On November 9, 2022 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported third quarter 2022 financial results and provided a business update (Press release, Cyclacel, NOV 9, 2022, View Source [SID1234623559]).

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"Our recent R&D Day highlighted interim clinical data emerging from our ongoing Phase 1/2 study of oral fadraciclib in solid tumors and lymphoma," said Spiro Rombotis, President and Chief Executive Officer. "We are excited about fadra’s tolerability profile, as well as clear evidence of its anticancer activity as a single agent in late-line patients with lymphoma, gynecological, liver and pancreatic cancers. Moreover, we are seeing this activity during dose-escalation which is designed to evaluate safety. We expect to shortly determine the recommended Phase 2 dose (RP2D) and advance into Phase 2 proof-of-concept stage. We look forward to reporting updated data from our ongoing Phase 1/2 studies of fadraciclib and CYC140 in 2023."

"We have presented progress with our two clinical-stage programs, oral fadraciclib (CDK2/9 inhibitor) and oral CYC140 (PLK1 inhibitor), at our recent R&D Day and the ENA 2022 meeting," said Mark Kirschbaum, M.D., Chief Medical Officer. "In the 065-101 study of oral fadra, we have reached the sixth dose level after observing that fadra was well tolerated in the first five dose levels. Two out of three lymphoma patients achieved partial response and 11/15 patients with cervical, endometrial, hepatocellular and ovarian cancers achieved stable disease with target lesion reductions. A pancreatic patient achieved stable disease for 5 cycles of treatment. In addition, we achieved levels of fadraciclib that are adequate to inhibit CDK2 and CDK9 for approximately 5 to 7 hours per dose on continuous dosing. At our R&D Day, we also reported preliminary data from the first two dose levels of our Phase 1/2 study of oral CYC140 in patients with advanced solid tumors and lymphoma. We were surprised to observe stable disease at the first dose level in an ongoing patient with metastatic, KRAS G12V mutated, non-small cell lung cancer for 6 cycles and a patient with metastatic ovarian cancer for 5 cycles. We believe that CYC140 is differentiated from other PLK1 inhibitors by its PLK-centric kinase profile and by inhibiting BRD4, a validated, epigenetic target in cancer biology."

Key Corporate Highlights

·On October 31, 2022 the Company held an R&D Day (Webcast replay) at which updated clinical and preclinical data on fadraciclib and CYC140 were presented:

Interim results from oral fadraciclib 065-101 Phase 1/2 study in advanced solid tumors and lymphoma

o18 evaluable patients with advanced solid tumors or lymphoma were treated in DL 1-5 (median treatment duration of 2.4 cycles; range 1-5 cycles)
oWell tolerated at all dose levels thus far
o2/3 partial responses (PR) in T-cell lymphoma patients; 4 patients with cervical, endometrial, hepatocellular and ovarian cancer) showed stable disease with target lesion reductions and a pancreatic cancer patient achieved stable disease for 5 cycles
oAchieved target engagement levels predicted to inhibit CDK2 and CDK9 for approximately 5 to 7 hours per dose on continuous dosing
oEnrollment continues at DL6 (150mg twice a day, Monday-Friday, weeks 1-4)
oA principal investigator from Seoul National University Hospital presented preclinical data showing sensitivity to fadra in biliary tract and pancreatic cancer cells obtained from patient specimens

Interim findings from oral CYC140 140-101 Phase 1/2 study in advanced solid tumors and lymphoma

oNo dose limiting toxicities observed to date in the first two doses levels (DL1-2)
oStable disease at dose level 1 in an ongoing patient with metastatic, KRAS G12V mutated, non-small cell lung cancer for 6 cycles and a patient with metastatic ovarian cancer for 5 cycles

·Enrollment continues in the 065-102 study of oral fadraciclib in patients with advanced leukemia.

·The Company will not be pursuing further development of sapacitabine and has advised Daiichi Sankyo Co., Ltd., the licensor, that it wishes to terminate their license agreement for commercial reasons with the termination expected to be effective as of March 23, 2023.

Key Near-Term Business Objectives and Expected Timeline

4Q 2022

·Determine recommended Phase 2 dose (RP2D) with oral fadraciclib from the Phase 1 stage of 065-101 study with oral fadraciclib in patients with advanced solid tumors and lymphoma

1H 2023

·First patient dosed with oral fadraciclib in Phase 2 proof-of-concept stage of 065-101 study in patients with advanced solid tumors and lymphoma

·Report final data from dose escalation stage of 065-101 study with oral fadraciclib in patients with advanced solid tumors and lymphoma

·Report interim data from 140-101 study with oral CYC140 in patients with advanced solid tumors and lymphoma

2H 2023

·Report interim data from initial cohorts in Phase 2 proof-of-concept stage of 065-101 study with oral fadraciclib in patients with advanced solid tumors and lymphoma

·Report interim data from dose escalation stage of 065-102 study with oral fadraciclib in patients with advanced leukemia

·Report final data from dose escalation stage of 140-101 study with oral CYC140 in advanced solid tumors and lymphoma

Financial Highlights

As of September 30, 2022, cash and cash equivalents totaled $23.7 million, compared to $36.6 million as of December 31, 2021. Net cash used in operating activities was $15.7 million for the nine months ended September 30, 2022 compared to $14.0 million for the same period of 2021. The Company estimates that its available cash will fund currently planned programs to the end of 2023. 

Research and development (R&D) expenses were $4.4 million for the three months ended September 30, 2022, as compared to $4.2 million for the same period in 2021. R&D expenses relating to fadraciclib were $2.5 million for the three months ended September 30, 2022, as compared to $3.3 million for the same period in 2021, due to decrease in clinical trial costs of $0.3 million associated with ongoing clinical trials evaluating fadraciclib in Phase 1/2 studies and a reduction of $0.5 million in non-clinical expenditures. R&D expenses related to CYC140 were $1.7 million for the three months ended September 30, 2022, as compared to $0.7 million for the same period in 2021, due to clinical trial costs associated with the CYC140 Phase 1/2 study.

General and administrative expenses for the three months ended September 30, 2022 were $2.1 million, compared to $1.8 million for the same period of the previous year, due to an increase in professional and legal costs.

Total other income, net, for the three months ended September 30, 2022 was $0.4 million, compared to $13,000 for the same period of the previous year. The increase of $0.3 million for the three months ended September 30, 2022, is primarily related to foreign exchange gains.

United Kingdom research & development tax credits were $1.0 million for each of the three months ended September 30, 2022 and September 30, 2021 and are directly correlated to qualifying research and development expenditure.

Net loss for the three months ended September 30, 2022 was $5.1 million, compared to $5.0 million for the same period in 2021.