WASHINGTON and TUSTIN, Calif., April 3 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. announced today that two groundbreaking preclinical studies being presented at the 97th Annual Meeting of the American Association for Cancer Research (AACR) demonstrate that a mouse equivalent to its first-in-class anti-phospholipid (PS) agent Tarvacin(TM) (bavituximab) significantly increases survival in cisplatin-resistant breast cancer and radiotherapy-resistant brain cancer when given as part of a combination regimen. In these studies, Tarvacin in combination with cisplatin or radiation was significantly more effective in increasing survival time than either agent alone. Both studies also confirmed that Tarvacin’s unique phospholipid target is up-regulated after cisplatin or radiation therapy, thereby contributing to the demonstrated efficacy of the combination regimens.
These studies, which were conducted by researchers at the University of Texas Southwestern Medical Center at Dallas in collaboration with Peregrine, are expected to facilitate the design of Tarvacin clinical studies in breast and brain cancer after completion of the current ongoing Phase l cancer trial.
“Resistance continues to be one of the greatest barriers to successful cancer treatment and cancers that have become resistant to therapies such as cisplatin or radiation typically signal end stage disease for these patients,” said Philip Thorpe, Ph.D., professor of pharmacology at UT Southwestern and a member of the Peregrine Scientific Resource Board. “We are therefore extremely pleased that Tarvacin in combination with cisplatin or radiation significantly increased survival times in these two studies. This remarkable result was predicted on the basis of Tarvacin’s anti-PS mechanism and has now been confirmed in these clinically relevant animal models of advanced breast and brain cancer. We look forward to the opportunity to confirm these exciting results in human trials.”
Tarvacin, or bavituximab, is a monoclonal antibody that binds to a phospholipid called phosphatidylserine, a component of the cell structure that is usually located inside normal cells but which becomes exposed on the outside of the cells that line the blood vessels of tumors, creating a specific target for anti-cancer treatments. In February Peregrine successfully completed enrollment in a Tarvacin Phase l clinical trial for the treatment of chronic hepatitis C virus infection, reporting that the drug appeared to be safe and well-tolerated. Peregrine currently is conducting a Tarvacin Phase l trial for the treatment of solid cancers.
In the first study, Dr. Thorpe and colleagues at UT Southwestern studied a Tarvacin equivalent antibody, 3G4, in combination with the standard-of-care chemotherapy drug cisplatin in a mouse model of cisplatin-resistant breast cancer. Tumor suppression and survival in the combination Tarvacin equivalent and cisplatin group were significantly better (p<0.01) than for either agent alone. Mice treated with cisplatin and the Tarvacin equivalent survived almost twice as long as mice treated with cisplatin alone, the Tarvacin equivalent alone, or a control antibody alone. The “50% survival time” was 105 days for mice treated with the combination of the Tarvacin equivalent plus cisplatin versus 50 days for those treated with the control antibody, 56 days for those treated with the Tarvacin equivalent alone, and 60 days for those treated with cisplatin alone.
In addition, the poster reports that mechanistic studies showed that exposure of the PS target of Tarvacin on tumor vascular endothelial cells in these mice was significantly increased by administration of cisplatin. Seventy-five percent of tumor blood vessel cells were PS positive after cisplatin treatment, as compared with just 30% that were PS positive in the untreated group. This up-regulation of Tarvacin’s PS target by cisplatin is believed to contribute to the combination regimen’s efficacy. The study authors conclude that the combination of the Tarvacin equivalent antibody with cisplatin holds the potential to overcome the common problem of cisplatin- resistance in cancer treatment.
In a second poster presentation, Dr. Thorpe and colleagues at UT Southwestern presented the findings of a study assessing the activity of a combination of a Tarvacin equivalent antibody, 2aG4, and irradiation in a rat brain cancer model of glioblastoma, a deadly brain cancer that kills most patients within months of diagnosis. Radiation is known to increase the expression of Tarvacin’s anti-PS target on tumor blood vessels, and in this study the subjects received radiation treatment prior to being dosed with the Tarvacin equivalent. In the group receiving the Tarvacin equivalent plus radiation, the animals achieved a median survival of 44 days, versus 27 days and 18 days survival respectively, for rodents treated with radiation alone or receiving no treatment (p=0.0001). Three out of 24 subjects (12.5%) treated with radiotherapy plus the Tarvacin equivalent had complete tumor regressions and remained disease free. In this study, researchers also confirmed that radiation up-regulated Tarvacin’s PS target, finding that after irradiation, around 50% of tumor blood vessels exhibited the PS target, as compared with no evidence of the PS target in the non-irradiated tumors.
The authors conclude that the anti-tumor effect of the Tarvacin equivalent antibody plus irradiation was equivalent to what would have been expected if 99.99% of brain cancer cells had been destroyed.
“These results in challenging pre-clinical models showing the potential of Tarvacin to work with existing therapies to successfully treat radiation and chemotherapy resistant cancers further support the way we believe Tarvacin will be used in the clinical setting,” said Steven W. King, president and CEO of Peregrine. “As a result of its unique target, mechanism of action and natural synergistic fit with existing therapies, we believe Tarvacin could be an ideal addition to current treatment regimens.”
Mr. King continued, “Building on the recently completed Tarvacin Phase I trial in an antiviral indication that supported its good safety profile in patients, we look forward to completing the ongoing Phase I clinical trial currently enrolling solid tumor patients. Safety data from these two studies should enable us to expeditiously move our Tarvacin cancer program into later stage clinical trials in combination with existing therapies.”
The two studies discussed in this press release, plus other selected posters relevant to Peregrine’s technology that are being presented at the AACR annual meeting, are listed below:
No. 570: Radiation-guided Vascular Targeting Therapy in A Syngeneic Rat Glioblastoma Model, Jin He, Troy Luster and Philip E. Thorpe. UT Southwestern Medical Center, Dallas, TX Sunday, April 02, 2006, 8:00 AM -12:00 PM
No. 2123: Overcoming cisplatin-resistance of breast cancer in mice by co- administering cisplatin and anti-phosphatidylserine antibody, 3G4, Xianming Huang, Dan Ye, Troy Luster, Jin He, Shuzhen Li, Linda Watkin, Janie Iglehart, Philip Thorpe. UT Southwestern Medical Center at Dallas, Dallas, TX Monday, April 03, 2006, 8:00 AM - 12:00 PM
No. 1053: Coincident exposure of phosphatidylethanolamine and phsophatidylserine on the surface of irradiated endothelial cells, Andrei Marconescu, Jin He, Troy A. Luster, Xianming Huang, Philip E. Thorpe. University of Texas Southwestern Medical Center, Dallas, Dallas, TX Sunday, April 02, 2006, 1:00 PM - 5:00 PM
No. 1998: Development of targeted tissue factor as vascular targeting agent coaguligand, Richard H. Archer, Jeanette R. Doerr, Rinal Shah, Steven W. King, Ronald T. Aimes. Peregrine Pharmaceuticals, Inc., Tustin, CA Monday, April 03, 2006, 8:00 AM - 12:00 PM
No. 2179: Binding of a monoclonal antibody that targets anionic phospholipids on tumor vasculature is dependent upon interaction with plasma protein beta2-glycoprotein I, Troy A. Luster, Jin He, Xianming Huang, Alan J. Schroit, Philip E. Thorpe. University of Texas Southwestern Medical Center, Dallas, TX, University of Texas MD Anderson Cancer Center, Houston, TX Monday, April 03, 2006, 8:00 AM - 12:00 PM
No. 4779: A novel method for the screening of vasopermeability and vascular leakage agents using an avian embryo system, John D. Lewis, Andries Zijlstra, Kelly A. Felton, Christian Frosch, Keith A. Luhrs, Heidi Stuhlmann, Missag H. Parseghian. Scripps Research Institute, La Jolla, CA, Peregrine Pharmaceuticals, Inc., Tustin, CA, BioBroker, Baesweiler, Germany Tuesday, April 04, 2006, 1:00 PM - 5:00 PM
About Peregrine
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative product candidates in clinical trials for the treatment of cancer and viral diseases. The company is pursuing three separate clinical trials in cancer and anti-viral indications with its lead product candidates Tarvacin(TM) and Cotara(R). Peregrine also has in-house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc. (http://www.avidbio.com), which provides development and bio-manufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at http://www.peregrineinc.com.
Safe Harbor Statement:
Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals’ intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that promising preclinical activity and results demonstrated by Tarvacin in combination with existing therapeutic agents will not be consistent in human testing and the risk that we may experience delays in enrolling patients, which could delay completion of our existing Phase I Tarvacin cancer trial and thus our planned commencement of later stage clinical trials using Tarvacin cancer in combination with existing therapies It is important to note that the company’s actual results could differ materially from those in any such forward-looking statements. Factors that could cause actual results to differ materially include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in our SEC reports including, but not limited to, the annual report on Form 10-K for the year ended April 30, 2005, and the quarterly report on Form 10-Q for the quarter ended January 31, 2006. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.
Investors Media Brod & Schaffer Barbara Lindheim (800) 987-8256 GendeLLindheim BioCom Partners ir@peregrineinc.com (212) 918-4650
Peregrine Pharmaceuticals, Inc.
CONTACT: Investors - Brod & Schaffer, +1-800-987-8256,ir@peregrineinc.com; Media - Barbara Lindheim of GendeLLindheim BioComPartners for Peregrine, +1-212-918-4650
Web site: http://www.peregrineinc.com//
