Kazia Therapeutics Announces First Patient Dosed in PNOC035 Clinical Study Evaluating Paxalisib for Recurrent Pediatric AT/RT Brain Cancer

First patient dosing in PNOC035 Arm A advances Kazia’s paxalisib program into Phase 2 testing for recurrent pediatric AT/RT brain cancer.

Rhea-AI Summary

Kazia Therapeutics (KZIA) has dosed the first patient in PNOC035 Arm A, a Phase 2 study of paxalisib plus gemcitabine in AT/RT.

The multicenter, open-label PNOC035 platform trial enrolls patients aged 1 to 39 with recurrent or progressive atypical teratoid/rhabdoid tumor, a highly aggressive pediatric brain cancer with no approved therapies. In Arm A, patients receive once-daily oral paxalisib and intravenous gemcitabine on Days 1, 8 and 15 of each 28‑day cycle. The combination increased median survival from 22 to 82.5 days (p<0.0001) in an orthotopic AT/RT preclinical model, supporting advancement into this clinical study.

Paxalisib holds both Orphan Drug and Rare Pediatric Disease Designations from the FDA for AT/RT, which, if development is successful and marketing approval is obtained, could make Kazia eligible for a pediatric priority review voucher. Paxalisib is an investigational PI3K/Akt/mTOR inhibitor that has been or is being evaluated in more than 15 clinical trials across multiple brain and systemic cancers.

Positive

• First patient dosed in PNOC035 Arm A, a Phase 2 trial of paxalisib plus gemcitabine in recurrent or progressive AT/RT.
• Preclinical survival benefit with paxalisib plus gemcitabine, increasing median survival from 22 to 82.5 days (p<0.0001) in an AT/RT model.
• FDA Orphan Drug and Rare Pediatric Disease Designations granted to paxalisib for AT/RT, potentially enabling a pediatric priority review voucher if approved.
• Broad clinical experience with paxalisib, which has been or is being studied in over 15 trials, including a completed Phase 2/3 GBM AGILE study.

Negative

• None.

News Explained

The FDA’s Orphan Drug and Rare Pediatric Disease designations for paxalisib in AT/RT do not constitute approval or endorsement; any priority review voucher remains conditional on successful development and FDA approval.

Market Context

KZIA was down 2.44% at the prior daily close before publication; the announcement added a Phase 2 fi...

Analysis

KZIA was down 2.44% at the prior daily close before publication; the announcement added a Phase 2 first-patient dosing milestone, while the supplied price move predates the clinical update and does not measure its reaction.

Key Figures

Trial Phase: Phase 2 Patient Age Range: 1 to 39 years Median Survival: 22 to 82.5 days +1 more

Trial Phase

Phase 2

PNOC035 platform study in recurrent or progressive AT/RT

Patient Age Range

1 to 39 years

Patients eligible for Arm A

Median Survival

22 to 82.5 days

Paxalisib plus gemcitabine in an orthotopic AT/RT preclinical model

P-value

p<0.0001

Preclinical median-survival comparison

Key Terms

orthotopic, orphan drug designation, rare pediatric disease designation, pi3k/akt/mTOR pathway

4 terms

orthotopic medical

"in an orthotopic AT/RT preclinical model"

Orthotopic describes placing tissue, cells, an organ, or a disease model in its normal anatomical location—for example, transplanting a liver into the liver bed or studying a tumor in the organ where it naturally grows. Investors watch for orthotopic approaches because they tend to produce results that better predict real-world safety and effectiveness than unnatural models, so they can improve the credibility of clinical data and influence regulatory and commercial prospects.

orphan drug designation regulatory

"granted both Orphan Drug Designation and Rare Pediatric Disease Designation"

Orphan drug designation is a special status given to medicines developed to treat rare diseases affecting only a small number of people. This status often provides benefits like faster approval processes and financial incentives, making it more attractive for companies to develop these drugs. For investors, it signals potential for exclusive market rights and reduced competition, which can impact the drug’s profitability.

rare pediatric disease designation regulatory

"Orphan Drug Designation and Rare Pediatric Disease Designation by the U.S."

A rare pediatric disease designation is an official regulatory status given to a drug or therapy that targets a serious or life‑threatening condition primarily affecting children and is uncommon in the population. It matters to investors because the status often brings financial and development perks — such as tax credits, reduced fees, faster review and periods of market protection — which can lower costs, speed approval and improve the commercial outlook; think of it as a VIP pass that makes bringing a scarce, child‑focused treatment to market easier and potentially more profitable.

pi3k/akt/mTOR pathway technical

"inhibitor of the PI3K/Akt /mTOR pathway"

A chain of proteins inside cells that passes signals controlling cell growth, survival and energy use; think of it like a thermostat and wiring that tells a cell when to grow, divide or conserve resources. It matters to investors because drugs or tests that alter this pathway are central to many cancer and metabolic disease treatments, influencing the value and risk of biotech pipelines, trial outcomes and future sales potential.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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Multicenter study to evaluate paxalisib plus gemcitabine for children and young adults with recurrent or progressive AT/RT, where no approved therapies currently exist

SYDNEY, Sept. 9, 2026 /PRNewswire/ -- 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, today announced that the first patient has been dosed in Arm A of PNOC035, a Phase 2 platform study evaluating paxalisib in combination with gemcitabine for patients ages 1 to 39 with recurrent or progressive atypical teratoid/rhabdoid tumor (AT/RT). AT/RT is widely recognized as one of the most aggressive forms of pediatric brain cancer.

PNOC035 is conducted by the Pediatric Neuro-Oncology Consortium (PNOC), an open-label, multi-center platform study. In Arm A, patients receive oral, once-daily paxalisib in combination with intravenous gemcitabine on Days 1, 8 and 15 of each 28-day treatment cycle.

The combination increased median survival nearly four-fold (22 to 82.5 days; p<0.0001) in an orthotopic AT/RT preclinical model and demonstrated complementary anti-tumor activity across multiple AT/RT cell lines. These preclinical findings provided the rationale for advancement into the multicenter PNOC035 clinical study evaluating paxalisib plus gemcitabine in children and young adults with recurrent or progressive AT/RT. These findings, previously presented at ISPNO, AACR and Neuro-Oncology meetings, provided the scientific rationale for PNOC035 and extend paxalisib's pediatric neuro-oncology development beyond diffuse midline glioma into another area of significant unmet need.

Paxalisib has been granted both Orphan Drug Designation and Rare Pediatric Disease Designation by the U.S. Food and Drug Administration (FDA) for AT/RT. These designations do not constitute FDA approval or endorsement of any therapeutic claim. If paxalisib were to receive marketing approval for this indication, which would require successful completion of clinical development and FDA regulatory approval, Kazia could become eligible to receive a pediatric priority review voucher from the FDA.

"AT/RT typically affects infants and very young children, and families facing this devastating diagnosis have limited treatment options," said Dr. John Friend II, Chief Executive Officer of Kazia Therapeutics. "Despite decades of research, there are still no approved therapies for recurrent or progressive AT/RT, underscoring the urgent need for new treatment options. We've remained committed to pediatric brain cancer because this is an area where the need is especially great and the options are often fewest. Reaching this milestone with the PNOC035 team is a meaningful step forward, and we look forward to working closely with PNOC as enrollment progresses."

About PNOC035

PNOC035 is a Phase 2 platform trial conducted by the Pediatric Neuro-Oncology Consortium (PNOC) for patients ages 1 to 39 with recurrent or progressive AT/RT. The platform design allows multiple treatment arms to be evaluated within a shared trial infrastructure, with patients enrolling in an arm based on availability and arm-specific eligibility criteria. Arm A evaluates paxalisib in combination with gemcitabine. Additional information about the study is available on ClinicalTrials.gov (NCT07447076).

About Kazia Therapeutics

Kazia Therapeutics Limited (NASDAQ: KZIA) is an oncology-focused drug development company, based in Sydney, Australia. The Company's lead asset, paxalisib, is an investigational brain penetrant inhibitor of the PI3K/Akt /mTOR pathway, which is being developed to treat multiple forms of cancer. Licensed from Genentech in late 2016, paxalisib is or has been the subject of over 15 clinical trials. A completed Phase 2/3 study in glioblastoma (GBM AGILE) was reported in 2024, and discussions are ongoing for designing and executing a pivotal registrational study in pursuit of a standard approval. Other clinical trials involving paxalisib are ongoing in advanced breast cancer, brain metastases, diffuse midline gliomas, and primary central nervous system lymphoma, with several of these trials having reported encouraging interim data. Paxalisib was granted Orphan Drug Designation for glioblastoma by the U.S. Food and Drug Administration (FDA) in February 2018, and Fast Track Designation (FTD) for glioblastoma in August 2020. Paxalisib was also granted FTD in July 2023 for the treatment of solid tumor brain metastases harboring PI3K pathway mutations in combination with radiation therapy. Additionally, paxalisib was granted Rare Pediatric Disease Designation and Orphan Drug Designation by the FDA for diffuse intrinsic pontine glioma in August 2020 and for atypical teratoid / rhabdoid tumors in June 2022 and July 2022, respectively. Kazia is also developing EVT801, a small molecule inhibitor of VEGFR3, which was licensed from Evotec SE in April 2021. In addition to its clinical-stage programs, Kazia is advancing NDL2, a potentially first-in-class intracellular PD-L1 protein degrader program targeting a newly identified mechanism of immunotherapy resistance and metastatic progression, as well as MSETC, a potentially first-in-class SETDB1 inhibitor program intended to restore immune signaling in tumors that have become resistant to immunotherapy, including checkpoint inhibitors. Both programs are currently in preclinical development. For more information, please visit http://www.kaziatx.com/ or follow us on X @KaziaTx.

Forward-Looking Statements

This announcement may contain forward-looking statements, which can generally be identified by words such as "may," "will," "estimate," "future," "forward," "anticipate," "expect," "plan," "believe," "potential," "could," or similar terms. Forward-looking statements in this release include, but are not limited to, statements regarding: the conduct, timing and progress of enrollment in the PNOC035 study; the potential therapeutic benefit of paxalisib in AT/RT; the possibility of clinical results that are consistent with the preclinical data; and the possibility that Kazia could become eligible to receive a priority review voucher if paxalisib were to receive marketing approval for AT/RT, which remains uncertain and is subject to the successful completion of clinical development and regulatory review; the design, execution and outcome of a potential pivotal registrational study of paxalisib for glioblastoma; the therapeutic potential and clinical development of paxalisib in other indications, including advanced breast cancer, brain metastases, diffuse midline gliomas and primary central nervous system lymphoma; and the preclinical development and potential of Kazia's earlier-stage programs, including NDL2 and MSETC. Such statements are based on Kazia's current expectations and are subject to risks and uncertainties that could cause actual results to differ materially, including those described in Kazia's Annual Report on Form 20-F and subsequent filings with the SEC. Kazia undertakes no obligation to update any forward-looking statement except as required by law.

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SOURCE Kazia Therapeutics Limited

FAQ

What patient population is eligible for the PNOC035 Arm A study with paxalisib and gemcitabine?

PNOC035 enrolls patients aged 1 to 39 years with recurrent or progressive atypical teratoid/rhabdoid tumor (AT/RT). Patients are allocated to specific treatment arms, such as Arm A for paxalisib plus gemcitabine, based on availability and arm‑specific eligibility criteria.

How are paxalisib and gemcitabine administered in Arm A of PNOC035?

In Arm A, patients receive oral, once‑daily paxalisib throughout each 28‑day treatment cycle. They also receive intravenous gemcitabine on Days 1, 8 and 15 of each 28‑day cycle.

Who is conducting the PNOC035 clinical trial and what is its design?

PNOC035 is conducted by the Pediatric Neuro-Oncology Consortium (PNOC) as an open-label, multicenter Phase 2 platform trial. The platform design allows multiple treatment arms to be evaluated within a shared infrastructure, with patients enrolling into arms according to availability and specific eligibility rules.

Where can more detailed information on the PNOC035 study be found?

Additional information about PNOC035, including eligibility and study design details, is available on ClinicalTrials.gov under the identifier NCT07447076.

What other indications is paxalisib being investigated for beyond AT/RT?

Paxalisib is being developed for multiple cancers. A completed Phase 2/3 GBM AGILE study in glioblastoma was reported in 2024, and discussions are ongoing to design a pivotal registrational study. Other ongoing clinical trials are evaluating paxalisib in advanced breast cancer, brain metastases, diffuse midline gliomas, and primary central nervous system lymphoma, with several reporting encouraging interim data.