On August 27, 2026 Kazia Therapeutics Limited (NASDAQ: KZIA) ("Kazia" or the "Company"), an oncology-focused biotechnology company developing therapies that selectively reprogram cancer biology, restore anti-tumor immunity and overcome treatment resistance, reported new data showing its lead asset, paxalisib, achieved a 100% clinical benefit rate in six evaluable patients with Stage IV triple-negative breast cancer (TNBC). Five of the six patients achieved an objective response – a measurable 30% or greater reduction in tumor burden after treatment – including one complete response and four partial responses, resulting in an objective response rate of 83 percent. The remaining patient achieved stable disease. Importantly, these results were achieved with the convenience of oral dosing and a favorable safety and tolerability profile, with no paxalisib-related serious adverse events and no grade 3 or higher hyperglycemia, stomatitis or mucositis, toxicities commonly associated with PI3K/mTOR pathway inhibition.
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"Metastatic triple-negative breast cancer is one of the toughest cancers to treat. Historically, only 12 percent of patients are alive five years after diagnosis. Once a patient’s disease progresses on immunotherapy, options run out quickly," said Dr. John Friend, CEO, Kazia Therapeutics. "Across the six evaluable patients treated, every one of them has benefited, and we haven’t seen a single serious adverse event tied to paxalisib. We’ve also demonstrated meaningful improvements in terminally exhausted T cells and drastic reductions in circulating tumor cell (CTC) clusters, providing early evidence that paxalisib may be addressing biological mechanisms associated with treatment resistance and metastasis. These results strengthen our confidence in this program as we continue enrollment in the Phase 1b trial."
Clinical responses were observed across a broad range of metastatic disease sites, including lung, liver, bone, lymph node and central nervous system target lesions, with responses emerging as early as approximately three months post-randomization. Most notably, a 44-year-old woman with Stage IV TNBC achieved a complete metabolic response and has had no evidence of disease since November 2025. Her response has remained durable through the most recent assessment and has been accompanied by sustained and complete abolishment of CTC clusters and significant reduction in terminally exhausted CD8+ T cells, alongside overall improvement in markers of immune function.
Translational analyses demonstrated reductions in terminally exhausted CD8+ T cells across all six patients, with a median reduction of 51 percent within approximately three weeks of treatment. These cells represent a dysfunctional population of cytotoxic T cells that has lost its ability to recognize and kill cancer cells. Notably, total CD8+ T cell counts remained unchanged, which suggests that paxalisib is not eliminating these exhausted cells or replacing them with new ones. Instead, the existing cells appear to be regaining function. Blood-based simultaneous multi-modal protein, RNA and plasma profiling supported this finding, demonstrating increases in immune cell populations associated with anti-tumor activity, reductions in markers of immune exhaustion and evidence of PI3K-AKT pathway target engagement. The marker findings provide evidence of improved overall immune function across all patients.
In parallel with the immune changes, all six patients demonstrated reductions in circulating tumor cell clusters, which are aggressive groupings of tumor cells in the bloodstream associated with metastatic spread. The median reduction was 83 percent within six to seven weeks of treatment.
"Two of the biggest challenges in treating triple-negative breast cancer are the dormant cancer cells that spread through the bloodstream, and an immune system too exhausted to fight them. It’s rare to see a treatment influence both at the same time. After years of studying this disease, it’s exciting to witness this in a clinical setting. The circulating tumor cell clusters that seed new metastases are being suppressed, while the exhausted T cells needed to fight the cancer are recovering function and showing signs of immune memory which may translate to more durable responses. These changes in the blood are tracking with what we are seeing on the scans, which suggests our liquid biopsy approach may be capturing both the tumor’s metastatic behavior and the immune system’s response to treatment in real time. It gives us a remarkable window into the disease, and we look forward to building on these findings as the trial progresses," said Dr. Sudha Rao, Chief Scientific Officer, Kazia Therapeutics.
These early biological findings represent what may be a first-in-class effect and suggest that paxalisib’s therapeutic effect may extend beyond cytoplasmic PI3K/mTOR inhibition. The rapid and consistent biological responses observed across all evaluable patients support the hypothesis that paxalisib may exert dual influence by restoring immune function and reducing metastatic dissemination, addressing two of the greatest challenges in the treatment of triple-negative breast cancer and fundamental drivers of cancer progression.
Enrollment in the Company’s ongoing Phase 1b study evaluating paxalisib in combination with pembrolizumab (Keytruda) and chemotherapy in advanced metastatic TNBC is expected to be completed by July 2027, with interim clinical updates anticipated throughout 2026 and 2027.
(Press release, Kazia Therapeutics, AUG 27, 2026, View Source [SID1234670379])