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CD33 inhibitor

Fc-engineered CD33 mAb


The FDA granted BI 836858* Orphan Drug Designation for the treatment of acute myeloid leukaemia (AML) in June 2014 and for the treatment of myelodysplastic syndrome (MDS) in March 2017. Several Phase I and II studies investigating BI 836858 for the treatment of AML and MDS are ongoing.

About BI 836858

BI 836858’s mechanism of action

BI 836858 is a fully human immunoglobulin G (IgG) 1 CD33 mAb that binds to CD33 through antigen specific binding sites. BI 836858 has been engineered to bind with higher affinity to Fcƴ receptors (FcƴRIIIa) of effector cells, such as natural killer (NK) cells, than plasma IgG, thereby mediating more potent antibody-dependent cellular cytotoxicity (ADCC).1

CD33 monoclonal antibody mechanism of action

Watch BI 836858’s mechanism of action

Watch BI 836858’s mechanism of action

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The role of CD33

CD33 is a cell surface antigen found on haematopoietic cells, primarily cells of myeloid lineage, for example monocytes and granulocytes; it is absent on haematopoietic stem cells.2,3 CD33 is widely expressed on malignant cells in AML2 and is a validated target, notably with the CD33-directed antibody-drug conjugate gemtuzumab ozagomicin showing improved overall survival.4 In addition, CD33 plays a direct role in the pathogenesis of MDS by acting as a receptor for S100A9 to initiate suppressive inflammatory signalling that can in turn lead to genomic instability.5

Preclinical studies

Preclinical studies with BI 836858 have shown high affinity binding of BI 836858 to CD33 and NK‑mediated ADCC against malignant CD33+ AML cells.1 Compared with the CD33 mAb, lintuzumab, BI 836858 showed slower internalisation resulting in higher levels of CD33 retained on the cell-surface and enhanced ADCC against human cells.1

Clinical development

BI 836858 is currently being investigated in Phase I/II trials for the treatment of the myeloid malignancies AML6-8 and MDS.9


BI 836858 haematology trials

AML, acute myeloid leukaemia; BSC, best supportive care; DLT, dose-limiting toxicity; GvHD, graft-vs-host disease; MDS, myelodysplastic syndrome; MTD, maximum tolerated dose; OS, overall survival; PFS, progression-free survival; RBC, red blood cell.

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Vasu S, et al. Blood 2016;127(23):2879–89.


Ehninger A, et al. Blood Cancer J 2014;4:e218.


Nguyen DH, et al. Exp Hematol 2006;34(6):728–35.


Hills RK, et al. Lancet Oncol 2014;15(9);986–96.


Eksioglu EA, et al. Leukemia 2017; [Epub ahead of print].

6 NCT01690624. (Accessed: July 2017).

7 NCT02632721. (Accessed: July 2017).

8 NCT03207191. (Accessed: July 2017).

9 NCT03013998. (Accessed: July 2017).

10 NCT02240706. (Accessed: July 2017).

*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.