Cyclacel opens enrollment of sapacitabine Phase 3 trial for AML

Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the "Company"), today announced that it has opened enrollment of the SEAMLESS pivotal Phase 3 trial for the Company's sapacitabine oral capsules as a front-line treatment of elderly patients aged 70 years or older with newly diagnosed acute myeloid leukemia (AML) who are not candidates for intensive induction chemotherapy. The study is being conducted under a Special Protocol Assessment (SPA) agreement that Cyclacel reached with the U.S. Food and Drug Administration (FDA). SEAMLESS builds on promising 1-year survival observed in elderly patients aged 70 years or older with newly diagnosed AML or AML in first relapse enrolled in a Phase 2 study of single agent sapacitabine.

"The opening of the SEAMLESS study for patient enrollment marks an important milestone for Cyclacel as this is the first pivotal Phase 3 trial ever conducted by the Company," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "If it reaches the market, sapacitabine will become an important treatment option for many elderly patients who are suffering from this life-threatening disease. We also look forward to interim data from the Phase 2 study of sapacitabine in Non-Small Cell Lung Cancer (NSCLC). Sapacitabine may be one of few cancer drugs with activity against both hematological malignancies and solid tumors."

The SEAMLESS study is chaired by Hagop M. Kantarjian, M.D., Chairman and Professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas. SEAMLESS is a multicenter, randomized, Phase 3 study comparing three treatment arms. In Arm A sapacitabine is administered in alternating cycles with decitabine, in Arm B sapacitabine is administered alone and in Arm C decitabine is administered alone. The primary efficacy endpoint is overall survival. The study is designed to demonstrate an improvement in overall survival of either of two pairwise comparisons: (1) Arm A versus Arm C or (2) Arm B versus Arm C. Approximately 150 patients per arm or a total of 450 patients from approximately 50 centers will be enrolled. SEAMLESS will be monitored by a Data Safety Monitoring Board (DSMB). A prespecified interim analysis for futility will be performed and reviewed by the DSMB.

"We chose decitabine as an active control arm as it is one of the treatment options recommended by the National Comprehensive Cancer Network's Clinical Practice Guidelines. We are pleased to learn that this active control arm is acceptable to AML investigators," said Judy Chiao, M.D., Vice President of Clinical Development and Regulatory Affairs of Cyclacel. "AML in the elderly is a life-threatening disease with high unmet medical need. Patients with AML aged 70 years or older have a poor prognosis, as the majority of these patients are not candidates for intensive induction chemotherapy because of poor tolerability to such therapy and a high risk of relapse because of the lack of effective consolidation and maintenance therapy. If the SEAMLESS study is successful, sapacitabine may significantly improve the outcome of this devastating disease in elderly patients."

The treatment regimen of sapacitabine administered in alternating cycles with decitabine has been found to be safe and efficacious in an on-going pilot study conducted at The University of Texas MD Anderson Cancer Center. In addition, SEAMLESS has a lead-in stage to further confirm the safety and efficacy of the alternating treatment regimen in the multicenter setting.

The FDA has designated sapacitabine as an orphan drug for the treatment of both AML and myelodysplastic syndromes (MDS).