On April 13, 2023 -Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) ("Infinity" or the "Company"), a clinical-stage biotechnology company developing eganelisib, a potential first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic, reported upcoming presentations including data on eganelisib by Infinity’s collaborator, Professor Judith A. Varner of the UCSD Moores Cancer Center, La Jolla, California, at the 2023 Annual Meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) to be held April 14 – 19, 2023 in Orlando, Florida (Press release, Infinity Pharmaceuticals, APR 13, 2023, View Source [SID1234630066]).
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Highlights of the presentations include preclinical and translational data further reinforcing the mechanism of action of PI3K-γ inhibition:
Single cell transcriptomics data showing PI3K-γ knockout switches tumor associated macrophages in head and neck squamous cell carcinoma (HNSCC) and non small cell lung cancer (NSCLC) tumor models to activated, antigen-presenting, T cell-stimulating macrophages.
Preclinical data supporting tumor growth delay of HNSCC tumor models in PI3K-γ knockout mice is mediated by intra-tumoral interleukin-12, interferon gamma and CD8+ T cells, key drivers of immune response to cancer.
Translational data from the MARIO-275 clinical trial showing increased systemic immune activation in patients treated with nivolumab in combination with eganelisib over nivolumab alone, with enrichment of genes from interferon signaling, antigen presentation, and T cell receptor pathways.
Translational data from the MARIO-3 clinical trial, showing immune activation within the tumor microenvironment in patients treated with eganelisib, nab-paclitaxel and atezolizumab, with up-regulation of interferon signaling, antigen presentation, and T cell receptor pathways.
Following translational data from MARIO-1 indicating increased expression of the TGF-β activating integrin αVβ8 in HNSCC patients treated with combination of eganelisib and nivolumab, initial preclinical studies showing anti-αVβ8 monoclonal antibody treatment prevents growth of HNSCC tumor model in PI3K-γ knock-out mice.
"Our presentations describe exciting aspects of the role of PI3K-γ as a fundamental molecular switch controlling immune response by myeloid cells in the tumor microenvironment," said Professor Varner. "Our preclinical data suggest key roles for antigen-presenting activated macrophages, intra-tumoral IL-12, IFN-γ release and activated CD8+ T cells in mediating the effect of PI3K-γ knockout or PI3K-γ inhibition in tumor models. In line with our preclinical studies, emerging translational data from the MARIO-275 and MARIO-3 clinical trials support the mechanism of action of eganelisib through reprogramming and activation of tumor associated macrophages to reshape the tumor microenvironment and favor anti-tumor activity. Altogether, these data continue to underscore the potential of eganelisib as a next generation macrophage reprogramming immunotherapeutic, in combination with checkpoint inhibitors or potentially new immuno-oncology agents like anti-αVβ8 monoclonal antibodies."
Details of the presentations are as follows:
Presentation time: Saturday, April 15, 2023, 8:30am-8:50am EDT
Title: Macrophages rule in cancer
Session: ED034 – Antigen Presentation: The Macrophage-Dendritic Cell Debate
Presenter: Judith A. Varner
Presentation time: Tuesday, April 18, 2023, 10:20am-10:40am EDT
Title: Basic and clinical impacts of targeting myeloid cells in tumors
Session: Session SY14 – Next Generation of Myeloid Checkpoints in Cancer
Presenter: Judith A. Varner