"CYC065, a second generation CDK2/9 inhibitor, has been evaluated in a first-in-human, Phase 1 trial in patients with advanced solid tumors and a recommended Phase 2 dose established. The study demonstrated that CYC065 durably suppresses MCL1, a member of the Bcl-2 family of survival proteins. CYC065 is mechanistically similar but has higher dose potency, in vitro and in vivo, and improved properties compared to seliciclib, a first generation CDK inhibitor. Similarly to FDA approved CDK4/6 inhibitors, CYC065 is investigated in combination with other anticancer drugs, including Bcl-2 inhibitors, such as venetoclax, or HER2 inhibitors, such as trastuzumab. Preclinical data show that CYC065 may benefit patients with adult and paediatric haematological malignancies, including acute myeloid leukaemias (AML), acute lymphocytic leukaemias (ALL), and in particular those with MLL rearrangements, chronic lymphocytic leukaemias (CLL), B-cell lymphomas, multiple myelomas, and certain solid tumors, including breast and uterine cancers, and neuroblastomas. The objective of this project is to evaluate safety and activity and recommend the most desirable dose of CYC065 for further testing in a phase II clinical trial, in patients with poor prognosis AML including those with the rearranged mixed lineage leukemia (_MLL_) gene. A key component of the project is the incorporation of pharmacodynamic and exploratory patient stratification markers. Depending on the outcome of the study, CYC065 would then be evaluated in expanded Phase 2 development."

Cyclacel has developed a clinical candidate NCE with characteristics enabling the targeting of a previously unexploited mechanism for treatment of oesophageal cancer (OEC), an orphan disease with a high unmet need. This potent and selective PLK1 kinase inhibitor has a strong preclinical rationale for use as a stratified medicine for OEC and other solid tumour indications having particular driver mutations. The drug development project encompasses preclinical validation of marker assays for clinical stratification of patients, 'First-In-Human' (FIH)-directed safety studies, clinical formulation and manufacture for Phase 1 testing, and testing of the compound in combination with approved and investigational therapeutic agents in models of the target diseases. Success will attract further investment in a UK and EU based development program, securing additional jobs and will provide access to a new investigational medicine for solid tumour patients with poor prognosis diseases.

Cyclacel has developed a novel clinical candidate NCE affecting previously unexplored pathways for treatment of acute leukaemia. The compound has a strong rationale for use as a stratified medicine for adult, infant and paediatric indications which have a high unmet medical need. The drug development project encompasses preclinical validation of marker assays for clinical stratification of patients, 'First-In-Man' (FIM)-directed preclinical development, clinical formulation and manufacture of the compound for Phase 1 testing, and testing of combinations with approved and investigational therapeutic agents to facilitate clinical development of the clinical candidate in the target diseases. Success will attract further investment in a UK and EU based development programme, securing additional jobs and will provide access to a new investigational medicine for both adult and infant patients with poor prognosis diseases.