine (PS)-targeting oncology clinical candidate bavituximab and the anti-tumor and imaging potential of other PS-targeting molecules. Bavituximab is currently being evaluated in several oncology clinical trials including the lead indication of second-line non-small cell lung cancer (NSCLC), which is anticipated to advance into a pivotal Phase III trial later this year.
"These studies yield important insights into the fundamental role that exposed PS plays in tumor immune evasion, and further support our lead clinical candidate bavituximab's ability to reactivate tumor immunity. This is now clearly evidenced by several specific measurements of both the immune-stimulating and anti-tumor mechanisms mediated by PS-targeting antibodies as well as imaging studies demonstrating that tumor growth inhibition is correlated with PS expression levels in tumors," said Jeff T. Hutchins, Ph.D., VP of Preclinical Research at Peregrine Pharmaceuticals. "Included in these presentations was a compelling finding of a pronounced antibody-mediated increase in tumor-fighting immune cells that is independently correlated with an impressive survival benefit in patients with NSCLC based on a published retrospective study of clinical data(1). When taken together, these results support PS as a promising oncology drug target and provide additional rationale for the impressive Phase II survival data we have seen in bavituximab's lead indication of second-line NSCLC."
Data presented from imaging studies(2) demonstrate that the chemotherapeutic drug docetaxel, a commonly prescribed second-line treatment for patients with advanced NSCLC, increases the exposure of bavituximab's target molecule, phosphatidylserine (PS), on tumor blood vessel cells and tumor cells. Results also showed that PS exposure in tumors is correlated with tumor burden and response to docetaxel treatment, supporting exposed PS as a promising biomarker of cancer and response to therapy. Peregrine's PS-targeting imaging agent I-124-PGN650 is currently being evaluated in a clinical trial to assess its safety and potential to image multiple tumor types in patients with cancer.
Additional data presented from a series of preclinical studies(3) demonstrate that PS-targeting antibodies mediate immuno-stimulatory changes in tumors resulting in an increase of tumor-fighting (M1) macrophages, immune cells strongly associated with survival benefits in patients with NSCLC(1). Peregrine recently reported promising data from a randomized, double-blind, placebo-controlled Phase II second-line NSCLC clinical trial demonstrating a 60% improvement in median overall survival (OS) in patients receiving 3 mg/kg bavituximab plus docetaxel compared to the control arm. The company plans to meet with the U.S. Food and Drug Administration (FDA) in the second quarter of calendar year 2013 with the goal of initiating a Phase III trial by calendar year-end.
Researchers also presented details of new PS-binding constructs(4). Termed "betabodies," the molecules consist of the PS-binding domain of the serum protein B2-glycoprotein I (B2GPI), fused to the constant region of an antibody. Betabodies bind to PS directly, are smaller in size and have a longer serum half-life than natural antibodies. Early studies indicate that betabodies hold potential as next-generation PS-binding agents that have the potential to be used for a broad number of applications including antibody-drug conjugates and next generation therapeutics for oncology and infectious diseases.
(1) ”The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time” Ma et al. BMC Cancer 2010, 10:112. Open access research article: http://www.biomedcentral.com/content/pdf/1471-2407-10-112.pdf
PRESENTATION DETAILS:
(2) Jian Gong(1), Richard Archer(1), Van Nguyen(1), Christopher C.W. Hughes(2), Jeff Hutchins(1), Bruce Freimark(1). 1. Peregrine Pharmaceuticals, Inc., Tustin, CA; 2. University of California, Irvine, Irvine, CA.
“Predicting Anti-Tumor Responses to Phosphatidylserine Targeting Antibodies Using Tumor Imaging”
In Proceedings of the 104th Annual Meeting of the American Association for Cancer Research (AACR); 2013 Apr 6-10; Washington, D.C. Abstract 2850
[ PDF of AACR’13 Poster #2850: http://www.peregrineinc.com/images/stories/pdfs/jian_2013.pdf ]
(3) Yi Yin, Xianming Huang, Dan Ye, Philip Thorpe. UT Southwestern Medical Ctr., Dallas, TX
“Phosphatidylserine-Targeting Antibody Reactivates Tumor Immunity and Destroys Tumor Vasculature in Mice”
In Proceedings of the 104th Annual Meeting of the American Association for Cancer Research (AACR); 2013 Apr 6-10; Washington, D.C. Abstract 1244
[ PDF of AACR’13 Poster #1244:
http://www.peregrineinc.com/images/stories/pdfs/yi_2013.pdf ]
(4) Xianming Huang(1), Dan Ye(1), Troy Luster(2), E. Sally Ward(1), Philip Thorpe(1). 1. UT Southwestern Medical Ctr., Dallas, TX; 2. Human Genome Science, Maryland
”Phosphatidylserine-Targeting 'Betabodies' for the Treatment of Cancer”
In Proceedings of the 104th Annual Meeting of the American Association for Cancer Research (AACR); 2013 Apr 6-10; Washington, D.C. Abstract 4326
[ PDF of AACR’13 Poster #4326:
http://www.peregrineinc.com/images/stories/pdfs/xianming_2013.pdf ]
Copies [PDF’s] of the AACR posters are available at Peregrine's website at http://www.peregrineinc.com/technology/bavituximab-oncology/recent-data.html
ABOUT BAVITUXIMAB
Bavituximab is a first-in-class phosphatidylserine (PS)-targeting monoclonal antibody that represents a new approach to treating cancer. Bavituximab is the lead drug candidate from the company's PS technology platform and is currently being tested in eight clinical trials, including three randomized Phase II trials in front-line and second-line non-small cell lung cancer and front-line pancreatic cancer, and five investigator-sponsored trials (ISTs) in additional oncology indications. PS is a highly immunosuppressive molecule usually located inside the membrane of healthy cells, but "flips" and becomes exposed on the outside of cells that line tumor blood vessels, creating a specific target for anti-cancer treatments. PS-targeting antibodies target and bind to PS and block this immunosuppressive signal, thereby enabling the immune system to recognize and fight the tumor.
ABOUT PEREGRINE PHARMACEUTICALS, INC.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials focused on the treatment and diagnosis of cancer. The company is pursuing multiple clinical programs in cancer with its lead product candidate bavituximab and novel brain cancer agent Cotara®. 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 or Jay Carlson
Peregrine Pharmaceuticals, Inc. (800) 987-8256
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Snapshots of Peregrine’s AACR’13 Posters – from http://www.peregrineinc.com/technology/bavituximab-oncology/recent-data.html
AACR’13 4-8-13/Mon Poster #1244: “Phosphatidylserine-Targeting Antibody Reactivates Tumor Immunity & Destroys Tumor Vasculature In Mice”
Yi Yin, Xianming Huang, Dan Ye, Philip Thorpe - UTSW-MC/Dallas
Session: Cytokines, Modification of the Tumor Microenvironment, and Intervention
AACR’13 4-9-13/Tue Poster #2850: “Predicting Anti-Tumor Responses to Phosphatidylserine-Targeting Antibodies Using Tumor Imaging”
Jian Gong 1, Richard Archer 1, Van Nguyen 1, Christopher C.W. Hughes 2, Jeff Hutchins 1, Bruce Freimark 1
1 Peregrine Pharmaceuticals; 2 Univ. of California/ Irvine
Session: Immune Therapeutics & Monoclonal Antibodies 1
AACR’13 4-9-13/Tue Poster #4326: “Phosphatidylserine-Targeting ‘Betabodies’ for the Treatment of Cancer”
Xianming Huang 1, Dan Ye 1, Troy Luster 2, E. Sally Ward 1, Philip Thorpe1
1 UTSW-MC/Dallas; 2 Human Genome Science, Maryland, MD
Session: Antibody Therapeutics & Novel Delivery Technologies
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“In Memoriam
Philip E. Thorpe, Ph.D.
1951-2013
Founder, scientist, and friend”
http://www.peregrineinc.com
“Phil will be sorely missed as a colleague and friend. At Peregrine, each of us is pursuing Phil's dream of bringing important drugs to patients who need them based on his basic research. We are more motivated than ever to see this dream through.”
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