Kazia Theraputics Limited Annual Report 2022 6 CEO’S REPORT Dear Shareholder, The past twelve months have been an extremely fertile period for Kazia’s research and development efforts, particularly in respect of our lead program, paxalisib. We have commenced two new clinical trials: one at Weill Cornell Medicine investigating paxalisib in combination with a low-insulin state for glioblastoma, and one in collaboration with the Pacific Pediatric Neuro-Oncology Consortium, examining paxalisib in combination with another drug for the treatment of diffuse midline gliomas (DMGs), a highly-aggressive group of childhood brain cancers. The work that we start is, in a sense, an investment whose return is the data we receive a year or two hence. Several of the studies that we began in the past few years have reported important milestones during FY2022. Our own phase II study of paxalisib has completed, with very encouraging results in the final efficacy data. The phase II study in brain metastases, run by the Alliance for Clinical Trials in Oncology, has graduated to a second stage in patients with breast cancer brain metastases. And, in early August, we saw extremely positive signals from a study of paxalisib in combination with radiotherapy for brain metastases, in which every evaluable patient demonstrated radiological response. The ever-growing body of data around paxalisib, derived from a very broad range of clinical trials and laboratory studies, helps to provide both confidence in its activity and breadth in its commercial opportunity. While clinical trials naturally more readily capture the imagination, we have also reported this year some very promising preclinical data in childhood brain cancer. A team from Johns Hopkins Medical School reported data in atypical teratoid / rhabdoid tumours (AT/ RT) at the AACR Conference in April 2022, and Professor Matt Dun of the University of Newcastle presented data on DIPG to the ISPNO Conference in June 2022. Together, these presentations, from leading scientists at firstrate institutions, have expanded our thinking in relation to the opportunity for paxalisib in childhood brain cancer. We see this as an increasingly important plank in paxalisib’s overall development. We have secured orphan designation and rare pediatric disease designation in both AT/RT and DIPG, and these achievements help to greatly facilitate our regulatory strategy in childhood brain cancer. If paxalisib is approved in either disease, we may be eligible to receive a pediatric priority review voucher (pPRV), which can be sold to other companies and which typically commands a price in excess of one hundred million dollars. No doubt, however, these important and exciting developments are coloured to some extent by the news we received at the end of July, that paxalisib would not ‘graduate’ to the second stage of the GBM AGILE pivotal study. It is important to be clear what this development may or may not mean for the drug’s further development. The two-stage design of GBM AGILE was designed primarily to increase the statistical power of the study. A drug which successfully clears both stages of the trial may be considered almost unimpeachable in terms of the statistical confidence that accompanies its data. However, this approach sets a high bar for any drug participating in the study, and it is very far from certain that failure to complete both stages is incompatible with an eventual product approval. GBM AGILE will likely provide for the evaluation of paxalisib a more substantial number of patients than were available to support the approval of temozolomide, the existing standard of care in glioblastoma, and the study remains ongoing. As is almost invariably the case in drug development, we will need to wait and see the data before we understand our position. We continue to anticipate that data in 2H CY2023 and, until then, all Kazia personnel remain ‘blinded’ to efficacy and safety. In the meantime, the patients who have enrolled in GBM AGILE continue to receive treatment and to undergo followup, per protocol, and will continue to provide data for analysis. As the data matures, we will no doubt learn a great deal more about paxalisib and will be much better placed to understand its potential benefit to patients with glioblastoma. A DIVERSE PORTFOLIO
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