Therapeutic Antibodies

Two therapeutic antibody programs are currently in preclinical development for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS): CSC030 ADC (antibody drug conjugate) and CSC012 (an anti-IL1RAP naked antibody).


CSC030 is the first AML leukemic stem cell (LSC) target identified by Cellerant for development. CSC030-ADC is a humanized monoclonal antibody-drug conjugate (ADC) that targets an antigen expressed specifically on AML blasts and LSCs, but not on normal hematopoietic stem cells. The CSC030 target antigen is expressed on leukemic cells within both the bone marrow and blood compartments. The target antigen is present across all AML French American British (FAB) classifications and cytogenetic risk categories and is expressed independent of FLT-3 status. The target is expressed in de novo and recurrent disease states. Expression of the CSC030 antigen in combination with multidrug resistance (MDR) is associated with poor disease prognosis and greater probability of relapse. In addition to being expressed in AML, the CSC030 target antigen is expressed in MDS and other myeloproliferative disorders (e.g., polycythemia vera, essential thrombocythemia and polymyelofibrosis), affording opportunity for indication expansion. Several target-specific, high-affinity antibodies have been developed against CSC030 and have shown promising in vitro and in vivo efficacy against AML cells. Conjugation of these antibodies with a cytotoxic drug (e.g., DNA damaging agent) exhibited excellent therapeutic activity in preclinical orthotopic tumor models. CSC030-ADC is anticipated to advance into the clinic in 2016.

CSC012 (Anti-IL1RAP)

Interleukin-1 (IL1) is a central regulator of both acute and chronic inflammatory responses mediated by the immune system. Interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor for IL1 that functions in the IL1 receptor signal transduction complex and in some contexts is necessary to link cell membrane events to downstream signaling pathways. IL1RAP is also expressed by bulk tumor cells and cancer stem cells. A series of function-blocking, specific, monoclonal antibodies have been generated against IL1RAP. Binding of these antibodies to AML patient cancer cells has been characterized by in vitro and in vivo assays. Their activity against AML cells indicates that targeting IL1RAP is a promising therapeutic approach for the treatment of AML and has the potential for effective eradication of AML LSCs to provide long-term remission in the clinic. In addition, overexpression of IL1RAP in cells from high risk MDS patients has been reported (Barreyro 2012), suggesting its utility as a target for treating MDS. The CSC012 antibody program is funded by a National Cancer Institute (NCI) Small Business Innovation Research (SBIR) grant.

CSC030-ADC and CSC012 are expected to have broad utility across a range of heterogeneous AML patient types given that the target antigen is widely expressed in a variety of disease stages and phenotypes. Cellerant anticipates both antibody candidates will have significantly higher therapeutic indices as compared with other anti-leukemic cell antibody candidates in development (e.g., anti-CD33-ADCs) due to the high and selective expression of the CSC030 and CSC012 target antigens on leukemic cells and the absence of expression on normal hematopoietic stem cells.


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