APOE was revealed by the RNA-DRIVEr™ platform as a tumor suppressor that becomes silenced at the protein level by RNA dysregulation. APOE dysregulation is influenced by genetic variants of APOE (E2 and E4) which are present collectively in ~40% of the population.
APOE dysregulation results in two major effects: 1) increased tumor angiogenesis and 2) expansion of immune-suppressive myeloid cells (MDSCs, M2 TAMs, tolerogenic DCs). Abequolixron (RGX-104) is a first-in-class oral small molecule NCE that activates APOE protein expression via selective targeting of the LXR-beta nuclear receptor.
Treatment of APOE dysregulated tumors with RGX-104 inhibits angiogenesis and activates tumor myeloid cells, resulting in T cell activation and anti-tumor immunity.
RGX-104 is currently being tested in a Phase 1b/2 clinical trial for the treatment of patients with advanced Non-Small Cell Lung Cancer (NSCLC) in combination with the standard-of-care therapy docetaxel, and is also being studied for the treatment of patients with advanced Endometrial Cancer in combination with the anti-CTLA4 antibody, ipilimumab (Yervoy).
Mechanism of Action

This next-generation therapy has two key effects on the innate immune system that drive tumor immunity: it depletes myeloid-derived suppressor cells (MDSCs) and stimulates dendritic cells (DCs). MDSCs block the ability of T cells to become active, while stimulated DCs are required for proper activation (priming) of T cells.
By effecting these two types of innate immune cells (MDSCs and DCs), RGX-104 can unleash tumor-targeting T cells to induce anti-tumor activity.
A Phase 1b/2 clinical study of RGX-104, in patients with advanced Non-Small Cell Lung Cancer (NSCLC) and advanced Endometrial Cancer, is in progress. For more information about our clinical trial, visit clinicaltrials.gov.
Pipeline
Ompenaclid (RGX-202)
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Pipeline
RGX-019
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