Company: HURA
Filing Date: 2025-02-07
Form Type: S-4
Source: 0001193125-25-022803
Chunk: 532

Company: TuHURA Biosciences, Inc./NV
Filing Date: 2025-02-07
Form: S-4
Chunk 532
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tokine induction observed 339

Pharmacokinetics (PK) and Receptor Occupancy (RO)

PK is the study of how the body interacts with KVA12123 for the entire duration of exposure after administration. KVA12123 exhibited a greater than dose-proportional pharmacokinetic profile in drug exposure across all doses, consistent with target-mediated drug disposition at lower doses and target saturation at higher doses.

Figure 18. VISTA-101 KVA12123 Pharmacokinetics

To guide the recommended phase 2 dose decision, Kineta developed a proprietary assay to evaluate VISTA receptor occupancy (“RO”) on immune cells from patients treated with KVA12123. This is an important metric for evaluating how well KVA12123 is blocking the VISTA target. KVA12123 achieved a greater than 90% VISTA RO at the 30 mg dose and a complete saturation of the target between two-dose interval was achieved at 1000 mg, indicating that KVA12123 RP2D or optimal clinical dose could be between 300 and 1000mg.

Figure 19. VISTA-101 KVA12123 VISTA receptor occupancy**

<div align='center'>340</div>

**Biomarkers

In drug development and clinical trials, biomarkers may be useful to identify patient populations for a study, monitor therapeutic response and identify side effects. KVA12123 demonstrated dose-proportional on-target biomarker immune responses involved in anti-tumor activity. KVA12123 demonstrated significant efficacy-related, dose-dependent cytokine induction of CXCL10, IFNg, CCL2 (MCP1), CCL3 (MIP1α), CCL4 (MIP1b) and CXCL8 (IL8), which are involved in immune cell activation and recruitment to the TME (Figure 19). Additionally, increases in anti-tumor immune cell subpopulations including nonclassical monocytes with an activated phenotype (increased of cell surface expression of HLA-DR and CD80), NK cells, CD4+ T cells and CD8+ T cells were observed during treatment (Figure 20).

Figure 20. VISTA-101 KVA12123 pro-inflammatory biomarkers**

<div align='center'>341</div>

Figure 21. VISTA-101KVA12123 immune cell responses KVA12123 demonstrated induction of pro-inflammatorymyeloid derived cytokines/chemokines involved in immune cell activation and recruitment in the TME. Changes in these