On November 10, 2022 Phio Pharmaceuticals (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL RNAi platform technology makes immune cells more effective in killing tumor cells, reported the results of several studies of its INTASYL compounds (Press release, Phio Pharmaceuticals, NOV 10, 2022, View Source [SID1234623674]).
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INTASYL compounds are chemically modified siRNA’s that provide efficient, spontaneous cellular uptake and potent, long lasting intracellular activity targeting a broad range of cell types and tissues.
INTASYL drugs precisely target specific proteins that reduce the body’s ability to fight cancer, without the need for specialized formulations or drug delivery systems. INTASYL demonstrated preclinical efficacy in both Direct-to-Tumor and Adoptive Cell Therapy (ACT) applications.
INTASYL is the only self-delivering RNA interference (RNAi) technology focused on immuno-oncology therapeutics. Phio is developing several INTASYL compounds, one of which is in an on-going Phase 1b clinical trial for the treatment of advanced melanoma.
The posters will be presented on November 10th and 11th at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), which is being held in Boston, MA from November 8 – 12, 2022.
About the Posters
Abstract #788 titled: A Phase 1b study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of neoadjuvant use of PH-762 administered intratumorally in subjects with advanced melanoma
About PH-762: PH-762 is an INTASYL compound that reduces the expression of PD-1, a protein that inhibits T cells’ ability to kill cancer cells. By suppressing PD-1, the T cells are re-activated to kill cancer cells. PH-762 is being developed as a standalone drug therapy (Direct-to-Tumor) and also in combination with ACT.
About the poster: This trial in progress poster reports on the clinical trial design and updates on the continuing enrollment in its Phase 1b study of PH-762 for the treatment of patients with advanced melanoma. The study is being conducted at the Gustave Roussy Institute, one of the largest cancer centers in Europe. Topline safety data from the first group of subjects is expected to be announced during the first quarter of 2023. [Review the poster]
Abstract # 1402 titled: PH-894, an INTASYL self-delivering siRNA targeting BRD4, has dual functions to sensitize tumor cell killing and activate CD8 T cells
About PH-894: PH-894 is an INTASYL compound that silences BRD4, a protein that controls gene expression in both T cells and tumor cells, thereby effecting the immune system as well as the tumor. What sets this compound apart is its dual mechanism: INTASYL PH-894 suppression of BRD4 in T cells results in T cell activation; additionally, suppression of BRD4 in tumor cells results in tumors becoming more sensitive to T-cell killing.
About the poster: This poster presentation includes data further exploring the antitumor mechanism of PH-894, a self-delivering RNAi compound that specifically silences the BRD4 gene. In this study, Phio showed that using PH-894 can activate T cells to improve their cancer cell killing ability and to target tumor cells to make them more sensitive to killing. [Review the poster]
Abstract #1431 titled: Intratumoral PH-109 INTASYL; self-delivering RNAi targeting connective tissue growth factor (CTGF) provides efficacy in vivo in a mouse model of metastatic breast cancer
About PH-109: PH-109 is an INTASYL compound that suppresses the Connective Tissue Growth Factor (CTGF) protein, a protein associated with poor prognosis in breast cancer.
About the poster: The poster presentation announces proof-of-concept in vivo data showing efficacy of intratumorally administered PH-109, in an orthotopic 4T1 model of metastatic mammary cancer. These results show that PH-109 reduced tumor growth and reduced metastatic lung lesions compared to the control arms. Mice were also treated with the chemotherapy drug, doxorubicin. In contrast to doxorubicin, PH-109 showed no evidence of toxicity. [Review the poster]
Abstract #537 titled: Local immunotherapy with INTASYL self-delivering RNAi targeting CTLA-4 provides robust tumor control in vivo
About CTLA-4: CTLA-4 is a protein that inhibits the ability of T cells to kill tumor cells. The CTLA-4 targeting INTASYL compound demonstrated dose-associated anti-tumor activity in two tumor models in vivo. Local delivery may avoid/minimize the severe systemic adverse events associated with current CTLA-4 therapeutics.
About the poster: The poster presentation demonstrates proof-of-concept in vivo data showing intratumoral efficacy of a novel INTASYL targeting murine CTLA-4 in two syngeneic mouse tumor models. These study results showed a dose-dependent anti-tumor effect that was comparable to that seen with antibodies. The Company expects treating intratumorally with an INTASYL compound targeting CTLA-4 may have less toxicity than with current antibody treatment, while maintaining similar efficacy. This shows that INTASYL can be used against multiple clinically proven checkpoint inhibitors – CTLA-4 and PD-1. [Review the poster]
Abstract #493 titled: PH-804, an INTASYL self-delivering RNAi compound that targets TIGIT enhances NK cell cytotoxicity to tumor cells
About PH-804: PH-804 is an INTASYL compound that targets TIGIT, a protein that inhibits the activity of Natural Killer (NK) cells.
About the poster: The poster presentation discusses results from a pre-clinical study demonstrating that NK cells, when treated with PH-804, increased activation and enhanced the ability of NK cells to kill cancer cells. [Review the poster]
Abstract #409 titled: Manufacturing of a clinical scale CD8 TIL product, AGX148, with and without gene silencing of PD-1 using self-delivering RNAi INTASYL PH-762
About the poster: This poster presentation by AgonOx, Inc., in collaboration with Phio and the Providence Cancer Institute’s Cell Processing Facility, shows that it has completed three full scale IND-enabling manufacturing runs of its ACT product, AGX148, CD8 tumor infiltrating lymphocytes (TIL) that are highly enriched for tumor-reactivity (DP TIL), with and without Phio’s PH-762, an INTASYL compound that knocks down PD-1 protein expression on cells. These manufacturing runs demonstrate the ability to scale up clinical grade DP TIL and that DP TIL treated with PH-762 demonstrated durable silencing of PD-1 in vivo. PD-1 knockdown also enhanced the activity of DP TIL in in vitro tumor co-culture assays. This step forward in manufacturing is an important part of AgonOx’s movement towards the clinic and will support an IND application with the FDA. AgonOx expects to start a clinical trial evaluating the safety, tolerability, and efficacy of AGX148 combined with PH-762 in subjects with advanced solid malignancies.