Kazia Therapeutics在2025 SABCS大会公布Paxalisib在her2阳性转移性乳腺癌和三阴性乳腺癌(TNBC)研究的最新数据

Sydney, Australia – December 10, 2025 (NASDAQ: KZIA) – Kazia Therapeutics Limited ("Kazia"or the "Company") today announced new data from two presentations at the 2025 San AntonioBreast Cancer Symposium (SABCS) providing compelling mechanistic and early clinicalevidence supporting the activity of paxalisib, the Company’s brain-penetrant dual PI3K/mTORinhibitor, across both HER2-positive metastatic breast cancer and triple-negative breast cancer(TNBC). 

The results, originating from advanced liquid biopsy profiling, immune phenotyping, and earlyclinical readouts, highlight paxalisib’s potential to disrupt highly aggressive circulating tumorcell (CTC) clusters, reverse epigenetically-driven resistance pathways, and reinvigorateexhausted T- and B-cell populations, thereby enhancing responsiveness to immunotherapy.Paxalisib Disrupted Drivers of Metastasis: Vim⁺/Snail⁺/NRF2⁺ CTC Clusters in HER2+Disease Ex VivoIn HER2-positive metastatic breast cancer, a population in which nearly all patients eventuallyrelapse despite HER2-directed therapies, investigators observed that even patients who wereradiographically responding continued to harbor substantial burdens of therapy-resistant CTCclusters—a key driver of metastatic spread.

Poster Presentation: PS2-10-02 : Liquid Biopsy Tracking of PI3K–mTOR Residual DiseaseSignatures in Metastatic HER2+ Breast Cancer 

Key findings: 

• Paxalisib reduced single CTCs by 42% and CTC clusters by 78% ex vivo, including largeclusters (≥5 cells), which are strongly associated with metastatic progression. 

• CTC clusters expressed a highly aggressive mesenchymal phenotype marked byVimentin⁺/Snail⁺/NRF2⁺, which paxalisib significantly disrupted. 

• Patients with poor clinical response demonstrated impaired cytotoxic function(reduced Granzyme B and Perforin) and expanded exhausted T-cell populations, whilepaxalisib treatment activated cytotoxic, interferon, chemokine, and inflammatorypathways in samples from these patients, supporting a more immunologically “hot”tumor environment. 

“These findings reveal an important biological gap left by existing HER2+ directed therapies,”said Prof. Sudha Rao, QIMR Berghofer. “CTC clusters persist even in responding patients, andpaxalisib is the first agent we have observed that can directly dismantle this highly aggressiveand clinically relevant compartment.”

TNBC Phase 1b Trial: Early Clinical Data from First Patient Show Robust Suppression ofCTC Clusters and Reversal of T-Cell Exhaustion 

Early longitudinal biomarker data from the first patient treated in the PaxPlus-ABC Phase 1bstudy (paxalisib + pembrolizumab + chemotherapy) indicate that paxalisib has had measurablebiological activity after only a single cycle. 

Poster Presentation: PS5-08-04: A phase 1b, multi-centre, open-label, randomized study toevaluate the safety, tolerability, and clinical activity of combining paxalisib with olaparib orpembrolizumab/chemotherapy in patients with advanced breast cancer 

Highlights from first patient include: 

• Marked reduction in CTC clusters following the first cycle of paxalisib. 

• Epigenetic reprogramming of CTCs toward less aggressive phenotypes, confirmedthrough digital pathology and Nanostring profiling. 

• Significant reduction of exhausted CD8 T cells, with revitalization of cytotoxic andantigen-presentation pathways. 

• CT imaging has demonstrated overall primary tumor volume reduction from baseline14mm x 11mm (154mm2) to 12mm x 3 mm (36mm2) 

• Notably, a temporary interruption of paxalisib (necessitated by a chemotherapy-relatedadverse event) resulted in a rapid resurgence of CTC clusters. Resumption of paxalisibafter a short 3-week pause restored suppression of CTC clusters, indicating thatpembrolizumab alone could not control these metastatic drivers and highlightingpaxalisib’s unique mechanistic role.

Pembrolizumab Alone May Not Control CTC Burden; A Mechanistic Opportunity forPaxalisib

Across HER2+ and TNBC ex-vivo datasets, a consistent theme emerges: 

• Pembrolizumab monotherapy does not meaningfully reduce CTC burden, and in TNBC,CTC clusters increased when paxalisib was withheld. 

• Paxalisib directly targets mesenchymal, metastatic, and epigenetically resistant CTCclusters. 

• It also reinvigorates immune effector cells, potentially overcoming the cytotoxicdysfunction and exhaustion that limit checkpoint inhibitor efficacy. 

This mechanistic direct suppression of metastasis-initiating cells plus restoration of immunefunction positions paxalisib as a potentially transformative immunotherapy-enhancing agent. 

Expanding Opportunity Across Breast Cancer: HER2+, TNBC, BRCA-Mutated, and Beyond 

Because mesenchymal CTC clusters and T-cell exhaustion are shared resistance mechanismsacross multiple breast cancer subtypes, paxalisib’s effects are highly relevant beyond TNBC. 

Emerging data suggest: 

• In HER2+ patients, despite targeted therapy, residual disease persists in the form ofaggressive CTC clusters—a new therapeutic window for paxalisib.

• In TNBC, paxalisib’s epigenetic and immunologic effects provide a strong rationale forcombination with pembrolizumab, PARP inhibitors, and chemotherapy. 

​• In BRCA-mutated and homologous recombination–deficient tumors, PI3K/mTORinhibition may synergize with synthetic lethal strategies such as olaparib. 

​“Kazia’s recent clinical and translational findings point to a unifying biology across breastcancer subtypes,” said Dr. John Friend, CEO of Kazia Therapeutics. “Paxalisib appears capableof disrupting metastatic machinery that is not adequately addressed by current HER2-targetedtherapies, checkpoint inhibitors, or chemotherapies. We believe these discoveriesmeaningfully expand the potential utility of paxalisib beyond our current developmentprograms.” 

For investor and media, please contact Alex Star, Managing Director LifeSci AdvisorsLLC, Astarr@lifesciadvisors.com, +1-201-786-8795.