Cyclacel Pharmaceuticals Announces Completion of Enrollment in the Biomarker-Enriched Patient Cohort of Its Phase 2 Study

- Patients are preselected for CDKN2A and/or CDKN2B abnormalities -

- Safety and efficacy data to be reported at an upcoming oncology medical conference -

BERKELEY HEIGHTS, N.J., Sept. 25, 2024 (GLOBE NEWSWIRE) -- Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC, NASDAQ:CYCCP, ", Cyclacel", or the ", Company", ))), a biopharmaceutical company developing innovative cancer medicines, today announced that enrollment of 12 patients has been completed as per protocol in Cohort 8 of its Phase 2 stage, proof of concept 065-101 study of fadraciclib ("fadra"), a CDK2/9 inhibitor, in patients with advanced solid tumors and lymphoma. Enrollment of Cohort 5 in patients with T-Cell Lymphoma is continuing.

"We are pleased to report that the Cyclacel team has achieved another important milestone by completing enrollment of the patient cohort with CDKN2A/B abnormalities," said Spiro Rombotis, President and Chief Executive Officer. "The rapid pace of enrollment of approximately six months, since opening the cohort in mid-May, underscores the great unmet medical need of cancer patients with CDKN2A/B abnormalities. Updated safety and efficacy data from the 065-101 study of fadra has been accepted for presentation during the upcoming 36^th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024, October 23-25, 2024)."

"We are grateful to the patients and their families, international investigator group and our collaborators participating in the 065-101 study for their support in achieving target enrollment of Cohort 8," said Brian Schwartz, M.D., interim Chief Medical Officer. "We are excited to observe stable disease and tumor shrinkage in a Phase 2 squamous cell cancer patient with unknown primary and CDKN2A abnormalities after two cycles of fadra oral tablets. As previously reported at ASCO 2024, in the Phase 1 study of oral fadra a patient with squamous non-small cell lung cancer (NSCLC) and CDKN2A/B abnormalities achieved 22% reduction in tumor burden at 4 weeks per RECIST 1.1 criteria. We expect to report more mature data as additional patients from Cohort 8 get scanned and followed up."

065-101 Study of Oral Fadraciclib

The Phase 2 part of the 065-101 study of oral fadra, a CDK2/9 inhibitor, is designed to evaluate fadra safety and efficacy in up to 8 cohorts defined by histology and/or biomarkers of interest. The 7 histology-based cohorts include: Cohort 1: endometrial and ovarian; 2: cholangiocarcinoma or biliary tract; 3: hepatocellular; 4: breast, including HR positive, HER2 negative, triple negative, and HER-2 positive; 5: T-Cell lymphoma; 6: B-Cell lymphoma; and 7: colorectal cancers. Cohort 8 is biomarker selected, specifically including patients with CDKN2A and/or CDKN2B abnormalities. The Phase 2 part of the study employs a Simon 2-stage design and is powered to demonstrate response in the molecular subtype suggested by the Phase 1 data and others that may be sensitive.

The Phase 1 dose escalation part of the study enrolled a total of 48 unselected, all comer patients with advanced solid tumors and lymphoma who were treated with oral fadra as monotherapy. Recommended Phase 2 dose (RP2D) was determined as 100mg twice daily for 5 days per week, 4 out of 4 weeks.

To date single agent activity with oral or intravenous fadra, including CR, PR and SD, has been observed in patients with advanced endometrial, squamous NSCLC lung cancer and T-cell lymphoma. Encouraging signals of activity were observed in patients with advanced cervical, hepatocellular, ovarian and pancreatic cancers.

The Company believes that fadra's inhibition of CDK2 and CDK9 may be superior to inhibiting either CDK2 or CDK9 alone. Fadra tablets can be given orally with repeat dosing which has led to transient suppression of anti-apoptosis proteins with generally good tolerability and no Grade 3 or higher hematological toxicity in the first cycle.

CDKN2A, CDKN2B Abnormalities

The most frequent CDKN2A or CDKN2B abnormalities are deletions or loss of function. CDKN2A gene deletions occur in over 40% of several solid tumors, including glioma, head and neck, pancreatic, esophageal, lung (incl. squamous), bladder, melanoma, and others. CDKN2B deletions occur in over 30% of several solid tumors, including bladder, glioma, pancreatic, esophageal, lung (incl. squamous), head and neck, melanoma, and others.¹

About Cyclacel Pharmaceuticals, Inc.

Cyclacel is a clinical-stage, biopharmaceutical company developing innovative cancer medicines based on cell cycle, transcriptional regulation and mitosis biology. The transcriptional regulation program is evaluating fadraciclib, a CDK2/9 inhibitor, and the anti-mitotic program plogosertib, a PLK1 inhibitor, in patients with both solid tumors and hematological malignancies. Cyclacel's strategy is to build a diversified biopharmaceutical business based on a pipeline of novel drug candidates addressing oncology and hematology indications. 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, among other things, statements related to Cyclacel's future plans and prospects, Cyclacel's anticipated cash runway and the planned timing of data results and continued development of fadraciclib. Factors that may cause actual results to differ materially include market and other conditions, 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, the risks associated with reliance on collaborative partners for further clinical trials, development and commercialization of product candidates and Cyclacel's ability to regain and maintain compliance with Nasdaq's continued listing requirements. 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.

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1</sup> www.cbioportal.org.