Cyclacel Provides Update on Clinical Progress With Sapacitabine in Solid Tumors Including Activity in BRCA Mutation-Positive Patients

Cyclacel Pharmaceuticals, Inc. (Nasdaq: CYCC) (Nasdaq: CYCCP) (Cyclacel or the Company) announced today interim topline data from ongoing clinical studies with sapacitabine in heavily pretreated patients with advanced solid tumors, including Phase 2 single-agent data in non-small cell lung cancer and Phase 1 data in combination with Cyclacel's seliciclib in breast, ovarian, pancreatic and other cancers. Partial responses and stable disease were observed in both studies. In the Phase 1 trial responding patients were found to be carriers of BRCA mutations.

"We are encouraged by the anti-tumor activity against solid tumors by single agent sapacitabine and its combination with seliciclib," said Judy H. Chiao, M.D., Vice President, Clinical Development and Regulatory Affairs of Cyclacel. "The responses in BRCA-mutation positive patients with breast, pancreatic and ovarian cancers may be directly related to sapacitabine's enhanced activity against cancer cells that are deficient in the homologous recombination DNA repair (HRR) pathway. Accordingly, BRCA status could be a potential biomarker for identifying responders across multiple solid tumor types. The interim data warrant further investigation of sapacitabine's utility in solid tumors, as we continue to progress our SEAMLESS Phase 3 pivotal trial of sapacitabine in patients with front-line acute myeloid leukemia (AML)," continued Dr. Chiao.

Phase 1 study of oral sapacitabine and oral seliciclib in patients with advanced cancers

In the ongoing Phase 1, single-arm study of sapacitabine, a nucleoside analogue, and seliciclib, a CDK inhibitor, as an orally-administered combination regimen in patients with advanced solid tumors, 27 patients have been treated to date. The primary objective of the study is to determine the recommended Phase 2 dosing schedule of the sapacitabine and seliciclib combination, which has been achieved. Among 11 patients treated at the recommended Phase 2 doses, 2 patients with advanced pancreatic cancer and breast cancer, respectively, achieved PR and 1 patient with advanced ovarian cancer achieved stable disease. All 3 responders were reported by the investigator to be carriers of BRCA mutations. The number of treatment cycles administered ranges from 7 to 9 cycles. The breast and ovarian cancer patients remain on study.

Phase 2 study of oral sapacitabine in patients with NSCLC who have had at least one prior chemotherapy

In the ongoing lead-in, dose escalation portion of a multicenter, Phase 2 study of sapacitabine as a single agent in patients with NSCLC who have had at least one prior chemotherapy, 48 patients were treated with two dosing schedules, either twice daily or once a day.

In the twice daily schedule 15 patients were treated with escalating doses. The recommended Phase 2 dose was reached at 75 mg twice daily for 5 days per week for 2 weeks every 3 weeks. Among 12 patients treated at this recommended Phase 2 dose, 4 achieved stable disease. All 4 responders had at least 2 prior therapies and have been discontinued from the study. Responders received an average of 7 treatment cycles.

In the once daily schedule 33 patients were treated with escalating doses. Maximum tolerated dose has not been reached at the upper limit of the dosing range as per protocol. Patients are currently being entered into the 200 mg once daily dosing level for 5 days per week for 2 weeks every 3 weeks. Among 25 patients treated with daily doses ranging from 100 mg to 175 mg, 2 patients achieved PR and 10 stable disease. The two PR responders had 3 or 4 prior therapies, respectively, and one remains on study. Among the 10 stable disease responders, 9 had at least 2 prior therapies and 2 remain on study. Responders received an average of 10 treatment cycles.

"Advanced non-small cell lung cancer patients are living longer and living better as a result of the availability of effective sequential therapies. Novel therapies are needed to build on our recent therapeutic advances," said Philip D. Bonomi, M.D., the Alice Pirie Wirtz Professor of Medical Oncology at Rush University Medical Center, Chicago and chair of the study. "Sapacitabine appears to be well tolerated and has activity against NSCLC. Future clinical development should focus on identifying a biomarker for patient selection and comparison to available therapies commonly used in this patient population," continued Dr. Bonomi.