Company: HURA
Filing Date: 2025-05-06
Form Type: S-4/A
Source: 0001193125-25-113920
Chunk: 435

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-05-06
Form: S-4/A
Chunk 435
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 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 APCs consists of 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 resistant murine 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 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 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 th