SYDNEY, Oct. 29, 2018 /PRNewswire/ -- Kazia Therapeutics
Limited (ASX: KZA; NASDAQ: KZIA), an Australian oncology-focused
biotechnology company, is pleased to provide an update to
shareholders regarding progress with GDC-0084, which is currently
in human trials for glioblastoma and several other forms of brain
cancer.
Key Points
- Phase II clinical trial of GDC-0084 in glioblastoma is
progressing well, with all sites open to recruitment and the first
cohort of patients fully enrolled and undergoing treatment
- Investigator-initiated clinical collaborations launched with St
Jude Children's Research Hospital in diffuse intrinsic pontine
glioma (DIPG), and with Dana-Farber Cancer Institute in breast
cancer brain metastases (BCBM)
- Poster on the Kazia glioblastoma study to be presented at
upcoming Society for Neuro-Oncology meeting in New Orleans, LA on 16
November 2018
- Manufacture of an additional batch of GDC-0084 capsules for
clinical trial use has commenced
Kazia CEO, Dr James Garner,
commented, "We are delighted with progress across the GDC-0084
program. Our own study in glioblastoma is off to an excellent
start, and we are very pleased to now also be working with two
top-tier research hospitals to explore additional uses of the drug
in other forms of brain cancer. The hard work that has been
undertaken over the past twelve to eighteen months is now paying
off, which sets the company up for several important and
value-driving data read-outs from the GDC-0084 program during
calendar 2019."
He added, "The PI3K inhibitor class has seen some dramatic
developments in the past six months. We were excited to see FDA
approve Copiktra (duvelisib) from Verastem in October 2018, bringing the number of FDA-approved
PI3K inhibitors to three. The recent European Society for Medical
Oncology (ESMO) meeting also saw promising data presented from
Novartis for their PI3K inhibitor, alpelisib, in certain forms of
breast cancer. It is clear that this class of drugs is
well-established and well-proven. However, GDC-0084 remains the
only PI3K inhibitor in mainstream development that is able to cross
the blood-brain barrier, and this gives it a unique advantage in
brain cancer."
Phase II Clinical Trial in Glioblastoma
All seven participating centres are fully open to recruitment.
To date, the first cohort of three patients has been enrolled and
are currently receiving treatment. If the first cohort is able to
complete treatment without experiencing significant toxicity, a
second cohort will be enrolled at a higher dose. A number of
potential patients have already been identified for the second
cohort and are undergoing pre-screening. Once the maximum tolerated
dose (MTD) has been established in this first part of the trial,
the remainder of the study will proceed at that dose.
Recruitment to date has exceeded expectations, and the study
remains on track to report initial data early in calendar 2019. It
is listed on clinicaltrials.gov as NCT03522298. The study is also
listed in the clinical trial finder section of the US National
Brain Tumor Society website.
Investigator-Initiated Collaborations
As previously announced, Kazia is supporting two leading US
hospitals to explore the potential use of GDC-0084 in other forms
of brain cancer.
St Jude Children's Research Hospital in Memphis, TN has commenced a phase I human
trial of GDC-0084 in children with diffuse intrinsic pontine glioma
(DIPG) and other diffuse midline gliomas. This study is currently
recruiting and is listed on clinicaltrials.gov as NCT03696355.
Dana-Farber Cancer Institute (DFCI) in Boston, MA is establishing a phase II human
trial of GDC-0084 in women with breast cancer brain metastases
(BCBM), which is breast cancer that has spread to the brain. This
study is expected to commence recruitment in early calendar 2019,
pending approval by the Institutional Review Board at DFCI, and is
not yet listed on clinicaltrials.gov.
Kazia has been pleased to observe very strong interest from
clinicians and scientists in a range of other potential exploratory
studies of GDC-0084 and remains in discussion regarding several
other potential clinical collaborations.
Publications
Kazia is gratified to have been accepted for a 'trials in
progress' poster presentation at the upcoming 23rd
Annual Scientific Meeting of the Society for Neuro-Oncology (SNO),
which will be held in New Orleans,
LA on 16-18 November 2018.
The Company will make the poster presentation available to all
shareholders at approximately the same time it is presented at
conference. The poster is expected to focus primarily on the design
of the company-sponsored ongoing phase II study in glioblastoma,
and the rationale for GDC-0084 in this group of patients, and it is
not anticipated that meaningful clinical data will be available at
this early stage.
Other presentations and publications of GDC-0084 data are
anticipated in the next six to twelve months, and the Kazia team
will be discussing appropriate opportunities with investigators at
the upcoming SNO meeting.
Manufacturing
Work has begun to manufacture a second batch of capsules for use
across the GDC-0084 clinical program, under international Good
Manufacturing Practice (GMP) conditions. The company obtained
approximately 48kg of drug substance as part of its transaction
with Genentech in October 2016, and
this remains highly stable. Kazia has planned to periodically
formulate a portion of this material into capsules for clinical
trial use, according to progress with the studies. Given the pace
of recruitment to date, it has been considered appropriate to
accelerate manufacture of a second batch of capsules to ensure
continuity of supply. Production of a second batch will also
strengthen the data available regarding GDC-0084 manufacture for
regulatory purposes, and will ultimately help to inform commercial
supply.
Regulatory Affairs
In accordance with FDA requirements, Kazia has been undertaking
a 13-week toxicology study of GDC-0084 in two animal species. This
is a routine requirement to support long-term use of the drug in
human patients. The study is progressing well according to plans,
and is on track to conclude before the end of calendar 2018.
Kazia has applied to the World Health Organisation (WHO) for an
International Non-proprietary Name (INN) for GDC-0084. It is common
for drugs to be referred to by a code number during early
development, but companies typically seek allocation of an INN
around the initiation of phase II development. INNs are a necessary
step for eventual regulatory approval and are determined centrally
by WHO. Kazia expects to receive the INN for GDC-0084 in late
calendar 2019.
Intellectual Property
Since assuming responsibility for GDC-0084 from Genentech in
October 2016, Kazia has continued to
pursue robust protection for the intellectual property associated
with the drug. Of note, patents have been granted in Australia (July
2017), the People's Republic of
China (March 2018), Hong Kong
SAR (March 2017), and the United States (January 2017), as well as in a number of other
jurisdictions. In general, the patents relating to GDC-0084 provide
comprehensive protection until at least 2031.
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 GDC-0084, a small molecule inhibitor of the
PI3K / AKT / mTOR pathway, which is being developed to treat
glioblastoma multiforme, the most common and most aggressive form
of primary brain cancer in adults. Licensed from Genentech in late
2016, GDC-0084 entered a phase II clinical trial in March 2018. Initial data is expected in early
calendar 2019. GDC-0084 was granted orphan designation for
glioblastoma by the US FDA in February
2018.
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 is currently
undergoing a phase I clinical trial in Australia and the
United States. Initial data was presented in June 2018 and the study remains ongoing.
Cantrixil was granted orphan designation for ovarian cancer by the
US FDA in April 2015.
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