Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP)
("Cyclacel" or the "Company"), a biopharmaceutical company
developing innovative medicines based on cancer biology, today
announced study design and preliminary data from two of the
Company’s Phase 1 studies evaluating a combination of CYC065, a
CDK2/9 inhibitor, with venetoclax, a BCL2 inhibitor, to treat
patients with relapsed or refractory (R/R) acute myeloid leukemia
(AML) or myelodysplastic syndromes (MDS) and chronic lymphocytic
leukemia (CLL) respectively. The data were presented on Saturday
December 7, 2019 at poster presentations during the 61st American
Society of Hematology Annual Meeting and Exposition in Orlando,
Florida.
“We are excited to report initial data from our
ongoing clinical evaluation of the combination regimen of CYC065
and venetoclax in patients with advanced leukemias,” said Spiro
Rombotis, President and Chief Executive Officer of Cyclacel. “The
rationale behind these two dose escalation studies is to
investigate a ‘dual hit’ strategy of simultaneously suppressing
MCL1 and BCL2 proteins. Suppression of these ‘pro-survival’
proteins is thought to enable apoptosis in cancer cells that have
become resistant to previous treatment. Preliminary evidence
suggests that the combination is active and well tolerated. Our
clinical program seeks to translate preclinical evidence of synergy
with the combination to benefit patients with relapsed or
refractory diseases.”
The CYC065-venetoclax combination was well
tolerated and no dose-limiting toxicities have been reported. No
tumor lysis syndrome was observed. Three of nine patients with R/R
AML/MDS enrolled in CYC065-03 at doses from 64 to 150mg/m2 achieved
decreases in leukemia blast cells in their peripheral blood as
reported by investigators. The first two R/R CLL patients enrolled
in CYC065-02 both failed ibrutinib and one also failed CAR-T cell
treatment. Both patients achieved shrinkage of enlarged lymph nodes
by CT scan on the combination of venetoclax and CYC065 dosed once
every two weeks at 64mg/m2. The patient who failed CAR-T cell
therapy was MRD negative on the combination.
CYC065 dosed once every three weeks has
demonstrated durable suppression of MCL1 in part 1 of a Phase 1
study in a majority of solid tumor patients treated at the
recommended Phase 2 dose (RP2D). In the ongoing part 2 of the same
study CYC065 is dosed four times every three weeks. One patient
with MCL1 amplified endometrial cancer has achieved a
radiographically confirmed partial response (PR) and a patient with
cyclin E amplified ovarian cancer has achieved shrinkage of target
tumor lesions of 20% after treatment with CYC065 as a single
agent.
The combination of CYC065 and venetoclax has
demonstrated preclinical synergy in both AML and CLL (including 17p
deleted) models. In AML/MDS upregulation of MCL1 is associated with
resistance to chemotherapy and/or venetoclax. In CLL upregulation
of MCL1 is thought to be an escape mechanism for venetoclax treated
cells.
Phase 1 CYC065-02 Study Details
(NCT03739554)
This ongoing clinical study is investigating a
combination of CYC065 with venetoclax in patients with
relapsed/refractory CLL. CYC065 is being administered intravenously
via four-hour infusion on days 1 and 15 in combination with daily
oral venetoclax. Initial dose escalation is 33% and 25% upon
occurrence of the first dose limiting toxicity (DLT). The primary
objective is determination of RP2D defined as the highest dose
level at which less than one-third of at least six patients
experience a DLT during the first treatment cycle. Treatment will
continue until progression of disease, unacceptable toxicity or
changes in patient condition that renders patients ineligible for
further treatment. Laboratory tests and CT scans will be performed
regularly to assess response according to standard criteria.
Phase 1 CYC065-03 Study Details
(NCT04017546)
This ongoing clinical study is investigating a
combination of CYC065 with venetoclax in patients with
relapsed/refractory AML or MDS. CYC065 is being administered
intravenously via four-hour infusion on days 1 and 15 in
combination with daily venetoclax on days 1 to 15. Initial dose
escalation is 33% and 25% upon occurrence of the first dose
limiting toxicity (DLT). The primary objective is determination of
RP2D defined as the highest dose level at which less than one-third
of at least six patients experience a DLT during the first
treatment cycle. Treatment will continue until progression of
disease, unacceptable toxicity or changes in patient condition that
renders patients ineligible for further treatment. Laboratory tests
and bone marrow aspirate/biopsy will be performed to assess
response according to standard criteria.
Cyclacel’s Presentations Details at ASH
2019
Title: A Phase I Study Combining CDK2/9
Inhibitor CYC065 with Venetoclax, a BCL2 Inhibitor, to Treat
Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)Session
Name: 642. CLL: Therapy, excluding Transplantation: Poster
IPublication Number: 1761
Title: Combining CDK2/9 Inhibitor CYC065 with
Venetoclax, a BCL2 Inhibitor, to Treat Patients with Relapsed or
Refractory AML or MDSSession Name: 616. Acute Myeloid Leukemia:
Novel Therapy, excluding Transplantation: Poster IPublication
Number: 1379
Title: An Oral Combination Study of Novel
Nucleoside Analogue Sapacitabine and BCL2 Inhibitor Venetoclax to
Treat Patients with Relapsed or Refractory AML or MDSSession Name:
Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation:
Poster IIIPublication Number: 3926About
CYC065Cyclin dependent kinases (CDKs) are critical for
cell cycle regulation and transcriptional elongation. Dysregulated
CDKs have been linked to the cancer hallmarks of uncontrolled
proliferation and increased survival. CYC065 is a potent, orally-
and intravenously‐available inhibitor of CDK2 and CDK9. CDK9
regulates transcription of genes through phosphorylation of RNA
polymerase II (RNAP II) C-terminal domain (CTD). Through inhibition
of CDK9, CYC065 suppresses CDK9-dependent gene expression and
reduces the level of MCL1, a key anti-apoptotic protein.
CYC065 is in an ongoing Phase 1, first-in-human
study in patients with advanced solid tumors. In this study, target
engagement and durable suppression of the MCL1 biomarker were
observed after a single dose of CYC065. Tumor shrinkage and stable
disease were observed in five patients with MCL1-, MYC- or cyclin
E-amplified advanced cancers treated at the recommended phase 2
dose. In part 2 of the study evaluating a more intensive dosing
regimen, a confirmed partial response has been observed in a
heavily pretreated patient with MCL1-amplified endometrial cancer.
An oral formulation is being evaluated in part 3 of the study.
CYC065 is also being evaluated in Phase 1 studies in combination
with venetoclax in relapsed or refractory CLL and in relapsed or
refractory AML or MDS. Preclinical data suggest that CYC065 may
benefit patients with adult and pediatric hematological
malignancies such as CLL, AML, ALL, B-cell lymphomas, multiple
myeloma and certain cyclin E-addicted or MYC-amplified solid
tumors, including HER2+ breast cancer, uterine serous carcinoma and
neuroblastoma.
About Cyclacel Pharmaceuticals,
Inc.Cyclacel Pharmaceuticals is a clinical-stage
biopharmaceutical company developing innovative cancer medicines
based on cell cycle, transcriptional regulation and DNA damage
response biology. The transcriptional regulation program is
evaluating CYC065 as a single agent in solid tumors and in
combination with venetoclax in patients with relapsed or refractory
CLL and AML/MDS. The DNA damage response program is evaluating an
oral combination regimen of sapacitabine and venetoclax in patients
with relapsed or refractory AML/MDS. An IST is evaluating an oral
combination regimen of sapacitabine and olaparib in patients with
BRCA mutant breast cancer. The anti-mitotic program is evaluating
CYC140, a PLK1 inhibitor, in AML/MDS patients. 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 StatementsThis
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, Jan Medina, (646) 942-5632 |
|
Jan.Medina@russopartnersllc.com |
© Copyright 2019 Cyclacel Pharmaceuticals, Inc.
All Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks
of Cyclacel Pharmaceuticals, Inc.
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