SUNACICLIB: A HIGHLY POTENT CDK9 INHIBITOR FOR TREATING HAEMATOLOGICAL AND SOLID TUMOURS

Sunaciclib is one the most potent CDK9 inhibitors identified to date that demonstrates potent anti-tumour efficacy against multiple haematological and solid tumour types including AML, CLL, triple-negative breast cancer, colorectal cancer, lung cancer, prostate cancer, and ovarian cancer by oral administration. Sunaciclib is currently under investigation in patients with AML.

AUCELICICLIB: A HIGHLY POTENT AND SELECTIVE CDK4/6 INHIBITOR

CDK4 and CDK6 are fundamental for the initiation and progression of the majority of malignancies. As such, components of the CDK4/6 signalling pathway represent molecular targets for cancer therapy. CDK4/6 inhibitors have been FDA-approved for the treatment of ER+ breast cancer and are demonstrating their success in the market. However, current agents are not specific to CDK4 and CDK6 and also inhibit other kinases, resulting in undesirable toxicity.

We have purposely developed a novel and highly potent inhibitor that exhibits a high selectivity to CDK4 and CDK6 against a panel of 369 human protein kinases. Auceliciclib inhibits the growth of Rb-positive cancer cells and demonstrates excellent in vivo anticancer efficacy by oral administration with superior safety profiles. Significantly, Auceliciclib is capable of accessing the brain, being readier than the FDA-approved CDK4/6 inhibitors, suggesting therapeutic potential for treating a wide range of human cancers including these metastasised into the brain.

AU2-94: A FIRST-IN-CLASS CDK4 INHIBITOR

We have developed a novel and highly potent inhibitor that exhibits an excellent selectivity for CDK4 over a large panel of protein kinases. Consistent with the CDK4-targeted mechanism this candidate inhibits the growth of Rb-positive cancer cells and demonstrates excellent in vivo anticancer efficacy by oral administration without showing any overt toxicity. Significantly, our CDK4 inhibitor is capable of access into the brain that is far readier than any of the FDA-approved CDK4/6 inhibitors, suggesting its therapeutic potential for treating glioblastoma and the tumours metastasised into the brain.

AU5-5: A HIGHLY POTENT AND SELECTIVE FLT3 INHIBITOR FOR TREATING LEUKAEMIA

FMS-like tyrosine kinase 3 (FLT3) is expressed at high levels in a spectrum of hematologic malignancies including 70-100% of AML of all subtypes, ALL, and CML. Patients with FLT3 mutations have a very poor prognosis, experience higher rates of relapse and subsequent death.

We have developed a selective FLT3 inhibitor (against a panel of 369 human protein kinases) that is highly cytotoxic in human leukaemia (FLT3+) cells. AU5-5 is particularly effective against multiple mutations, including FLT3 (ITD), FLT3 (D835Y), FLT3 (F594_R595insR), FLT3 (F594_R595insREY), FLT3 (ITD)-NPOS, FLT3 (ITD)-W51, FLT3 (R595_E596insEY) and FLT3 (Y591V592insVDFREYEYD) with low picomolar potencies. Thus, it has an advantage of effectively blocking these mutations that have been clinically shown to confer resistance to the current chemotherapies and FLT3 inhibitor treatment.

AU7-55: A HIGHLY POTENT TAM INHIBITOR FOR THE TREATMENT OF BLOOD CANCERS 

TAM kinases are over-expressed in a wide variety of cancers and are often associated with poorer patient survival, drug resistance and metastasis.  TAMs act as immune checkpoints, similar to CTLA-4, PD-1 and PD-L1 and inhibition of TAM kinases improves tumour immunity.  We have identified a potent TAM inhibitor, which selectively targets key kinases involved in immune suppressive pathways.  This orally available candidate has shown anti proliferative activity in a range of cancer cell lines, high efficacy in AML xenograft models and demonstrates low toxicity.

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