Company: HURA
Filing Date: 2025-09-18
Form Type: S-1/A
Source: 0001193125-25-207395
Chunk: 100

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-09-18
Form: S-1/A
Chunk 100
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. 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-specific ADCs all have one thing in common: they target tumor-associated receptors with a tumor receptor-specific antibody which carries with it either a payload toxin or other tumor cell cycle disruptors or checkpoint inhibitor. To our knowledge, we are the only company developing APCs or ADCs targeting MDSCs where our 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 a checkpoint inhibitor, like TBS-2025, where the tumor resides. These two functions are intended to work together with the goal of overcoming acquired resistance, preventing T cell exhaustion and allowing checkpoint inhibitors and cellular therapies to be safer and more effective. |

TuHURA’s IFx Clinical Development Program For purposes of the below descriptions of TuHURA’s Phase 1 and 1b clinical trials, the response rates for IFx-2.0 aredetermined under best clinical practice by the principal investigators, evaluating and confirming clinical progression prior to or during therapy utilizing conventional and appropriate radiographic or metabolic (Positron Emission Tomography – PET) methodologies. Response determination utilizes conventional terminologies under standardized response evaluation criteria. A “complete response”, or CR