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Phase 2-Ready Small Molecule MCT-1 Inhibitor (AZD3965)

The Opportunity: 

AZD3965 is a Phase 2 ready, first-in-class oral and highly selective inhibitor of MCT-1 that has shown promising signs of efficacy in early phase clinical trials in DLBCL. Initially developed by AstraZeneca, CRUK now holds exclusive rights to the programme. We are seeking a partner for out-licensing, with the opportunity to leverage the CRUK network to support further clinical development.

MCT-1 is a proton-linked transporter of lactate and other monocarboxylates, and high levels of the transporter have been associated with poor prognosis in haematological and some solid cancers. It is thought that, in haematological cancers, upregulation of MCT-1 may be due to the increased need to export lactate due to the cancer’s increased reliance on glycolysis for energy production. Inhibition of MCT-1 can therefore target cancer cells by focussing on their metabolic abnormalities.

Preclinical work has shown that AZD3965 has efficacy in models of Diffuse Large B-Cell Lymphoma (DLBCL) and Burkitt’s lymphoma and that treatment with the inhibitor enhanced in vivo efficacy of the standard-of-care therapy Rituximab. Further combination studies have also demonstrated synergistic potential with other metabolic agents.

As one the first anti-cancer agents to specifically target metabolism to enter the clinic, AZD3965 has shown that it is well tolerated and has promising efficacy even in the late stage, heavily pre-treated setting. In the expansion phase of the Phase 1 trial, which focussed on late stage DLBCL patients’ treatment with AZD3965 at 10mg bid, one prolonged stable disease and one complete response were observed among the 11 patients enrolled.

The molecule is protected by a granted composition-of-matter patent (priority date 17 January 2003) with extensive worldwide coverage. Additionally, given the population and observed efficacy, it is believed that there is potential for rapid approval and a potential orphan drug designation. CRUK’s Centre for Drug Development has developed a high level plan for its submission.