Linker ID	LIN0ZYKKZ
Linker Name	MP-Ala-Ala
Linker Type	Flexible reactive (thiol) linker
Antibody-Linker Relation	Cleavable
Structure
	3D MOL			2D MOL
Formula	C13H19N3O7
Isosmiles	CC(NC(=O)C(C)NC(=O)CCNC(=O)/C=C/C(=O)O)C(=O)O
InChI	InChI=1S/C13H19N3O7/c1-7(12(21)16-8(2)13(22)23)15-10(18)5-6-14-9(17)3-4-11(19)20/h3-4,7-8H,5-6H2,1-2H3,(H,14,17)(H,15,18)(H,16,21)(H,19,20)(H,22,23)/b4-3+
InChIKey	ZQVJQQOWKADMBI-ONEGZZNKSA-N
Pharmaceutical Properties	Molecule Weight		329.309	Polar area		161.9
	Complexity		23	xlogp Value		-1.7725
	Heavy Count		23	Rot Bonds		9
	Hbond acc		5	Hbond Donor		5

Experiment 1 Reporting the Activity Date of This ADC					[1]
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					[2]
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					[3]
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					[4]
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					[4]
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					[4]
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					[4]
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					[4]
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					[4]
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					[4]
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					[4]
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					[4]
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					[4]
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

Experiment 1 Reporting the Activity Date of This ADC					[5]
Patients Enrolled	Eligible participants include B-cell malignancy patients (WHO-confirmed, measurable disease) with lab values meeting protocol criteria; prior CD19-targeting therapy requires post-treatment biopsy. Exclusions: active CNS disease/lymphoma, uncontrolled infections, or ECOG ≥2.
Related Clinical Trial
NCT Number	NCT05512390	Clinical Status	PHASE1
Clinical Description	A First In Human Multicenter, Open-Label Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-319 in B-cell Malignancies
Primary Endpoint	The study evaluates ABBV-319 safety through DLT assessment (within 42 days) and tracks AEs (≤30 months). PK parameters (Cmax, Tmax, t½, AUC) and ADA incidence are monitored for ≤6 months to assess drug exposure and immunogenicity.
Other Endpoint	Efficacy endpoints measure PR or better (≤6 months), DOR, and time to response (CR/PR). PFS (≤30 months) tracks progression from first treatment, while OS records time to death from any cause.

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Paw swelling AUC	74%	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					[4]
Efficacy Data	Paw swelling AUC	96%	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 1 Reporting the Activity Date of This ADC					[4]
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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	43.7 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Paw swelling AUC	76%	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					[4]
Efficacy Data	Paw swelling AUC	85%	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					[4]
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 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 4 Reporting the Activity Date of This ADC					[4]
Efficacy Data	P1NP inhibition	3%	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 5 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Ear swelling inhibition	73%	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					[4]
Efficacy Data	Ear swelling inhibition	86%	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					[4]
Efficacy Data	Corticosterone inhibition	7%	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 8 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Corticosterone inhibition	9%	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 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.04 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Paw swelling AUC	92%	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					[4]
Efficacy Data	Paw swelling AUC	100%	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					[4]
Efficacy Data	P1NP inhibition	3%	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					[4]
Efficacy Data	P1NP inhibition	32%	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					[4]
Efficacy Data	Ear swelling inhibition	73%	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					[4]
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					[4]
Efficacy Data	Corticosterone inhibition	35%	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					[4]
Efficacy Data	Corticosterone inhibition	71%	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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Paw swelling AUC	96%	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					[4]
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					[4]
Efficacy Data	P1NP inhibition	14%	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					[4]
Efficacy Data	P1NP inhibition	27%	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					[4]
Efficacy Data	Ear swelling inhibition	78%	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					[4]
Efficacy Data	Ear swelling inhibition	94%	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					[4]
Efficacy Data	Corticosterone inhibition	12%	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					[4]
Efficacy Data	Corticosterone inhibition	17%	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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	P1NP inhibition	17%	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 2 Reporting the Activity Date of This ADC					[4]
Efficacy Data	P1NP inhibition	53%	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 3 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Ear swelling inhibition	59%	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 4 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Ear swelling inhibition	92%	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 5 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Corticosterone inhibition	23%	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 6 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Corticosterone inhibition	74%	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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	3.9 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	P1NP inhibition	25%	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 2 Reporting the Activity Date of This ADC					[4]
Efficacy Data	P1NP inhibition	58%	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 3 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Ear swelling inhibition	72%	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 4 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Ear swelling inhibition	94%	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 5 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Corticosterone inhibition	36%	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 6 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Corticosterone inhibition	74%	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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.8 ng/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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	10.7 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	P1NP inhibition	34%	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 2 Reporting the Activity Date of This ADC					[4]
Efficacy Data	P1NP inhibition	57%	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 3 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Ear swelling inhibition	68%	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 4 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Ear swelling inhibition	94%	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 5 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Corticosterone 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 corticosterone level.    Click to Show/Hide
In Vivo Model	Acute contact hypersensitivity (CHS) model
Experiment 6 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Corticosterone inhibition	18%	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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.2 ng/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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	12.1 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	12 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	2.8 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	11.9 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	8.5 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	1.4 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.03 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.77 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	36.8 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.12 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	> 50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.12 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	> 50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.16 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	4.7 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.19 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	2.9 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.2 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	3.1 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.29 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					[4]
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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.38 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	6.4 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.45 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	3.4 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.55 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	> 50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	1.08 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	> 50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	2.18 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	> 50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	2.18 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					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	> 50 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

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	7.03 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	Erythroleukemia	HEL 92.1.7 cells (Multidrug resistance)		CVCL_2481
Experiment 2 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Half Maximal Effective Concentration (EC50)	> 50 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 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (RA)
Ref 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, NCT03823391
Ref 3	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 4	Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate. J Med Chem. 2022 Dec 8;65(23):15893-15934.
Ref 5	A Study to Assess the Adverse Events, Change in Disease Activity, and How Intravenously Infused ABBV-319 Moves Through the Bodies of Adult Participants With Relapsed or Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), or Chronic Lymphocytic Leukemia (CLL)