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. 

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

Logo: https://photos.prnasia.com/prnh/20171120/1996749-1LOGO

Source: Kazia Therapeutics Ltd