NEW YORK – Phio Pharmaceuticals on Monday said its development partners AgonOx and Providence Cancer Institute of Oregon have begun dosing patients with advanced solid tumors in a Phase I trial of the autologous adoptive T-cell therapy AGX148 with the PD-1-targeted small interfering RNA PH-762.
AgonOx's AGX148 comprises a subpopulation of CD8-positive tumor-infiltrating lymphocytes that also express CD103 or CD39 and are able to recognize and kill tumor cells. These "double positive" CD8-expressing cells are expanded and infused into the patient for treatment. Phio's PH-762 is a self-delivering siRNA designed to silence PD-1 expression on T cells developed using Phio's Intasyl platform, which generates siRNA compounds that target genes tumors use to evade the immune system.
PD-1 is the main receptor that inhibits activation of CD8-positive T cells, and in preclinical studies, researchers found that silencing PD-1 in tumor cells with an siRNA can enhance the potency of cell therapies. Based on these studies, AgonOx, a spinout of Providence Cancer Institute in Portland, Oregon, believes that knockdown of PD-1 expression will lead to a more persistent anti-tumor response to the cell therapy without increased toxicity. Preclinical experiments have also shown that administration of interleukin-2 with the cell therapy enhances anti-tumor effects.
In the recently launched first-in-human Phase I trial taking place at the Providence Cancer Institute, researchers are comparing the safety and anti-tumor activity of AGX148 and PH-762 against AGX148 alone. About 18 participants will undergo adoptive cell transfer of AGX148 following lymphodepleting chemotherapy. Within 24 hours of the cell transfer, patients will receive interleukin-2 for up to three weeks. The companies are tracking patients' objective responses in the trial and the combination regimen's safety and persistence in peripheral blood.
Phio partnered with AgonOx in 2021 to study the activity of PH-762 with AGX148. Marlborough, Massachusetts-based Phio is financially supporting the trial and is entitled to future development milestone payments from AgonOx, as well as royalties based on sales of AGX148.