ArQule Presents Results from Ongoing Phase 1 Dose Escalation Study of its Reversible BTK Inhibitor, ARQ 531

On June 15, 2018 ArQule, Inc. (Nasdaq:ARQL) today is presenting preliminary results from the Company’s Phase 1 dose escalation study for ARQ 531, an orally bioavailable, potent and reversible inhibitor of both wild type and C481S-mutant Bruton’s tyrosine kinase (BTK) in patients with relapsed or refractory hematologic malignancies at the 23rd Congress of European Hematological Association (EHA) (Free EHA Whitepaper) in Stockholm, Sweden (Press release, ArQule, JUN 15, 2018, View Source [SID1234527333]).

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"Preliminary data from our Phase 1 dose escalation trial highlights the potential of ARQ 531 to become a new therapeutic option for patients with B-cell malignancies," commented ArQule Chief Medical Officer and Head of Research and Development, Brian Schwartz, M.D. "There is a significant unmet need for patients with relapsed or refractory B-cell malignancies, in particular those with C481S-mediated resistance to irreversible BTK inhibitors such as ibrutinib. We are especially encouraged by the early signs of anti-tumor activity observed in the first three cohorts."

The reported data from the ongoing Phase 1, open label, single arm dose escalation 3+3 study are from the first three cohorts at dose levels of 5 (n=3), 10 (n=4) and 15 mg (n=4) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), Waldenstrom’s macroglobinemia and B-cell Non-Hodgkin lymphoma.

ARQ 531 demonstrated preliminary anti-tumor activity at all dose levels, resulting in an observed tumor reduction of 35% at 5mg, 33% at 10mg, and 29% at 15mg doses. The 29% tumor reduction in the 15mg cohort was achieved after 8 weeks of treatment in a patient with the BTK C481S-mutation, after 5 prior systemic regimens including ibrutinib and venetoclax, with treatment still ongoing. Overall treatment duration ranged from 1 to 46 weeks with 4 of 11 patients treated still ongoing.

ARQ 531 was well tolerated at all three dose levels, supporting continued dose escalation. No dose limiting toxicities or ARQ 531-related Grade 3 or greater adverse events were observed, and the maximum tolerated dose has not been reached.

The half-life of ARQ 531 was between 22-27 hours suggesting the potential for sustained target inhibition and supporting a once daily dosing regimen with preliminary pharmacokinetics showing increases in exposure that are approximately dose proportional.

The poster, A Phase 1 Dose Escalation Study of ARQ 531 in Selected Patients with Relapsed or Refractory Hematologic Malignancies, is available on ArQule’s website, www.arqule.com, under "Publications and Presentations": View Source

About BTK and ARQ 531

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