Overview of Blueprint Medicines' kinase drug discovery strategy published in JCI

Blueprint Medicines (NASDAQ: BPMC) today announced that the Journal of Clinical Investigation (JCI) published an overview of the Company's kinase drug discovery and development strategy. The publication underscores Blueprint Medicines' focus on identifying novel genomically defined disease drivers and the use of novel chemistry from its proprietary compound library to craft highly selective kinase inhibitors for new and difficult-to-drug kinase targets. "Targeting cancer with kinase inhibitors," authored by Blueprint Medicines' scientists, was published in the May 2015 issue of JCI, a leading journal focused on science and clinical research to advance medicine.

"Despite the success of kinase inhibitors in treating cancer, approved drugs focus on less than 5 percent of all kinases and the function of most kinases remains unknown," said Sir Philip Cohen, PhD, Professor of Enzymology, Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland. "There is a tremendous need and opportunity to further our understanding of kinase biology, identify novel disease drivers and design highly targeted therapies. Blueprint Medicines' approach of using novel chemistry to target newly discovered genomic drivers of cancer as well as known drivers that have been historically difficult to drug has the potential to greatly improve the lives of patients who currently have no or limited treatment options."

The JCI review article describes how the abnormal activation of kinases drives many hallmarks of tumor biology. Kinases are proven cancer drug targets, but progress in recent years has been largely incremental. In the article, Blueprint Medicines scientists call attention to important opportunities for advancing the field that serve as the foundation for the Company's drug discovery and development strategy:

• Uncovering novel disease drivers and drug targets: New genomics and sequencing approaches are needed to elucidate the biology of the full kinome, which is comprised of 518 kinases, and to uncover the function of kinases of unknown biology (or KUBs) and their potential for drug discovery.
• Crafting highly selective kinase inhibitors: Novel chemical matter and structure-informed design are needed to create more selective and potent therapies that can inhibit new and difficult-to-drug kinase targets. Complete target inhibition with minimal off-target effects is also needed to provide more durable responses with few toxicities, improving outcomes for patients.
• Predicting resistance mutations: Novel approaches in structural biology and computational chemistry are needed to predict future resistance mutations which arise from targeted therapies. Novel chemistry is needed to design a single therapy that can target both the original primary disease driver and the subsequent mutations that cause patients to become refractory to treatment.
• Developing novel combination therapies: Combinations of highly targeted kinase inhibitors acting within a single kinase pathway or between parallel kinase pathways are needed to mount a multi-pronged attack that improves efficacy and delays the onset of treatment resistance.

"We're entering a new era of precision medicine, in which we can craft highly selective kinase inhibitors against previously unaddressed drivers of disease and identify patients who are most likely to respond based on the molecular profile of their cancers," said Christoph Lengauer, PhD, MBA, Blueprint Medicines Chief Scientific Officer. "The strategies we describe in the JCI paper are at the heart of our drug discovery and development efforts. We believe that our ability to identify new drug targets, coupled with our proprietary library of compounds, will enable us to uniquely fulfill our mission of delivering targeted medicines for patients with genomically defined diseases."

Blueprint Medicines expects to advance its lead programs into Phase 1 clinical trials in mid-2015: BLU-554, a selective inhibitor of fibroblast growth factor receptor 4 (FGFR4), in hepatocellular carcinoma, and BLU-285, a selective inhibitor of PDGFRα D842V and KIT Exon 17 mutants, in gastrointestinal stromal tumors and systemic mastocytosis. The company also has a drug discovery program targeting RET kinase fusions and predicted resistance mutations.