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 initial efficacy and safety
data from the Phase 1 dose-escalation portion of its ongoing Phase
1/2 clinical trial of ZN-c3 in patients with advanced solid tumors
who are refractory to or ineligible for standard therapy or for
whom no standard therapy is available. Initial results showed that
monotherapy ZN-c3 use resulted in Exceptional Responses in heavily
pre-treated patients in a range of solid tumors, including Partial
Responses (PRs) in ovarian cancer, colorectal cancer, non-small
cell lung carcinoma and uterine serous carcinoma. Data were
reviewed as a late-breaking abstract during the American
Association of Cancer Research (AACR) Annual Meeting, being held
virtually April 10-15, 2021 and May 17-21, 2021.
“The initial clinical data on our WEE1 inhibitor are extremely
promising and showcase ZN-c3’s strong potential to improve outcomes
in patients with advanced solid tumors who have exhausted available
treatment options,” commented Dr. Anthony Sun, Chairman and Chief
Executive Officer of Zentalis. “Our WEE1 candidate, which we
believe is potentially a best-in-class small molecule, demonstrated
favorable safety results with a wide therapeutic window, and
resulted in Partial Responses in five patients with a range of
cancers. Having identified a recommended dose for future studies,
we look forward to advancing clinical trials in a larger number of
patients, as well as novel biomarkers that may help select patients
who are likely to respond to treatment with ZN-c3. We are looking
to make Exceptional Responses commonplace.”
Initial Efficacy and Safety Data
In the Phase 1 dose-escalation trial, ZN-c3 was dosed starting
at 25 mg and going as high as 450 mg QD in patients with advanced
or metastatic solid tumors. At the time of the data cutoff on
February 12, 2021, 55 patients were evaluated for safety, the
primary endpoint. The study remains ongoing and based on the data
presented at AACR, ZN-c3 generated 5 Partial Responses.
Best Overall Responses:
- Two confirmed PRs in ovarian
cancer and colorectal cancer (CRC) patients
- After receiving 18 prior lines of
therapy, 11 prior lines in the advanced metastatic setting, a
patient with Stage IV ovarian cancer had a RECIST-confirmed PR with
a 56% reduction in overall target lesions. The patient also
experienced a large rapid drop in CA-125 from 610 kU/L at baseline
to 125 kU/L within 4 weeks on treatment, with her CA-125 level
normalizing 3 weeks later. The patient was on study for 186 days
and remains on study drug.
- After receiving 5 prior lines of
therapy in the advanced metastatic setting, a patient with Stage IV
CRC had a RECIST-confirmed PR with a 42% reduction in overall
target lesions, as well as a rapid decrease in CEA tumor marker
from 327 ng/mL at baseline to <50 ng/mL after 3 weeks on
treatment. The patient remained on study for 169 days until
clinical disease progression.
- In addition, three unconfirmed
PRs—one in non-small cell lung carcinoma (NSCLC) and two in uterine
serous carcinoma (USC) patients
- After receiving 3 prior lines of
therapy in the advanced metastatic setting, a patient with Stage IV
NSCLC had an unconfirmed (per RECIST) PR with a 50% reduction in
overall target lesions. The patient was on study for 145 days and
remains on study drug.
ZN-c3 was generally well-tolerated as a single agent. As of the
cutoff date, the most common treatment-related adverse events were
mainly Grade 1/2, including nausea (49.0% of patients), diarrhea
(32.7% of patients), fatigue (29.0% of patients) and vomiting
(29.0% of patients) across all doses. Significant hematological
adverse events were limited; treatment-related white blood cell
count decrease / neutropenia (7.2% all Grades, 3.6% Grade ≥3),
anemia (7.2% all Grades, 5.4% Grade ≥3) and thrombocytopenia (7.2%
all Grades, 3.6% Grade ≥3).
Results from this study indicate that an oral dose of 300 mg QD
with continuous dosing is the recommended Phase 2 dose of ZN-c3
when used as a monotherapy. The 300 mg QD dose demonstrated high
plasma exposure levels, while minimizing adverse events. In
addition, the pharmacodynamic marker of pCDK1 levels in skin punch
biopsies showed active target engagement at relevant
pharmacological doses. The Company initiated the Phase 1 expansion
portion of the trial with the 300 mg QD dose earlier in 2021 and is
exploring this candidate’s potential in combination trials
including in ovarian cancer and osteosarcoma. Using this
recommended dose, Zentalis will also coordinate with Zentera
Therapeutics, Zentalis’ majority-owned joint venture, to initiate a
Phase 1b trial investigating ZN-c3 as a single agent in China.
“WEE1 is a promising target for cancer therapy, and this dataset
provides further validation on the importance of candidates like
ZN-c3 that are designed to inhibit the DNA damage checkpoint,
resulting in tumor cell death,” said Dr. Anthony Tolcher, CEO,
Founder and Director of Clinical Research at NEXT Oncology. “ZN-c3
was shown to be tolerable in this heavily pretreated patient
population. Furthermore, this candidate’s early signals of
anti-tumor activity are very exciting, and I am even more
optimistic that WEE1 inhibition may become an important treatment
approach for a wide range of cancers.”
KOL Webcast Event:
Zentalis will host a webcast event with key opinion leaders
Monday, April 12, 2021 at 4:00 p.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 ZN-c3
ZN-c3 is an oral inhibitor of WEE1 in development for the
treatment of advanced solid tumors. The inhibition of WEE1, a DNA
damage response protein, aims to generate sufficient DNA damage in
cancer cells, causing cell death, thereby preventing tumor growth
and potentially causing tumor regression. Zentalis is currently
conducting a Phase 1/2 clinical trial in patients with advanced
solid tumors and reported initial data from the Phase 1 portion at
the AACR Annual Meeting 2021. In addition, the Company is also
conducting a Phase 1b trial evaluating ZN-c3 in combination with
chemotherapy in patients with advanced ovarian cancer, with plans
to initiate a Phase 1/2 in combination with chemotherapy in
osteosarcoma and a Phase 2 trial investigating ZN-c3 as a
monotherapy in patients with uterine serous carcinoma in 2021.
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, plans and
timing for the initiation of and the release of data from our
clinical trials and our ability to meet other key milestones, and
our participation in upcoming events and presentations. 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
outbreak of the novel coronavirus disease, COVID-19, 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 candidate; 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; interim, initial, “topline”,
and preliminary data from our clinical trials that we announce or
publish from time to time may change as more patient data become
available and are subject to audit and verification procedures that
could result in material changes in the final data; 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 Annual Report on Form 10-K for the year ended
December 31, 2020 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:Thomas HoffmannSolebury
Trout1.646.378.2931thoffmann@soleburytrout.com
Media Contact:Julia DeutschSolebury
Trout1.646.378.2967jdeutsch@soleburytrout.com
Zentalis Pharmaceuticals (NASDAQ:ZNTL)
Historical Stock Chart
From Mar 2024 to Apr 2024
Zentalis Pharmaceuticals (NASDAQ:ZNTL)
Historical Stock Chart
From Apr 2023 to Apr 2024