Company: HURA
Filing Date: 2025-05-06
Form Type: S-4/A
Source: 0001193125-25-113920
Chunk: 434

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-05-06
Form: S-4/A
Chunk 434
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ukin 10 (“IL-10”) and recruitment and induction of immune inhibitory cells such as regulatory T cells (T regs) and M2 polarized tumor associated macrophages (“TAMs”). Accumulating evidence demonstrates that the enrichment and activation of MDSCs correlates with tumor progression, metastasis and recurrence. In addition, MDSCs circulating in the blood of patients with cancer is highly correlated to poor clinical outcome.

The company believes that inhibiting and reprograming MDSC function represents a promising novel approach to overcome MDSC-induced tumor microenvironment immunosuppression and the resulting acquired resistance to cancer immunotherapies. Various companies are focusing on several strategies, including blocking MDSC recruitment to the microenvironment or inhibiting their production in the bone marrow. Another potential strategy is inhibiting MDSC-mediated immunosuppression by developing inhibitors to individual MDSC-related immune suppressing compounds such as IDO, iNOS or COX2 inhibitors.

TuHURA’s Delta Opioid Receptor (DOR) inhibitors: bi-specific,bi-functional antibody peptide or drug conjugates (APC, ADCs)

The Delta Opioid Receptor, or DOR, is the first cloned G protein-coupled receptor. Many recent studies on Delta Opioid Receptor functions have determined that the Delta Opioid Receptor is involved in the regulation of malignant transformation and tumor progression in multiple cancers. In hepatocellular carcinoma (HCC), higher expression of Delta Opioid Receptor was observed in liver tumor tissue cells compared to normal liver tissue/cells. When DOR gene expression was silenced or inhibited, the proliferation of HCC ells was inhibited, and tumor cells underwent apoptosis, the cell cycle was arrested and tumor cell invasion and migration.

While Delta Opioid Receptor overexpression and its role in tumor biology is well established in the literature, the company believes that TuHURA, along with scientists at Moffitt Cancer Center, are the first to**

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describe the high differential expression of the Delta Opioid Receptor on tumor associated MDSCs compared to bone marrow (BM) or spleen derived MDSCs either in tumor free or tumor bearing models. (See Figures 1 and 2 below, courtesy of P Rodriguez, Moffitt Cancer Center).

As a previously unrecognized target to reprogram tumor associated MDSCs immunosuppressive functions on the tumor microenvironment, developing small molecule or peptide antagonists of the Delta Opioid Receptor