General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0IJNAM
ADC Name
D3-GPC2-PBD
Drug Status
Investigative
Indication
In total 2 Indication(s)
Neuroblastoma [ICD11:2A00]
Investigative
Small cell lung cancer [ICD11:2C25]
Investigative
Drug-to-Antibody Ratio
2.6
Antibody Name
Fully human D3-GPC2-IgG1
 Antibody Info 
Antigen Name
Glypican-2 (GPC2)
 Antigen Info 
Payload Name
PBD dimer
 Payload Info 
Therapeutic Target
Human Deoxyribonucleic acid (hDNA)
 Target Info 
Linker Name
Undisclosed
General Information of The Activity Data Related to This ADC
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type Value Units Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI) 
≈ 86.8
%
COG-N-421x PDX model
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
10
pM
SK-N-AS cells
Neuroblastoma
Half Maximal Inhibitory Concentration (IC50) 
26.6
pM
NB-SD cells
Neuroblastoma
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 86.80% (Day 2) High GPC2 expression (GPC2+++)
Method Description
Tumors were typically implanted into the flanks of female 5-9 week-old C.B-17 scid mice. Each mouse was then given a single dose of their respective ADC treatments in PBS or vehicle (Day 0) via intraperitoneal (IP) injection. In some efficacy studies, one cohort of mice received 3 subsequent ADC 1 mg/kg IP injections over the following 2 weeks (1 mg/kg x 4 cohort).

   Click to Show/Hide
In Vivo Model COG-N-421x PDX model
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 10.00 pM High GPC2 expression (GPC2+++)
Method Description
Cells were incubated with increasing concentrations in tested compounds for 96 h and cell viability was determined by MTS assay.
In Vitro Model Neuroblastoma SK-N-AS cells CVCL_1700
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 26.60 pM Positive GPC2 expression (GPC2 +++/++)
Method Description
Cell lines were plated in 96-well plates (typically between 1,000 and 5,000 cells/well) and treated with serial dilutions of each ADC payload, the D3-GPC2-PBD ADC, or vehicle the following day. After four additional days, cell viability was determined using a CellTiter-Glo Assay.
In Vitro Model Neuroblastoma NB-SD cells CVCL_LF68
References
Ref 1 A GPC2 antibody-drug conjugate is efficacious against neuroblastoma and small-cell lung cancer via binding a conformational epitope. Cell Rep Med. 2021 Jul 21;2(7):100344.
Ref 2 A GPC2 antibody-drug conjugate is efficacious against neuroblastoma and small-cell lung cancer via binding a conformational epitope. Cell Rep Med. 2021 Jul 21;2(7):100344. doi: 10.1016/j.xcrm.2021.100344.
Ref 3 Antibody-Drug Conjugate Efficacy in Neuroblastoma: Role of Payload, Resistance Mechanisms, Target Density, and Antibody Internalization. Mol Cancer Ther. 2021 Nov;20(11):2228-2239. doi: 10.1158/1535-7163.MCT-20-1034.

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