plogosertib (CYC140) / Cyclacel - LARVOL DELTA

CYCLACEL PHARMACEUTICALS HIGHLIGHTS PRECLINICAL DATA SHOWING THAT CANCER OF THE BILIARY TRACT IS SENSITIVE TO PLOGOSERTIB (GlobeNewswire) - "Cyclacel Pharmaceuticals...highlighted a preclinical study from independent investigators...in the journal, Cancer Research, previously reported in a poster at the American Association of Cancer Research 2025 annual meeting. The investigators found that several BTC cancer cell lines were sensitive to plogosertib both as monotherapy and in combinations. Consistently with its antimitotic mechanism of action, plogosertib promoted mitotic checkpoint complex (MCC) formation in prometaphase, which induced mitotic arrest resulting in apoptosis of BTC cells. The authors have also found that BUBR1, a critical mitotic checkpoint protein, may be useful as a biomarker to assess plogosertib’s effectiveness. BTC cells with high BUBR1 expression were found to be more sensitive to plogosertib compared to those with low expression."

Biomarker • Preclinical • Biliary Tract Cancer

CYCLACEL PHARMACEUTICALS HIGHLIGHTS PUBLICATION OF PRECLINICAL DATA SHOWING THAT PLOGOSERTIB IS ACTIVE IN A HARD-TO-TREAT SUBTYPE OF LIVER CANCER (GlobeNewswire) - "Cyclacel Pharmaceuticals...highlighted a publication from independent investigators...published online in the journal Gut, a leading, peer-reviewed medical journal focused on gastroenterology and hepatology....The researchers found that PLK1 is essential for FLC cells making them highly sensitive to loss of PLK1. A direct interaction was found between DNAJ-PKAc fusions present in the centrosome and PLK1, thus promoting mitotic progression. Pharmacologic inhibitors of PLK1, such as plogosertib, significantly reduced FLC growth but spared normal liver cells in patient-derived in vitro and in vivo xenograft models and an orthotopic model of FLC."

Preclinical • Liver Cancer

CYCLACEL PHARMACEUTICALS REPORTS FIRST QUARTER FINANCIAL RESULTS AND PROVIDES BUSINESS UPDATE (GlobeNewswire) - "As part of the Company’s efforts to reduce operating costs it has determined to focus on the development of the plogosertib ('plogo') clinical program only. Accordingly, on March 10, 2025, the Company repurchased certain assets related to plogo from Cyclacel Limited for approximately $0.3 million in cash, to allow us to continue our efforts on developing an alternative salt, oral formulation of plogosertib with improved bioavailability"

Commercial • Breast Cancer • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Solid Tumor

PLK1 and multi-CDKs dual inhibition as a novel approach for the treatment of adrenocortical carcinomas (ESPE-ESE 2025) - "Plogosertib and dinaciclib were the most effective inhibitors in all cell lines, representing interesting novel targeted treatment options for ACC. Moreover, the combination of these drugs showed a synergistic effect, suggesting a potential benefit of using both PLK1i and multi CDKi that need to be further investigated in vivo."

Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • ACACB • CASP3 • CASP7 • CCNB1 • CDK1 • MUC1 • PLK1

Evaluation of antitumor effects of plogosertib, PLK1 inhibitor in biliary tract cancer with BUBR1 as a potential biomarker (AACR 2025) - "We used plogosertib (PLK1 inhibitor), ceralasertib (ATR inhibitor) and panobinostat (HDAC2/3 inhibitor). BTC cells with high BUBR1 expression are sensitive to the PLK1 inhibitor plogosertib, which shows synergistic effects when combined with an ATR inhibitor. In contrast, BTC cells with low BUBR1 expression which are relatively insensitive to plogosertib, HDAC2/3 inhibition increases the sensitivity to plogosertib. These findings suggest that targeting PLK1 could be an effective strategy for BTC treatment, especially with BUBR1 expression as a potential biomarker to inform optimal combination therapies."

Biomarker • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • ANXA5 • AURKA • BUB1B • HDAC2

Dual inhibition of PLK1 and multi-CDKs: A novel approach for the treatment of adrenocortical carcinomas (Sarcoma-RC 2025) - "Here, we tested the efficacy of 1) the polo-box domain (PBD)-targeting PLK1 inhibitor (PLK1i) Poloxin and the kinase domain (KD)-targeting PLK1i Plogosertib; 2) the CDK1/2 inhibitor (CDKi) Dinaciclib; 3) the combination of Plogosertib and Dinaciclib. Legal entity responsible for the study The authors. Funding Has not received any funding."

Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CASP3 • CASP7 • CDK1 • MUC1 • PLK1

Cyclacel Pharmaceuticals Reports Fourth Quarter Financial Results and Provides Business Update (GlobeNewswire) - "'Our new, alternative salt, oral formulation of plogosertib with improved bioavailability is under development.'....Research and development (R&D) expenses were $0.9 million and $6.7 million for the three months and year ended December 31, 2024, as compared to $3.5 million and $19.2 million for the same period in 2023. R&D expenses relating to fadraciclib were $0.8 million and $5.0 million for the three months and year ended December 31, 2024, as compared to $2.7 million and $13.4 million for the same period in 2023 due to decrease in clinical trial and other non-clinical expenditures. R&D expenses related to plogosertib were $0.1 million and $1.6 million for the three months and year ended December 31, 2024, as compared to $0.7 million and $5.0 million for the same period in 2023 due to decrease in clinical trial and other non-clinical expenditures."

Commercial • Pipeline update • Hematological Malignancies • Solid Tumor

Efficacy of plogosertib (CYC149462), a novel orally bioavailable PLK1 inhibitor, on patient-derived models of colorectal cancer. (ASCO-GI 2025) - "Drug screens were performed for standard of care agents 5FU, oxaliplatin, and SN38... Together, our study shows that pharmacological inhibition of Plk1 using plogosertib represents a promising therapeutic approach for advanced CRC."

Clinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PLK1

A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS (clinicaltrials.gov) - P1 | N=7 | Terminated | Sponsor: Cyclacel Pharmaceuticals, Inc. | N=50 ➔ 7 | Recruiting ➔ Terminated; Switch to oral formulation of CYC140 (plogosertib)

Enrollment change • Metastases • Trial termination • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Cyclacel Announces Notice of Intention to Grant New European Patent Covering Plogosertib Pharmaceutical Compositions (GlobeNewswire) - "Cyclacel Pharmaceuticals, Inc...today announced the receipt of a notice from the European Patent Office of the intention to grant a patent which includes claims to novel pharmaceutical compositions of plogosertib, a PLK1 inhibitor. Once granted, the European patent will provide exclusivity until August 2040 not including any extensions. The Company is prosecuting patent applications from the same family in other jurisdictions."

Patent • Oncology

Cyclacel Pharmaceuticals Reports Third Quarter Financial Results and Provides Business Update (Yahoo Finance) - "Research and development (R&D) expenses were $5.2 million for the three months ended September 30, 2023, as compared to $4.4 million for the same period in 2022. R&D expenses relating to fadraciclib were $3.6 million for the three months ended September 30, 2023, as compared to $2.5 million for the same period in 2022 due to due to increased costs associated with manufacture scale up and introduction of the tablet form. R&D expenses related to plogosertib were $1.5 million for the three months ended September 30, 2023, as compared to $1.7 million for the same period in 2022."

Commercial • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Cyclacel Pharmaceuticals Reports Second Quarter 2023 Financial Results and Provides Business Update (BioSpace) - "Key Upcoming Milestones: Report final data from dose escalation stage and RP2D determination from the 065-101 study of oral fadraciclib in patients with advanced solid tumors and lymphoma; 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 Phase 1 data from 140-101 study of oral plogosertib in patients with advanced solid tumors and lymphoma; Elaborate novel mechanism of action of plogosertib..."

P1 data • P1/2 data • Trial status • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Cervical Cancer • Cutaneous T-cell Lymphoma • Endometrial Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Hematological Malignancies • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Peripheral T-cell Lymphoma • Sarcoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma • Triple Negative Breast Cancer • Uterine Cancer

Cyclacel Pharmaceuticals Reviews 2022 Achievements and Announces Key Business Objectives for 2023 (GlobeNewswire) - "Key Business Objectives for 2023 - 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 and RP2D determination from the 065-101 study of oral fadraciclib in patients with advanced solid tumors and lymphoma at a major medical meeting; Report interim Phase 1 data from 140-101 study of oral plogosertib in patients with advanced solid tumors and lymphoma."

P1 data • P1/2 data • Trial status • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Cyclacel Pharmaceuticals Reviews 2022 Achievements and Announces Key Business Objectives for 2023 (GlobeNewswire) - "Key Business Objectives for 2023 - 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 plogosertib in advanced solid tumors and lymphoma."

P1/2 data • P2 data • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Oncology • Solid Tumor

Cyclacel Pharmaceuticals Reports Third Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "Key Near-Term Business Objectives and Expected Timeline - 2H 2023: (i) 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; (ii) Report interim data from dose escalation stage of 065-102 study with oral fadraciclib in patients with advanced leukemia; (iii) Report final data from dose escalation stage of 140-101 study with oral CYC140 in advanced solid tumors and lymphoma."

P1/2 data • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Oncology • Solid Tumor

Cyclacel Pharmaceuticals Reports Third Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "Key Near-Term Business Objectives and Expected Timeline - 1H 2023: (i) 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; (ii) Report final data from dose escalation stage of 065-101 study with oral fadraciclib in patients with advanced solid tumors and lymphoma; (iii) Report interim data from 140-101 study with oral CYC140 in patients with advanced solid tumors and lymphoma."

P1/2 data • Trial status • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Cyclacel Reports Preliminary Data From Its Phase 1/2 Clinical Trial of Oral Fadraciclib in Patients With Solid Tumors and Lymphoma at ENA 2022 (GlobeNewswire) - P1/2 | N=330 | NCT04983810 | Sponsor: Cyclacel Pharmaceuticals, Inc. | "...'We look forward to reviewing fadraciclib and CYC140 preclinical and clinical data at our upcoming Research & Development Day on Monday, October 31'....As of September 30, 2022, 18 evaluable patients were treated with oral fadraciclib as a single agent. Patients were heavily pretreated with various tumor types, including breast, cholangiocarcinoma, gynecological, head & neck, hepatocellular carcinoma, T-cell lymphoma, pancreatic and prostate cancers....Two partial responses (PRs) have been observed in T-cell lymphoma patients, one with CTCL and one with angioimmunoblastic PTCL. Four patients (with cervical, endometrial, HCC, and ovarian cancers) achieved target lesion reductions. A patient with pancreatic cancer achieved stable disease for 5 cycles."

Clinical data • P1/2 data • Preclinical • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hematological Malignancies • Hepatocellular Cancer • Liver Cancer • Lymphoma • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Urothelial Cancer

A Study to Investigate CYC140, in Subjects With Advanced Solid Tumors and Lymphoma (clinicaltrials.gov) - P1/2 | N=330 | Recruiting | Sponsor: Cyclacel Pharmaceuticals, Inc.

New P1/2 trial • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Cyclacel Pharmaceuticals, Inc. | Trial completion date: Feb 2021 ➔ Sep 2023 | Trial primary completion date: Oct 2020 ➔ Apr 2023

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Cyclacel Announces Dosing of First Patient in Phase 1/2 Study of Oral Cyc140 in Patients With Advanced Solid Tumors and Lymphomas (GlobeNewswire) - "Cyclacel Pharmaceuticals...announced dosing of the first patient in the Company’s streamlined, multi-cohort Phase 1/2 study of oral CYC140 in patients with advanced solid tumors and lymphomas....'The Phase 2 stage will enroll up to seven cohorts by histology and also a basket cohort. We expect initial data from this trial during the first half of 2023. We also look forward to reporting initial data from the fadraciclib clinical study in advanced solid tumors during the first half of 2022'."

P1/2 data • Trial status • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Cyclacel Pharmaceuticals Reviews 2021 Achievements And Announces Key Business Objectives for 2022 (GlobeNewswire) - "Key Business Objectives for 2022: (i) First patient to be dosed with oral CYC140 in the 140-101 solid tumor study; (ii) Initial data from Phase 1 dose escalation of the 065-101 solid tumor study of oral fadraciclib; (iii) First patient to be dosed with oral CYC140 in the 140-102 leukemia study; (iv) Commence Phase 2 proof of concept stage in the 065-101 solid tumor study of oral fadraciclib; (v) Initial data from Phase 1 dose-escalation of the 065-102 leukemia study of oral fadraciclib; (vi) Commence Phase 2 proof of concept stage of oral fadraciclib in the 065-102 leukemia study."

P1 data • Trial status • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

Cyclacel Pharmaceuticals Reports Third Quarter 2021 Financial Results and Provides Business Update (GlobeNewswire) - "Key Near-Term Business Objectives: (i) FDA clearance of IND filing and initiation of oral CYC140 Phase 1/2 advanced solid tumor study; (ii) Initial data from first part of 065-101 study with oral fadraciclib in advanced solid tumors; (iii) First patient to be dosed with oral CYC140 in Phase 1/2 leukemia study; (iv) Initial data from first part of 065-102 study with oral fadraciclib in leukemia."

Enrollment status • IND • New P1/2 trial • P1/2 data • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Cyclacel Pharmaceuticals Reports Second Quarter 2021 Financial Results and Provides Business Update (GlobeNewswire) - "Key Near-Term Business Objectives and Expected Timeline: 2H 2021 First patient to be dosed with oral fadraciclib in 065-102 Phase 1/2 leukemia study, FDA clearance of IND filing; begin oral CYC140 Phase 1/2 advanced solid tumor study. 1H 2022 First patient to be dosed with oral CYC140 in Phase 1/2 leukemia study, Phase 1 data with oral fadraciclib in advanced solid tumor 065-101 study."

New P1/2 trial • P1 data • Trial status • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Cyclacel Announces Dosing of First Patient in Phase 1/2 Study of Oral Fadraciclib in Patients With Advanced Solid Tumors and Aggressive Lymphomas (GlobeNewswire) - “Cyclacel Pharmaceuticals…announced dosing of the first patient in the Company’s multi-cohort Phase 1/2 study of oral fadraciclib in patients with advanced solid tumors…‘This is the first of four streamlined Phase 1/2 studies we plan to open over the coming months as we expand our clinical programs to evaluate the potential of fadraciclib and CYC140’…The cohorts will include patients with breast cancer (selected for metastatic, hormone receptor positive, HER-2 negative, post-CDK4/6 inhibitor; HER-2 refractory; or triple negative), colorectal (including KRAS mutant), endometrial, hepatocellular and ovarian cancers, as well as certain lymphomas. An additional basket cohort will enroll patients with biomarkers relevant to the drug’s mechanism, including MCL1, MYC and cyclin E, regardless of histology.”

Biomarker • Trial status • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Hematological Malignancies • Hepatocellular Cancer • HER2 Negative Breast Cancer • Lymphoma • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer

Cyclacel Pharmaceuticals Reports Fourth Quarter and Full Year 2020 Financial Results (GlobeNewswire) - "Key Business Objectives for 2021: First patient dosed with oral fadraciclib in Phase 1b/2 advanced solid tumor and leukemia studies; First patient dosed with oral CYC140 in Phase 1/2 advanced solid tumor and leukemia studies; Manufacture clinical supplies of oral fadraciclib and oral CYC140 for registration-enabling studies; Data on safety and antileukemic activity from the i.v. fadraciclib-venetoclax Phase 1 study in relapsed/refractory AML and CLL; Data from the sapacitabine-venetoclax Phase 1/2 study in relapsed/refractory AML or MDS; Initial data from the i.v. CYC140 Phase 1 First-in-Human study in patients with advanced leukemias; Data from the Phase 1b/2 IST of sapacitabine-olaparib combination in patients with BRCA mutant metastatic breast cancer when reported by the investigators."

Clinical • P1 data • P1/2 data • Trial status • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor