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Target Overview
CD22 is restrictively expressed on the surface of B cells and their malignant counterparts including B-cell lymphomas and leukemias. Across multiple B-cell malignancies, CD22 positivity rates are reported as approximately 80% or greater.1-4 The high prevalence of CD22 expression in B-cell malignancies, combined with its distinctive internalization and recycling mechanism, makes it an attractive target for antibody drug conjugate (ADC)–mediated delivery of cytotoxic anti cancer payloads.5
Compound Overview
AZD4512 is a novel ADC composed of a CD22-directed monoclonal antibody conjugated via a novel cleavable linker to a cytotoxic topoisomerase 1 inhibitor payload, enabling selective payload delivery and killing of CD22-expressing B-cell leukemia & lymphoma tumor cells.6 The design of AZD4512 is intended to confer an improved safety profile and wider therapeutic index compared with previous ADCs targeting B-cell malignancies.
In the preclinical setting, AZD4512 demonstrated potent and selective killing of CD22-expressing cells and exhibited significant anti-tumor activity in patient-derived models of B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkin Lymphoma (B-NHL).6
AZD4512 is being evaluated in two clinical trials for the treatment of patients with relapsed or refractory B-ALL or B-NHL (NCT07109219, NCT07123454).
Mechanism of Action
References
1. Lejeune M, Köse MC, Duray E, Einsele H, Beguin Y, Caers J. Front Immunol. 2020;11:762. 2. Ding S, Mao X, Cao Y, Wang N, Xu H, Zhou J. Target Oncol. 2020;15(3):365-375. 3. Boué DR, LeBien TW. Blood. 1988;71(5):1480-1486. 4. Raponi S, De Propris MS, Intoppa S, et al. Leuk Lymphoma. 2011;52(6):1098-1107. 5. O'Reilly MK, Tian H, Paulson JC. J Immunol. 2011;186(3):1554-1563. 6. Han H, Klink M, Daita K, et al. Blood. 2025;146(Supplement 1):3296.
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Abbreviations
ADC
antibody drug conjugate
B-ALL
B-cell acute lymphoblastic leukemia
B-NHL
B-cell non-hodgkin lymphoma
CD22
cluster of differentiation 22
Target Overview
CD22 is restrictively expressed on the surface of B cells and their malignant counterparts including B-cell lymphomas and leukemias. Across multiple B-cell malignancies, CD22 positivity rates are reported as approximately 80% or greater.1-4 The high prevalence of CD22 expression in B-cell malignancies, combined with its distinctive internalization and recycling mechanism, makes it an attractive target for antibody drug conjugate (ADC)–mediated delivery of cytotoxic anti cancer payloads.5
Compound Overview
AZD4512 is a novel ADC composed of a CD22-directed monoclonal antibody conjugated via a novel cleavable linker to a cytotoxic topoisomerase 1 inhibitor payload, enabling selective payload delivery and killing of CD22-expressing B-cell leukemia & lymphoma tumor cells.6 The design of AZD4512 is intended to confer an improved safety profile and wider therapeutic index compared with previous ADCs targeting B-cell malignancies.
In the preclinical setting, AZD4512 demonstrated potent and selective killing of CD22-expressing cells and exhibited significant anti-tumor activity in patient-derived models of B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkin Lymphoma (B-NHL).6
AZD4512 is being evaluated in two clinical trials for the treatment of patients with relapsed or refractory B-ALL or B-NHL (NCT07109219, NCT07123454).
Mechanism of Action
References
1. Lejeune M, Köse MC, Duray E, Einsele H, Beguin Y, Caers J. Front Immunol. 2020;11:762. 2. Ding S, Mao X, Cao Y, Wang N, Xu H, Zhou J. Target Oncol. 2020;15(3):365-375. 3. Boué DR, LeBien TW. Blood. 1988;71(5):1480-1486. 4. Raponi S, De Propris MS, Intoppa S, et al. Leuk Lymphoma. 2011;52(6):1098-1107. 5. O'Reilly MK, Tian H, Paulson JC. J Immunol. 2011;186(3):1554-1563. 6. Han H, Klink M, Daita K, et al. Blood. 2025;146(Supplement 1):3296.
Clinical trial information
Select trial for more information
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Abbreviations
ADC
antibody drug conjugate
B-ALL
B-cell acute lymphoblastic leukemia
B-NHL
B-cell non-hodgkin lymphoma
CD22
cluster of differentiation 22