Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)

ADC ID	DRG0OHTUI
ADC Name	Trastuzumab-C239I-SG3249
Synonyms	Trastuzumab-C239i-SG3249 Click to Show/Hide
Drug Status	Investigative
Indication	In total 2 Indication(s) Breast cancer [ICD11:2C60-2C65] Investigative Gastric cancer [ICD11:2B72] Investigative
Drug-to-Antibody Ratio	2
Structure
	3D MOL	2D MOL
Antibody Name	Trastuzumab		Antibody Info
Antigen Name	Receptor tyrosine-protein kinase erbB-2 (ERBB2)		Antigen Info
Payload Name	SG3199		Payload Info
Therapeutic Target	Human Deoxyribonucleic acid (hDNA)		Target Info
Linker Name	Mal-PEG8-Val-Ala-PABC		Linker Info
Conjugate Type	Conjudating to SG3249 using sulfhydryl groups obtained by reduction of interchain cysteines in the flexmab hinge region, Michael addition reaction.
Combination Type	SG3249

General Information of The Activity Data Related to This ADC

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 2 Activity Data Related to This Level

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 94	%	NCI-N87 cells	Gastric tubular adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 94.2	%	NCI-N87 cells	Gastric tubular adenocarcinoma

Revealed Based on the Cell Line Data

Click To Hide/Show 1 Activity Data Related to This Level

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	14.4	pM	SK-BR-3 cells	Breast adenocarcinoma

Full List of Activity Data of This Antibody-drug Conjugate

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 2 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.00% (Day 50)	Low HER2 expression (HER2+)
Method Description	The in vivo efficacy of trastuzumab-C239i-SG3249 was investigated after single-dose injections (0.30 mg/kg) in female athymic mice bearing NCI-N87 HER2-positive subcutaneous xenografts. NCI-N87 cells (5 x10⁶) in 50% Matrigel were inoculated subcutaneously into 46 week-old female athymic nude mice. Five mice per group were dosed intravenously five days after their tumors reached a volume of 200 mm³. Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.20% (Day 40)	Low HER2 expression (HER2+)
Method Description	The in vivo efficacy of trastuzumab-Flexmab-SG3710 and trastuzumab-C239i-SG3249 ADCs was investigated after single-dose injections (1 mg/kg) in female athymic mice bearing NCI-N87 HER2-positive subcutaneous xenografts,and tumor growth was monitored for 85 days. NCI-N87 cells (5 x10⁶) in 50% Matrigel were inoculated subcutaneously into 46 week-old female athymic nude mice. Five mice per group were dosed intravenously five days after their tumors reached a volume of 200 mm³. Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Revealed Based on the Cell Line Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	14.40 pM	Low HER2 expression (HER2+)
Method Description	The cytotoxic effect of Trastuzumab-C239i-SG32490 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing breast and gastric cancers. The potency of trastuzumab-Flexmab-SG3710 was assessed on the SKBR-3 cell line after five days of incubation.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033

References

Ref 1	Design and characterization of homogenous antibody-drug conjugates with a drug-to-antibody ratio of one prepared using an engineered antibody and a dual-maleimide pyrrolobenzodiazepine dimer. MAbs. 2019 Apr;11(3):500-515.