ADC ID	DRG0FBKIO
ADC Name	ABBV-3373
Synonyms	ABBV-3373    Click to Show/Hide
Organization	AbbVie (Top20 MNC) (Originator)
Drug Status	Phase 2 (discontinued)
Drug-to-Antibody Ratio	4
Structure
	3D MOL			2D MOL
Antibody Name	Adalimumab					Antibody Info
Antigen Name	Tumor necrosis factor (TNF)					Antigen Info
Payload Name	Glucocorticoid receptor modulator					Payload Info
Therapeutic Target	Glucocorticoid receptor (NR3C1)					Target Info
Linker Name	MP-Ala-Ala					Linker Info
Conjugate Type	Random Cysteines

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	1.5	ug/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg SC.	[1]
Time to Maximum Concentration (Tmax)	3	day	Pharmacokinetic parameters of ABBV-3373, 30 mg SC.	[1]
Area Under the Concentration-Time Curve (AUC)	390	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	475	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg SC, AUCinf.	[1]
Maximum Observed Concentration (Cmax)	4.76	ug/mL	Pharmacokinetic parameters of ABBV-3373, 100 mg SC.	[1]
Time to Maximum Concentration (Tmax)	2.5	day	Pharmacokinetic parameters of ABBV-3373, 100 mg SC.	[1]
Area Under the Concentration-Time Curve (AUC)	1210	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 100 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	1260	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 100 mg SC, AUCinf.	[1]
Maximum Observed Concentration (Cmax)	28	ug/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg SC.	[1]
Time to Maximum Concentration (Tmax)	3.5	day	Pharmacokinetic parameters of ABBV-3373, 300 mg SC.	[1]
Area Under the Concentration-Time Curve (AUC)	10100	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	10200	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg SC, AUCinf.	[1]
Maximum Observed Concentration (Cmax)	10.4	ug/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg IV.	[1]
Time to Maximum Concentration (Tmax)	2.5	h	Pharmacokinetic parameters of ABBV-3373, 30 mg IV.	[1]
Area Under the Concentration-Time Curve (AUC)	1280	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	1310	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg IV, AUCinf.	[1]
Maximum Observed Concentration (Cmax)	85.7	ug/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg IV.	[1]
Time to Maximum Concentration (Tmax)	1.2	h	Pharmacokinetic parameters of ABBV-3373, 300 mg IV.	[1]
Area Under the Concentration-Time Curve (AUC)	18000	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	18100	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg IV, AUCinf.	[1]
Maximum Observed Concentration (Cmax)	298	ug/mL	Pharmacokinetic parameters of ABBV-3373, 900 mg IV.	[1]
Time to Maximum Concentration (Tmax)	4	h	Pharmacokinetic parameters of ABBV-3373, 900 mg IV.	[1]
Area Under the Concentration-Time Curve (AUC)	55400	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 900 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	55600	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 900 mg IV, AUCinf.	[1]
Maximum Observed Concentration (Cmax)	4.7	ug/mL	Concentrations of ABBV-3373 over time, week 2.	[2]
Maximum Observed Concentration (Cmax)	6.6	ug/mL	Concentrations of ABBV-3373 over time, week 6.	[2]
Maximum Observed Concentration (Cmax)	5.6	ug/mL	Concentrations of ABBV-3373 over time, week 10.	[2]
Maximum Observed Concentration (Cmax)	6.4	ug/mL	Concentrations of ABBV-3373 over time, week 12.	[2]
Maximum Observed Concentration (Cmax)	3	ug/mL	Concentrations of ABBV-3373 over time, week 14.	[2]
Maximum Observed Concentration (Cmax)	1	ug/mL	Concentrations of ABBV-3373 over time, week 16.	[2]
Maximum Observed Concentration (Cmax)	0.3	ug/mL	Concentrations of ABBV-3373 over time, week 20.	[2]
Maximum Observed Concentration (Cmax)	0.1	ug/mL	Concentrations of ABBV-3373 over time, week 24.	[2]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	390	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	475	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg SC, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	1210	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 100 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	1260	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 100 mg SC, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	10100	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	10200	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg SC, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	1280	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	1310	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg IV, AUCinf.	[1]
Volume of Distribution (Vd)	3780	mL	Pharmacokinetic parameters of ABBV-3373, 30 mg IV.	[1]
Area Under the Concentration-Time Curve (AUC)	18000	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	18100	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg IV, AUCinf.	[1]
Volume of Distribution (Vd)	5010	mL	Pharmacokinetic parameters of ABBV-3373, 300 mg IV.	[1]
Area Under the Concentration-Time Curve (AUC)	55400	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 900 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	55600	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 900 mg IV, AUCinf.	[1]
Volume of Distribution (Vd)	5010	mL	Pharmacokinetic parameters of ABBV-3373, 900 mg IV.	[1]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	390	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	475	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg SC, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	1210	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 100 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	1260	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 100 mg SC, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	10100	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	10200	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg SC, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	1280	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	1310	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg IV, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	18000	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	18100	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg IV, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	55400	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 900 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	55600	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 900 mg IV, AUCinf.	[1]

Standard Type	Value	Units	Description	Reference
Elimination Half-Life (t1/2)	4.52	day	Pharmacokinetic parameters of ABBV-3373, 30 mg SC.	[1]
Area Under the Concentration-Time Curve (AUC)	390	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	475	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg SC, AUCinf.	[1]
Elimination Half-Life (t1/2)	3.09	day	Pharmacokinetic parameters of ABBV-3373, 100 mg SC.	[1]
Area Under the Concentration-Time Curve (AUC)	1210	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 100 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	1260	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 100 mg SC, AUCinf.	[1]
Elimination Half-Life (t1/2)	7.37	day	Pharmacokinetic parameters of ABBV-3373, 300 mg SC.	[1]
Area Under the Concentration-Time Curve (AUC)	10100	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg SC, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	10200	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg SC, AUCinf.	[1]
Elimination Half-Life (t1/2)	4.44	day	Pharmacokinetic parameters of ABBV-3373, 30 mg IV.	[1]
Area Under the Concentration-Time Curve (AUC)	1280	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	1310	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 30 mg IV, AUCinf.	[1]
Clearance (CL)	22.8	mL/h	Pharmacokinetic parameters of ABBV-3373, 30 mg IV.	[1]
Elimination Half-Life (t1/2)	6.61	day	Pharmacokinetic parameters of ABBV-3373, 300 mg IV.	[1]
Area Under the Concentration-Time Curve (AUC)	18000	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	18100	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 300 mg IV, AUCinf.	[1]
Clearance (CL)	16.6	mL/h	Pharmacokinetic parameters of ABBV-3373, 300 mg IV.	[1]
Elimination Half-Life (t1/2)	7.73	day	Pharmacokinetic parameters of ABBV-3373, 900 mg IV.	[1]
Area Under the Concentration-Time Curve (AUC)	55400	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 900 mg IV, AUCtau.	[1]
Area Under the Concentration-Time Curve (AUC)	55600	ug*h/mL	Pharmacokinetic parameters of ABBV-3373, 900 mg IV, AUCinf.	[1]
Clearance (CL)	16.2	mL/h	Pharmacokinetic parameters of ABBV-3373, 900 mg IV.	[1]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Undisclosed	NCT03823391	PHASE2	A Randomized, Double-Blind, Double-Dummy, Active Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Subjects With Moderate to Severe Rheumatoid Arthritis    Click to Show/Hide
Undisclosed	NCT03823391	Phase 2	A randomized, double-blind, double-dummy, active controlled study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ABBV-3373 in subjects with moderate to severe rheumatoid arthritis.    Click to Show/Hide
Undisclosed	NCT03823391	Phase 2	A randomized, double-blind, double-dummy, active controlled study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ABBV-3373 in subjects with moderate to severe rheumatoid arthritis.    Click to Show/Hide

Standard Type	Value	Units	Animal Model (No. of PDX)
Paw swelling AUC	81	%	Collagen-induced arthritis (mCIA) model
Paw swelling AUC	98	%	Collagen-induced arthritis (mCIA) model
P1NP inhibition	0	%	Acute contact hypersensitivity (CHS) model
P1NP inhibition	19	%	Acute contact hypersensitivity (CHS) model
Ear swelling inhibition	55	%	Fluorescein isothiocyanate (FITC)-induced CHS model
Ear swelling inhibition	88	%	Fluorescein isothiocyanate (FITC)-induced CHS model
Corticosterone inhibition	6	%	Acute contact hypersensitivity (CHS) model
Corticosterone inhibition	15	%	Acute contact hypersensitivity (CHS) model

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Effective Concentration (EC50)	0.08	ug/mL	K-562 cells (TNF expression)	Chronic myelogenous leukemia
Half Maximal Effective Concentration (EC50)	5.8	ug/mL	K-562 cells	Chronic myelogenous leukemia

Experiment 1 Reporting the Activity Date of This ADC					[3]
Patients Enrolled	Inclusion criteria require confirmed RA (1987 ACR/2010 EULAR criteria) lasting >3 months, with &ge;4 swollen/tender joints (28-count), DAS28-CRP &ge;3.2, and inadequate MTX response (stable dose 15-25mg/week [&ge;10mg/week if intolerant] for &ge;4 weeks). Exclusions include prior anti-TNF use (e.g., adalimumab) or non-anti-TNF biologics/tsDMARDs (unless used <3 months without efficacy/intolerability issues).    Click to Show/Hide
Administration Dosage	Participants will be administered with 100 mg ABBV-3373 by intravenous infusion and placebo to adalimumab by subcutaneous injection every other week for 12 weeks. After 12 weeks, participants will receive placebo to adalimumab every other week until Week 22.
Related Clinical Trial
NCT Number	NCT03823391	Clinical Status	PHASE2
Clinical Description	A Randomized, Double-Blind, Double-Dummy, Active Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Subjects With Moderate to Severe Rheumatoid Arthritis
Primary Endpoint	The primary endpoint is the change from baseline to Week 12 in Disease Activity Score 28 (DAS28-CRP), a composite index evaluating tender/swollen joint counts (28 joints), patient global assessment (VAS 0-100mm), and hsCRP (mg/L). Scores range from 0.96-10 (higher=worse activity); negative change indicates improvement.
Other Endpoint	Secondary endpoints include Week 12 changes in CDAI (sum of tender/swollen joints + patient/physician global assessments [VAS 0-10cm]; score 0-76), SDAI (CDAI+CRP; score 0-86), and DAS28-ESR (similar to DAS28-CRP but using ESR). Negative changes denote improvement. Additional measures: proportion achieving DAS28-CRP ≤3.2 (low disease activity) and American College of Rheumatology 50% (ACR50) response (≥50% improvement in joint counts + ≥3 of 5 key parameters).    Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC					[4]
Related Clinical Trial
NCT Number	NCT03823391	Clinical Status	Phase 2
Clinical Description	A randomized, double-blind, double-dummy, active controlled study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ABBV-3373 in subjects with moderate to severe rheumatoid arthritis.
Experiment 3 Reporting the Activity Date of This ADC					[5]
Patients Enrolled	RA (based on the 1987 American College of Rheumatology [ACR] classification criteria or 2010 ACR/EULAR criteria [16, 17]), with disease duration >3 months, and active disease defined as a Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) (18) of 3.2 and 4 of 28 swollen joints and 4 of 28 tender joints.
Administration Dosage	Intravenously (IV) ABBV-3373 100 mg every other week for 12 weeks, followed by placebo for 12 weeks, or subcutaneous adalimumab 80 mg every other week for 24 weeks.
Related Clinical Trial
NCT Number	NCT03823391	Clinical Status	Phase 2
Clinical Description	A randomized, double-blind, double-dummy, active controlled study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ABBV-3373 in subjects with moderate to severe rheumatoid arthritis.
Primary Endpoint	48 patients were randomized to ABBV-3373 (n=31) or adalimumab (n=17). At week 12, ABBV-3373 reduced DAS28 (CRP) versus historical adalimumab (2.65 versus 2.13; P=0.022) and combined in-trial/historical adalimumab (2.65 versus 2.29; probability=89.9%), with numerically greater improvement than in-trial adalimumab (2.51).
Other Endpoint	For secondary endpoints, greater efficacy was observed with ABBV-3373 versus historical adalimumab; ABBV-3373 was predicted with 79.30-99.50% probability to be better than adalimumab based on combined in-trial/historical adalimumab data.

Experiment 1 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Paw swelling AUC	81%	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					[6]
Efficacy Data	Paw swelling AUC	98%	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
Experiment 3 Reporting the Activity Date of This ADC					[6]
Efficacy Data	P1NP inhibition	0%	Positive TNF expression (TNF+++/++)
Method Description	In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 3 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess P1NP level.    Click to Show/Hide
In Vivo Model	Acute contact hypersensitivity (CHS) model
Experiment 4 Reporting the Activity Date of This ADC					[6]
Efficacy Data	P1NP inhibition	19%	Positive TNF expression (TNF+++/++)
Method Description	In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 10 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess P1NP level.    Click to Show/Hide
In Vivo Model	Acute contact hypersensitivity (CHS) model
Experiment 5 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Ear swelling inhibition	55%	Positive TNF expression (TNF+++/++)
Method Description	In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 3 mg/kg once prior to FITC sensitization.
In Vivo Model	Fluorescein isothiocyanate (FITC)-induced CHS model
Experiment 6 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Ear swelling inhibition	88%	Positive TNF expression (TNF+++/++)
Method Description	In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 10 mg/kg once prior to FITC sensitization.
In Vivo Model	Fluorescein isothiocyanate (FITC)-induced CHS model
Experiment 7 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Corticosterone inhibition	6%	Positive TNF expression (TNF+++/++)
Method Description	In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 3 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess corticosterone level.    Click to Show/Hide
In Vivo Model	Acute contact hypersensitivity (CHS) model
Experiment 8 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Corticosterone inhibition	15%	Positive TNF expression (TNF+++/++)
Method Description	In an acute in vivo model of contact hypersensitivity (CHS) mice were sensitized with fluorescein isothiocyanate (FITC) on the abdomen and challenged 6 days later with FITC on the ear,which resulted in an increase in ear swelling that was measured 24 h postchallenge. Anti-mTNF GRM ADCs were dosed at either 10 mg/kg once prior to FITC sensitization. Mice were challenged with adrenocorticotropic hormone (ACTH) 72 h following ADC dosing and plasma was collected 30 min later to assess corticosterone level.    Click to Show/Hide
In Vivo Model	Acute contact hypersensitivity (CHS) model

Experiment 1 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.08 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					[6]
Efficacy Data	Half Maximal Effective Concentration (EC50)	5.8 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

Ref 1	A first-in-human study of the novel immunology antibody-drug conjugate, ABBV-3373, in healthy participants
Ref 2	Efficacy and Safety of ABBV-3373, a Novel Anti-Tumor Necrosis Factor Glucocorticoid Receptor Modulator Antibody-Drug Conjugate, in Adults with Moderate-to-Severe Rheumatoid Arthritis Despite Methotrexate Therapy: A Randomized, Double-Blind, Active-Controlled Proof-of-Concept Phase IIa Trial
Ref 3	A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (RA)
Ref 4	A Randomized, Double-Blind, Double-Dummy, Active Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Subjects With Moderate to Severe Rheumatoid Arthritis, NCT03823391
Ref 5	Efficacy and Safety of ABBV-3373, a Novel Anti-Tumor Necrosis Factor Glucocorticoid Receptor Modulator Antibody-Drug Conjugate, in Adults with Moderate-to-Severe Rheumatoid Arthritis Despite Methotrexate Therapy: A Randomized, Double-Blind, Active-Controlled Proof-of-Concept Phase IIa Trial. Arthritis Rheumatol. 2023 Jun;75(6):879-889.
Ref 6	Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate. J Med Chem. 2022 Dec 8;65(23):15893-15934.