On April 8, 2022 Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a clinical stage biotechnology company developing the next generation of therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported positive new preclinical data showing PH-894, a self-delivering RNAi compound targeting the bromodomain-containing protein 4 (BRD4), provides abscopal efficacy toward untreated distal tumors and potentiates the efficacy of systemic anti-PD-1 antibody therapy (Press release, Phio Pharmaceuticals, APR 8, 2022, View Source [SID1234611664]). These new data will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, which is being held in New Orleans, Louisiana, from April 8-13, 2022.
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Data from in vivo studies demonstrated that PH-894 inhibits tumor growth in both PD-1 inhibition responsive, as well as PD-1 inhibition insensitive models. In both models, after local administration, strong antitumor efficacy was seen in directly treated as well as distal, untreated tumors. Additionally, intratumoral treatment with PH-894 enhanced the antitumor efficacy of systemic anti-PD-1 antibody therapy, not only for the PH-894 locally treated tumors, but for the PH-894 untreated distal tumors. In the PD-1 inhibition insensitive model, local PH-894 therapy was shown to be efficacious as a systemic anti-PD-1 antibody treatment, and enhanced the antitumor efficacy of anti-PD-1 treatment when used together.
"We are excited by these new data on PH-894, our second product candidate, for various reasons," said Dr. Simon Fricker, Phio’s VP of Research & Development. "First, these data show that local administration of PH-894 resulted in systemic efficacy, similar to what we have shown with PH-762. In addition, these studies have shown PH-894 to be a potent standalone treatment in a challenging model, while also enhancing the efficacy of systemic anti-PD-1 antibodies. We believe these data provide a strong rationale for the clinical use of PH-894 as a monotherapy, as well as in combination with systemic PD-1 therapy. Considering the novel mechanism of action of PH-894, there is potential for it to play an important role in treating patients who do not respond to anti-PD-1 therapy, or patients who progress after initially responding to such therapy, addressing an important medical unmet need."
Studies were conducted in colon and liver cancer animal models in which the cancer cell lines were implanted subcutaneously into the bilateral flanks of mice. Tumors on only one side were treated with PH-894, and tumors on the opposite side were left untreated. Some of the animals also received systemic anti-PD-1 antibody treatment in addition to local PH-894 administration. These data showed that locally administered PH-894 inhibited tumor growth of both directly-treated and distal tumors in two cancer models. In addition, PH-894 also potentiated the efficacy of a systemic anti-PD-1 antibody toward PH-894 treated and untreated distal tumors. Ex vivo analysis showed that PH-894 silenced BRD4 and its downstream effector PD-L1 in tumor dendritic cells and increased migratory dendritic cells in the tumor, suggesting a mechanism by which local PH-894 treatment confers systemic tumor control.
Phio’s presentation detailing the data presented at AACR (Free AACR Whitepaper) titled, "Local administration of BRD4-targeting self-delivering RNAi (PH-894) provides abscopal efficacy toward untreated distal tumors and potentiates the efficacy of systemic anti-PD-1 antibody therapy" will be made available on the "Investors – Events and Presentations" section of the Company’s website (click here).