IDN-13389 is a potential oral therapy in multiple tumor types including breast, colon, pancreatic and lymphomas. IDN-13389 is a potent small molecule mimic of the apoptosis-stimulating protein known as SMAC (Second Mitochondrial Activator of Caspases). Preclinical studies have demonstrated that IDN-13389 is orally effective as a monotherapy and reduces tumor burden in established models of breast and ovarian cancer. Furthermore, combining IDN-13389 with the established cancer therapeutics taxol or cisplatin leads to enhanced efficacy over either therapeutic alone. Conatus Pharmaceuticals plans to develop IDN-13389 as a potential novel therapeutic that could be efficacious alone or in combination with existing approved cancer therapeutics.
IDN-13389 was selected as a development candidate following extensive preclinical evaluation in in vitro assays and in vivo xenograft tumor models. IDN-13389 demonstrated potent activity in models of breast (MDA-MB-231) and ovarian (SK-OV-3) cancer following once daily oral dosing. An example of one study using IDN-13389 as a monotherapy is shown in the figure below.
IDN-13389 activity as a monotherapy after oral administration to mice bearing tumors derived from breast cancer cell line.
IDN-13389 was evaluated in a wide variety of human tumor cell lines in combination with multiple chemotherapeutic agents and evaluated for synergism or additivity. Based on these data, in vivo studies were carried out in combination with chemotherapeutic combinations where additivity or synergy was observed. One example of synergistic in vivo activity is shown in the following figure, where IDN-13389 was evaluated in combination with paclitaxel (taxol) in a xenograft model of breast cancer.
Combination therapy: IDN-13389 in combination with paclitaxel (Taxol) in mice bearing tumors derived from breast cancer cell line.
Conatus is pursuing the development of IDN-13389 and Phase 1/2 studies for the treatment of solid tumors could start by mid-2012.