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-0449 in an in vivo Ptch+/- medulloblastoma allograft model ( 5mg/kg IMP5471 as same as 50 mg/kg GDC-0449), and 15 and 30 mg/kg of IMP5471 was more efficacious than 50 mg/kg of GDC-0449. No toxicity was observed in rat acute toxicity studies up to 200 mg/kg (50, 100 and 200 mg/kg), and in 2-week rat toxicity studies up to 80 mg/kg (40, 80 and 160 mg/kg). IMP5471 has the potential to be developed as a ”best-in-class” Hedgehog pathway for the treatment of cancers with mutations in Hedgehog pathway, 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： We plan to develop our hedgehog inhibitor IMP5471 for the treatment of basal cell carcinoma and medulloblastoma. IND enabling studies of IMP5471 has been initiated, and we plan to file IND in China in 15-18 months.