IDE397 is targeting a select patient group: those whose tumors are MTAP-deleted. This represents ~15% of all cancers, across tumor types. Currently, precision medicine represents a only small fraction of oncology therapies. And there are no therapies specific to MTAP-deleted patients. There are ~75,000 MTAP-deleted patient estimated in US, EU5 and JP across six indications, including non small cell lung cancer, head and neck cancer, bladder cancer, gastric cancer, pancreatic cancer and esophageal cancer. Current standard of care therapies for these cancers, such as chemotherapy, are broad - affecting both healthy and tumor cells, and being given to all kinds of patients. IDE397 provides a biomarker-driven approach to treat MTAP-deleted patients specifically and to treat only the tumor cells, sparing healthy cells.
Current standard of care therapies for MTAP-deleted cancers, such as chemotherapy, are broad - affecting both healthy and tumor cells, and being given to all kinds of patients (not limited to MTAP-deleted patients). IDE397 provides a biomarker-driven approach to treat MTAP-deleted patients specifically and to treat only the tumor cells, sparing healthy cells. In phase 1 studies (ongoing), we have shown remarkable safety and tolerability, along with robust early pharmacodynamic (PD) modulation.
We have evaluated the efficacy of IDE397 as monotherapy in over forty solid tumor patient derived xenograft, or PDX, models with homozygous MTAP deletions. Results of this IDE397 MTAP-deletion PDX Panel Study were reported at AACR 2021 and showed in vivo efficacy in multiple MTAP-deleted xenograft models demonstrating tumor growth inhibition (TGI) when MAT2A was pharmacologically inhibited with IDE397. In this study, we observed > 60% TGI in ~ 75% of the models and > 75% TGI in ~ 50% of models We also observed tumor regressions, with > 100% TGI, in multiple PDX models and across multiple solid tumor types, including in NSCLC as well as in bladder and gastric cancer PDX models. Additionally, we have observed dose-dependent modulation of selected PD biomarkers in these in vivo models We also observed a correlation of in vivo efficacy with dose-dependent PD modulation in MTAP-deletion CDX model in NSCLC. Through our participation in the DepMap (Cancer Dependency Map) consortium led by the Broad Institute we have conducted a PRISM screen of a panel of over 800 cell lines for sensitivity to IDE397. This PRISM screen has identified differential selectivity across tumor lineages, potentially enabling additional biomarker discovery and clinical expansion for IDE397.
IDE397 has the potential to be a new standard of care cancer therapy for MTAP-deleted patients - a group that currently has no biomarker-driven treatment options. A best-in-class potency and selectivity profile, couple with strong early data, position IDE397 to be the treatment of choice for MTAP-deleted patients across solid tumor types