4:44 PM
 | 
Nov 03, 2017
 |  BioCentury  |  Product Development

Liver X factor

How Rgenix’s liver X agonist could help overcome checkpoint resistance in cancer

Rgenix Inc. is preparing to test its RGX-104 in combination with checkpoint inhibitors after Phase I data confirmed the company’s belief that the liver X receptor agonist depletes suppressive immune cells and increases T cell activating dendritic cells in humans.

In a poster presented on Oct. 29 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Rgenix reported results from an ongoing Phase Ia/Ib study of the small molecule agonist of liver X receptor beta (NR1H2; LXR-b) in treatment-experienced patients with solid tumors or lymphomas. At the time of analysis, four of 12 evaluable patients had stable disease at eight weeks. The maximum tolerated dose (MTD) had not been reached in the dose escalation phase.

The company also reported mechanistic data from the trial showing RGX-104 activates the immune system via multiple mechanisms that include direct effects on at least two innate immune cell types and indirect effects on T cells. CEO Masoud Tavazoie told BioCentury the multipronged mechanism could address more than one of the tactics tumor cells use to resist checkpoint inhibitors.

The company’s preclinical work has shown that RGX-104 and other LXR agonists also have non-immune effects on tumors, namely in preventing angiogenesis and metastasis.

“It’s an activation of the innate immune system by removing the brakes by depleting MDSCs, and putting the foot on the accelerator by activating dendritic cells.”

Masoud Tavazoie, Rgenix

Tavazoie said all of the compound’s effects in cancer appear to stem from up-regulation of a single target, apolipoprotein E. APOE constitutes the protein component of a lipoprotein particle that interacts with a variety of cell types throughout the body as it transports triglycerides and cholesterol...

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