Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)

ADC ID	DRG0IFQQN
ADC Name	M9346A-4a-Cxxx-Mal-CX-DM1
Synonyms	M9346A 4a Cxxx Mal CX DM1 Click to Show/Hide
Drug Status	Investigative
Indication	In total 1 Indication(s) Cervical cancer [ICD11:2C77] Investigative
Drug-to-Antibody Ratio	2
	3D MOL	2D MOL
Antibody Name	Mirvetuximab (engineered cysteine LC-C205)		Antibody Info
Antigen Name	Folate receptor alpha (FOLR1)		Antigen Info
Payload Name	Mertansine DM1		Payload Info
Therapeutic Target	Microtubule (MT)		Target Info
Linker Name	Cxxx-Mal-CX		Linker Info
Conjugate Type	Random conjugation through reduced inter-chain cysteines.

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)	≈ 41.22	%	KB cells	Human papillomavirus-related endocervical adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 99.58	%	KB cells	Human papillomavirus-related endocervical adenocarcinoma

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)	0.15	nM	KB cells	Human papillomavirus-related endocervical adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	5	nM	KB cells	Human papillomavirus-related endocervical 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)	≈ 41.22% (Day 23)	Positive FOLR1 expression (FOLR1 +++/++)
Method Description	M9346A-4a-Cxxx-Mal-CX-DM1 (200 ug/kg, every seven days x3) induces efficient tumor cell killing in cell line-derived models of KB cells with HER2 expression with high expression.
In Vivo Model	KB CDX model
In Vitro Model	Human papillomavirus-related endocervical adenocarcinoma	KB cells		CVCL_0372
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.58% (Day 23)	Positive FOLR1 expression (FOLR1 +++/++)
Method Description	M9346A-4a-Cxxx-Mal-CX-DM1 (100 ug/kg, every seven days x3) induces efficient tumor cell killing in cell line-derived models of KB cells with HER2 expression with high expression.
In Vivo Model	KB CDX model
In Vitro Model	Human papillomavirus-related endocervical adenocarcinoma	KB cells		CVCL_0372

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					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.15 nM	Positive FOLR1 expression (FOLR1 +++/++)
Method Description	Cytotoxic IC50 Values (as a Function of [ADC] and [DM1]) for Various M9346A-CX-DM1 ADCs against FR-Expressing KB Cells in the absence of 1 M unconjugated M9346A antibody.
In Vitro Model	Human papillomavirus-related endocervical adenocarcinoma	KB cells		CVCL_0372
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	5.00 nM	Positive FOLR1 expression (FOLR1 +++/++)
Method Description	Cytotoxic IC50 Values (as a Function of [ADC] and [DM1]) for Various M9346A-CX-DM1 ADCs against FOLR1-Expressing KB Cells in the presence of 1 M unconjugated M9346A antibody.
In Vitro Model	Human papillomavirus-related endocervical adenocarcinoma	KB cells		CVCL_0372

References

Ref 1	A Case Study Comparing Heterogeneous Lysine- and Site-Specific Cysteine-Conjugated Maytansinoid Antibody-Drug Conjugates (ADCs) Illustrates the Benefits of Lysine Conjugation. Mol Pharm. 2019 Sep 3;16(9):3926-3937. doi: 10.1021/acs.molpharmaceut.9b00529. Epub 2019 Jul 31.