Dual HIF-1 and HIF-2 inhibitor
Hypoxia Inducible Factor (HIF) is a transcriptional complex that allows cells to adapt to a lack of oxygen (hypoxia), for example, in the core of solid tumours. The upregulation of HIF-1 and HIF-2 in many solid tumours generally correlates with poor clinical outcomes.
Using a rational approach and structural data from its Microcycle hits, Curve has developed first-in-class, non-peptide, small molecule hits that inhibit both HIF-1 and HIF-2. Lead optimisation is underway.
Curve’s dual HIF inhibitors are expected to deliver a significant clinical advantage over HIF-2 selective inhibitors currently in development.
Mutant KRAS (G12D)
RAS is an important oncogene with a single point mutation frequently leading to aggressive and treatment-resistant cancers. Mutations are seen in 20-25% of all tumours and up to 90% in certain cancers. More than a million deaths are caused by mutant RAS every year.
Although there are many known RAS mutations, KRAS (G12D) is a common mutation in many solid tumours, including pancreatic and colorectal cancer.
FOXA1 is a pioneer factor and key determinant of the interactions between chromatin and Estrogen Receptor (ER). FOXA1 plays an essential role on the growth and invasiveness of ER-positive, endocrine resistant breast tumours. Despite significant interest in this target, no inhibitors have been identified to date.
Curve is deploying the key features of its Microcycle platform to identify first-in-class FOXA1 inhibitors for the treatment of hormone refractory breast and prostate cancer.
Our Microcycle® platform is a major step forward, enabling hit selection solely on the basis of biological function against disease targets in their native cellular environment.
Partnering for success
Curve’s platform has multiple applications beyond our in-house pipeline and there are clear opportunities for collaborative research and development with partners that have a depth of knowledge in target biology and expertise in drug development.