Company: HURA
Filing Date: 2025-05-23
Form Type: 424B3
Source: 0001193125-25-125499
Chunk: 541

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-05-23
Form: 424B3
Chunk 541
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 cohorts. KVA12123 has been shown to de-risk the VISTA target and provides a novel approach to address the problem of immunosuppression in
the TME with a mechanism of action that is differentiated and complementary to T cell focused therapies. KVA12123 may be an effective immunotherapy for many types of cancer including high VISTA expressing cancers including NSCLC, CRC, OC, RCC and
HNSCC.

VISTA (V-domain Ig suppressor of T cell activation) is a negative immune checkpoint that
suppresses T cell function in a variety of solid tumors. High VISTA expression in tumor correlates with poor survival in cancer patients and has been associated with a lack of response to other immune checkpoint inhibitors. Blocking VISTA
induces an efficient polyfunctional immune response to address immunosuppression and drives anti-tumor responses.

There is a strong
clinical rationale for targeting VISTA with an antibody immunotherapy. The innate immune target VISTA is highly expressed in NSCLC, OC, colon cancer, melanoma, pancreatic cancer and gastric cancer and correlates with poor outcomes in cancer
patients. VISTA is also up-regulated after CPI therapy (e.g., Keytruda, pembrolizumab) and is associated with treatment failure (Figure 3).

Figure 3.VISTA expression is associated with poor overall survival and treatment failure with CPI

Sources: 1. Kuklinski et al. 2018; 2. Kakavand et al. 2017

Blocking VISTA drives an efficient polyfunctional immune response to turn cold tumors hot. VISTA is a novel immuno-oncology target due to its
unique expression and activity. First, high VISTA expression on immunosuppressive myeloid cells (tumor associated macrophages and myeloid-derived suppressor cells (MDSCs)) is consistent across tumor types, making it a relevant target across multiple
types of cancer. Re-programmed myeloid cells can drive tumor inflammation. VISTA-blockade decreases immune suppression and provides single agent tumor growth inhibition and also improves efficacy of T cell
focused therapies like anti-PD(L)1 and anti-CTLA4.

Second, blocking VISTA induces activation of
dendritic cells and natural killer (“NK”) cells and ultimately proliferation and infiltration of T cells into the tumor. The combination of myeloid, NK and T cell responses can reverse immunosuppression and drive anti-tumor activity. While
many immuno-onc