ONCOLOGY: PI3Kα
PI3Kα inhibitor program targets the under-addressed E542 and E545 driver mutations in breast cancer and other solid tumors
Prevalence of E542 and E545 by cancer type
| Cancer type | Percent of people with PIK3CA mutations | Percent of PIK3CA mutations that are E542 or E545 |
| Breast | ~35% | ~40% |
| Endometrial | ~25% | ~50% |
| Colorectal | ~20% | Majority |
First and second generation PI3Kα inhibitors have demonstrated clinical benefit, validating the target. But they often lack selectivity for mutant PI3Kα over wild-type, which can lead to treatment-limiting side effects that shorten progression-free survival and reduce tolerability.
Developing a potentially best-in-class, mutant-selective, wild-type sparing PI3Kα inhibitor
Preclinical highlights
Tumor regression without inducing hyperglycemia or hyperinsulinemia.
Efficacy in vivo comparable to or exceeding that of alpelisib.
