Company: HURA
Filing Date: 2025-09-18
Form Type: S-1/A
Source: 0001193125-25-207395
Chunk: 97

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-09-18
Form: S-1/A
Chunk 97
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 immune system. When VSIR, the gene that encodes for VISTA is silenced, an immune response is observed and survival is enhanced in murine models of mutNPM1 AML

Recently, several new drugs called menin inhibitors have received accelerated approval in patients with relapsed and refractory mutNPM1. Menin is the “carrier” protein that exerts the proliferative effect on leukemic**

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**blasts. While the response rates of 25% to 30% that are seen following therapy with menin inhibitors are encouraging, they are short of short duration followed by leukemia recurrence and subsequent short survival. We believe adding TBS-2025 in treatment of patients with mutNPM1 r/r AML who are receiving a menin inhibitor may improve both response rate and duration of response by allowing immune recognition and attack against leukemic cells. We plan on investigating menin +/- TBS-2025 in mutNPM1 in r/r AML in a proof of concept study among 30 patients. If positive, this application of TBS-2025 would address an unmet medical need, and we believe it may qualify for development under the FDA’s accelerated approval pathway. We intend to start this Phase 2 randomized trial late in the fourth quarter of 2025.

DOR Technology and Bi-functional, bi-specific APCs and ADCs: Inhibiting MDSC immune suppressing functions

MDSCs

MDSCs are among the most common cells present in the tumor microenvironment, which is the tissue surrounding the tumor, where they are a major regulator of suppression of the immune system. MDSCs are normally produced during pregnancy where they migrate to and populate the placenta, creating an immunologic sanctuary for the fetus. Since half of the genetic make-up of the fetus comes from the father, this is necessary to prevent the mother’s immune system from attacking the fetus. They are also produced in settings of chronic inflammation or autoimmune disease as a mechanism to decrease inflammation or autoimmunity. Under normal conditions MDSCs represent less than 2% of circulating peripheral blood mononuclear cells (PBMCs) and lack potent immune suppressing characteristics.

In cancer, MDSCs are hijacked by tumors, being recruited to and creating an immunosuppressive environment in the tissues in which the tumor lives. Multiple effector molecules and signaling pathways are used by MDSCs to regulate immune suppression. One main mechanism involves depletion of necessary amino acids like arginine through