8 PIPELINE REVIEW ADVANCING THE CLINICAL PIPELINE PAXALISIB Kazia’s lead program is paxalisib, an investigational brain-penetrant inhibitor of the PI3K / Akt / mTOR pathway, that was specifically designed to treat brain cancer. Brain cancers account for about 15% of paediatric cancers and are the second most common type of cancer in children whereas over 300,000 adults are diagnosed every year with primary brain cancer. We believe that as a brain-penetrant therapy, paxalisib, by design, has the potential to be an integral component of precision medicine for brain tumours. Many of the ongoing trials are evaluating paxalisib in patients who have PI3K pathway mutations. Enrolling paxalisib clinical trials with patients who have the potential to have the greatest response and benefits may accelerate clinical trial recruitment and time to potential regulatory approval. The overall clinical development strategy for paxalisib has been crafted into three core pillars: • Treatment for adult brain cancer: 4 active trials over 3 different patient populations • Treatment for paediatric brain cancer: 2 active and one recently completed trial • Treatment of brain metastasis of solid tumours: 3 active trials Paxalisib in Adult Brain Cancer Glioblastoma (GBM) is a fast-growing and aggressive brain tumour. Paxalisib is being developed primarily for the ~65% of newly-diagnosed unmethylated GBM patients who generally do not respond to chemotherapy with temozolomide. At two global conferences in 2023, we presented final data from a phase II study in newly diagnosed GBM patients which reported promising signals of clinical activity with paxalisib. GBM AGILE Pivotal study Our GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment) study is evaluating investigational therapies for patients with newly diagnosed and recurrent GBM. The goal of the study is to expedite the approval of new drugs for this disease. Final data is expected from the GBM AGILE pivotal study of paxalisib in GBM in 2H CY2023. Depending on the results of the study, Kazia may use such data to support submission of a new drug application (NDA) for marketing authorisation to the U.S. Food and Drug Administration (FDA). LUMOS2 phase II study Kazia is supporting the University of Sydney on a molecularly guided phase II clinical study, LUMOS2, evaluating paxalisib in adult patients with recurrent/ progressive isocitrate dehydrogenase (IDH) mutant grade 2 and 3 gliomas (G2/3 gliomas). The LUMOS2 study is sponsored by the University of Sydney with a goal of investigating targeted therapeutics in these patients who have limited options. The study is expected to enrol up to 76 patients with PI3K pathway mutations and will be a multi-centre study at several Australian sites, with the potential to expand internationally. We anticipate enrolment to commence in 4Q CY2023. Paxalisib with metformin and ketogenic diet in GBM This clinical study, which is being sponsored by and being conducted at Weill Medical College of Cornell University in the United States is exploring the use of paxalisib in combination with metformin and a ketogenetic diet for patients with GBM. A significant and growing body of research has suggested the potential for ketogenic diets to provide benefit in a range of tumour types, including GBM. The study is actively enrolling in two cohorts of GBM patients, and we anticipate providing an update to this study in 4Q CY2023. Primary CNS lymphoma (PCNSL) In June 2021, Kazia announced that the phase II investigator-initiated study of paxalisib in relapsed/ refractory patients with primary CNS lymphoma had commenced recruitment at the Dana Farber Cancer Institute. As a brain penetrant PI3K inhibitor in development for PCNSL, we believe paxalisib has unique potential in the form of this disease that occurs within the central nervous system, and we anticipate providing a clinical update to this study in 2H CY2023.