On September 1, 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 preclinical data demonstrating the safety and anti-tumor activity of paxalisib in HR+/HER2- breast cancer, including evidence that paxalisib resensitized CDK4/6 inhibitor-resistant tumors to standard-of-care therapy. Based on these findings, the Company is moving rapidly to expand its ongoing TNBC clinical trial into hormone receptor-positive ("HR+"), HER2-negative ("HER2-") advanced breast cancer to evaluate this effect directly and filed a related provisional patent application.
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"HR+/HER2- breast cancer accounts for approximately 60–70% of all breast cancer diagnoses, and we expect nearly 322,000 new cases in the U.S. alone this year," said Dr. John Friend, Chief Executive Officer of Kazia Therapeutics. "That scale, combined with the persistent need for better options once patients progress on standard therapy, represents a significant area of unmet medical need where paxalisib may play a role. Our preclinical data showing statistically significant, additive antitumor activity when paxalisib is combined with standard-of-care therapy gives us strong confidence in this approach, and we are moving quickly to bring this combination into the clinic for these patients. With the completion of our recent financing, based on our current plans and projections, we now have the capital in place to fund this program through completion."
In addition to these findings, paxalisib in combination with fulvestrant, and paxalisib in combination with fulvestrant and palbociclib, showed consistent safety and resulted in statistically significant reductions in tumor volume across preclinical models. Kazia has filed a patent that is supported by the Company’s preclinical findings and has identified a high-risk subset of metastatic HR+/HER2- breast cancer defined by a novel PI3K/mTOR biomarker, with tissue- and blood-based tests associated with poor survival. Extensive benchmarking studies show that paxalisib can resensitize treatment-resistant tumors to combination therapy through a distinct epigenetic mechanism, an effect not observed with gedatolisib, an FDA-approved intravenous PI3K/mTOR inhibitor, indicating a paxalisib-specific effect rather than a class effect. In a HR+ xenograft model, paxalisib in combination with fulvestrant and palbociclib reduced tumor burden without added toxicity and showed primary tumor growth inhibition comparable to gedatolisib in combination with the same regimen.
"Our extensive benchmarking shows that paxalisib is differentiated in targeting the PI3K/mTOR–epigenetic resistance axis and importantly, this is not a class effect," said Dr. Sudha Rao, Chief Scientific Officer, Kazia Therapeutics. "Paxalisib’s unique attributes are uncovering a broader role for PI3K/mTOR beyond conventional cytoplasmic signalling, with alternative pathways that may drive metastatic disease and resistance. In HR+ breast cancer, we have identified a novel epigenetic PI3K/mTOR biomarker, with both liquid and tissue tests, that is enriched in patients with poor prognosis. This gives us the opportunity to enrich for the patients where this biology matters most and brings precision medicine to HR+ breast cancer."
This benchmarking work is ongoing, and Kazia expects to present additional data later this year, including further cellular, molecular and epigenetic characterization of paxalisib relative to other PI3K/mTOR inhibitors.
Current development strategies in this setting have primarily focused on sequencing additional lines of endocrine therapy, targeted agents or antibody-drug conjugates after resistance emerges. Kazia’s preclinical findings suggest that paxalisib may address resistance mechanisms at an earlier biological level through epigenetic and transcriptional effects that extend beyond conventional PI3K/mTOR pathway inhibition.
Alongside its IP filing, Kazia is amending the protocol of its ongoing TNBC clinical trial to add a three-arm expansion evaluating paxalisib in patients with pre-treated HR+/HER2- metastatic breast cancer. Patients will be randomized to one of three arms: paxalisib at 15mg plus fulvestrant (hormone therapy), with CDK4/6 inhibitor palbociclib; paxalisib at 30mg plus fulvestrant, with palbociclib; or a standard-of-care comparator arm of fulvestrant. The primary endpoint is safety and tolerability, with progression-free survival, overall response rate and overall survival as secondary endpoints.
The Company expects sites for this expansion to be activated and the first patient enrolled before the end of 2026, with full enrollment anticipated by the end of 2027. Clinical updates are anticipated throughout 2027, with a full readout anticipated in 2028.
(Press release, Kazia Therapeutics, SEP 1, 2026, View Source;breast-cancer-supported-by-preclinical-data-showing-strong-clinical-activity-and-safety-in-hr-breast-cancer-302865460.html [SID1234670500])