SYDNEY, Oct. 16, 2020 /PRNewswire/ -- Kazia Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian oncology-focused biotechnology company, is pleased to announce that it has executed a definitive agreement with the Global Coalition for Adaptive Research (GCAR) to commence Kazia's participation in the GBM AGILE pivotal study in glioblastoma. The study will open a new arm with Kazia's investigational new drug, paxalisib (formerly GDC-0084), and will now move into an operational phase with recruitment of patients to the paxalisib arm expected to begin in Q1 CY2021.

Key Points

• GBM AGILE (NCT03970447) is intended to serve as the pivotal study for registration of paxalisib in key markets
• Dr Ingo Mellinghoff (Memorial Sloan Kettering Cancer Center) and Dr Eudocia Q Lee (Dana-Farber Cancer Institute) have been named as Principal Investigators for the paxalisib arm; Dr Timothy Cloughesy (UCLA) is the Principal Investigator for the overall study
• Kazia will pay an initial fee of US$ 5 million to GCAR, with further milestone payments payable throughout the course of the study
• The duration of paxalisib's enrollment period in GBM AGILE is expected to total approximately 30 – 36 months, plus follow-up, but will depend on emerging study data, recruitment rates, and other variables

Kazia CEO, Dr James Garner, commented, "we have spent the last nine months or so working closely with the GCAR team to plan paxalisib's entry into GBM AGILE, and we are very gratified to now be moving into the operational phase of the study. GBM AGILE is truly a ground-breaking clinical trial, driven by some of the world's leading experts in the field, and we are proud to be a part of it. We expect GBM AGILE to provide definitive clinical evidence for the approval of paxalisib by regulatory agencies in key markets. This is a faster, more cost effective, and higher quality study than any company of our size could mount independently, and we are confident that it will provide the best possible opportunity for paxalisib to demonstrate its potential in this very challenging disease."

Dr Meredith Buxton, Chief Executive Officer at GCAR added, "We are pleased to welcome paxalisib into GBM AGILE. Our mission is to help drive the development of new therapies for glioblastoma, by creating an efficient model for testing and confirming new potentially beneficial treatments for patients with GBM. We look forward to continuing to work closely with the Kazia team to bring paxalisib into the study and support its evaluation."

Principal Investigators

Dr Ingo Mellinghoff and Dr Eudocia Q Lee will serve as Principal Investigators for the paxalisib arm. Dr Timothy Cloughesy is the Principal Investigator for the overall study.

Dr Mellinghoff is the Chair of the Department of Neurology at Memorial Sloan Kettering Cancer Center in New York, NY. He is a highly experienced neuro-oncologist with an extensive track record of published research in brain tumours, and is a Professor at the Gerstner Sloan Kettering Graduate School of Biomedical Sciences and the Graduate School of Medical Sciences at Weill Cornell University. His laboratory focuses on the study of biochemical pathways that regulate the growth of brain cancer, and he has participated in numerous clinical trials for glioblastoma and other forms of brain cancer.

Dr Mellinghoff commented, "we have seen little progress in the treatment of glioblastoma for over two decades, and the need for new therapies is urgent. We have seen encouraging signals from the paxalisib program thus far, and my colleagues and I look forward to exploring its potential in the GBM AGILE pivotal study."

Dr Lee is a neuro-oncologist at Dana-Farber Cancer Institute in Boston, MA, Director of Clinical Research at the Center for Neuro-Oncology at Dana-Farber, and an Assistant Professor of neurology at Harvard Medical School. She is a widely published clinical researcher, with a primary research interest in tumours of the brain and spinal cord, and their neurologic complications. Dr Lee has been an investigator in previous clinical trials of paxalisib in glioblastoma and has first-hand clinical experience with the drug.

Dr Lee added, "GBM AGILE has been designed to provide a definitive assessment of the efficacy of new drugs for glioblastoma. Paxalisib has already been evaluated in two clinical trials in this disease, and GBM AGILE will now greatly enrich our understanding of how best to use it for the benefit of patients."

GBM AGILE

GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment) is an international platform study that has been established specifically to facilitate the approval of new medicines for glioblastoma.

The scientific leadership of GBM AGILE comprises many of the leading experts in glioblastoma, and they have worked in collaboration with the US FDA on its development. It is sponsored by the Global Coalition for Adaptive Research (GCAR), a US-based 501(c)(3) non-profit organisation. At present, the study is underway in 30 sites in the United States and Canada, with plans to launch in Europe and China during CY2021. One drug candidate is currently participating, and paxalisib will be the second candidate to join the study.

GBM AGILE is an adaptive study, so the number of patients recruited, and their allocation within the study, will be continuously adjusted in the light of emerging results. It is expected that between 50 and 200 patients will receive paxalisib, depending on the safety and efficacy of the drug. The data from these patients will be compared against data from an estimated several hundred patients in a shared control arm, allowing for considerable operational efficiency.

The paxalisib arm of GBM AGILE will recruit newly diagnosed patients with unmethylated MGMT promotor status, which is the same population that has been investigated in Kazia's ongoing phase II study. In addition, GBM AGILE will recruit recurrent patients to the paxalisib arm. The drug may ultimately be considered efficacious in either or both of these patient groups, and Kazia will frame any future application for regulatory approval on the basis of this data.

Dr Mellinghoff added, "we see interesting signals of activity in the phase I study of paxalisib in recurrent glioma patients, and so my colleagues and I consider it important to evaluate the drug also in this later-stage group, where the unmet medical need is very substantial. Including both newly diagnosed and recurrent patients in GBM AGILE enables us to observe how paxalisib performs across the spectrum of the disease, and provides us with a significant amount of additional data as we move towards registration."

The primary endpoint of GBM AGILE is overall survival (OS), which is considered the gold standard endpoint for the assessment of new cancer therapies.

Indicative Costs and Timelines

Kazia will initially pay a fee of US$ 5 million to GCAR in consideration for paxalisib joining GBM AGILE. Additional payments will be due throughout the duration of the study, dependent on the attainment of key milestones. The full financial terms of the agreement between Kazia and GCAR are considered commercially confidential. In addition, the total cost of the study will depend on the number of patients ultimately recruited and other operational variables.

Kazia and GCAR expect that necessary regulatory filings and submissions to institutional review boards will be actioned during 4Q CY2020. First patient in to the paxalisib arm is currently anticipated to occur early in CY2021.

The duration of paxalisib's participation in GBM AGILE is unpredictable due to the adaptive nature of the study. As an indicative base case estimate, Kazia expects at this stage that paxalisib will enrol patients for between 30 – 36 months, plus follow-up. However, this figure could change, either in an upward or downward direction, depending on emerging data from the study as well as operational matters such as recruitment rates.

About Kazia Therapeutics Limited

Kazia Therapeutics Limited (ASX: KZA, NASDAQ: KZIA) is an innovative oncology-focused biotechnology company, based in Sydney, Australia. Our pipeline includes two clinical-stage drug development candidates, and we are working to develop therapies across a range of oncology indications.

Our lead program is paxalisib (formerly GDC-0084), a small molecule inhibitor of the PI3K / AKT / mTOR pathway, which is being developed to treat glioblastoma, the most common and most aggressive form of primary brain cancer in adults. Licensed from Genentech in late 2016, paxalisib entered a phase II clinical trial in 2018. Interim data was reported most recently at AACR in June 2020, and further data is expected in 2H 2020. Five additional studies are in start-up or ongoing in other forms of brain cancer. Paxalisib was granted Orphan Drug Designation for glioblastoma by the US FDA in February 2018, and Fast Track Designation for glioblastoma by the US FDA in August 2020. In addition, paxalisib was granted Rare Pediatric Disease Designation and Orphan Designation by the US FDA for DIPG in August 2020.

TRX-E-002-1 (Cantrixil), is a third-generation benzopyran molecule with activity against cancer stem cells and is being developed to treat ovarian cancer. TRX-E-002-1 has completed a phase I clinical trial in Australia and the United States with the final data expected in the second half of calendar 2020. Interim data was presented most recently at the AACR conference in June 2020. Cantrixil was granted orphan designation for ovarian cancer by the US FDA in April 2015.

For more information, please visit www.kaziatherapeutics.com^[1].

This document was authorized for release to the ASX by James Garner, Chief Executive Officer, Managing Director.

References

1. ^{^} www.kaziatherapeutics.com (www.kaziatherapeutics.com)