Curve is developing a cancer pipeline addressing high value, challenging disease targets.
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) in the core of solid tumours. Both HIF-1 and HIF-2 play a central role in tumour cell growth and proliferation in renal cell carcinoma and in many other solid and haematological cancers.
Using a rational approach and structural data from its Microcycle hits, Curve is developing a first-in-class non-peptide small molecule dual HIF-1 and HIF-2 inhibitor designed to deliver a clinical advantage over HIF-2 selective inhibitors in clear-cell renal cell carcinoma. This dual inhibitor has the potential for further application in HIF-1 driven solid tumours.
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 1 million deaths a year are caused by mutant RAS.
Although there are many known RAS mutations, G12D is the most common and is frequently found in pancreatic, colorectal and lung cancer. However, this mutation is yet to be selectively targeted
FOXA1 is a pioneer factor and key determinant of the interactions between chromatin and Estrogen Receptor (ER). FOXA1 plays a key 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.