Company: HURA
Filing Date: 2025-02-07
Form Type: S-4
Source: 0001193125-25-022803
Chunk: 422

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-02-07
Form: S-4
Chunk 422
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 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 immunosupressive 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), 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 TME to an immunogenic phenotype more favorable to cancer immunotherapies |

| • |     | Immune modulation of TME/potentiating the effects of checkpoint inhibitors, inhibiting tumor related invasion and metastasis Unlike other APCs or ADCs, TuHURA’s APCs, and ADCs are designed to be bi-specific/ bi-functional, i.e., affecting two targets and having two functions: inhibiting tumor associated MDSC-related immune suppression and thereby making tumor susceptible to attack, while localizing checkpoint inhibitors where the tumor resides. In addition to their immune modulating effects on the TME, TuHURA’s APCs have also demonstrated the ability to target DOR expressed on cancers, thereby inhibiting many of elements associated with tumor malignant phenotype, most notably ability to invade and metastasize. These two functions are intended to work together with the goal of |

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| overcoming acquired resistance, preventing T cell exhaustion and allowing checkpoint inhibitors and cellular therapies to be safer and more effective while interfering with the tumor’s ability to invade and spread throughout the body. |

TuHURA’s Clinical Development Program For purposes of the below descriptions of TuHURA’s phase 1 and 1b clinical trials, the response rates for IFx-2.0are determined under best clinical practice by the principal investigators, evaluating and confirming clinical