EpiAxis is pursuing three parallel arms to its development plan, namely a clinical, a pre-clinical and a discovery inhibitor arm.
In the clinical arm, the aim is to firstly validate the target LSD1 & PKC theta in a cohort of patients with metastatic breast cancer by monitoring their CSC burden and immune response in situ. Later, patients will be enrolled in a Phase 1 study of Abraxane® in combination with Phenelzine Sulfate to assess whether their CSC burden can be abated through LSD1 inhibition.Â In addition, patient derived CSCs from the Phase 1 study will be treated ex-vivo with the Company’s proprietary inhibitors, arising from the discovery arm.
The pre-clinical arm aims to undertake dose finding and pharmacodynamic studies involving Abraxane® and Phenelzine Sulfate using MDA-MD 231 cells in a breast xenograft model with nude mice. Those studies will also have a focus of confirming the Mechanism of Action (MoA) associated with LSD1 & PKC theta modulation. Imaging will be performed on the CSC burden, LSD1, PKC theta and PD-L1 status. The immune status arising from LSD1 & PKC theta modulation will be further examined using the 4T1 model in which the mice have a normal immune system, unlike the nude mice.
The discovery arm aims to identify at least two druggable candidates for further pre-clinical development, based on the proprietary nuclear profile of LSD1 & PKC theta and their candidates. These are being screened using human cancer cell lines, with lead candidates entering into the pre-clinical arm, where they will be further evaluated using breast xenograft models, in combination with SoC chemotherapies and checkpoint inhibitors.
There is a substantial unmet clinical need when it comes to fighting recurrent, metastatic breast cancer. This is the major cause of death in women with breast cancer. We aim to address that unmet need by the novel targeting of breast cancer stem cells, which are resistant to conventional systemic anticancer therapies and therefore contribute to the failure of these therapies in patients.
Professor Sudha Rao
Founder & Director at EpiAxis Therapeutics