DUO-307

DUO-307 is a novel ultrasmall nanomedicine developed by Duo Oncology. It is designed as a high drug-loading combination of a chemotherapeutic and an immunomodulatory agent, encapsulated within a patent-pending gemcitabine-conjugated copolymer nanocarrier micelle (PGEM). This nanomedicine aims to overcome immune resistance in stroma-rich cancers by stimulating anti-tumor immunity and blocking the recruitment of immunosuppressive immune cells to the tumor microenvironment. Specifically, the PGEM nanocarrier can penetrate dense stroma tissue, activating the DNA-sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which leads to the production of Type I interferon and the recruitment of cytotoxic lymphocytes. Additionally, DUO-307 encapsulates a chemokine receptor type 2 antagonist (CCR2a) to further inhibit the influx of immunosuppressive cells. This dual mechanism enhances anti-tumor immunity and sensitizes tumor-infiltrating lymphocytes to immune checkpoint inhibitors like anti-PD1 therapy. Preclinical studies have shown that combination therapy with DUO-307 and anti-PD1 resulted in significant tumor regression in mouse models of pancreatic cancer.