On November 28, 2018, Masoud Tavazoie, Co-Founder and CEO of Rgenix, made a presentation at AACR’s Tumor Immunology and Immunotherapy conference in Miami, Fl.
As part of his presentation, Masoud described the LXR/ApoE pathway and its role in regulating the innate immune system in cancer. The LXR/ApoE pathway was discovered as a cancer pathway by Rgenix founding scientists utilizing an unbiased experimental approach to identify key drivers of cancer progression. This approach forms the foundation of the Rgenix target discovery platform which has yielded novel clinically relevant targets for first-in-class therapeutics currently under development at the company. This includes Rgenix’s lead drug candidate RGX-104, a novel immunotherapy agent that targets the LXR/ApoE pathway to activate anti-tumor immunity.
Dr. Tavazoie provided an overview of the role of the LXR/ApoE pathway in regulating cancer progression, highlighting its potential as a therapeutic target. Research has revealed that activation of the LXR/ApoE pathway with the small molecule LXR agonist RGX-104 can generate an anti-tumor immune response by targeting the innate immune system. In many cancers, cells of the innate immune system – such as immature myeloid cells – can inhibit the anti-tumor immune response by blocking T cell activation, which is required for successful immune attack against tumors. By depleting immature myeloid cells, RGX-104 shifts the innate immune response from immune-suppressive to immune-stimulatory. This effect is associated with activation of dendritic cells and relevant T cell populations, resulting in shrinkage of tumors in animal models and in advanced cancer patients treated with the agent.
Additionally, RGX-104 has also demonstrated the potential to enhance the efficacy of checkpoint blockade and T cell adoptive transfer therapy in mouse models. Pre-clinical and clinical data presented at the meeting establish the drug candidate RGX-104 as a novel immunotherapy agent with a unique mechanism of action and the capacity to shrink tumors via modulation of the LXR/ApoE pathway.