Atheron therapeutics announced that it will present updates on the advancement of three key programs at the upcoming AACR conference: a KAT6A degrader for HR+HER2- breast cancer, a CCNE1 molecule glue for CCNE1-amplified cancer, and an ITK inhibitor for T-cell lymphomas.
KAT6A, a member of the MYST family of histone acetyltransferases, regulates gene transcription by acetylating histone H3K23 and thereby participates in multiple cellular processes. Amplification or overexpression of KAT6A has been observed in various cancers, including breast cancer. While the first KAT6A/B inhibitor PF-07248144 demonstrated anti-tumor activity in phase 1 clinical studies, it also showed hematologic dose-limiting toxicities, potentially due to the simultaneous inhibition of KAT6A/6B. Furthermore, emerging evidence suggests that KAT6A has non-enzymatic function in DNA damage repair and cell proliferation. These findings provide the rationale for developing a KAT6A-selective degrader with the potential for improved and reduced hematotoxicity.
CCNE1 is a key cell cycle regulatory protein that binds CDK2 to form the CCNE1-CDK2 complex, which is essential for driving the cell cycle progression to S-phase for subsequent DNA replication. Amplification of the CCNE1 locus on chromosome 19q12 is prevalent across multiple tumor types, particularly in breast, high-grade serous ovarian, uterine and gastro-esophageal cancers. Compared with CDK2 inhibitors, CCNE1 molecular glues exhibit better selectivity, thereby reducing the adverse effects caused by CDK2 inhibitors in clinical trials.
ITK is a member of the TEC family of kinases and plays important roles in TCR signaling and T cell differentiation. ITK knockout mice show defects in Th2 differentiation, while retaining the ability to differentiate into Th1 cells, a phenomenon known as Th1 skewing. It is generally accepted that Th1 cells are the primary Th cell subtype associated with tumor elimination. ITK and RLK double knockout in T cells has a more substantial signaling defect, resulting in a profound loss of normal T cell function. Thus, it holds great therapeutic promise to treat cancer with selective ITK inhibitors while sparing RLK.
Poster Details:
Title: Discovery of a highly potent and selective KAT6A degraders that demonstrates robust anti-tumor activities in preclinical studies
Session Category: Experimental and Molecular Therapeutics
Session Title: Epigenetic Modulators 2
Session Start: 4/22/2026 9:00:00 AM
Session End: 4/22/2026 12:00:00 PM
Location: Poster Section 12
Poster Board Number: 23
Poster Number: 7076
Title: Discovery of a novel, potent and highly selective CCNE1 molecule glue shows robust anti-tumor activities and better safety profile
Session Category: Experimental and Molecular Therapeutics
Session Title: Proximity-Induced Drug Discovery 2
Session Start: 4/21/2026 2:00:00 PM
Session End: 4/21/2026 5:00:00 PM
Location: Poster Section 15
Poster Board Number: 7
Poster Number: 5780
Title: Identification of a highly selective ITK inhibitor which promotes Th1 differentiation and alleviates T cell exhaustion in vitro and in vivo
Session Category: Clinical Research
Session Title: Tumor Microenvironment Modulators
Session Start: 4/22/2026 9:00:00 AM
Session End: 4/22/2026 12:00:00 PM
Location: Poster Section 49
Poster Board Number: 21
Poster Number: 7946