Phio Pharmaceuticals Corp., a clinical stage biotechnology company developing the next generation of therapeutics based on its proprietary self-delivering RNAi (INTASYL™) therapeutic platform, today presented new preclinical data showing that silencing BRD4 with PH-894, a self-delivering RNAi INTASYL compound, can be used to improve the characteristics of CAR-T cell products during the activation and expansion phases of the cell manufacturing process.
These new data will be presented at the American Society of Gene & Cell Therapy (ASGCT) 25th Annual Meeting, which is being held in Washington D.C., from May 16-19, 2022.
“Hurdles that are faced with current CAR T-cell therapy treatment for solid tumors include cell persistence and cell exhaustion. Due to the immunosuppressive environment of the tumor, CAR T-cells may become exhausted, thereby limiting the efficacy of treatment for cancer patients,” said Dr. Simon Fricker, Phio Pharmaceuticals VP of Research and Development.
He added, “These data demonstrate that PH-894 could enhance the activity of CAR-T cells by improving the quality of the final CAR-T cell product by overcoming immunosuppression, reversing exhaustion, and preserving a phenotype associated with cell persistence. There is potential for PH-894 to play a role in boosting the potency of the next generation of CAR-T cell products to enhance adoptive cell therapy for solid tumors without using genetic manipulation.”
Data from the studies conducted assessed the potential of PH-894 to improve the quality and potency of HER2-targeted CAR-T cells in a CAR-T expansion model. CAR-T cells were activated with an OKT3 antibody and treated with PH-894. Results showed that PH-894 reduced the expansion-associated production of BRD4 and BRD4-regulated genes and mitigated the production of inhibitory receptors and markers of T cell exhaustion, PD-1, TIGIT and TIM3. Additionally, PH-894 preserved putative T cell stem-cell memory and central memory, phenotypes associated with cell persistence, on HER2-CAR-T cells that were otherwise depleted by cell expansion without the use of PH-894.
Phio’spresentation detailing the data presented at ASGCT titled, “Self-delivering RNAi Targeting BRD4 (PH-894) Improves the Phenotype of HER2-CAR-T Cells During Expansion” will be made available on the “Investors – Events and Presentations” section of the Phio Pharmaceuticals website.