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 positive data from
the Phase 1b trial of azenosertib, the Company’s potentially
first-in-class WEE1 inhibitor, in combination with chemotherapy in
patients with platinum-resistant ovarian cancer. Azenosertib was
well tolerated in combination with multiple types of chemotherapy
and demonstrated encouraging clinical activity, with noteworthy
improvements in objective response rates (ORRs) and median
progression free survival (mPFS) in all patients, especially those
with Cyclin E1+ tumors, a subgroup recognized to have a poor
prognosis and be refractory to chemotherapy. Results will be
presented in a poster discussion session at the 2023 ASCO Annual
Meeting on June 5th (Abstract #5513).
“Azenosertib is emerging as a very promising clinical candidate,
with demonstrated anti-tumor activity in difficult-to-treat tumor
types when used in combination with standard chemotherapy
regimens,” said Kimberly Blackwell, M.D., Chief Executive Officer
of Zentalis. “The addition of azenosertib increased ORRs and mPFS
over those observed historically with chemotherapy alone, or
compared to adavosertib in combination with chemotherapy. We are
very encouraged by our robust chemotherapy combination data,
particularly the strong efficacy and tolerability results when
dosing azenosertib intermittently. These data provide a compelling
rationale to advance azenosertib into a registrational study in
combination with either carboplatin or paclitaxel in Cyclin E1+
ovarian cancer. We look forward to providing additional insights
into our azenosertib clinical programs and the franchise potential
we see for this product candidate during our June 6 investor
webcast.”
Efficacy and Safety
Results:
A total of 115 patients were enrolled in the study across all
chemotherapy combination groups. At the data cut-off of April 10,
2023, 94 were efficacy evaluable. Across all dosing schedules,
azenosertib plus paclitaxel demonstrated the highest ORR of 50.0%
(mPFS of 7.4m), followed by an ORR of 38.5% (mPFS of 8.3m) for
azenosertib plus gemcitabine. Azenosertib plus carboplatin
demonstrated an ORR of 35.7% (mPFS of 10.4m), and azenosertib plus
PLD demonstrated an ORR of 19.4% (mPFS of 6.3m).
A total of 82 response-evaluable patients had available Cyclin
E1 expression data by immunohistochemistry (IHC). Cyclin E1+ status
(H-score >50) was associated with a superior ORR and a longer
mPFS across the total patient population (ORR of 40.0% vs 8.3%;
mPFS of 9.86 vs 3.25 months, HR = 0.37; P = 0.0078), showcasing the
potential synergy of WEE1 inhibition with chemotherapy in this
patient population.
Overall, the tolerability of azenosertib dosed intermittently in
combination with either paclitaxel or carboplatin compares
favorably to historical data from standard of care chemotherapy
doublets of either paclitaxel-carboplatin or PLD-carboplatin.
Frequent Grade ≥3 treatment-related adverse events (%) across all
azenosertib intermittent dosing groups were thrombocytopenia
(27.5%), neutropenia (25.5%), anemia (15.7%), and fatigue (9.8%). A
recommended Phase 2 dose was determined for each of the azenosertib
combinations with paclitaxel, carboplatin, and PLD.
Based on these results, the Company is planning to initiate a
Phase 3 study comparing azenosertib dosed intermittently in
combination with either carboplatin or paclitaxel in patients with
Cyclin E1+ platinum-sensitive ovarian cancer. The Company expects
to initiate the Phase 3 study in the first quarter of 2024.
“The results thus far for azenosertib in combination with
chemotherapy are very promising, as there remains high unmet need
in this patient population, particularly patients with Cyclin E1+
tumors who historically have not responded well to chemotherapy,”
said Joyce Liu, M.D., M.P.H., Associate Chief and Director of
Clinical Research for the Division of Gynecologic Oncology at the
Dana-Farber Cancer Institute. “I look forward to continuing to work
with the Zentalis team to advance azenosertib in the clinic and, if
approved, ultimately into medical practice as an important and
novel treatment option for platinum-sensitive ovarian cancer
patients.”
Premal H. Thaker, M.D., Professor of Obstetrics and Gynecology,
Director of Gynecological Oncology Clinical Research, Division of
Gynecologic Oncology, Washington University School of Medicine, and
an investigator on the study added, “The data for azenosertib in
combination with chemotherapy are increasingly robust and
encouraging. Moreover, the enrichment of patients by Cyclin E1+
status provides a compelling strategy for future clinical trials. I
look forward to the initiation of a study examining the role of
azenosertib in combination with chemotherapy in earlier lines of
therapy.”
The Company will host a webcast on Tuesday, June 6, 2023 at 8:00
a.m. ET to provide a clinical update, including an overview of the
ASCO data, as well as safety, pharmacology and efficacy results for
azenosertib as a monotherapy, and plans for future development of
azenosertib as a monotherapy and in combination with chemotherapy.
The corporate 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.
ASCO Presentation Details:
Poster Title: Correlation of Cyclin E1
expression and clinical outcomes in a Phase 1b dose-escalation
study of Azenosertib (ZN-c3), a WEE1 inhibitor, in combination with
chemotherapy in patients with platinum-resistant or refractory
(R/R) epithelial ovarian, peritoneal, or fallopian tube
cancerPresenter: Dr. Liu, M.D., M.P.H., Associate
Chief and Director of Clinical Research for the Division of
Gynecologic Oncology at the Dana-Farber Cancer Institute.
Session Title: Gynecologic CancerSession
Date and Time: Monday, June 5, 2023, 1:15 – 4:15 p.m. CT
Location: Hall APoster Board
Number: 208Poster Discussion Session Date and
Time: Monday, June 5, 2023, 4:30 – 6:00 p.m.
CTLocation: S100bc Abstract Presentation
Number: 5513
A video summary of the poster by Dr. Liu will be available on
the ASCO virtual platform.
Once presented, the poster can be found on the Company’s website
using this link.
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 focused on 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 the
potential benefits of azenosertib in combination with chemotherapy;
the potential for azenosertib to be first-in-class and
best-in-class; the potential benefits of azenosertib and its
promise as a clinical candidate and, if approved, a treatment used
in medical practice; our plans to provide additional insights into
and information with respect to our azenosertib clinical program
and the franchise potential for azenosertib, and the timing and
content thereof; future initiation of clinical studies and the
expected timing thereof; the potential for synergy of WEE1
inhibition with chemotherapy in patients with Cyclin E1+ tumors;
plans to advance azenosertib in the clinic; and the potential
benefits of the design of azenosertib. The terms “continuing,”
“design,” “encouraging,” “expects,” “look forward,” “plan,”
“potential,” “promising,” “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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