Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC) (NASDAQ:CYCCP)
(Cyclacel or the Company), 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, announced today the
selection of a recommended Phase 2 dose (RP2D) from part 1 of a
dose-escalating, Phase 1, first-in-human, clinical study of CYC065,
a Cyclin Dependent Kinase (CDK) 2/9 inhibitor. RP2D was determined
to be dosing level 6 which enrolled 9 evaluable patients with
advanced cancers. Prolonged reduction of the Mcl-1 biomarker was
observed in 7 out of the 9 patients for at least 24 hours following
a single dose of CYC065, which was generally well tolerated.
Preliminary anticancer activity was observed in three patients with
Mcl-1, MYC and Mcl-1/cyclin E amplified cancers.
“Our early clinical results and selection of
RP2D support progressing clinical evaluation of CYC065 in selected,
molecularly-defined, patient populations,” said Spiro Rombotis,
President and Chief Executive Officer of Cyclacel. “Durable
reduction of Mcl-1 expression in the majority of patients at RP2D
is an important differentiator, as other CDK inhibitors only do so
transiently. Like other CDK inhibitors, we expect CYC065 to work
best in combination with existing anticancer drugs. Indications of
anticancer activity after a single dose of CYC065 alone in patients
with molecular features related to the drug’s mechanism are
unexpected and potentially exciting. We plan to apply part of
the net proceeds from our July financing to progress CYC065
studies, alone and in combinations, in both liquid and solid
cancers with such molecular features. There are currently no drugs
available for patients with such features. Our highest
priority is to finalize designs for a Phase 1/2 study testing
CYC065 in combination with venetoclax, a Bcl-2 inhibitor approved
for chronic lymphocytic leukemia, where we believe Mcl-1
suppression will be beneficial, while in parallel enrolling a new
part 2 of the Phase 1 study in patients with advanced solid
tumors.”
Phase 1 first-in-human
trial
The objective of part 1 of the Phase 1 dose
escalating, monotherapy study was to evaluate safety,
pharmacokinetics (PK), pharmacodynamics (PD) and identify RP2D.
Certain key features of the trial are as follows:
- 24 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;
- Ten patients were treated at DL6, of which 9 are evaluable at
present;
- PK parameters have demonstrated dose proportional 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 7 out of 9 evaluable patients at DL6; and
- Anticancer activity was reported by the investigators in
patients with Mcl-1 (ovarian cancer: reduction of CA-125 tumor
marker levels), MYC (larynx: radiographic tumor shrinkage) and
Mcl-1/cyclin E (ovarian: radiographic tumor shrinkage) amplified
tumors
Having successfully achieved the objectives of part 1 of the
study, part 2 of the study has been initiated aiming to enroll
patients with advanced solid tumors, and in particular cyclin E
amplified tumors. Such tumors include subsets of high grade
serous ovarian and uterine cancers. Part 2 will evaluate
CYC065 in a more intensive schedule for 2 days per week for 2 weeks
of a three week cycle. Biospecimens will be collected for
assessment of biomarkers related to CYC065’s mechanism of
action.
About CYC065Cyclacel's second
generation CDK2/9 inhibitor, CYC065, is being evaluated in an
ongoing, first-in-human, Phase 1 trial in patients with advanced
solid tumors. In part 1, CYC065 was well tolerated, there were
robust and durable effects on the Mcl-1 biomarker and the
recommended Phase 2 dose has been selected. Evidence of target
engagement was observed by decreases in target cyclin-dependent
kinase substrate phosphorylation accompanied by robust and
prolonged Mcl-1 suppression in peripheral blood cells in patient
samples from the study, consistent with the Company's preclinical
data. CYC065 is mechanistically similar but has much higher dose
potency, in vitro and in vivo, and improved metabolic stability
than seliciclib, Cyclacel's first generation CDK inhibitor.
As with palbociclib, the first CDK inhibitor approved by FDA in
2015, and ribociclib approved in 2017, CYC065 may be most useful in
combination with other anticancer agents, including Bcl-2
antagonists, such as venetoclax, or HER2 inhibitors, such as
trastuzumab.
CYC065 is a highly-selective, orally- and
intravenously-available, second generation inhibitor of CDK2 and
CDK9. It causes apoptotic death of cancer cells at
sub-micromolar concentrations. Antitumor efficacy has been achieved
in vivo with once a day oral dosing at well tolerated doses in
preclinical models. Evidence from published nonclinical studies
show that CYC065 may benefit patients with adult and pediatric
hematological malignancies, including certain Acute Myeloid
Leukemias (AML), Acute Lymphocytic Leukemias (ALL), Chronic
Lymphocytic Leukemias (CLL), B-cell lymphomas, multiple myelomas,
and certain solid tumors, including breast and uterine cancers and
neuroblastomas. Independent investigators published nonclinical
evidence that CYC065 induced regression or tumor growth inhibition
in a model of HER2-positive breast cancer addicted to cyclin E that
is resistant to trastuzumab, reduced tumor growth in models of
CCNE1-amplified uterine serous carcinoma and reduced tumor burden
and prolonged survival in several neuroblastoma models in vivo.
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 is analyzing stratified and
exploratory subgroups from a Phase 3 study of sapacitabine in
elderly patients with AML. 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.
© Copyright 2017 Cyclacel Pharmaceuticals, Inc. All Rights
Reserved. The Cyclacel logo and Cyclacel® are trademarks of
Cyclacel Pharmaceuticals, Inc.
Contacts
Company: Paul McBarron, (908) 517-7330, pmcbarron@cyclacel.com
Investor Relations: Russo partners LLC, Alexander Fudukidis, (646) 942-5632, alex.fudukidis@russopartnersllc.com
Cyclacel Pharmaceuticals (NASDAQ:CYCC)
Historical Stock Chart
From Apr 2024 to May 2024
Cyclacel Pharmaceuticals (NASDAQ:CYCC)
Historical Stock Chart
From May 2023 to May 2024