Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)

ADC ID	DRG0HRDSA
ADC Name	Anti-TNF ADC 121
Synonyms	Anti-TNF-ADC-121 Click to Show/Hide
Organization	AbbVie, Inc.
Drug Status	Investigative
Indication	In total 1 Indication(s) Rheumatoid arthritis [ICD11:FA20] Investigative
Drug-to-Antibody Ratio	2
Structure
	3D MOL	2D MOL
Antibody Name	Anti-TNF mAb alpha-TNF		Antibody Info
Antigen Name	Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)		Antigen Info
Payload Name	GRM cpd 17		Payload Info
Therapeutic Target	Glucocorticoid receptor (NR3C1)		Target Info
Linker Name	MP-Ala-Ala		Linker Info
Conjugate Type	The free sulfhydryl group obtained by the reduction of interchain cysteine is site-specific conjugated with maleimide, michael addition reaction, followed by incubation at basic ph to hydrolyze-open the maleimide ring.

General Information of The Activity Data Related to This ADC

Obtained from the Model Organism Data

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

Standard Type	Value	Units	Animal Model (No. of PDX)
Paw swelling AUC	74	%	Collagen-induced arthritis (mCIA) model
Paw swelling AUC	96	%	Collagen-induced arthritis (mCIA) 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 Effective Concentration (EC50)	0.09	ug/mL	K-562 cells (TNF expression)	Chronic myelogenous leukemia
Half Maximal Effective Concentration (EC50)	43.7	ug/mL	K-562 cells	Chronic myelogenous leukemia

Full List of Activity Data of This Antibody-drug Conjugate

Obtained from the Model Organism Data

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

Experiment 1 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Paw swelling AUC	74.00%	Positive TNF expression (TNF+++/++)
Method Description	To evaluate the impact of the anti-mTNF GRM ADCs on inflammation in a chronic inflammatory setting,we progressed several ADCs into a mouse collagen-induced arthritis (mCIA) model. A single 3 mg/kg dose of the ADC was given at the first clinical signs of disease,a time point of intervention where anti-TNF treatment has a moderate impact.
In Vivo Model	Collagen-induced arthritis (mCIA) model
Experiment 2 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Paw swelling AUC	96.00%	Positive TNF expression (TNF+++/++)
Method Description	To evaluate the impact of the anti-mTNF GRM ADCs on inflammation in a chronic inflammatory setting,we progressed several ADCs into a mouse collagen-induced arthritis (mCIA) model. A single 10 mg/kg dose of the ADC was given at the first clinical signs of disease,a time point of intervention where anti-TNF treatment has a moderate impact.
In Vivo Model	Collagen-induced arthritis (mCIA) 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					[1]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.09 ug/mL	Positive TNF expression (TNF+++/++)
Method Description	All the DAR purified ADCs were screened in both the TNF-expressing and wild-type K562 GRE reporter cell assay to confirm that their activity was consistent with ADCs having heterogeneous average DAR.
In Vitro Model	Chronic myelogenous leukemia	K-562 cells (TNF expression)		CVCL_0004
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Effective Concentration (EC50)	43.70 ug/mL	Negative TNF expression (TNF-)
Method Description	All the DAR purified ADCs were screened in both the TNF-expressing and wild-type K562 GRE reporter cell assay to confirm that their activity was consistent with ADCs having heterogeneous average DAR.
In Vitro Model	Chronic myelogenous leukemia	K-562 cells		CVCL_0004

References

Ref 1	Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate. J Med Chem. 2022 Dec 8;65(23):15893-15934.