CAMBRIDGE, Mass.--(BUSINESS WIRE)--Acceleron Pharma, Inc., a biopharmaceutical company developing protein therapeutics for cancer and orphan diseases, announced that collaborators at Beth Israel Deaconess Medical Center presented preclinical data today at the American Association for Cancer Research (AACR) Annual Meeting 2012 which showed that ACE-041, an activin-receptor like kinase 1 (ALK1) receptor ligand trap, when used in combination with sunitinib, inhibited tumor growth in a model of VEGF-inhibitor-resistant renal cell carcinoma (RCC).
Anti-angiogenesis therapies, including the VEGF-inhibitor sunitinib, are currently the standard of care in metastatic RCC. While these treatments cause tumor shrinkage and extend progression-free survival in many patients, the responses are typically short-lived due to the development of drug resistance. Mice bearing A498 and 786-0 human RCC xenografts that receive anti-VEGF treatment mirror this clinical experience with a period of tumor stabilization that is followed by the restoration of angiogenesis and resumption of growth despite continued drug administration. The preclinical data, presented by Rupal Bhatt, M.D., Ph.D., Assistant Professor, Hematology-Oncology, Beth Israel Deaconess Medical Center provide evidence that combining two distinct anti-angiogenic drugs, a VEGF inhibitor and ACE-041, may produce an enhanced therapeutic effect in the treatment of metastatic RCC.
Preclinical Study Description and Results
Two renal cell carcinoma cell lines (A498 and 786-O) were used in a mouse xenograft model. In each tumor cell line, mice treated with the combination of ACE-041 and sunitinib slowed tumor growth to a greater extent than either agent alone. Additionally, the combination of ACE-041 and sunitinib prevented the restoration of tumor perfusion during the resistant phase of sunitinib-alone treatment and lowers tumor perfusion to a greater extent than sunitinib-alone.
“These data demonstrate that blocking ALK1 ligand signaling, either alone or in combination with other anti-angiogenesis therapies, may be an attractive strategy for treatment of renal cell carcinoma,” said Dr. Bhatt.
“There is increasing evidence that combining anti-angiogenesis inhibitors with distinct mechanisms of action, such as a VEGF inhibitor with an ALK1 ligand trap, like ACE-041, can more effectively inhibit tumor angiogenesis,” said Matthew Sherman, M.D., Chief Medical Officer at Acceleron. “We believe this approach holds great promise and we’re excited to pursue Phase 2 studies of ACE-041 in combination with VEGF inhibitors later this year.”
About ACE-041
ACE-041 is an ALK1 ligand trap that inhibits angiogenesis by preventing BMP9 and BMP10, members of the TGFβ protein superfamily, from interacting with activin receptor-like kinase 1 (ALK1), a receptor found on proliferating endothelial cells. ACE-041 inhibits ALK1 signaling, which is required for the development of mature, functional capillary networks. In animal studies, treatment with ACE-041 inhibits tumor angiogenesis and growth. In a clinical study of patients with advanced, refractory solid tumors, treatment with ACE-041 was generally well-tolerated and antitumor activity was observed, resulting in tumor shrinkage and stabilization of disease. ACE-041 is being studied in a Phase 2 clinical trial in patients with squamous cell carcinoma of the head and neck.
About Acceleron
Acceleron is a privately-held biopharmaceutical company committed to discover, develop, manufacture and commercialize novel protein therapeutics for orphan diseases and cancer. Acceleron’s scientific approach takes advantage of its unique insight to discover first-in-class therapies based on the TGF-β protein superfamily. Acceleron utilizes proven biotherapeutic technologies and capitalizes on the company’s internal GMP manufacturing capability to advance its therapeutic programs rapidly and efficiently. The investors in Acceleron include Advanced Technology Ventures, Alkermes, Avalon Ventures, Bessemer Ventures, Celgene, Flagship Ventures, MPM BioEquities, OrbiMed Advisors, Polaris Ventures, QVT Financial, Sutter Hill Ventures and Venrock. For further information on Acceleron, please visit www.acceleronpharma.com.