Description: IMPACT has discovered three series of novel Hedgehog pathway inhibitors, and has identified more than 10 compounds that are 10-100 folds more potent than the approved Hedgehog inhibitor GDC-0449 (Vismodegib) in multiple in vitro assays. Several potent compounds have been found to have good oral bioavailability and good brain penetration. Based on overall in vitro and in vivo profile, we have selected IMP5471 as a clinical candidate for development. In efficacy studies IMP5471 has been found to be highly efficacious, and was 10-fold more potent than GDC-009 in an in vivo Ptch+/- medulloblastoma allograft model. Importantly, IMP5471 caused tumor regression with little body weight change (<5%), and was much more efficacious than GDC-0449. IMP5471 has the potential to be developed as a “best-in-class” Hedgehog pathway for the treatment of cancers with Hedgehog mutations, including basal-cell carcinoma (BCC) and medulloblastoma.
IP: Three patent applications have been filed for these novel compounds.
Current Plan: We have initiated IND enabling studies for IMP5471. We plan to file the IND in China and outside of China in 18-24 months.
Future Plan: Our plan is to initially develop IMP5471 as a treatment for medulloblastoma.