KZIA News & Events

Kazia Therapeutics announced "compelling" preclinical and translational data supporting the development of NDL2, a potentially first-in-class protein degrader that is designed to selectively eliminate nuclear PD-L1, a previously unrecognized intracellular driver of immunotherapy resistance and metastatic progression that is not addressed by currently approved PD-1/PD-L1 antibodies. Across multiple preclinical models and patient-derived samples, NDL2 demonstrated reversal of immune exhaustion, suppression of metastatic biology, and enhanced anti-tumor activity, including in combination with anti-PD-1 therapy. The data collectively support nuclear PD-L1 as a mechanistically distinct and therapeutically actionable driver of immune evasion, disease progression, and metastasis. Unlike PD-1/PD-L1 antibodies that block extracellular signalling, NDL2 is designed to target nuclear PD-L1 proteins that are linked to aggressive and therapeutically resistant mesenchymal and stem-like cancer phenotypes. In murine triple-negative breast cancer preclinical models, NDL2 reduced primary tumor volume by 49% as monotherapy and 73% in combination with anti-PD-1, with 50% reduction in lung metastases in the combination setting, with no observed toxicity, no hemolysis, preserved immune checkpoint function at the cell surface, and favorable plasma stability. Nuclear PD-L1 was shown to be enriched in immunotherapy-resistant tumor cells, metastatic lesions, and circulating tumor cells, and to regulate gene programs associated with invasion, survival, and immune suppression. These findings support a precision-guided development strategy, integrating therapy and diagnostics from the outset.

Kazia Therapeutics provided a clinical update from its ongoing Phase 1b study evaluating paxalisib in combination with pembrolizumab and chemotherapy in patients with late-stage, metastatic triple-negative breast cancer, or TNBC. To date, three patients with metastatic TNBC treated with paxalisib-based regimens have demonstrated meaningful clinical responses, including two partial responses in trial participants and one confirmed complete metabolic response in a patient treated under an expanded access program. 2 of 2 evaluable patients enrolled in the Phase 1b trial achieved partial responses. One advanced metastatic TNBC patient achieved a confirmed complete metabolic response following re-treatment with pembrolizumab/chemotherapy plus paxalisib. Responses observed in patients with visceral disease and multi-organ metastases. Median time on treatment to date is approximately 6.1 months, with all patients continuing on therapy at the time of this update. Paxalisib continues to demonstrate a generally favorable safety and tolerability profile when combined with pembrolizumab and chemotherapy at the 30 mg daily dose. Approximately 75% of adverse events were assessed as unlikely or unrelated to paxalisib. The paxalisib-related AEs were expected and predominantly mild to moderate, consistent with prior studies. The company expects to activate two additional clinical sites by April 2026, with two further sites planned for mid-2026. Kazia continues to anticipate the targeted enrollment of twelve TNBC pts target by the end of 2026 and topline data readout in early 2027.