Xencor doses first patient in phase 1 clinical trial of XmAb14045

"XmAb14045 is a bispecific antibody that engages the immune system against AML," said Paul Foster, M.D., chief medical officer at Xencor.

"Built on the scaffold of Xencor's XmAb bispecific Fc domain, XmAb14045 simultaneously binds to CD123, a protein on AML cells, and CD3, a protein on cytotoxic T cells, to activate a targeted immune response against the cancer cells. XmAb14045 has shown highly potent killing of tumor cells in preclinical studies and we look forward to studying its safety, tolerability and antitumor activity in clinical trials."

The purpose of the trial is to determine the safety and tolerability of weekly intravenous administration of XmAb14045 and to determine the maximally tolerated dose/dosing schedule.

Approximately 60 patients with AML or other CD123-expressing hematologic malignancies will receive XmAb14045. XmAb14045 showed very effective and potent depletion of target cells in primate studies from a well-tolerated single IV dose.

XmAb14045 is Xencor's lead bispecific candidate within the company's broad portfolio of CD3 bispecific antibody immunotherapies.

Xencor and Novartis share worldwide development costs for XmAb14045 with Xencor maintaining U.S. commercial rights and Novartis having commercial rights in the rest of the world. Xencor expects to advance additional candidates using Xencor's XmAb bispecific technology into the clinic by the end of 2017.

About XmAb14045

XmAb14045 is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in Phase 1 clinical trials 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 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.

About Xencor's XmAb Bispecific Technology

As opposed to traditional monoclonal antibodies that target and bind to a single antigen, bispecific antibodies are designed to elicit multiple biological effects that require simultaneous binding to two different antigen targets. 

Xencor's XmAb bispecific Fc domain technology is designed to maintain full-length antibody properties in a bispecific antibody, potentially enabling favorable in vivo half-life and simplified manufacturing.

Efforts at bispecific antibody design are typically frustrated by poor molecular stability, difficulties in production and short in vivo half-life. 

Xencor has engineered a series of Fc domain variants that spontaneously form stable, heterodimeric bispecific antibodies and that can be made and purified with standard antibody production methods. These bispecific Fc domains are used to generate a broad array of novel drug candidates in a range of molecule formats.

Xencor's initial bispecific programs are T-cell engaging cancer immunotherapies that bind to cancer cells at one end and bind to cytotoxic T-cells at the other end, resulting in a highly potent and targeted killing of cancer cells.

The XmAb Fc domain format allows Xencor to tune the potency of the T-cell killing, potentially improving the tolerability of cancer immunotherapy. 

About Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a cancer of the blood and bone marrow characterized by rapid growth of abnormal blood cells that interfere with production of normal cells. It is estimated 20,000 patients in the United States will be diagnosed with AML each year. Without treatment AML can progress quickly and become fatal.