In developing our science and progressing our pipeline, our approach is to establish strategic collaborations with leading biopharmaceutical companies who are commercialising innovative anti-cancer therapeutics.

We have two Phase I clinical assets now available for partnering worldwide, KA2237 and KA2507.

KA2237: a PI3K β/δ isoform-selective inhibitor

KA2237 has completed a Phase I clinical trial at The University of Texas MD Anderson Cancer Center, investigating its safety and efficacy in patients with B cell lymphoma. Data were presented at the American Society of Hematology (ASH) Annual Meeting on 9 December 2019.

KA2237 showed efficacy in relapsed/refractory B cell lymphoma, including complete responses in patients with aggressive disease. KA2237 achieved an overall response rate of 50% (6/12) in evaluable patients treated with a starting dose that matched or exceeded the recommended Phase II dose, or 37% in all 19 evaluable patients. KA2237 has an acceptable safety profile comparable with approved agents in this class. KA2237 has significant potential in the treatment of solid and haematological cancers, as a single agent or in combination therapy.

For more information, please visit ClinicalTrials.gov: NCT02679196.

The phosphoinositide 3-kinases (PI3Ks) constitute a family of lipid kinase enzymes. Our clinical programme has focused on isoforms PI3K-β and PI3K-δ.

  • PI3K-β is oncogenic when over-expressed, and, notably, can drive the growth of tumours that are defective in PTEN, a negative-regulator of PI3K signalling. A role for PI3K-β in tumour metastasis has also emerged, and rare mutations of the enzyme have been reported in cancer.
  • PI3K-δ is primarily expressed in the haematopoietic system and plays a critical signalling role in haematological cancers. A role for PI3K-δ in regulatory T cell (Treg) activity has also been discovered, with inhibition resulting in T cell activation and tumour growth inhibition.

KA2507: a selective HDAC6 inhibitor

KA2507 has completed a Phase I clinical trial at The University of Texas MD Anderson Cancer Center, investigating its safety and efficacy in patients with solid tumours. KA2507 showed excellent tolerability with good target engagement and selectivity. Data were presented at the American Association for Cancer Research (AACR) annual meeting on 27 April 2020. KA2507 has significant potential in the treatment of cancer, as a single agent or in combination therapy.

For more information, please visit ClinicalTrials.gov: NCT03008018.

We had plans in place for a Phase II clinical study in patients with cholangiocarcinoma, ABC-11, within a network of UK hospitals led by the UCL-CRUK Clinical Trials Centre. However, these were disrupted by the unprecedented impact of the COVID-19 pandemic on the UK health service, leading to cancellation of the trial.

Histone deacetylase 6 (HDAC6) is structurally-, expressionally-, and functionally-distinctive within the HDAC superfamily, and represents an important drug target for cancer therapy. Despite its name, it is principally a non-histone protein deacetylase, regulating the acetylation status of several substrates implicated in cancer, including α-tubulin and HSP90.

Its attractiveness as a cancer drug target stems from its overexpression in several solid tumour types, its regulation of cell motility, and its role in apoptosis, stress response and aggresomal protein degradation. HDAC6 has also been implicated in cell signal transduction and in oncogenic processes such as dysregulation of ciliation. More recently, a role for HDAC6 in the control of anti-tumour immunity has emerged.