Kazia Annual Report 2022

10 PIPELINE REVIEW A BROAD CLINICAL PIPELINE PAXALISIB Although glioblastoma remains very much the lead indication, childhood brain cancer has emerged as a very important second element in the paxalisib story. Brain cancer is the most common cause of cancer death in children, and it remains terribly poorly treated. Both diffuse intrinsic pontine glioma (DIPG) and atypical teratoid / rhabdoid tumours (AT/ RT), two diseases which have been a strong focus for Kazia in the past year, have no FDA-approved drug treatments and, as a consequence, the prognosis is very poor. The second quarter of CY2022 saw important preclinical data presented at international conferences in this area. Professor Jeffrey Rubens and colleagues at Johns Hopkins Medical School presented very positive data for paxalisib in AT/RT at the American Association of Cancer Research (AACR) Annual Meeting in April 2022. This data enabled paxalisib to receive Orphan Drug Designation (ODD) for this disease in June 2022. Kazia is currently in discussion about potential opportunities to translate this very promising work into a clinical trial. In June 2022, Associate Professor Matt Dun from the Hunter Medical Research Institute at the University of Newcastle, Australia, presented very powerful results from his research in the combination of paxalisib with a drug called ONC201 (manufactured by Chimerix, Inc) in the treatment of DIPG. This data has already enabled a clinical trial of the combination in this disease, which began recruitment in November 2021. Professor Dun’s presentation also included several very promising case studies from compassionate use experience with the two drugs in combination. Kazia’s pipeline is remarkable for its diversity. Paxalisib, the lead program, is in clinical trials for multiple forms of brain cancer. EVT801 has potential applications in a wide range of solid tumours. Together, they give Kazia an extensive breadth of opportunity for a company of its size. Another element of the paxalisib program that has been emerging as a very promising opportunity has been brain metastases, a collective term for cancer which spreads to the brain from other parts of the body. More than 200,000 patients each year develop brain metastases in the United States alone, and treatment options are limited. Three clinical trials have been examining paxalisib as a potential treatment for these patients. One of these studies, run by the Alliance for Clinical Trials in Oncology, has already seen positive data for paxalisib in patients with breast cancer brain metastases and, on that basis, has moved the drug into an expansion phase. The study remains in an exploratory phase for patients with lung cancer brain metastases, and for patients with brain metastases from other primary tumours. A second study, at Memorial Sloan Kettering Cancer Center, has similarly moved into an expansion phase, with initial data from the first part of the trial accepted for a prestigious oral presentation at a specialist scientific conference on brain metastases organised jointly by the Society for Neuro-Oncology (SNO) and the American Society for Clinical Oncology (ASCO). Excitingly, this data showed all evaluable patients responding to the combination of paxalisib with whole brain radiotherapy, suggesting the potential for our drug to play an important role in augmenting the efficacy of this ubiquitous therapy. In addition, paxalisib is also the subject of a clinical trial in primary CNS lymphoma, a less common form of brain cancer that remains very challenging to treat. Paxalisib belongs to a class of medicines known as PI3K inhibitors, and four

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