Company: HURA
Filing Date: 2025-09-18
Form Type: S-1/A
Source: 0001193125-25-207395
Chunk: 99

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-09-18
Form: S-1/A
Chunk 99
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pressive 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 of tumor-associated MDSC functionality to guide its selection of both APCs and ADCs for further invitroand in vivocharacterization and development. The Company anticipates utilizing TBS-2025,its VISTA inhibiting antibody, as the first APC or ADC to enter preclinical development. The Company believes that its tumor associated MDSC-targeting APCs and ADCs have a number of potential benefits over current approaches to overcoming acquired resistance to cancer immunotherapies, including the following:

| • |     | Inhibiting tumor associated MDSC production of multiple immune suppressing factors. The Delta Opioid Receptor on tumor-associated MDSCs functions like a “master switch” controlling the regulation of multiple immune suppressing factors such as, iNOS, Arg-1, IDO, TGF-b, S100A9 and COX2. Inhibiting the receptor results in “shutting off” production of these and other immune suppressing factors as compared to the industry focus of developing inhibitors targeting a single factor. |

| • |     | Blocking tumor-associated MDSC recruitment to the microenvironment. To exhibit their immunosuppressive phenotype, MDSCs have to be recruited to the tumor site, transitioning to tumor-associated MDSCs which display maximum immunosuppressive properties