Tankyrase appears to be the central druggable biotarget in the Wnt/b-catenin signalling pathway, which is involved in a number of malignancies, including cancer. Targeting tankyrase represents a novel therapeutic strategy for cancer, which has attracted substantial industry interest. However, to date, no tankyrase-specific inhibitor has progressed to clinical trials. We are seeking partners for co-development and licensing of the technology.
In melanoma patient samples, high levels of -catenin has been defined as the major factor that prevents CD8+ T cell invasion. -catenin is the central mediator of WNT signalling. It is therefore hypothesized that reducing -catenin levels in melanoma cells may re-enable T cells to invade the cancer cells, and to render PD-1 / PD-L1 based immune therapy effective in previously non-sensitive patients. We have developed a class of novel WNT inhibitor compounds exhibiting high specificity for tankyrase and demonstrated proof of concept in mouse models for cancer by effectively reducing catenin levels in selected cancer cells by targeting the pathway gate keeper Tankyrase . The compound will be extensively characterized by PK/ADME, and for properties highly suitable for formulation as a topical drug for skin cancers. Other lead compounds are being developed for systemic administration of other cancers and disorders. Formulation as a topical formulation and demonstration of PoC for skin cancers is planned. Further medicinal chemistry for development of a systemically administered drug is ongoing.
The class of molecules is protected by an international patent application (WO 2012/076898A1) which has led to a granted patent in the US (9096587), and is pending in other jurisdictions. A provisional patent application covering the new leading compounds will be filed within 2016.