Kazia Annual Report 2022

11 KEY GLOBAL REGULATORY AGENCIES Kazia Theraputics Limited Annual Report 2022 of the five PI3K inhibitors that have been approved by FDA have been approved for types of lymphoma. Since none of these drugs cross the blood-brain barrier, they are far from ideal to treat lymphoma in the brain, but paxalisib is very well suited to this patient group. Meanwhile, paxalisib is now some eighteen months into GBM AGILE, the pivotal clinical trial for registration in glioblastoma. Completion of a pivotal clinical trial is one of the most critical landmarks in the development of a new medicine. We learned at the end of July that the drug would not ‘graduate’ to the second stage of the GBM AGILE study. For any participating drug to do so requires it to clear a very ambitious statistical hurdle as soon as it completes recruitment to the first stage. Graduation would have provided an exceptionally high degree of confidence in paxalisib’s eventual success, but failure to graduate certainly does not mean that the drug will not yet show a statistically significant and clinically meaningful benefit. Stage 1 is fully recruited, and patients remain on treatment or in follow-up, per protocol, and we anticipate receiving final data in 2H CY2023. Whatever the results may indicate now, there is substantial opportunity for the picture to evolve as the data matures. All Kazia personnel remain blinded to the study, as is typically required of ongoing pivotal studies by regulatory agencies. As such, it is impossible to make any meaningful inferences about the performance of paxalisib. In common with most clinical trials at this stage of development, we will need to wait for final data before we can assess how best to proceed. Operationally, GBM AGILE has been progressing well. In January 2022, the Global Coalition for Adaptive Research (GCAR) announced that the study had screened over one thousand patients. Not every screened patient is enrolled, but this nevertheless represents a phenomenal pace of recruitment, and has far exceeded Kazia’s expectations at the time of joining the study. That pace has only increased, with several European countries joining the United States and Canada in recruiting to the study. Indeed, GBM AGILE has been so successful in an operational sense that two new arms have been welcomed into the study, adding to the three drugs that were already participating. If GBM AGILE ultimately proves successful for paxalisib, data from the trial will be packaged with information on manufacturing, toxicology, and other activities for submission to regulatory agencies such as the US Food and Drug Administration (FDA), as the basis of a New Drug Application (NDA). Drugs which complete a pivotal study successfully have more than a 90% likelihood of becoming a commercial product. With this inflection point fast approaching, Kazia has become increasingly focused on preparing paxalisib for a potential regulatory filing. Behind the scenes, a great deal of work has been underway 2022 at a Glance Chairman’s Letter CEO’s Report Key Milestones Pipeline Review ESG Financial Reports Our Collaborators

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