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BERKELEY HEIGHTS, NJ, July 22, 2019 (GLOBE NEWSWIRE) – Cyclacel Pharmaceuticals, Inc. (Nasdaq: CYCC, Nasdaq: CYCCP) ("Cyclacel" or "the Company"), a biopharmaceutical company developing novel cancer biology-based drugs , announced the treatment of the first patient in a phase 1/2 study evaluating the safety and efficacy of oral sapacitabine, a nucleoside badogue, in combination with oral BCL2 inhibitor venetoclax in patients with patients with recurrent or refractory AML or MDS.
"Sapacitabine is an active oral nucleoside badogue in AML and MDS relapsed or refractory to previous therapies, such as cytarabine or hypomethylating agents. The combination of sapacitabine and venetoclax may provide an effective oral treatment for patients failing primary-line treatment, "said Spiro Rombotis, President and CEO of Cyclacel. "We are delighted to follow the hypothesis generated by our SEAMLESS study on the results obtained with a concomitantly administered concomitant oral combination of sapacitabine and venetoclax. This study is the fourth protocol to be part of our strategic alliance with the MD Anderson Cancer Center of the University of Texas in order to evaluate three drug candidates based on Cyclacel in patients with hematologic malignancies ".
The phase 1/2 study (NCT01211457) is intended to include up to 40 patients with recurrent or refractory AML or MDS in order to determine the safety and effectiveness of the badociation. Secondary objectives include duration of response, CR, CRp, RA or major IH, transfusion requirements, number of days of hospitalization, and overall survival.
Preclinical data on combinations of sapacitabine and BCL2 inhibitors in AML
Oral sapacitabine is metabolized to CNDAC, which causes single-strand breaks in the DNA of growing cells, resulting in double-strand breaks and death of cancer cells when DNA is not present. not repaired. The combined effect of CNDAC and the BCL2 inhibitor, ABT-737, has been studied in vitro in AML cellular models. A synergistic increase in the induction of apoptosis of cancer cells was observed when AML MV4-11 cells were simultaneously treated with CNDAC and the BCL2 inhibitor. Treatment with cytarabine and BCL2 inhibitors resulted in a similar synergy (Frame S et al., 14th Congress of the European Association of Hematology, 2009).
About Venetoclax in AML
The FDA has promptly approved venetoclax (ABT-199) tablets in combination with azacitidine or decitabine or low-dose cytarabine for the treatment of newly diagnosed AML in the 75-year-old or older adult. more or with comorbidities preventing any intensive use. induction chemotherapy (Venetoclax PDF Prescription Information). The approval is based on two non-randomized open clinical trials (NCT02203773 and NCT02287233) in which complete remission rates of 54%, 37% and 21% were observed for combinations of decitabine, azacitidine or low dose cytarabine with venetoclax, respectively. Azacitidine, cytarabine and decitabine are nucleoside badogues administered by intravenous or subcutaneous injection. Continued approval of this indication may be contingent upon verification and description of the clinical benefit observed in confirmatory testing.
About clinical studies on sapacitabine in AML / MDS
Sapacitabine is active in relapsed or refractory AML or MDS. In a single dose escalating trial of sapacitabine alone, 11 patients with relapsed or refractory AML or MDS responded (4 CR, 2 CRp, 5 CRi). In a single-agent phase 2 study in 63 patients with MDS who had progressed or relapsed after decitabine or azacitidine, 9 patients responded (2 CR, 2 CRp, 5 major IH).
Sapacitabine as a single agent is active in previously untreated AML. In a randomized Phase 2 trial of sapacitabine in 105 patients 70 years of age or older with untreated or first-time LMA, 28 out of 86 previously untreated patients responded (9 CR, 1 CRp, 3 CRi , 2 PR and 13 IH). In a pilot / main trial of sapacitabine alternating with decitabine, 46 newly diagnosed AML patients aged 70 years or older received the same regimen as the experimental arm of SEAMLESS. Nineteen patients responded (10 CR, 4 PR and 5 HI).
The randomized, open-label Phase 3 study of SEAMLESS included 482 patients aged 70 and over with newly diagnosed AML who were neither candidates nor refused intensive treatment. Patients were stratified by white blood cell count (WBC), hematologic antecedent disease (AHD) and bone marrow blasts and randomized to 1/1 to receive either intravenous decitabine administered alternately with oral sapacitabine or intravenous decitabine alone. The primary endpoint of the evaluation of the demonstration of a statistically significant improvement in overall survival (OS) has not been achieved. A higher CR rate, a secondary endpoint, was observed in the decitabine-sapacitabine arm (17% versus 11%). Other parameters and security were similar between the arms. Layered subgroup badyzes showed that in a large subgroup of patients (n = 319) with low GB, there was a tendency for improvement in SG (HR = 0.84). [0.66, 1.06], p nominal = 0.14) and a significantly higher CR rate (21% versus 9%, nominal p = 0.0017) were observed in favor of decitabine-sapacitabine. The opposite effect was observed in the high WBC subgroup.
About Cyclacel Pharmaceuticals, Inc.
Cyclacel Pharmaceuticals is a clinical-stage biopharmaceutical company that uses the cell cycle, transcriptional regulation and biology of the DNA damage response to develop innovative drugs based on the biology of cancer. Cyclacel's transcriptional regulation program evaluates CYC065, a CDK 2/9 inhibitor, in patients with refractory and relapsed CLL and AML. The recommended dose of CYC065 for phase 2 has been determined in advanced solid tumors and an oral formulation is ready to be evaluated. The DNA Damage Response Program is evaluating a sequential regimen of sapacitabine and seliciclib, a CDK inhibitor, in patients with advanced solid cancer advanced by the BRCA gene. The anti-mitotic program is evaluating CYC140, a PLK1 inhibitor in patients with AML. Cyclacel's strategy is to create a diversified biopharmaceutical company focused on hematology and oncology, based on a portfolio of new drug candidates. For more information, please visit www.cyclacel.com.
Forward-looking statements
This press release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to differ materially from historical results or any future results expressed or implied by such statements. These forward-looking statements include, but are not limited to, statements regarding the effectiveness, safety, and intended use of Cyclacel's product candidates, the conduct and results of future clinical trials, regulatory filing projects, future research and testing. clinics and partnership projects. Among the factors that could cause a significant difference between the actual results and the risk that product candidates that looked promising in early research and clinical trials do not demonstrate the safety and / or efficacy of clinical trials at larger scale or subsequent tests may have difficulties to be recruited, Cyclacel may not obtain authorization to market its product candidates, the risks badociated with dependence on external funding to meet the capital requirements, and the risks badociated with trusting collaborative partners for the continuation of clinical trials, development and commercialization of product candidates. You are urged to consider statements containing the words "may", "will", "could", "could", "should", "believes", "estimates", "plans", "potential", "expects" "," plans "," plans "," intends "," continues "," plans "," intended "," purpose ", or the negative of those words or other comparable words is uncertain and looking to the future. For a more detailed listing and a description of the risks and uncertainties facing the Company, please refer to our most recent annual report on Form 10-K and other periodic and other documents filed with the Securities and Exchange. Commission and are available at www.sec. gov. These forward-looking statements speak only as of the date they are made, and we badume no obligation to update such statements, whether as a result of new information, future events or otherwise.
© Copyright 2019 Cyclacel Pharmaceuticals, Inc. All rights reserved. The Cyclacel and Cyclacel logo® are trademarks of Cyclacel Pharmaceuticals, Inc.
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