On December 4, 2016 ArQule, Inc. (Nasdaq: ARQL) reported that preclinical data was presented on Bruton’s tyrosine kinase (BTK) inhibitor, ARQ 531, in a poster presentation by The Ohio State University at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The presentation highlighted preclinical studies of ARQ 531 in Chronic Lymphocytic Leukemia (CLL) (Press release, ArQule, DEC 4, 2016, View Source [SID1234516920]). ARQ 531 is an investigational, orally bioavailable, potent and reversible BTK inhibitor.

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ARQ 531 Poster Presentation Highlights

Title: The Bruton’s Tyrosine Kinase (BTK) Inhibitor ARQ 531 Effectively Inhibits Wild Type and C481S Mutant BTK and Is Superior to Ibrutinib in a Mouse Model of Chronic Lymphocytic Leukemia

Multi-targeted inhibition of cytokine, chemokine, and BCR pathways by ARQ 531 decreases activation, migration, and viability of CLL cells.
Unlike ibrutinib, ARQ 531 inhibits activation of C481S mutated BTK variants and maintains cytotoxicity in ibrutinib resistant clones.
ARQ 531 demonstrates remarkable efficacy in an in vivo TCL1 adoptive transfer model, improving survival to a greater extent than ibrutinib and restoring granulocyte production.
The company plans to complete preclinical studies and file an Investigational New Drug (IND) application in early 2017 to begin clinical testing later in the year.
The presentation can be viewed at View Source

"Irreversible kinase inhibitors directed at BTK have really changed the landscape of CLL but at extended follow up, we are beginning to see a subset of high risk patients who are relapsing," said Dr. Jennifer Woyach, M.D., of The Ohio State University College of Medicine. "Small molecules that target BTK that are not dependent upon the C481 site represent an exciting option for future clinical trials. We are excited to be working with ArQule on this project and look forward to initiating the first in man study with ARQ 531."

"We began our BTK discovery program in 2011 which ultimately lead to the selection of ARQ 531, a potent reversible inhibitor of both wild type and mutant BTK," said Dr. Giovanni Abbadessa, M.D., PhD., Vice President of Clinical Development, Translational Medicine and Medical Affairs at ArQule. "With the recent emergence in 2015 of BTK resistance we concentrated our efforts in this growing CLL patient population. We are pleased to be working with The Ohio State University to finish preclinical studies on this exciting program. We remain on track to file an IND application early next year."

About BTK and ARQ 531

ARQ 531 is an investigational, orally bioavailable, potent and reversible Bruton’s tyrosine kinase (BTK) inhibitor. Biochemical and cellular studies have shown that ARQ 531inhibits both the wild type and C481S-mutant forms of BTK. The C481S mutation is a known emerging resistance mechanism for first generation irreversible BTK inhibitors. ARQ 531 has high oral bioavailability as well as good ADME, pharmacokinetic and metabolic properties. The company plans to file an IND for ARQ 531 in early 2017. BTK is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers.