ADC ID	DRG0DWCPC
ADC Name	TWEAKR-KSP-ADC 2.2
Synonyms	TWEAKR-KSP-ADC-2.2    Click to Show/Hide
Drug Status	Investigative
Indication	In total 3 Indication(s) Colorectal cancer [ICD11:2B91] Investigative Non-small cell lung cancer [ICD11:2C25] Investigative Pancreatic cancer [ICD11:2C10] Investigative
Drug-to-Antibody Ratio	2.9
	3D MOL			2D MOL
Antibody Name	Anti-TWEAKR mAb					Antibody Info
Antigen Name	Tumor necrosis factor receptor superfamily member 12A (TNFRSF12A)					Antigen Info
Payload Name	Pyrrole based kinesin spindle protein inhibitor					Payload Info
Therapeutic Target	Kinesin-like protein KIF11 (KIF11)					Target Info
Linker Name	Kinesin spindle protein inhibitor (KSPi)-ADC linker 6					Linker Info
Conjugate Type	Random conjugation through reduced inter-chain cysteines.

Standard Type	Value	Units	Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI)	≈ 96.95	%	Urothelial cell cancer PDX model (PDX: BXF1218)

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 89.98	%	NCI-H292 cells	Lung mucoepidermoid carcinoma

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	0.94	nM	NCI-H292 cells	Lung mucoepidermoid carcinoma
Half Maximal Inhibitory Concentration (IC50)	58	nM	LoVo cells	Colon adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	600	nM	BxPC-3 cells	Pancreatic ductal adenocarcinoma

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 96.95% (Day 13)	High TWEAKR expression (TWEAKR +++)
Method Description	Efficacy of TWEAKR-ADCs 1.4 with aglycosylated TWEAKR mAb BAY-356 in the BXF1218 UCC PDX model in NMRI nude micewith 10 mg/kg.
In Vivo Model	Urothelial cell cancer PDX model (PDX: BXF1218)

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 89.98% (Day 13)	High TWEAKR expression (TWEAKR +++)
Method Description	Efficacy of TWEAKR-ADCs 2.2with aglycosylated TWEAKR mAb BAY-356 in the NCI-H292 NSCLC xenograft model in NMRI nude micewith 10 mg/kg.
In Vivo Model	NCI-H292 CDX model
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.94 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	58.00 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Colon adenocarcinoma	LoVo cells		CVCL_0399
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	600 nM	High TWEAKR expression (TWEAKR +++)
Method Description	In vitro potency of SMOL KSPi compound A and of TWEAKR-KSPiADCs 1.1., 1.2, 1.3, 1.4, 2.1, and 2.2 in TWEAKR-expressing cell lines versus selected respective isotype control ADCs 1.4 and 2.2 with same linker payload chemistry.
In Vitro Model	Pancreatic ductal adenocarcinoma	BxPC-3 cells		CVCL_0186

Ref 1	Antibody-Drug Conjugates with Pyrrole-Based KSP Inhibitors as the Payload Class. Angew Chem Int Ed Engl. 2018 Nov 12;57(46):15243-15247. doi: 10.1002/anie.201807619. Epub 2018 Oct 15.