Company: HURA
Filing Date: 2025-05-06
Form Type: S-4/A
Source: 0001193125-25-113920
Chunk: 560

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-05-06
Form: S-4/A
Chunk 560
---
 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-oncology targets address either T cell or myeloid functions, VISTA has the potential to regulate both.

KVA12123 has demonstrated activity on important innate and adaptive immune cells (Figure 4) present in the TME in preclinical assays (in vitro).

<div align='center'>349</div>

#### Figure 4.Blocking VISTA with KVA12123 activates both innate and adaptive immune cellsAdditionally, KVA12123 drives an integrated innate and adaptive anti-tumor immune response in tumor models like MB49 bladder tumor (ex vivo).Figure 5. Blocking VISTA with KVA12123 drives anti-tumor responses in MB49 modelIn preclinical models, KVA12123 has been observed to show strong single agent tumor growth inhibition in poorly immunogenic “cold tumors” models and complementary tumor growth inhibition when dosed in combination with CPIs likePD-1orCTLA-4as shown in Figure 6 below.