Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC) (NASDAQ:CYCCP)
("Cyclacel" or the "Company"), a biopharmaceutical company
developing oral therapies that target the various phases of cell
cycle control for the treatment of cancer and other serious
disorders, today announced results from a Phase 1 safety,
pharmacokinetic and pharmacodynamic study of CYC065, the Company’s
novel cyclin dependent kinase, or CDK2/9 inhibitor, in patients
with advanced cancers. Data were reported at an oral presentation
on Sunday, April 15, at 3:35 PM CT at the American Association for
Cancer Research (AACR) Annual Meeting held in Chicago, IL.
“Our findings show that CYC065 is effective in
suppressing the cancer survival protein Mcl-1 in peripheral blood
for at least 24 hours,” said Geoffrey Shapiro, MD, PhD, Director,
Early Drug Development Center, Dana-Faber Cancer Institute and
Professor of Medicine, Harvard Medical School, Boston, MA. “The
durable target inhibition achieved at the recommended Phase 2 dose
provides a rationale to further evaluate this novel agent in Mcl-1,
MYC or cyclin E amplified tumors.”
"The clinical data support biomarker-driven
clinical development of CYC065 in selected patient populations,"
said Spiro Rombotis, President and Chief Executive Officer of
Cyclacel. "In addition, the durable suppression of the Mcl-1
survival protein presents an exciting opportunity to combine CYC065
with other agents targeting the apoptosis pathway, such as
venetoclax. We will soon be starting a clinical study testing
CYC065 in combination with venetoclax in patients with
relapsed/refractory chronic lymphocytic leukemia."
Details of the Phase 1
study
The objective of part 1 of the Phase 1 dose
escalating, monotherapy, first-in-human study was to evaluate
safety, pharmacokinetics (PK), pharmacodynamics (PD) and identify
RP2D. Certain features of the trial are as follows:
- 26 heavily treated patients with various advanced solid tumors
were enrolled;
- The trial advanced through seven DL cohorts with a range of 8
to 288 mg/m2/day, administered as a 4-hour intravenous infusion
once every 3 weeks;
- Dose limiting toxicity at DL7 was reversible neutropenia,
febrile neutropenia and diarrhea;
- Thirteen patients were treated at DL6;
- PK parameters have demonstrated increases in CYC065 exposure
with increasing dosing levels;
- A biologically effective dose was established from analysis of
surrogate tissue, supporting a RP2D of 192 mg/m2/day;
- Consistent Mcl-1 suppression over 24 hours after a single dose
was observed in 11 out of 13 patients at DL6;
- Clinical response was reported in patients with Mcl-1 (ovarian
cancer, parotid acinic cell carcinoma), MYC (uterine
carcinosarcoma, ovarian cancer) and cyclin E (ovarian cancer)
amplified tumors; and
- Stable disease was best response, longest response
approximately one year.
Having successfully achieved the objectives of
part 1 of the study, part 2 has been initiated to evaluate CYC065
in a more intensive schedule for 2 days per week for 2 weeks of a
three week cycle. Part 2 will enroll patients with advanced
cancers to evaluate efficacy in Mcl-1, MYC and cyclin E amplified
cancers. The Company also plans to initiate a clinical study in
patients with chronic lymphocytic leukemia in combination with
venetoclax, a Bcl-2 inhibitor, where durable suppression of Mcl-1
may be beneficial.
Details of the oral presentation are as
follows:
Title: |
|
Phase
I safety, pharmacokinetic and pharmacodynamic study of CYC065, a
cyclin dependent kinase inhibitor, in patients with advanced
cancers (NCT02552953) |
Presenter/Authors: |
|
K. T.
Do, N. Chau, A. Wolanski, B. Beardslee, F. Hassinger, K. Bhushan,
S. Pruitt-Thompson, A. Scotton, S. Frame, D. I. Zheleva, D. Blake,
J. Chiao, G. I. Shapiro. |
Category: |
|
Phase
I Adult Clinical Trials |
Session: |
|
CTMS01
- New Treatment Approaches for Breast and Ovarian Cancer |
Abstract #: |
|
CT037 |
Location: |
|
Room
N427 - McCormick Place North (Level 4) |
Date and Time: |
|
Sunday, April 15, 2018, 3:35 PM |
About CYC065
CYC065, a second generation CDK2/9 inhibitor, is
being evaluated in a first-in-human, Phase 1 trial in patients with
advanced solid tumors. It is mechanistically similar but has higher
dose potency, in vitro and in vivo, and improved properties
compared to seliciclib, a first generation CDK inhibitor. Similarly
to FDA approved CDK4/6 inhibitors, CYC065 may be most useful in
combination with other anticancer drugs, including Bcl-2
inhibitors, such as venetoclax, or HER2 inhibitors, such as
trastuzumab. Preclinical data show that CYC065 may benefit
patients with adult and pediatric hematological malignancies,
including acute myeloid leukemias (AML), acute lymphocytic
leukemias (ALL), and in particular those with MLL rearrangements,
chronic lymphocytic leukemias (CLL), B-cell lymphomas, multiple
myelomas, and certain solid tumors, including breast and uterine
cancers, and neuroblastomas.
About Cyclacel Pharmaceuticals,
Inc.
Cyclacel Pharmaceuticals is a clinical-stage
biopharmaceutical company using cell cycle, transcriptional
regulation and DNA damage response biology to develop innovative,
targeted medicines for cancer and other proliferative diseases.
Cyclacel's transcriptional regulation program is evaluating CYC065,
a CDK inhibitor, in patients with advanced cancers. The DNA damage
response program is evaluating a sequential regimen of sapacitabine
and seliciclib, a CDK inhibitor, in patients with BRCA positive,
advanced solid cancers. Cyclacel's strategy is to build a
diversified biopharmaceutical business focused in hematology and
oncology based on a pipeline of novel drug candidates. For
additional information, please visit www.cyclacel.com.
Forward-looking Statements
This news release contains certain
forward-looking statements that involve risks and uncertainties
that could cause actual results to be materially different from
historical results or from any future results expressed or implied
by such forward-looking statements. Such forward-looking statements
include statements regarding, among other things, the efficacy,
safety and intended utilization of Cyclacel's product candidates,
the conduct and results of future clinical trials, plans regarding
regulatory filings, future research and clinical trials and plans
regarding partnering activities. Factors that may cause actual
results to differ materially include the risk that product
candidates that appeared promising in early research and clinical
trials do not demonstrate safety and/or efficacy in larger-scale or
later clinical trials, trials may have difficulty enrolling,
Cyclacel may not obtain approval to market its product candidates,
the risks associated with reliance on outside financing to meet
capital requirements, and the risks associated with reliance on
collaborative partners for further clinical trials, development and
commercialization of product candidates. You are urged to consider
statements that include the words "may," "will," "would," "could,"
"should," "believes," "estimates," "projects," "potential,"
"expects," "plans," "anticipates," "intends," "continues,"
"forecast," "designed,\" "goal," or the negative of those words or
other comparable words to be uncertain and forward-looking. For a
further list and description of the risks and uncertainties the
Company faces, please refer to our most recent Annual Report on
Form 10-K and other periodic and other filings we file with the
Securities and Exchange Commission and are available at
www.sec.gov. Such forward-looking statements are current only as of
the date they are made, and we assume no obligation to update any
forward-looking statements, whether as a result of new information,
future events or otherwise.
Contacts |
Company: |
|
Paul McBarron, (908)
517-7330, pmcbarron@cyclacel.com |
Investor
Relations: |
|
Russo Partners LLC,
Alexander Fudukidis, (646) 942-5632,
alex.fudukidis@russopartnersllc.com |
© Copyright 2018 Cyclacel Pharmaceuticals, Inc. All
Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks of
Cyclacel Pharmaceuticals, Inc.
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