Company: HURA
Filing Date: 2025-05-23
Form Type: 424B3
Source: 0001193125-25-125499
Chunk: 420

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-05-23
Form: 424B3
Chunk 420
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 microenvironment and resulted in a significant and dramatic improvement in survival when compared to treatment with anti-PD-1 antibody alone. 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 invitro and invivo characterization and development.

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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 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), promotes repolarizing M2 to M1 phenotype decreasing Th-2 cytokines                                                                                   
 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/p