Monoclonal Antibody Bavituximab Well-Tolerated by HIV/HCV Coinfected People

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Monoclonal Antibody Bavituximab Well-Tolerated by HIV/HCV Coinfected People

SUMMARY: An experimental monoclonal antibody that inhibits HCV replication was safe and well-tolerated in a clinical trial of HIV positive people coinfected with chronic hepatitis C, researchers reported at EASL 2011.

Bavituximab is an investigational monoclonal antibody that targets phosphatidylserine (a phospholipid component) on the membrane of virus-infected cells. Preclinical studies have shown that this type of antibody can inhibit viral replication and enhance immune response. Phosphatidylserine is expressed on cells infected with a variety of viruses -- including hepatitis C virus (HCV), HIV, influenza, and herpes viruses -- suggesting that targeted antibodies could be beneficial in a number of diseases.Prior studies found that single and twice-weekly intravenous infusions of bavituximab up to 6

mg/kg were well-tolerated and showed transient antiviral activity in people with chronic hepatitis C. As reported at the European Association for the Study of the Liver's International Liver Congress (EASL 2011) this month in Berlin, researchers then evaluated the safety, tolerability, pharmacokinetics, and viral kinetics of up to 8 weekly infusions of bavituximab in HIV/HCV coinfected people.Below is an edited excerpt from a Peregrine Pharmaceuticals press release describing the study and its findings.

Peregrine Presents Phase Ib HCV/HIV Data on Single-Agent Bavituximab at EASL

Bavituximab Safe and Well Tolerated, Ongoing Phase II Trial Evaluating Bavituximab With RibavirinTustin, CA, and Berlin, Germany -- April 4, 2011 -- 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 data from its Phase Ib dose escalation safety study of bavituximab in patients coinfected with chronic hepatitis C virus (HCV) and HIV. In a poster presented at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL), data show bavituximab administered as a single agent for 8 weeks was generally safe and well tolerated at all four dose levels.

"Bavituximab used as a single agent has demonstrated a consistent, acceptable safety profile in three Phase I HCV trials to date, and we have seen enhanced antiviral activity when using bavituximab in combination with the antiviral agent ribavirin in several preclinical viral disease models," said ph S. Shan, vice president of clinical and regulatory affairs at Peregrine Pharmaceuticals. "Our recently initiated randomized Phase II trial will assess early virology response of genotype 1 HCV patients after 12 weeks of therapy combining bavituximab with ribavirin as a potential alternative to the current interferon-based regimen." Peregrine's Phase Ib safety study included 27 patients (85% genotype 1 HCV) coinfected with HCV and HIV. Coinfected patients typically have higher HCV viral loads and more rapid progression compared to patients infected with HCV alone. Patient

cohorts received ascending dose levels of bavituximab weekly (0.3 mg/kg, 1.0 mg/kg, 3 mg/kg and 6 mg/kg) for up to 8 weeks. Adverse events (AEs) were considered mild or moderate and were consistent with other bavituximab trials. Three serious adverse events were reported, two of which were drug-related (rash and hypersensitivity). Patients were not premedicated. No dose-limiting toxicities occurred and a maximum tolerated dose of bavituximab was not reached. Although not a primary endpoint of this safety study, HCV and HIV antiviral activity (> 0.5 log10 reduction) were observed in all treatment groups during bavituximab therapy. In an ongoing randomized Phase II HCV trial, Peregrine is evaluating the 12-week early virologic response (EVR) rate of previously untreated genotype-1 HCV patients treated with Peregrine's bavituximab (0.3 mg/kg or 3 mg/kg) in combination with the antiviral drug ribavirin (1000 mg) versus current standard of

care, pegylated interferon alpha-2a (180 mcg) and ribavirin. For further information about this trial, which is being conducted outside of the U.S., please visit www.peregrinetrials.com or www.clinicaltrials.gov/ct2/show/NCT01273948?term=bavituximab & rank=3. A copy of the poster is available at Peregrine's website www.peregrineinc.com/pipeline/cot.html. About Bavituximab's Antiviral ApproachBavituximab is the first in a new class of patented antibody therapeutics that target and bind to phosphatidylserine (PS), a specific phospholipid component of cell membranes. Bavituximab helps reactivate and direct the body's immune system to destroy infected cells and virus particles that exhibit this specific phospholipid on their surface. Since

their target is host-derived rather than pathogen-derived, PS-targeting antibodies have the potential for broad-spectrum antiviral activity and are also expected to be much less susceptible to the viral mutations that often lead to drug resistance. Researchers have found that PS is exposed on the outer membrane of cells infected with HCV, HIV, influenza, herpes viruses, hemorrhagic fever viruses, respiratory syncytial virus, measles as well as other viruses. A growing body of scientific publications, including Nature Medicine and The Journal of Experimental Medicine, has highlighted data on the role of PS and Peregrine's PS-targeting therapies in infectious diseases. About Peregrine PharmaceuticalsPeregrine 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. (www.avidbio.com), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com. Investigator affiliations: Infectious Diseases, Saint 's Medical Center, Newark, NJ; Center for Viral Hepatitis, 's Hopkins University, Baltimore, MD; Peregrine Pharmaceuticals, Inc., Tustin, CA.

4/15/11

ReferenceJ Slim, MS Sulkowski, and JS Shan. Escalating repeat-dose study of bavituximab in patients co-infected with chronic hepatitis C virus (HCV) and human immunodeficiency virus. 46th Annual Meeting of the European Association for the Study of the Liver (EASL 2011). Berlin. March 30-April 3. Abstract 1117. Other SourcePeregrine Pharmaceuticals. Peregrine Presents Phase Ib HCV/HIV Data on Single-Agent Bavituximab at EASL. Press release. April 4, 2011.

http://www.hivandhepatitis.com/2011_conference/easl2011/docs/0415_2010_b.html