On December 3, 2018 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing monoclonal antibodies for the treatment of autoimmune disease, asthma and allergic diseases, and cancer, reported initial data from its ongoing Phase 1 dose-escalation study of XmAb14045, a CD123 x CD3 bispecific antibody, in patients with relapsed/refractory acute myeloid leukemia (AML) (Press release, Xencor, DEC 3, 2018, View Source [SID1234531893]). The data were presented in an oral session at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by Farhad Ravandi, M.D., Professor of Medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at the University of Texas – MD Anderson Cancer Center.

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Key Highlights

66 patients with relapsed/refractory AML received XmAb14045. Patients were a median of 61 years old and were heavily pretreated, having had a median of three prior therapies and 30% (n=20) with a history of allogeneic stem cell transplantation. 86% of patients (n=57) were refractory to their last therapy, and 53% (n=35) were categorized as adverse risk at diagnosis by the European LeukemiaNet (ELN 2017) system.
A maximum tolerated dose (MTD) has not been reached. Cytokine release syndrome (CRS) was the most common toxicity occurring in 55% of patients (n=36). 6% of patients (n=4) experienced Grade 3 or 4 CRS. CRS was more severe on the initial dose and was generally manageable with premedication. Additional adverse events consistent with CRS but not reported as such, including chills, fever, tachycardia, hypotension and hypertension within 24 hours of infusion, were reported in an additional 29% of patients (n=19).
28% of evaluable patients with AML achieved either complete remission (CR) or CR with incomplete hematologic recovery (CRi) at the two highest initial dose levels studied (1.3 and 2.3 mcg/kg weekly; n=5/18).
Two patients with responses were bridged to stem cell transplantation, and a third transplant-ineligible patient has remained in remission for 16+ weeks after discontinuation of therapy.
"We have observed multiple complete remissions in heavily pretreated, relapsed/refractory AML patients from XmAb14045 dosed weekly, and we continue to optimize dosing regimen," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "Xencor’s XmAb technology enables bispecific antibodies to retain natural antibody properties, simplifying their use and production. Our platform enables the rapid development of new bispecific antibody drug candidates addressing a breadth of targets, and throughout 2019 we anticipate several new clinical trial initiations and additional data readouts."

The data presentation is available under Archived Scientific Presentations on the Events & Presentations page in the Investors section of www.xencor.com.

Analyst & Investor Event and Webcast Information
Xencor will host an analyst and investor event tonight from 8:00 to 10:00 p.m. PST with formal remarks at 8:30 p.m. PST. The formal remarks will feature a discussion of the data presented at ASH (Free ASH Whitepaper) and Xencor’s bispecific oncology pipeline. It will be webcast live and can be accessed under Events & Presentations in the Investors section of www.xencor.com, where it will be archived for 30 days.

About XmAb14045
XmAb14045 is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies. An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb14045. CD123 is highly expressed on AML cells and leukemic stem cells, and it is associated with poorer prognosis in AML patients. Engagement of CD3 by XmAb14045 activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.