KAT6A
There is a high unmet need for novel modalities to treat advanced breast cancer & other solid tumors.
KAT6A and KAT6B are part of the 8p11 amplicon and histone acetyltransferase (HAT) complex which regulates the expression of a number of genes involved in regulating cancer cell growth and survival, including the estrogen receptor (ER), progesterone receptor (PR) and MYC. Recently, a clinical stage KAT6A/B dual inhibitor demonstrated PoC in ER+ breast cancer, albeit with 45% Gr3 neutropenia as DLT 1. Prelude is advancing the Industry’s First* Oral KAT6A Selective Degraders. Prelude’s KAT6A selective degraders demonstrate potential for better efficacy than a dual inhibitor, as well as improved tolerability and combinability2.
Targeting KAT6A
Prelude scientists hypothesized that KAT6A selective degraders would have potential for even better efficacy as degrading KAT6A disrupts the HAT complex with differential downstream effects on ER and other biomarkers. Dual inhibition of KAT6A/B results in clinically significant neutrophil reduction. Prelude’s KAT6A selective degraders also show potential for lower hematologic toxicity and improved combinability with other agents commonly used in the treatment of breast cancer.2
* Based on publicly disclosed information and published patents available as of April 2025
1 – T. Mukohara et. al., “PF-07248144, a first-in-class KAT6 inhibitor, in patients with HR+ HER2− metastatic breast cancer: Updated results from phase 1 dose expansion study”. SABCS 2024
2 – J. Carter et. al., Discovery of first-in-class potent and selective oral degraders of KAT6A that demonstrate anti-cancer activity in pre-clinical models, AACR2025; Abstract #1649 (http://www.preludetx.com/science/publications)
