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4-5-11 PR: AACR #3643: Sorafenib Enhances Anti-tumor Effects of Bavituximab – supports Ph.2 Bavi+Sorafenib LIVER IST Trial initiated 12-2010

Peregrine's PS-Targeting Antibody Significantly Improves Anti-Tumor Effect of Sorafenib in Models of Advanced Liver Cancer
• AACR Data Presentation Supports Phase I/II Investigator-Sponsored Clinical Trial in Advanced Liver Cancer
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=561859

TUSTIN & ORLANDO, 4/5/11: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced that its phosphatidylserine (PS)-targeting antibody significantly enhanced the anti-tumor effects of sorafenib (Nexavar®) in models of hepatocellular carcinoma (HCC) [Liver & Bile Duct Cancers], with 69% less tumor growth compared to sorafenib alone. This study, one of four poster presentations on Peregrine's PS-targeting antibodies at the Annual Meeting of the American Association of Cancer Research (AACR), was the basis for initiating a Phase I/II investigator-sponsored trial (IST) evaluating the company's lead antibody bavituximab with sorafenib in patients with advanced HCC. Bavituximab is currently in three randomized Phase II clinical trials in lung cancer and pancreatic cancer and several ISTs for additional oncology indications.

"Our studies show that sorafenib more than doubles the amount of the immunosuppressive molecule PS exposed on the blood vessels of HCC tumors," said Philip E. Thorpe, Ph.D., professor of pharmacology at UT Southwestern Medical Center, scientific adviser to Peregrine and inventor of the company's PS-targeting antibody technology. "These data suggest that the growth-blocking mechanisms of sorafenib combined with the vascular-targeting and immune-reactivation mechanisms of bavituximab may offer additive anti-tumor effects for patients with HCC."

As presented today at AACR, tumor growth was 69% less for the group receiving Peregrine's antibody in combination with sorafenib than for the group receiving sorafenib alone (mean tumor weight of 127 mg versus 409 mg, n=10, p < 0.01) after 59 days of treatment in an animal model study. Immunofluorescence analysis showed that treatment with Peregrine's antibody in combination with sorafenib decreased tumor blood vessel density from 14.2% to 4.5% (p < 0.01), versus 10.3% (p < 0.05) for Peregrine's antibody or 8.4% (p < 0.01) for sorafenib alone.

A copy of the AACR poster is available at Peregrine's website at http://www.peregrineinc.com/technology/bavituximab-oncology/recent-data.html .
[ Direct link: http://www.peregrineinc.com/images/stories/pdfs/aacr_hcc.pdf ]

ABOUT THE PHASE I/II HCC INVESTIGATOR-SPONSORED TRIAL
In an ongoing open-label Phase I/II trial, patients with advanced HCC are receiving bavituximab weekly and sorafenib (400 mg) twice daily, until disease progression or toxicity. Phase I of the trial is dose escalation (0.3, 1 or 3 mg/kg) to determine the maximum tolerated dose (MTD) and Phase II is expansion of the study at the MTD. Approximately 50 patients are being enrolled in this trial, which is being conducted at UT Southwestern Medical Center. Primary objectives are to determine the MTD of bavituximab in patients with advanced HCC treated with sorafenib and the radiographic median time to progression. Secondary objectives include response rate, progression free-survival, overall survival, safety and tolerability. Further information about this trial is available at http://PeregrineTrials.com , UT Southwestern Medical Center Clinical Trials, and http://ClinicalTrials.gov [ http://clinicaltrials.gov/ct2/show/NCT01264705 ] .

ABOUT PEREGRINE'S INVESTIGATOR-SPONSORED TRIALS (IST) PROGRAM
Peregrine's IST program offers oncologists the opportunity to conduct clinical trials using bavituximab in solid tumor indications.

ABOUT BAVITUXIMAB
Bavituximab is a first-in-class phosphatidylserine (PS)-targeting monoclonal antibody that represents a new approach to treating cancer. 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 HEPATOCELLULAR CARCINOMA (HCC)
According to the National Cancer Institute, primary liver and bile duct cancers are the 6th most common cause of cancer death in men, and 9th most common in women. Approximately 24,000 new cases of these 2 cancers are expected to be diagnosed this year in the United States, with approximately 19,000 deaths attributable to these forms of cancer. The most common risk factor for liver cancer is chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection. Currently approved treatment options for HCC are surgery, radiation, chemotherapy, targeted therapeutics, tumor ablation, and tumor embolization.

Xiaoyun Cheng and Philip E. Thorpe, UT Southwestern Medical Center, Dallas, TX
”Phosphatidylserine-targeting Antibody Combined with Sorafenib has Strong Anti-Tumor Activity Against Human Hepatocellular Carcinomas in Mice”
In Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research (AACR); 2011 Apr 2-6; Orlando, FL. Abstract #3643.

ABOUT PEREGRINE PHARMACEUTICALS
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing multiple clinical programs in cancer and hepatitis C virus infection 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 outside customers. Additional information about Peregrine can be found at http://www.peregrineinc.com .
Nexavar® (sorafenib) is a registered trademark of Onyx Pharmaceuticals/Bayer Healthcare.
Safe Harbor *snip*
Peregrine Contact: Amy Figueroa, Peregrine Pharmaceuticals, [phone], [e-mail]

= = = = = = = = = = = From PeregrineInc.com (4-5-11):
Bavituximab Oncology > Recent Additional Data
http://www.peregrineinc.com/technology/bavituximab-oncology/recent-data.html
Broad-Spectrum Therapeutic & Diagnostic Potential Highlighted at AACR Annual Meeting
2011 AACR POSTER PRESENTATIONS
• AACR#3643: Advanced Liver Cancer: ”Phosphatidylserine-Targeting Antibody Combined with Sorafenib has Strong Anti-Tumor Activity Against Human Hepatocellular Carcinomas in Mice”
View poster (PDF): http://www.peregrineinc.com/images/stories/pdfs/aacr_hcc.pdf
Thumbnail:

INTRODUCTION
Hepatocellular Carcinoma (HCC) is the 3rd leading cause of cancer-related deaths in the world. HCC is refractory to most forms of therapy. Sorafenib is the only chemotherapeutic agent approved for the treatment of advanced HCC. Therefore, there is a huge unmet need for a new systemic therapy for HCC patients. A promising approach would be to combine sorafenib with bavituximab to treat HCC. Bavituximab is a vascular targeting antibody that is in Phase II clinical trials in patients with non-small cell lung cancer (NSCLC) and pancreatic cancer. Bavituximab targets phosphatidylserine (PS), which is normally intracellular but becomes exposed on the external surface of vascular endothelium in tumors. Bavituximab binds to PS-expressing tumor vascular endothelial cells and causes monocytes and macrophages to attack the vessels by antibody-dependent cellular cytotoxicity (ADCC). This results in death of tumor cells through deprivation of oxygen and nutrients. Chemotherapy and irradiation increase the exposure of PS on tumor vessels and enhance the anti-tumor activity of bavituximab-related antibodies in multiple rodent tumor models.
HYPOTHESIS:
Sorafenib will induce exposure of PS on HCC vasculature because it interferes with anti-apoptotic signaling, and therefore, the combination of sorafenib with bavitauximab will have an enhanced anti-tumor effect on HCC tumors.
CONCLUSIONS:
• Sorafenib induces PS exposure on human microvascular endothelial cells in vitro.
• Sorafenib increases PS exposure on tumor vessels in mice bearing subcutaneous HCC tumors in vivo.
• Combining a murine version of bavituximab with sorafenib significantly decreases tumor vasculature in the PLC/PRF/5 xenograft model.
• Combining a murine version of bavituximab with sorafenib significantly improves the anti-tumor effect in the PLC/PRF/5 xenograft model.
Bavituximab in combination with sorafenib has promise as a new systemic therapy for the treatment of advanced HCC patients.
• AACR#621: Prostate Cancer. . .
• AACR#3651: Mechanism of Action. . .
• AACR#4880: Imaging. . .

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AACR’11 Home: http://www.aacr.org/home/scientists/meetings--workshops/aacr-102nd-annual-meeting-2011.aspx
AACR’11 Abstracts Search: http://www.abstractsonline.com/plan/AdvancedSearch.aspx
2-28-11 PR: 4 PPHM Anti-PS abstracts (posters) accepted by AACR'11 for Apr3-6
- details here: http://tinyurl.com/4aofbso

H. First Investigator-Sponsored (IST) Ph.I/II Trial (Bavi+Sorafenib vs. Liver Cancer, open-label)
...Note: Sorafenib = Bayer's Nexavar - see http://www.nexavar.com
Protocol: http://clinicaltrials.gov/ct2/show/NCT01264705
UTSW: http://tinyurl.com/2che4us (4 sites: 3/UTSW, 1/Parkland-Hosp.)
...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.”