Antibody-drug Conjugate Information

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
	3D MOL	2D MOL
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.