Company: HURA
Filing Date: 2025-08-12
Form Type: S-1
Source: 0001193125-25-179009
Chunk: 99

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-08-12
Form: S-1
Chunk 99
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 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. This process is mediated mainly by chemokines secreted in the tumor microenvironment and chemokine receptors expressed on MDSCs. There are a number of strategies to prevent the recruitment of MDSCs to the microenvironment through the development of inhibitors of chemokines such as CCL2/CCR2 blockade. However, brain, heart, kidney, liver, lung, ovary, pancreas, spinal cord, spleen, and thymus also express CCR2, introducing the potential for off-target side effects with this approach. Inhibiting the Delta Opioid Receptor prevents the proliferation and production of tumor-associated MDSC-monocyte subpopulations (M-MDSC), promoting repolarizing M2 to M1 phenotype decreasing Th-2 cytokines |

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| while increasing Th-1 (g-IFN, IL-2) cytokines. Thus, changing the immunosuppressive phenotype of the tumor microenvironment to an immunogenic phenotype more favorable to cancer immunotherapies. |

| • |     | Immune modulation of tumor microenvironment/potentiating the effects of checkpoint inhibitors To date the prior and future development of ADCs, ADC-checkpoint inhibitors, ADC-degraders or bi