Kazia Therapeutics Annual Report 2021

PIPELINE REVIEW: TWO FIRST-CLASS DEVELOPMENT CANDIDATES FOR THE LAST FIVE YEARS, KAZIA’S STORY HAS BEEN PRINCIPALLY THE STORY OF PAXALISIB. A NEW DRUG CANDIDATE, EVT801, HAS NOW ENTERED THE KAZIA PIPELINE, CREATING RICHER AND MORE NUMEROUS OPPORTUNITIES FOR THE YEARS AHEAD. PAXALISIB One of the most important milestones in the entire development of paxalisib occurred on 4 January 2021. On that day, and right on schedule, paxalisib began recruitment to a pivotal study for registration – GBM AGILE, which is being driven by the Global Coalition for Adaptive Research. A pivotal study is the final chapter in the development of any new medicine, and the results that emerge from GBM AGILE will provide the basis on which FDA, EMA, and other regulatory agencies determine whether to grant paxalisib a marketing authorisation. GBM AGILE will test paxalisib both in newly diagnosed glioblastoma patients, and those with recurrent disease, and the drug may show benefit in either or both of these patient populations. The primary endpoint of paxalisib is overall survival (OS), which is a measure of the ability of a drug to prolong life. It is the most demanding criterion on which to judge a cancer drug and is rightly considered the ‘gold standard’ by regulatory agencies. In glioblastoma, no drug this century has shown convincing evidence of an ability to improve OS. If our participation in GBM AGILE is a success, then paxalisib may be the first new therapy, at least for newly diagnosed patients, in twenty years. GBM AGILE will recruit up to 200 patients on paxalisib. However, the study uses a sophisticated and novel statistical approach called an ‘adaptive design’ to readjust its statistical power as it goes. Consequently, if an answer becomes clear after fewer than 200 patients, the study will conclude early and Kazia will look to submit a new drug application to FDA with the final data in hand. As a base case, we expect that the duration of the study will be around two-and-a-half years, but the adaptive design means that it may be longer or shorter, depending on the data that emerges. The initial focus of GBM AGILE has been on the United States, where more than forty leading cancer hospitals are now participating. During FY2022, paxalisib will additionally become available to patients in Canada, Europe, and China, which will substantially accelerate recruitment. SURGING AHEAD Kazia Therapeutics Limited 10 Annual Report 2021