| Microcycle® Screening | Functional Hit | Lead Optimisation |
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Dual HIF-1 and HIF-2 inhibitor
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Elevated levels of HIF-1 and HIF-2 in cancer cells promotes tumor survival, increased angiogenesis and immune evasion; and always correlates with poor survival. Despite the importance of these transcription factors, only HIF-2 inhibitors have been developed to date.
Using a rational approach and structural data from its Microcycle hits, Curve has developed first-in-class, non-peptide, small molecules that inhibit both HIF-1 and HIF-2. Lead optimization is underway.
Curve’s dual HIF inhibitors are differentiated from the current HIF-2 inhibitors and are expected to show a clinical advantage in multiple tumors, including those with mutant and wild-type VHL including ccRCC, HCC, TNBC and NSCLC.
ATIC
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ATIC is a validated target that catalyzes the final two steps of de novo purine biosynthesis in mammalian cells. In cancer cells that have lost the ability to salvage purines following MTAP deletion, ATIC becomes the Achilles heel for therapeutic intervention.
Curve has identified inhibitors of ATIC homodimerization, using a unique non-folate-dependent mechanism that has the potential to treat a diverse range of tumors.
FOXA1
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FOXA1 is a pioneer factor and key determinant of the interactions between chromatin and the estrogen receptor (ER). FOXA1 plays an essential role in the growth and invasiveness of ER-positive, endocrine resistant breast tumors. Despite significant interest in this target, no inhibitors have been identified to date.
Curve is deploying the key attributes of its Microcycle platform to identify first-in-class FOXA1 inhibitors for the treatment of hormone refractory breast cancer.
Immunology/Inflammation Target
Curve is working to identify antagonists of an undisclosed immunology/inflammation target.
Science
Our revolutionary gene-encoded Microcycle® platform can discover functional macrocycles and, potentially, small molecules through high-throughput functional screening in the real world setting of a live mammalian cell, unlocking the therapeutic potential of intracellular targets.
Partnering for success
Beyond our pipeline and focus there are multiple applications with clear opportunities for collaborative programs with partners that have a depth of knowledge in target biology and expertise in drug development.
