In addition to IFx-2.0 our innate immune agonist product candidate and TBS-2025, our VISTA-inhibiting antibody product candidate, we are using proprietary Delta Opioid Receptor (DOR) technology to develop peptidomimetic or small molecule bi-specific/bi-functional immune modulating antibody-peptide conjugates (“APCs”) and antibody-drug conjugates (“ADCs”) designed to inhibit the immune suppressing effects of tumor-associated MDSCs on the tumor microenvironment to prevent T cell exhaustion and acquired resistance to checkpoint inhibitors. The DOR represents a novel target to inhibit the immunosuppressive capacity of MDSCs through its control of the production of multiple immunosuppressive soluble factors, chemokines and direct cell-cell interactions. 

The tumor microenvironment is the tissue surrounding a tumor, including the normal cells, blood vessels, and molecules that surround and feed a tumor cell and shield it from immune attack and eradication. MDSCs are a heterogeneous group of immature myeloid cells, which, when recruited from the bone marrow to the tumor microenvironment, transform into tumor-associated MDSCs and are characterized by their ability to suppress both innate and adaptive immune responses. Tumor-associated MDSCs are generally believed to be a major contributor to T cell exhaustion (which is the loss of ability of T cells to proliferate and to kill cancer cells) and for acquired resistance to checkpoint inhibitors and cellular therapies like T cell therapies. The presence of tumor-associated MDSCs in the tumor microenvironment or circulating in the bloodstream is highly correlated with poor prognosis and outcome in a wide variety of solid tumors and blood related cancers. 

We are developing first-in-class small molecule DOR-selective inhibitors to incorporate into our bi-specific, bi-functional APCs and ADCs. Traditional ADCs are a class of drugs in which a monoclonal antibody is chemically linked to a cancer-fighting substance. The antibody carries the cancer fighting payload to the tumor cell, improving the selectivity of the resulting anti-cancer activity. Next generation ADCs incorporate non-chemotherapeutic technologies to interfere with tumor cell cycle growth or to carry with the antibody a checkpoint inhibitor (so called “checkpoint ADCs”). In contrast, our APCs or ADCs do not target tumor associated receptor targets but rather target the Delta Opioid Receptor on MDSCs, while carrying with them an immune effector to target a second receptor target like VISTA with a VISTA inhibiting antibody or other checkpoint inhibitor(s) producing novel bi-specific, bi-functional conjugates. 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 while interfering with the tumor’s ability to invade and spread throughout the body.

TuHURA’s Bi-Specific Immune Modulating ADCs represent a new class of ADCs and a paradigm shift in this important therapeutic class of drugs

First to identify the presence of a novel Delta receptor present in high quantities on the surface of tumor associated MDSCs

Delta receptor represents a “master switch” controlling multiple MDSC pathways responsible for creating immune sanctuary where tumor lives

Developing Delta specific and selective small molecule inhibitors as core for Company’s bi-specific immune modulating antibody-drug conjugates (ADCs)