SYDNEY, Nov. 21,
2023 /PRNewswire/ -- Kazia Therapeutics Limited
(NASDAQ: KZIA), an oncology-focused drug development company, is
pleased to provide key highlights of the clinical and preclinical
paxalisib related presentations given by key thought leaders at the
Society of Neuro-Oncology 2023 Annual Meeting. "The 2023 SNO Annual
Meeting was another successful event with the latest advances in
clinical trials, diagnosis and treatment of pediatric and adult
patients with CNS malignancies," stated Dr. John Friend, CEO Kazia. "We are highly
encouraged with the preliminary overall survival data from the
PNOC022 clinical study that we believe will provide an alternative
to the current therapies considered as standard of care."
Key paxalisib highlights from the meeting:
Friday, November
17th
Combining ONC201 and paxalisib for the
treatment of diffuse midline glioma (DMG); the preclinical results
underpinning the international Phase II clinical trial
(NCT05009992).
Presenter: Evangeline R. Jackson; University of Newcastle,
NSW, Australia
- The mechanism of action of both paxalisib and ONC201 were
reviewed as well as the synergistic effects of their combination in
DMG preclinical models
- Specifically, the authors observed how ONC201 over activates
the PI3K-AKT pathway, which is the target pathway for
paxalisib
- Consistent and statistically significant improvements were
observed with the combination of paxalisb and ONC201 in DMG
preclinical mouse models
- Two patient case studies were discussed; each receiving the
combination of paxalisib and ONC201 through compassionate
access
- 16-year old female with advanced and relapsed diffuse
intrinsic pontine glioma (DIPG) who demonstrated significant
neurological improvements as well as rapid tumour regression after
receiving the combination
- Six-year old female with DIPG who received the combination of
paxalisib and ONC201 after upfront radiation therapy. Tumor
regression has been maintained for more than two years on paxalisib
and ONC201
Exploiting the genetic dependency on PI3K/mTOR signaling for
the treatment of H3-altered Diffuse Midline
Glioma
Presenter: Ryan
Duchatel, PhD; University of Newcastle, NSW, Australia
- PI3K pathway activation is observed in >80% of all DMGs
and was shown to be required for DMG cell growth
- The authors stated that the success of a monotherapy in
DMG is highly unlikely; therefore they explored several
combinations [of other therapies] with paxalisib with the aim of
optimizing tolerability and efficacy of such combinations in
preclinical mouse studies
- Adding metformin to paxalisib was observed to improve
hyperglycemia (elevated blood glucose) as well as extend the
overall survival rate
- The combination of paxalisib and enzastaurin (PKC
inhibitor) was observed to further extend the overall survival when
combined to radiation treatment
- Authors concluded the triple combination of paxalisib,
enzastaurin and metformin warranted further investigation in
clinical trials
Phase I study of paxalisib and radiotherapy for CNS disease
harboring PI3K pathway mutations: pilot analysis of circulating
tumor DNA for patient eligibility confirmation and post-treatment
response
Presenter: Brandon
Imber, MD, Memorial Sloan Kettering Cancer Center, NYC,
USA
- This is a multi-institutional, Phase I trial of
concurrent paxalisib and radiation therapy in patients with
brain metastases with documented PI3K pathway mutations
- Study has expanded after data from the initial stage identified
the maximal tolerated dose (45mg once daily) along with observed
signals of clinical activity (100% response rate)
- The authors observed that plasma circulating tumor DNA (ctDNA)
was able to accurately confirm the tumor's genetic mutations at
baseline and can potentially be used as a biomarker to assess
patient treatment response
- The authors presented a representative case from the ongoing
Phase I study:
- 70-year-old woman with metastatic breast cancer with tumor
harboring PIK3CA mutation received radiation therapy in combination
with paxalisib for brain metastases
- Her baseline plasma ctDNA test before starting treatment
detected the same PIK3CA mutation as her tumor
- MRI scan three months after treatment demonstrated radiographic
response. In addition, a 99% reduction in the amount of ctDNA with
PIK3CA mutation compared to baseline was detected, indicating ctDNA
can potentially be used as an accurate method to monitor response
after radiation therapy in combination with paxalisib
- This is the first time in this patient population to
demonstrate a link between MRI findings and a blood-based
measure of tumor burden (ctDNA)
Sunday, November 19
PNOC022: a combination therapy trial using an adaptive platform
design for patients with diffuse midline gliomas (DMGs) at initial
diagnosis, post-radiation therapy and at time of
therapy
Presenter: Sabine
Mueller, MD, UCSF, San
Francisco, USA
- 30 sites open to enrollment in North
America, Europe and
Australia
- Total enrollment to date: 137 patients
- Cohort 1 (newly diagnosed) = 37 patients
- Cohort 2 (post radiation therapy) = 69 patients (one patient
was replaced due to physician preference)
- Cohort 3 (at the time of recurrence) = 31 patients
- Cohort 2 preliminary analyses (median follow-up time was
approximately 9 months)
- Median Overall Survival rate was 16.5 months
- Median Progression Free Survival (PFS) was 9.9 months (central
review is ongoing)
- Analysis of preliminary data from all cohorts is still ongoing
and the protocol is subject to amendment to refine dosing with the
aim of improving tolerability and efficacy at which time the
enrollment of new patients will start
- Additional data includes ctDNA, microbiome and quality of
life measures
This announcement was authorized for release by Dr. John Friend, CEO.
About Kazia Therapeutics Limited
Kazia
Therapeutics Limited (NASDAQ: KZIA) is an oncology-focused drug
development company, based
in Sydney, Australia.
Our lead program is paxalisib, a brain-penetrant inhibitor of
the PI3K / Akt / mTOR pathway, which is being developed to
treat multiple forms of brain cancer. Licensed from Genentech in
late 2016, paxalisib is or has been the subject of ten
clinical trials in this disease. A completed Phase II study
in glioblastoma reported promising signals of clinical
activity in 2021, and a pivotal study, GBM AGILE, is ongoing, with
final data expected in CY2023. Other clinical trials are ongoing in
brain metastases, DMGs, and primary CNS
lymphoma, with several of these having reported encouraging interim
data.
Paxalisib was granted
Orphan Drug Designation for glioblastoma by the US
Food and Drug Administration (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, and for atypical teratoid
/ rhabdoid tumors in June
2022 and July 2022, respectively.
Kazia is also developing EVT801, a small-molecule inhibitor of
VEGFR3, which was licensed from Evotec SE in April 2021. Preclinical data has shown EVT801 to
be active against a broad range of tumor types and has provided
evidence of synergy with immuno-oncology agents. A Phase I study in
advanced solid
tumors commenced recruitment in November 2021.
For more information, please
visit www.kaziatherapeutics.com or follow
us on Twitter @KaziaTx.
Forward-Looking Statements
This announcement may
contain forward-looking statements, which can generally be
identified as such by the use of words such as "may," "will,"
"estimate," "future," "forward," "anticipate," or other similar
words. Any statement describing Kazia's future plans, strategies,
intentions, expectations, objectives, goals or prospects, and other
statements that are not historical facts, are also forward-looking
statements, including, but not limited to, statements regarding:
the timing for results and data related to Kazia's clinical and
preclinical trials, and Kazia's strategy and plans with respect to
its programs, including paxalisib and EVT801, as well as any
potential future indications and timing for the release of interim
or final data for such programs. Such statements are based on
Kazia's current expectations and projections about future events
and future trends affecting its business and are subject to certain
risks and uncertainties that could cause actual results to differ
materially from those anticipated in the forward-looking
statements, including risks and uncertainties: associated with
clinical and preclinical trials and product development, including
the risk that preliminary or interim data may not reflect final
results, related to regulatory approvals, and related to the impact
of global economic conditions. These and other risks and
uncertainties are described more fully in Kazia's Annual Report,
filed on form 20-F with the United States Securities and Exchange
Commission (SEC), and in subsequent filings with the SEC. Kazia
undertakes no obligation to publicly update any forward-looking
statement, whether as a result of new information, future events,
or otherwise, except as required under applicable law. You should
not place undue reliance on these forward-looking statements, which
apply only as of the date of this announcement.
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