Zentalis Pharmaceuticals Announces Updates Across its Pipeline Including Promising New Interim Clinical Data on ZN-c3 (WEE1i)...
June 28 2021 - 7:00AM
Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage
biopharmaceutical company focused on discovering and developing
small molecule therapeutics targeting fundamental biological
pathways of cancers, today announced key clinical and regulatory
updates across its pipeline.
“We continue to build substantial value in Zentalis’ portfolio,
driving toward approval of our differentiated cancer therapeutics
to help patients worldwide,” commented Dr. Anthony Sun, Chairman
and Chief Executive Officer of Zentalis. “Based on our clinical
results reported to date, the emerging clinical profiles of our
candidates support the potential for best-in-class positioning for
a range of tumor types addressing large patient populations, is use
as a monotherapy or in combinations. In particular, we are excited
about the compelling profile of ZN-c3, our WEE1 inhibitor, as it
demonstrated additional, deepening and durable tumor responses as a
monotherapy in heavily pretreated solid tumors. These promising
data set the stage for the many upcoming planned trials – two of
which have the potential to be registrational monotherapy studies
in indications with significant unmet medical needs. We look
forward to a productive second half of 2021, as we focus on
delivering on our milestones across our entire pipeline.”
ZN-c3: Oral WEE1 Inhibitor for Solid Tumors
Updates from our ongoing trials of ZN-c3 continue to support the
potential for our WEE1 inhibitor, ZN-c3, to be both first-in-class
and best-in-class. Since our last update at AACR in April 2021, and
as of the data cut-off date of May 15, 2021:
- The 2 unconfirmed Partial Responses
(PRs) reported at AACR were confirmed, bringing the total number of
confirmed PRs from our monotherapy trial from 3 to 5. Since AACR,
an additional unconfirmed PR was reported in a patient with uterine
serous carcinoma (USC), resulting in 3 out of 7 USC patients
enrolled having responded to treatment. Overall, the objective
response rate (ORR) in the USC population increased from 40% to 43%
based on RECIST criteria.
- Additionally, within the exceptional
responder population in the Phase 1 monotherapy trial, we have
observed a patient with an ongoing treatment duration of more than
8 months, with a deepening response of 65% to 69% tumor size
decrease based on RECIST criteria.
- Lower overall severe hematological
adverse event rates – severe neutropenia adverse event rates
decreased from 2.9% to 2.2% with an additional 11 patients enrolled
since AACR 2021.
- Following an End-of-Phase 1 meeting,
the U.S. Food and Drug Administration (FDA) concurred in principle
with the proposal that ZN-c3 has the potential for an accelerated
approval pathway based on the proposed global study design of a
Phase 2 monotherapy trial in women with recurrent or persistent
USC. The trial has initiated with multiple sites open.
- Zentalis is planning to launch a
biomarker-driven Phase 2 study pending FDA feedback. The
tumor-agnostic trial will investigate ZN-c3 in patients with solid
tumors that express the identified predictive biomarker, and is
expected to initiate by year-end.
- ZN-c3 has received orphan drug
designation, and rare pediatric disease designation from the FDA
for pediatric osteosarcoma. The Phase 1/2 trial of ZN-c3 in
combination with chemotherapy in pediatric patients with
osteosarcoma is expected to initiate in 3Q 2021. If ZN-c3 were to
obtain approval for the designated indication, it could be eligible
for a rare pediatric disease priority voucher upon approval.
- Zentalis will also support two
planned additional investigator-initiated trials: a trial with the
Ivy Brain Center in glioblastoma multiforme (GBM) and a trial with
immunotherapy with Dana Farber in triple negative breast
cancer.
- Zentalis’ China JV Zentera is
advancing corresponding clinical trials in China with ZN-c3.
ZN-c5: Oral SERD for ER+/HER2- Advanced or Metastatic
Breast Cancer
Based on the interim results from multiple ongoing trials, ZN-c5
has demonstrated the potential to support best-in-class
tolerability in both monotherapy and combination settings, with
strong clinical results observed. As of May 11, 2021, the following
data were collected:
Monotherapy Trials (Expansion and Dose Escalation)
- In total, 56 patients with 2 median prior lines of treatment
were evaluated for safety and efficacy. Across all doses from 50 mg
QD to 300 mg QD, the observed CBR was 33% and the ORR was 5%. ZN-c5
generated 2 PRs at the 150 mg and 300 mg doses. Adverse events
(AEs) were found in less than 10% of the patients and there were no
observed cases of bradycardia, visual disturbances, QTC or
dizziness. Of note, treatment related diarrhea adverse event rate
was 3.6%, with only grade 1 or 2 events observed. The Phase 2
monotherapy trial has been initiated and Zentalis may take multiple
doses into this study.
- An oral dose of 50 mg QD (n=16) demonstrated a CBR of 40%, with
many patients in this dose cohort remaining on study drug and in
the trial. Final determination of the monotherapy RP2D will occur
following completion of this 50 mg QD dose cohort.
Combination Dose Escalation Trials with Pfizer’s CDK4/6
Palbociclib and Lilly’s CDK4 and 6 Abemaciclib
- Tolerability data for ZN-c5 suggests it could be best-in-class
in oral SERDS, making this candidate ideal for further evaluation
in combination. The two separate trials will continue to enroll
patients and the Company expects to report interim results in 1H
2022 from one or more of these trials.
Window of Opportunity Trial
- The Window of Opportunity trial (n=35) demonstrated ER
degradation across all doses tested.
ZN-d5: Highly Selective Oral BCL-2 Inhibitor for
Hematologic Tumors
- The Phase 1 monotherapy dose-escalation trial, initiated in 4Q
2020, has enrolled 14 patients with relapsed/refractory
non-Hodgkin's lymphoma (NHL) thus far in the fifth dose cohort.
Additionally, no dose-limiting toxicities have been identified.
Patients with acute myeloid leukemia will begin enrollment in 3Q
2021. Interim results from this Phase 1 trial are expected in 1H
2022.
ZN-e4: 3rd Generation
Oral EGFR Inhibitor for Non-Small-Cell Lung Carcinoma
- The Phase 1/2 dose-escalation trial in patients with advanced
non-small cell lung cancer is ongoing with 26 patients (both
osimertinib-naïve and experienced) enrolled to date. ZN-e4 has been
well-tolerated at all doses as of the March 25, 2021 data cut-off,
and clinical activity was identified at doses greater than 80 mg
QD. Interim results from the Phase 1/2 trial are expected in 4Q
2021.
Webcast Event:Zentalis will host a webcast
event today, June 28, 2021 at 8:30 a.m. EDT. To register and access
the event, the webcast link is available on the Investors &
Media section of the Zentalis website at www.zentalis.com.
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. The Company is developing a broad pipeline of
potentially best-in-class oncology candidates, all internally
discovered, which include ZN-c5, an oral selective estrogen
receptor degrader (SERD) for ER+/HER2- breast cancer, ZN-c3, a WEE1
inhibitor for advanced solid tumors, ZN-d5, a BCL-2 inhibitor for
hematologic malignancies, and ZN-e4, an EGFR inhibitor for
non-small cell lung carcinoma (NSCLC). Zentalis has licensed ZN-c5,
ZN-c3 and ZN-d5 to its majority-owned joint venture, Zentera
Therapeutics, to develop and commercialize these candidates in
China. 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 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 without limitation statements
regarding our expectations surrounding the development, potential,
safety, efficacy, and regulatory and clinical progress of our
product candidates in the Unites States and globally, and plans and
timing for the initiation of and the release of data from our
clinical trials and our ability to meet other key milestones. 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: the
COVID-19 pandemic has adversely impacted and may continue to
adversely impact our business, including our preclinical studies
and clinical trials; 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 substantial dependence on the success of
our lead product candidates; failure to identify additional product
candidates and develop or commercialize marketable products; the
early stage of our development efforts; 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 significant costs as a result of
operating as a public company. These and other important factors
discussed under the caption “Risk Factors” in our Quarterly Report
on Form 10-Q for the quarter ended March 31, 2021 filed with the
U.S. Securities and Exchange Commission (SEC) and our other filings
with the SEC could cause actual results to differ materially from
those indicated by the forward-looking statements made in this
press release. 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.
Investor Contact:
Gitanjali Jain Ogawa
Solebury Trout
gogawa@soleburytrout.com
Media Contact:
Julia Deutsch
Solebury Trout
jdeutsch@soleburytrout.com
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