Peregrine Pharmaceuticals, Inc, clinical stage biopharmaceutical company developing targeted monoclonal antibodies for the treatment of cancer and hepatitis C virus (HCV) infection, reported that preclinical data presented at IBC's 5th Annual International Anti-Angiogenesis Conference showed that its anti-VEGF antibody R84 was as effective as Avastin (bevacizumab) in inhibiting tumour growth in a mouse model of human breast cancer.
R84 is a selective, fully human monoclonal antibody that blocks the cancer-promoting agent vascular endothelial growth factor (VEGF). R84 selectively blocks VEGF from binding only to VEGF receptor 2 (VEGFR2), while non-selective agents such as Avastin block binding to both VEGFR2 and VEGF receptor 1 (VEGFR1). Selective anti-VEGF agents may have potential advantages over non-selective approaches and Peregrine is now assessing R84 as a candidate for clinical development. R84 is a product of the collaboration between Peregrine and antibody developer Affitech AS of Oslo, Norway.
The data demonstrating the potential anti-cancer efficacy of R84 in xenograft models of human cancer was part of a presentation by Dr. Rolf Brekken, assistant professor of surgery and pharmacology and Effie Marie Cain Scholar in Angiogenesis Research at UT Southwestern Medical Centre, and an advisor to Peregrine. Dr. Brekken's study treated tumour-bearing animals with R84, Avastin, or a placebo in an orthotopic model of breast cancer. Treatment with R84 reduced the growth of well-established breast tumours by 55 per cent, equivalent to the reduction achieved with Avastin. The researchers also demonstrated that R84 and Avastin were equally effective at controlling tumour growth in a preclinical model of sarcoma. In every preclinical tumour model evaluated thus far, the anti-tumour activity of R84 has been comparable to that of Avastin.
"These encouraging findings build on positive preclinical data we presented at the 2007 AACR meeting showing that Peregrine's selective anti-VEGF mouse antibody 2C3 and its fully human counterpart R3 demonstrated potent anti-cancer efficacy equivalent to Avastin in a model of pancreatic cancer," said Steven W. King, president and CEO, Peregrine. "We are delighted that R84 is generating similar, and potentially superior, results in preclinical cancer models. As a result of these positive developments, we are initiating additional preclinical studies to advance R84 as our next potential clinical candidate."
The study results also showed that tumour-associated macrophages, immune system cells found in tumours, are reduced after R84 therapy. Tumour-associated macrophages are often associated with poor prognosis as these cells are linked to increased angiogenesis and metastasis. In addition, the study data showed that when given for a prolonged period, R84 decreased microvessel density and expression of VEGFR2, demonstrating that the antibody is acting to reduce VEGF-induced angiogenesis in tumour tissue.
Dr. Brekken commented, "VEGF binding to VEGFR2 on blood vessels is a primary driver in promoting the development and maintenance of the blood vessels needed by tumours to survive and grow. These new studies further tested the hypothesis that selectively inhibiting VEGFR2 is an equally effective anti-tumour strategy as blocking both VEGF receptors. Most of the anti-angiogenic agents currently being developed or marketed, such as Avastin, block the activity of both VEGF receptors. The data we previously presented on 2C3, our selective anti-VEGF mouse antibody, along with the current study results demonstrate that selective inhibition of VEGFR2 alone can reduce tumour growth. They also suggest that inhibiting VEGFR1 is not necessary to effectively limit VEGF-induced angiogenesis. We look forward to further assessing R84 as a potential anti-angiogenic clinical candidate."
Peregrine in association with Affitech has filed a patent application for R84 with the United States Patent and Trademark Office to preserve the right to obtain patent protection in the United States, all member countries of the European Union and the rest of the world.
This research was supported in part by a sponsored research agreement between UT Southwestern and Peregrine Pharmaceuticals. These studies were also supported in part by Susan G. Komen for the Cure and the Department of Surgery at UT Southwestern.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative product candidates in clinical trials for the treatment of cancer and hepatitis C virus (HCV) infection. The company is pursuing three separate clinical programs in cancer and HCV infection in the US and India with its lead product candidates bavituximab and Cotara. Peregrine also has in-house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc, which provides development and bio-manufacturing services for both Peregrine and outside customers.