Company: HURA
Filing Date: 2025-02-07
Form Type: S-4
Source: 0001193125-25-022803
Chunk: 421

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-02-07
Form: S-4
Chunk 421
---
 or inhibited, the proliferation of HCC ells was inhibited, and tumor cells underwent apoptosis, the cell cycle was arrested and tumor cell invasion and migration.

While DOR overexpression and its role in tumor biology is well established in the literature, the company believes that TuHURA, along with scientists at Moffitt Cancer Center, are the first to describe the high differential expression of the Delta Opioid Receptor (DOR) on tumor associated MDSCs compared to bone marrow (BM) or spleen derived MDSCs either in tumor free or tumor bearing models. (Figures 1 and 2 courtesy P Rodriguez, Moffitt Cancer Center ).

As a previously unrecognized target to reprogram tumor associated MDSCs immunosuppressive functions on the TME, developing small molecule or peptide antagonists of the DOR represents a novel approach to reprograming MDSC functionality to overcome acquired resistance to checkpoint inhibitors and othe cancer immunotherapies

<div align='center'>257</div>

Inhibition of the DOR on tumor associated MDSCs is designed to block MDSC production of multiple immunosuppressing factors through a single point of intervention. TuHURA’s bi-specificAPCs consists of a patented peptidomimetic DOR specific inhibitor conjugated to a checkpoint inhibitor like anti-PD-1antibody. Moffitt Cancer Center scientists demonstrated that in DOR expressing, PD-1resistant murine lung cancer models treatment with its APC resulted in a significant improvement in survival when compared to treatment with anti-PD-1antibody alone. The company has establish multiple functional assay screens to investigate the effects of both novel peptidomimetic or small molecule DOR specific inhibitors of tumor associated MDSC functionality to guide its selection of both APCs and ADCs for further invitro and invivo characterization and 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 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