Blueprint Medicines, manufacturer of kinase drugs to treat patients with genomically defined diseases, announced the first preclinical data for its drug candidate BLU6864, a RET-specific kinase inhibitor. In preclinical studies, BLU6864 induced tumour regression in disease models driven by the primary RET fusion and all predicted secondary resistance mutations.

RET is a key disease driver in multiple cancers. These data were presented at the EACR-AACR-SIC special conference on 'Anticancer Drug Action and Drug Resistance' in Florence, Italy.

"One of the greatest challenges in treating cancer is cancer cell's ability to mutate and become resistant to treatment," said Alexander Drilon, M.D., a medical oncologist at Memorial Sloan Kettering Cancer Center. "RET fusions fuel the development and growth of multiple cancers, including lung and thyroid cancers. By targeting both the main cancer driver and predicted resistance mutations that arise from targeted therapy, we hope to provide patients with transformative medicines that mount a more effective attack on this subset of cancers and prevent recurrences of the disease."

In the preclinical data presented at the EACR-AACR-SIC special conference, BLU6864 inhibited tumour growth and induced tumour regression at well-tolerated doses in a model of cancer driven by RET fusions, inhibited tumour growth and induced tumour regression in a model harbouring a resistance mutation that renders cancer cells insensitive to treatment with an approved multi-kinase inhibitor with activity against RET, and spared VEGFR2, a kinase often inhibited together with RET and whose inhibition is associated with dose-limiting toxicities.

BLU6864 is one of the first kinase inhibitors designed specifically to inhibit RET. The drug candidate builds on Blueprint Medicines' work to identify novel drivers of disease. In addition to lung and thyroid cancers, the company's scientists discovered that RET fusions are drivers in a subset of colon and breast tumours. Leveraging its expertise in genomics and structural biology, Blueprint Medicines was able to predict and validate the complete spectrum of future resistance mutations and designed drug candidates to target both the primary RET fusions and secondary treatment-resistant mutants.

In addition to BLU6864, Blueprint Medicines has two drug candidates on track to begin phase 1 clinical trials in mid-2015, including BLU-554 in hepatocellular carcinoma and BLU-285 in metastatic and treatment-resistant gastrointestinal stromal tumours as well as systemic mastocytosis.