Company: HURA
Filing Date: 2025-08-12
Form Type: S-1
Source: 0001193125-25-179009
Chunk: 98

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-08-12
Form: S-1
Chunk 98
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 suppressing compounds such as IDO, iNOS or COX2 inhibitors.

TuHURA’s Delta Opioid Receptor (DOR) inhibitors: bi-specific, bi-functionalantibody 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.

While Delta Opioid Receptor overexpression and its role in tumor biology has been studied, we believe that TuHURA, along with scientists at Moffitt Cancer Center, are the first to 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 below; source: TuHURA research files)**

<div align='center'>60</div>

MDSC: MDSC isolated from BM, spleen and tumor. * p ≤ 0.05, ** p ≤ 0.01 As a previously unrecognized target to reprogram tumor associated MDSCs immunosuppressive functions on the tumor microenvironment, developing non-immunogenicpeptidomimetic antagonists or small molecule antagonists with high specificity and avidity for the Delta Opioid Receptor represents a novel approach to reprograming MDSC functionality to overcome acquired resistance to checkpoint inhibitors and other cancer immunotherapies. Inhibition of the Delta Opioid Receptor on tumor-associated MDSCs is designed to block MDSC production of multiple immunosuppressing factors through a single point of intervention. TuHURA’s bi-specific, bi-functional APCsconsists, among other diverse candidates, a patented peptidomimetic Delta Opioid Receptor specific inhibitor conjugated to a checkpoint inhibitor like anti-PD-1 antibody.Moffitt Cancer Center scientists demonstrated that, in Delta Opioid Receptor-expressing PD-1 resistantmurine lung cancer models, treatment with its APC accumulated in the tumor microenvironment and resulted in a significant and dramatic improvement in survival when compared to treatment with two times higher dose of the anti-PD-1 antibodyalone. The Company has established multiple functional assay screens to investigate the effects of both novel peptidomimetic or small molecule Delta Opioid Receptor specific inhibitors