Zentalis® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage
biopharmaceutical company discovering and developing clinically
differentiated small molecule therapeutics targeting fundamental
biological pathways of cancers, today announced the monotherapy
recommended Phase 2 dose (RP2D) for azenosertib, the Company's
potentially first-in-class WEE1 inhibitor. Based on encouraging
Phase 1 dose optimization clinical data, the RP2D for azenosertib
as a monotherapy is 400 mg daily (QD) on a 5 days on, 2 days off
(5:2) weekly administration schedule. This intermittent dosing
schedule more than doubled steady state drug exposure in comparison
to continuous dosing, and achieved promising efficacy signals,
while maintaining safety and improving tolerability.
"With this new optimized monotherapy dosing schedule for
azenosertib, we believe we have unlocked the therapeutic potential
of WEE1 inhibition, achieving monotherapy activity levels few
oncology agents have been able to attain,” said Kimberly Blackwell,
M.D., Chief Executive Officer of Zentalis. “Having demonstrated
favorable anti-tumor activity as both a monotherapy and in
combination with chemotherapy, we are confident azenosertib has
tremendous promise to help patients with difficult-to-treat
cancers. With our focus on platinum-resistant ovarian cancer for
azenosertib as a monotherapy and platinum-sensitive ovarian cancer
for azenosertib in chemotherapy combinations, we have the potential
to address the majority of ovarian cancer patients. We are
committed to rapidly advancing our azenosertib clinical strategy,
concentrating on the fastest paths to market to reach patients in
need.”
Summary of Phase 1 Monotherapy Dose Optimization
Data:
As of April 24, 2023, a total of 127 heavily pretreated patients
with advanced solid tumors were treated with monotherapy
azenosertib at doses ≥ 300 mg at either continuous daily dosing or
intermittent weekly administration schedules. Across all tumor
types, 74 patients were treated with continuous dosing schedules
and 53 patients were treated with intermittent dosing
schedules.
- The confirmed objective response
rate (ORR) was 36.8% (7/19) in the combined ovarian cancer and
uterine serous carcinoma (USC) subgroups who received an
intermittent dosing schedule, versus 19.2% (5/26) in those who
received a continuous dosing schedule.
- Steady state exposure, as measured
by AUC0-24, more than doubled at the new intermittent RP2D,
compared to AUC observed at 300 mg QD with continuous
administration.
- Intermittent dosing maintained
azenosertib safety and improved tolerability as compared to
continuous dosing. Gastrointestinal, fatigue, and hematologic Grade
3 and 4 treatment-related adverse events (TRAEs) were comparable or
favorable versus continuous dosing. No discontinuations due to
TRAEs were observed in the intermittent cohorts.
- The Company is currently enrolling
patients at the new RP2D in three ongoing Phase 2 trials evaluating
monotherapy azenosertib in the following patient populations:
- Cyclin E1+, platinum-resistant
high-grade serous ovarian cancer
- USC
- PARP inhibitor-resistant and
platinum-resistant ovarian cancer (new cohort of ongoing
study)
“WEE1 inhibition by monotherapy azenosertib has the potential to
address the significant unmet need in ovarian cancer and uterine
serous carcinoma, where patients often have limited treatment
options,” said Funda Meric-Bernstam, M.D., Chair of the Department
of Investigational Cancer Therapeutics -- the Phase 1 Program at
The University of Texas MD Anderson Cancer Center, and a member of
the Zentalis Scientific Advisory Board. “Today’s data supporting
the newly established monotherapy dose – which demonstrates
promising efficacy and improved tolerability – coupled with data
supporting the combination of azenosertib with chemotherapy,
suggest that this promising molecule has potential to be a highly
effective therapeutic tool to fight difficult-to-treat
cancers.”
Dr. Blackwell added, “These data sets underpin our broader
strategy to expand options for patients in a broad array of tumor
types.”
Conference Call
The Company will host a webcast today at 8:00 a.m. ET to review
the azenosertib Phase 1 monotherapy data supporting dose selection,
as well as the positive azenosertib plus chemotherapy Phase 1b
combination data presented at the 2023 ASCO Annual Meeting. The
webcast will be accessible via the Investors page of Zentalis’
website, www.zentalis.com. The archived webcast and presentation
will be available on the Company’s website after the event.
About Azenosertib
Azenosertib is a potentially first-in-class and best-in-class
small molecule WEE1 inhibitor in development for the treatment of
cancer. Inhibition of WEE1, a DNA damage response kinase, drives
cancer cells into mitosis without being able to repair damaged DNA,
resulting in cell death. Currently, there are no FDA-approved WEE1
inhibitors, and azenosertib has been designed for superior
selectivity and pharmacokinetic properties. Azenosertib is being
developed in therapeutic areas of high unmet need and is being
evaluated as a monotherapy, in combination with chemotherapy, and
in combination with molecularly targeted agents.
About Zentalis Pharmaceuticals
Zentalis® Pharmaceuticals, Inc. is a clinical-stage
biopharmaceutical company discovering and developing small molecule
therapeutics targeting fundamental biological pathways of cancers.
Utilizing its Integrated Discovery Engine, the Company is
developing a focused pipeline of potentially best-in-class oncology
candidates, which include azenosertib (ZN-c3), a WEE1 inhibitor for
advanced solid tumors, ZN-d5, a BCL-2 inhibitor for hematologic
malignancies and related disorders, and a heterobifunctional
degrader of BCL-xL for solid and hematological malignancies. The
Company is also leveraging its extensive experience and
capabilities across cancer biology and medicinal chemistry to
advance its research on protein degraders. Zentalis has operations
in both New York and San Diego.
For more information, please visit www.zentalis.com. Follow
Zentalis on Twitter at @ZentalisP and on LinkedIn at
www.linkedin.com/company/zentalis-pharmaceuticals.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the U.S. Private Securities Litigation Reform Act of
1995. All statements contained in this press release that do not
relate to matters of historical fact should be considered
forward-looking statements, including statements regarding our
plans to provide clinical data and program timeline updates, and
the timing thereof; the potential for azenosertib to be
first-in-class and best-in-class; the potential benefits of
azenosertib; our belief that we have unlocked the therapeutic
potential of WEE1 inhibition; our belief and confidence that
azenosertib has tremendous promise to help patients with
difficult-to-treat cancer; the potential addressable patient
population of azenosertib, including the ovarian cancer patient
population; our plans to rapidly advance our azenosertib clinical
and regulatory strategy; the potential for azenosertib to address
significant unmet need in ovarian cancer and USC; the potential for
azenosertib to be a highly effective therapeutic tool to fight
difficult-to-treat cancers; our broader strategy to expand options
for patients in a broad array of tumor types; the potential
benefits of the design of azenosertib; and the potential for our
product candidates to be best-in-class. The terms “believe,”
“committed,” “confident,” “design,” “encouraging,” “plan,”
“potential,” “promising,” “strategy,” “suggest,” “to be,” “will,”
and similar references are intended to identify forward-looking
statements, although not all forward-looking statements contain
these identifying words. These statements are neither promises nor
guarantees, but involve known and unknown risks, uncertainties and
other important factors that may cause our actual results,
performance or achievements to be materially different from any
future results, performance or achievements expressed or implied by
the forward-looking statements, including, but not limited to, the
following: our limited operating history, which may make it
difficult to evaluate our current business and predict our future
success and viability; we have and expect to continue to incur
significant losses; our need for additional funding, which may not
be available; our plans, including the costs thereof, of
development of any diagnostic tools; the outcome of preclinical
testing and early trials may not be predictive of the success of
later clinical trials; failure to identify additional product
candidates and develop or commercialize marketable products;
potential unforeseen events during clinical trials could cause
delays or other adverse consequences; risks relating to the
regulatory approval process or ongoing regulatory obligations;
failure to obtain U.S. or international marketing approval; our
product candidates may cause serious adverse side effects;
inability to maintain our collaborations, or the failure of these
collaborations; our reliance on third parties; effects of
significant competition; the possibility of system failures or
security breaches; risks relating to intellectual property; our
ability to attract, retain and motivate qualified personnel, and
risks relating to management transitions; significant costs as a
result of operating as a public company; and the other important
factors discussed under the caption “Risk Factors” in our most
recently filed periodic report on Form 10-K or 10-Q and subsequent
filings with the U.S. Securities and Exchange Commission (SEC) and
our other filings with the SEC. Any such forward-looking statements
represent management’s estimates as of the date of this press
release. While we may elect to update such forward-looking
statements at some point in the future, we disclaim any obligation
to do so, even if subsequent events cause our views to change.
ZENTALIS® and its associated logos are trademarks of Zentalis
and/or its affiliates. All website addresses and other links in
this press release are for information only and are not intended to
be an active link or to incorporate any website or other
information into this press release.
Investor Contacts:Adam D. Levy, PhD,
MBAalevy@zentalis.com
Emily WhiteSolebury Strategic
Communicationsewhite@soleburystrat.com
Media Contact:Danielle CanteyEvoke
Canaledanielle.cantey@evokegroup.com(619) 826 4657
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