Company: HURA
Filing Date: 2025-09-18
Form Type: S-1/A
Source: 0001193125-25-207395
Chunk: 110

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-09-18
Form: S-1/A
Chunk 110
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2025 demonstrated induction of pro-inflammatory myeloid-derived cytokines/chemokines involved in immune cell activation and recruitment in the tumor microenvironment. Changes in these key biomarkers and immune cell populations are indicative of the anti-tumor effects of blocking VISTA that is consistent with data from preclinical models (NHP and KO mice). These data validate their use as potential biomarker of VISTA target engagement with TBS-2025

Phase 2 Randomized controlled trial of menin inhibitor +/- TBS-2025in mutNPM1 r/r AML

VISTA is a novel checkpoint expressed on quiescent (resting) T cells and highly expressed on myeloid cells. While VISTA is expressed on a wide variety of solid tumor cancers, its role in resistance or failure of cancer- immunotherapy is not well established. Emerging scientific evidence demonstrates that mutNPM1 and mutDNM3TA, two of the most common mutations in AML and other myeloid (blood related) malignancies, drive the expression of VISTA on leukemic blasts in AML and are reported to be the primary mechanism by which AML has a poor response to and high relapse rate following current therapies. VISTA expression is linked to high relapse rate in AML due to its ability to allow leukemic blasts to evade immune recognition and attack by the patient’s 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 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 Phase 2 trial among 30 patients. If positive, this application of TBS-2025 would address an unmet medical need, and we believe it