ADC Therapeutics’ proprietary ADCs are highly targeted drug constructs that combine monoclonal antibodies specific to surface tumor targets with a novel class of highly potent PBD-dimer toxins.
PBD dimers do not distort the DNA structure, which makes them invisible to repair mechanisms and allows the cross-links to persist within the DNA. Unlike earlier generation PBD chemistry, ADC Therapeutics’ proprietary PBD dimers are not a substrate for multi-drug resistance proteins—even in hard-to-treat tumors.
ADCT has multiple PBD-based ADCs in ongoing clinical trials and numerous preclinical ADCs in development.
Some of the agents represented in this pipeline chart are investigational. Efficacy and safety have not yet been established.
Expand each compound to learn more.
Loncastuximab tesirine-lpyl is an ADC composed of a humanized monoclonal antibody that binds to human CD19 and is conjugated through a linker to a PBD–dimer toxin. CD19 is a clinically validated target for the treatment of B-cell malignancies.
Camidanlumab tesirine, ADCT’s second lead candidate, has demonstrated significant clinical activity in heavily pretreated patients with Hodgkin lymphoma.
ADCT-602 is an ADC composed of a monoclonal antibody that binds to CD22 conjugated to a PBD-dimer toxin. CD22 is highly expressed on most malignant B-cells, including expression in more than 90% of patients with B-cell acute lymphoblastic leukemia (ALL). ADCT-602 is being evaluated in a phase I/II clinical trial in patients with relapsed or refractory B-cell ALL.
ADCT-601 is an ADC composed of a humanized monoclonal antibody that binds to human AXL (licensed from BerGenBio), conjugated using Glycoconnect™ technology (licensed from Synaffix BV) to a linker with a PBD-dimer toxin. AXL is highly overexpressed in many solid tumors and hematological malignancies. ADCT-601 is being evaluated in a phase 1 clinical trial in patients with selected advanced solid tumors.
ADCT-901 is an ADC composed of a humanized monoclonal antibody (3A4) directed against human KAAG1 and conjugated through a cathepsin-cleavable linker to SG3199, a PBD–dimer cytotoxin. KAAG1 has high expression in tumors with high unmet medical need, while its expression on healthy tissue is very restricted. ADCT-901 is being developed for the treatment of advanced solid tumors with high unmet medical needs, including platinum resistant ovarian cancer and triple negative breast cancer.
ADCT-701 is an ADC composed of a humanized monoclonal antibody (HuBa-1-3D) directed against human DLK-1 and conjugated through a cathepsin-cleavable linker to SG3199, a PBD-dimer cytotoxin. DLK-1 is an attractive novel tumor target for ADC development as it is expressed in adults in several tumors. ADCT-701 is being developed for the treatment of advanced solid tumors with high unmet medical needs, neuroblastoma, hepatocellular carcinoma, and small cell lung cancer.
Anticipated milestones set forth in this chart are subject to further future adjustment based on, among other factors, the impact of the COVID-19 pandemic.
*We believe that our Phase 1/2 clinical trial of a CD19-targeted investigational lead compound in combination with ibrutinib for the treatment of R/R DLBCL and MCL, our Phase 2 clinical trial of a CD19-targeted investigational lead compound for the treatment of R/R FL, and our Phase 2 clinical trial of a CD25-targeted investigational compound for the treatment of R/R HL, are pivotal clinical trials (i.e., a clinical trial intended to serve as the basis for BLA submission). Therefore, we believe that subsequent Phase 3 clinical trials will be confirmatory clinical trials.
2L, second line; 3L, third line; ADC, antibody drug conjugate; BLA, Biologics License Application; CD, cluster of differentiation; COVID-19, coronavirus disease 2019; DLBCL, diffuse large B-cell lymphoma; FDA, US Food and Drug Administration; FL, follicular lymphoma; HL, Hodgkin lymphoma; MCL, mantle cell lymphoma; NTE, non-transplant eligible; PBD, pyrrolobenzodiazepine; R/R, relapsed or refractory.
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