Company will initiate Phase II studies of Zybrestat, a vascular disrupting agent.

Biopharma firm Oxigene negotiated exclusive worldwide rights to IP and knowhow relating to Angiogene Pharmaceuticals’ vascular disrupting agent (VDA) program in the field of carcinoid syndrome. The assets will be used to support Phase II development of Zybrestat™ (combretastatin A4 phosphate, or CA4P) for the treatment of carcinoid syndrome associated with metastatic carcinoid and neuroendocrine tumors. OxiGene says that the combination of the inlicensed IP with its own R&D in the field of carcinoid syndrome provides a “compelling therapeutic rationale” to take the drug into Phase II trials.

“Oxigene has contemplated developing Zybrestat in carcinoid syndrome for some time, given the compelling scientific basis for using a VDA to disrupt blood flow to induce tumor necrosis and reduce production of well-validated biologic mediators,” notes Peter Langecker, M.D., CEO. “Embolization is a well-established method for the treatment of carcinoid tumors, but it is limited to those tumors that have readily accessible blood vessels. The use of a systemic treatment with a VDA to achieve a comparable effect on more disseminated tumors may open up new treatment paradigms for carcinoid patients.”

Oxigene is focused primarily on the development of vascular disrupting agents for the treatment of cancer and ophthalmic disorders. Lead compound Zybrestat is in Phase III trials for treating anaplastic thyroid cancer, and undergoing separate Phase II studies in the treatment of non-small cell lung cancer and platinum-resistant ovarian cancer. A topical formulation of Zybrestat is undergoing Phase II evaluation against age-related macular degeneration.

A second clinical-stage VDA compound, OXi4503 (combretastatin A1 di-phosphate (CA1P) is a structural analog of Zybrestat in development against leukemias. The drug is currently undergoing Phase I evaluation as a potential treatment for acute myelogenous leukemia (AML) or myelodysplastic syndrome. The open-label, dose-escalating study is being conducted by researchers at the University of Florida and is sponsored in part by The Leukemia & Lymphoma Society’s Therapy Acceleration Program.

Earlier this month Oxigene reported positive data from a Phase I Zybrestat study in patients with advanced solid tumors. The results demonstrated that combination therapy with Zybrestat and the anti-VEGF antibody bevacizumab led to disease stabilization in 60% of patients. One ovarian cancer patient exhibited a CA125 response that lasted for over a year. Oxigene says the trial was the first to study treatment using both a vascular disrupting agent and an anti-angiogenic monoclonal antibody.

U.K.-based Angiogene is developing a pipeline of VDA, nitric oxide synthase inhibitor, and hypoxia-activated prodrugs for the treatment of cancer. Lead Phase II-stage VDA candidate ZD6126 was originally licensed to AstraZeneca, but reacquired by Angiogene in 2006. A new development partner is being sought. Another VDA candidate, MN029, is licensed to MediciNova, and has completed Phase II studies. 

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