Azeria Therapeutics is the world’s first pioneer factor drug discovery company developing breakthrough treatments for hormone resistant breast cancer patients where there are significant areas of unmet clinical need.
Founded in 2017 by the leading expert in pioneer factors in cancer, Prof Jason Carroll, Azeria is developing a pipeline of small molecules designed to selectively inhibit pioneer factors.
Azeria is initially targeting the pioneer factor FOXA1, which has shown to be pivotal in the tumour development and maintenance of oestrogen receptor (ER) positive luminal breast cancer.
Our mission is to develop breakthrough treatments based on targeting pioneer factors, including for the treatment of breast and prostate cancer patients.
Our therapies will target pioneer factors, the ‘foundation’ proteins of transcription factor complexes deregulated in cancer that are unique in their ability to directly bind condensed chromatin in the absence of any other factor. Until now, these factors have been considered undruggable.
Cancer causes one in eight deaths worldwide, and cancer drug discovery poses substantial challenges. Strategies to discover novel anti-cancer drugs are often based on differences in the activity or expression of the molecular targets driving cancer or specific cellular phenotypes in cancer cells versus normal cells. However, to date such approaches frequently fail to substantially improve patient outcomes.
Fundamental to the cellular transformation observed in cancer is aberrant gene expression and the deregulation of transcription factors and their cofactors is observed in many, if not all, forms of human cancer.
Azeria is targeting these fundamental pathways via pioneer factors, the ‘foundation’ proteins of transcription factor complexes. Pioneer factors dictate where in the genome the transcription factors associate with DNA and what genes are regulated, and in many cases, are essential for transcription factor DNA binding.
In its lead programme, Azeria is targeting the essential pioneer factor FOXA1, which has shown to be pivotal in the tumor development and maintenance of Estrogen receptor (ER) positive luminal breast cancer.
Estrogen receptor (ER) is the driving and defining transcription factor in 75% of breast cancers and is currently inhibited by targeted therapies such as tamoxifen and aromatase inhibitors.
Work by Azeria’s Founder, Dr Jason Carroll, showed for the first time that DNA interactions and transcriptional potential of ER depend on the pioneer factor FOXA1¹, which plays an essential role in determining tumor growth and progression – even when resistance to existing drugs has developed.
FOXA1 is required for all ER-DNA interactions and in the absence of FOXA1, ER does not associate with DNA, switch genes on or cause cells to grow. Importantly, FOXA1 is also required for growth of cells that have acquired resistance to standard therapies, such as tamoxifen. Therefore, FOXA1 constitutes an attractive drug target for women with drug resistant breast cancer.
1 Carroll et al., Cell. 122(1):33-43.2, 2005 and Carroll et al., Nat Genet. 38(11): 1289-97, 2006
Major unmet medical need