SYDNEY,
Nov. 10,
2023 /PRNewswire/ -- Kazia Therapeutics Limited
(NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development
company, is pleased to announce the publication in Molecular Cancer
Therapeutics highlighting paxalisib preclinical data stemming from
the research collaboration with the Huntsman Cancer Institute at
the University of Utah in Salt Lake City, UT.
The paper by Dr Gennie
Parkman and colleagues, working in the laboratory of
Professor Sheri Holmen, has shown
paxalisib to be active in vitro and in vivo against
preclinical models of metastatic melanoma, the most aggressive form
of skin cancer. Dr Parkman's data highlights paxalisib as a dual
inhibitor of both the PI3K and MTOR pathways and cites in the
manuscript that paxalisib, "may represent a promising therapeutic
strategy in this disease in both the first line and MAPK inhibitor
resistant setting" for BRAF-mutant cutaneous melanoma.
"This is promising data for paxalisib, which
reinforces its potential for use in an area outside of our
traditional brain cancer areas of focus," commented Dr
John Friend, Kazia's CEO. "We are
privileged to be working with one of the world's leading melanoma
centers on this outstanding research project and hope it may lead
to a new way of treating melanoma for patients without suitable
therapies."
Key Points from the Publication
- Activation of the PI3K / Akt / mTOR pathway, which is the
target of paxalisib, is common in melanoma and has been identified
as a key resistance mechanism to some established therapies.
- In vitro: Treatment with paxalisib was observed to lead
to a significant decrease in melanoma cell growth in multiple cell
lines and was also observed to inhibit downstream signaling through
the PI3K/AKT cascade, leading to its negative effect on melanoma
cell growth.
- In vivo:
- Mice bearing tumors who were dosed with 15 mg/kg paxalisib
daily; paxalisib was observed to inhibit of tumor growth and
significantly extended the overall survival of these mice
(p=0.0003) compared to vehicle
- In a MTG004 patient derived xenograft mouse model that is
resistant to dabrafenib and trametinib (inhibitors of mutant BRAF
and MEK, respectively). At day 21, the mean tumor volume in the
paxalisib treated mice was observed to be significantly lower than
vehicle (P = .05) or dabrafenib/trametinib treated mice (P =
.01)
- The authors concluded: "Our results support the use of
paxalisib as a single agent either in the first line or MAPK
inhibitor resistant setting for BRAF-mutant cutaneous melanoma. In
this paper, we demonstrate the beneficial use of next generation
PI3K/mTOR inhibitors, notably paxalisib, to inhibit melanoma cell
growth."
The paper has been published online in Molecular
Cancer Therapeutics and can be accessed at the following website:
https://pubmed.ncbi.nlm.nih.gov/37931033/
Melanoma
Approximately 1 in 50 people will be diagnosed
with melanoma during their lifetime. Most cases are localized to
the skin and can be cured through surgical resection. However,
about 20% of cases spread (metastasis) and require more complex and
ongoing treatment.
Melanoma represents approximately 1% of all skin
cancers, but accounts for the majority of deaths from skin cancer.
For melanoma that is confined to the skin at the time of diagnosis,
the five-year survival rate is 99.5%. However, for melanoma that
has spread to distant sites (metastatic melanoma), the five-year
survival rate falls to 32%.
Approximately 50% of patients harbor activating
mutations in the BRAF gene. Such patients are typically treated
with the combination of a BRAF inhibitor and a MEK inhibitor. The
introduction of targeted therapies has improved the average
survival of patients with BRAF-mutant metastatic melanoma from
approximately 6 months to approximately 24 months. However, we
believe there remains a need for additional therapeutic options to
further improve survival.
Next Steps
Kazia anticipates further data from the ongoing
collaboration with the Huntsman Cancer Institute in CY2024.
Depending on the results, Kazia may evaluate future opportunities
to launch a clinical trial of paxalisib in melanoma.
This announcement was authorized for release by
Dr. John Friend, CEO.
About Kazia Therapeutics Limited
Kazia
Therapeutics Limited (NASDAQ: KZIA; ASX: KZA) 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 2 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, diffuse midline gliomas, 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 tumours (AT/RT) 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 tumour types and
has provided evidence of synergy with immuno-oncology agents. A
Phase 1 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 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, 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 SEC, and in subsequent filings
with the United States Securities and Exchange Commission. 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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