Clinical trial

EpiAxis has completed a pioneering proof of concept (POC) clinical trial known as EPI-PRIMED. In this study, we explored epigenetic reprogramming of aggressive cellular phenotypes via inhibition of LSD1.

In this POC study, phenelzine sulfate was used to inhibit LSD1 and was administered in combination with nanoparticle albumin bound paclitaxel (Abraxane® – nab-paclitaxel). The patient population selected was advanced MBC including triple negative breast cancer (TNBC).

The study was designed to have up to 16 participants allocated to 4 dose levels of phenelzine: 45 mg/day, 60 mg/day, 75 mg/day and 90 mg/day in combination with a weekly dose of IV nab-paclitaxel (100 mg/m2). However, the study was terminated after 8 participants had enrolled following an interim analysis of the biomarker data.

Study Results

LSD1 inhibition by phenelzine resulted in rapid and significant reductions in both nuclear and cytoplasmic LSD1, as illustrated below. These data suggest that, following initial depletion, long term nuclear LSD1 suppression could be achieved via use of a maintenance dose.

These above biomarker changes were associated with encouraging overall survival (OS) data. Post-trial follow-up (as of June 2022) indicates 3 out of 8 participants remain alive with a 27-month median OS estimate.

The results of this novel and pioneering clinical study provide biological “proof of concept” for successful epigenetic reprogramming via use of LSD1 inhibition and provide a strong rationale for clinical development of the EPI-1xx peptide series. Further clinical trial details are available from the below links.

Link to Clinical Trials: https://clinicaltrials.gov/ct2/show/NCT03505528?term=phenelzine&cond=cancer&cntry=AU&draw=2&rank=1

Link to Frontiers in Oncology: https://doi.org/10.3389/fonc.2022.862427