Mivavotinib (CB-659)

In early phase studies, mivavotinib showed deep and durable single-agent activity in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and other NHL. In addition, recent preclinical studies have shown enhanced SYK activity and sensitivity to SYK inhibition in DLBCL and other NHLs harboring mutations in MyD88 and/or CD79, which comprise a distinct genetic subset of DLBCL known to have poor outcomes with standard-of-care therapy. In NHLs with certain mutations, including MYD88 and CD79, SYK activation is essential for proliferation and survival.

Mivavotinib has demonstrated clinically meaningful overall response rate (ORR) and duration of response (DOR) in unselected relapsed/refractory DLBCL patients, and higher ORR and DOR than other SYK inhibitors in this setting.

Recent preclinical studies suggest MyD88/CD79 mutations in DLBCL and Waldenstrom macroglobulinemia (WM) may be particularly vulnerable to SYK inhibition.

DLBCL is the most common subtype of NHL with more than 18,000 people in the U.S. diagnosed with DLBCL each year, which is approximately 30% of all cases. MyD88 mutations occur in 30% and CD79 mutations occur in 10-15% of DLBCL tumors.

WM is a rare type of lymphoma diagnosed in approximately 1,000-1,500 Americans each year. 90% of WM tumors have MyD88 mutations.

Calithera plans to initiate a Phase 2 study of mivavotinib in the first quarter of 2022 for the treatment of patients with DLBCL with and without mutations in MyD88 and CD79. Beyond DLBCL, both preclinical and clinical data support expansion across additional NHL subtypes and other hematologic malignancies as part of long-term plans.