Cyclacel Pharmaceuticals, Inc. (Nasdaq: CYCC) (Nasdaq: CYCCP)
(Cyclacel or the Company), a biopharmaceutical company developing
innovative medicines based on cancer cell biology, announced
clinical data demonstrating safety, anti-tumor activity and good
oral bioavailability of Cyclacel's CDK2/9 inhibitor
fadraciclib in patients with advanced solid tumors. The data were
presented at an oral presentation at the Plenary Session of
the 32nd EORTC-NCI-AACR (ENA) Symposium 2020 held virtually
on October 24-25, 2020.
"In addition to good oral bioavailability, we
are pleased to report a durable PR with continuing shrinkage of
target lesions reaching 92% in a patient with MCL1 amplified
endometrial cancer. Four other patients achieved stable disease,"
said Spiro Rombotis, Chief Executive Officer of Cyclacel. “The
data support clinical development of fadraciclib in our planned
Phase 1b/2a study in advanced endometrial and ovarian cancer and
CDK4/6 inhibitor resistant breast cancer. Along with safety and
efficacy the study will evaluate cyclin E, MCL1 and/or MYC
biomarkers which are relevant to fadraciclib’s mechanism of action.
In addition to our studies in solid tumors we are encouraged by
evidence of antileukemic activity in our studies of fadraciclib in
hematological malignancies. We are looking forward to reporting
updated data from ongoing studies of fadraciclib and CYC140, our
selective PLK1 inhibitor.”
Presentation
Highlights: Phase 1 Safety,
Pharmacokinetic and Pharmacodynamic Study of Fadraciclib (CYC065),
a Cyclin-Dependent Kinase Inhibitor, in Patients with Advanced
Cancers
Twenty-four heavily pretreated patients with
various advanced solid tumors, including ovarian,
endometrial/uterine, breast, and fallopian cancer, were enrolled in
part 2 with intravenous (i.v.) administration and five patients in
part 3 with oral administration of this ongoing Phase 1, open
label, dose escalation study.
Primary Objective:
- Determine MTD and recommended phase 2
dose (RP2D)
Secondary Objectives:
- Evaluate pharmacokinetics
- Assess pharmacodynamic markers
Design:
- Administration schedule of flat dosing
schedule of single-agent fadraciclib (CYC065) given either by
1-hour infusion or orally on days 1, 2, 8 and 9 every 3 weeks
Safety:
- The trial advanced through four dose
levels (DL) with a range of 90mg to 213mg, administered as a 1-hour
intravenous infusion on days 1, 2, 8 and 9 and two DL with a range
of 75mg to 150mg as an orally administered formulation on days 1,
2, 8 and 9; both in 3-week cycles.
- Eleven patients were treated at DL4
(213 mg). Dose limiting toxicity at DL4 was reversible neutropenia.
The 160mg dose level is being expanded to define RP2D.
- No major or unexpected toxicities were
observed.
Efficacy (n=24, i.v. formulation only):
- One confirmed partial response and two
stable disease (SD) out of 11 patients on 213mg i.v.
formulation:• PR after a month and a half on fadraciclib:
MCL1-amplified endometrial cancer; failed seven lines of prior
therapy; continuing treatment for more than 16 months with 92%
reduction in target tumor lesions.• SD: Cyclin E amplified
ovarian cancer with 29% tumor shrinkage after four months.•
SD: Fallopian tube adenocarcinoma (undetermined protein
level).
Pharmacokinetics (PK):
- Increases in fadraciclib exposure with
increasing dosing levels.
- High oral bioavailability and
comparable PK profile after oral or 1 hour-infusion
administration.
The presentation was part of the
32nd EORTC-NCI-AACR (ENA) Symposium 2020 and is available on
the "Presentation and Events" section of the Cyclacel website
at https://investor.cyclacel.com/events-and-presentations/events.
Presentation
Details:
Title: Phase 1 safety,
pharmacokinetic and pharmacodynamic study of fadraciclib (CYC065),
a cyclin dependent kinase inhibitor, in patients with advanced
cancers (NCT02552953)Session Title: Late
Breaking and Best Proffered Papers Session Date and
Time: Saturday 24 October 15:05
CETPresentation Number: ORAL-002
About Cyclin-Dependent Kinases and
Fadraciclib
Cyclin-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. Fadraciclib is a potent
orally and intravenously available inhibitor of CDK2 and CDK9.
Fadraciclib is in an ongoing Phase 1,
first-in-human study in patients with advanced solid tumors. In
part 1 of the study, target engagement and durable suppression of
the MCL1 biomarker were observed after a single dose of fadraciclib
by 4-hour infusion. Tumor shrinkage and stable disease were
observed in five patients with cyclin E, MCL1 or MYC amplified
advanced cancers treated at the RP2D. In the ongoing part 2 of the
study evaluating a more intensive dosing regimen, a heavily
pretreated patient with MCL1 amplified endometrial cancer achieved
a radiographically confirmed partial response (PR) after a month
and a half on fadraciclib. This patient continues on therapy for
more than a year and reduction in her target tumor lesions has
reached 92%. An additional patient with cyclin E amplified ovarian
cancer achieved stable disease with 29% tumor shrinkage. Part 3 is
investigating an oral dose formulation.
Fadraciclib is also being evaluated in Phase 1
combination studies with venetoclax in relapsed or refractory CLL
and in relapsed or refractory AML or MDS. Similarly
to FDA-approved CDK4/6 inhibitors, fadraciclib may be most
useful in combination with other anticancer drugs, including BCL2
inhibitors, such as venetoclax, or HER2 inhibitors, such as
trastuzumab. Preclinical data suggest that fadraciclib 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 certain forms of breast cancer, neuroblastoma,
ovarian cancer and uterine serous carcinoma.
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 fadraciclib as a single agent in solid tumors and in
combination with venetoclax in patients with relapsed or refractory
AML/MDS and CLL. The anti-mitotic program is evaluating CYC140, a
PLK1 inhibitor, in advanced leukemias/MDS patients. The DNA damage
response program is evaluating an oral combination of sapacitabine
and venetoclax in patients with relapsed or refractory AML/MDS. An
investigator-sponsored trial (IST) is evaluating an oral
combination of sapacitabine and olaparib in patients with BRCA
mutant breast cancer. Cyclacel's strategy is to build a diversified
biopharmaceutical business focused on 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 Cyclacel files with
the Securities and Exchange Commission which are available at
www.sec.gov. Such forward-looking statements are current only as of
the date they are made, and Cyclacel assumes 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, Eric Ando, (646) 218-4604,
eric.ando@russopartnersllc.com |
© Copyright 2020 Cyclacel Pharmaceuticals, Inc.
All Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks
of Cyclacel Pharmaceuticals, Inc.
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