ONCOLOGY: PI3Kα
Our pan-mutant PI3Kα inhibitor program targets kinase- and helical-driver mutations
Prevalence of E542 and E545 by cancer type
| Cancer type | Frequency of PIK3CA mutations | Percent of PIK3CA mutations that are E542 or E545 |
| Breast | ~35% | ~40% |
| Endometrial | ~25% | ~50% |
| Colorectal | ~20% | Majority |
The phosphoinositide 3-kinase alpha (PI3Kα) plays a critical role in cell growth, metabolism, and survival. Mutations in the PIK3CA gene, which encodes the catalytic subunit of the PI3Kα protein, are present in approximately 17% of all solid tumors, making PIK3CA one of the most common genetic drivers in cancer. Specifically, hotspot mutations in the kinase (H1047X) and helical (E545X, E542X) domains drive uncontrolled pathway activation that results in cancer formation.
Developing a potentially best-in-class, mutant-selective, wild-type sparing PI3Kα inhibitor
Preclinical highlights
In vivo efficacy comparable to that of alpelisib.
Efficacious doses do not trigger toxicities associated with inhibiting wild-type PI3Kα.
