We are designing a highly selective rearranged during transfection proto-oncogene (RET) inhibitor.
RET mutations account for a syndrome that runs in families called multiple endocrine neoplasia type 2 (MEN 2), which is associated with medullary thyroid cancer, pheochromocytoma, and other problems. Patients without MEN 2 can get medullary thyroid cancer if they spontaneously acquire the activating mutation in RET known as M918T.
RET gene fusions, much like TRK gene fusions, occur when the RET gene abnormally fuses to another gene. The hybrid gene that is created as a result drives tumor growth. RET gene fusions have been identified in lung cancer, colon cancer, and papillary thyroid cancer.
We have designed a series of potent and highly specific RET inhibitors that optimizes on-target potency for RET gene fusions, mutations and clinically-identified resistance mutations. We expect to advance a RET inhibitor as our next Investigational New Drug (IND) application with the goal of initiating a Phase 1 study of a selective RET inhibitor in early 2017.
Data presented at the 2016 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics illustrated the potency, specificity, and favorable in vivo properties in animals of LOXO-292, our clinical candidate. Read the poster presented at AACR-NCI-EORTC here.
Data presented at the 2015 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics showed that our RET inhibitors offer high oral bioavailability and favorable PK properties in animals. Several demonstrated potent inhibition of RET in enzyme and cellular assays, with minimal activity against highly related kinases. Read the poster presented at AACR-NCI-EORTC here.