Linker Information

Linker Name

Kinesin spindle protein inhibitor (KSPi)-ADC linker 4

Linker Type

Thiol-sensitive linker

Antibody-Linker Relation

General Information of This Linker

Each Antibody-drug Conjugate Related to This Linker

Full Information of The Activity Data of The ADC(s) Related to This Linker

TWEAKR-KSP-ADC 1.4 [Investigative]

ADC Info

Discovered Using Patient-derived Xenograft Model

Click To Hide/Show 1 Activity Data Related to This Level

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 5 mg/kg.
In Vivo Model	Urothelial cell cancer PDX model (PDX: BXF1218)

Discovered Using Cell Line-derived Xenograft Model

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

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 61.71% (Day 13)	High TWEAKR expression (TWEAKR +++)
Method Description	Efficacy of TWEAKR-ADCs 1.4 with aglycosylated TWEAKR mAb BAY-356 in the NCI-H292 NSCLC xenograft model in NMRI nude micewith 5 mg/kg.
In Vivo Model	NCI-H292 CDX model
In Vitro Model	Lung mucoepidermoid carcinoma	NCI-H292 cells		CVCL_0455
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 86.40% (Day 13)	High TWEAKR expression (TWEAKR +++)
Method Description	Efficacy of TWEAKR-ADCs 1.4 with 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

Revealed Based on the Cell Line Data

Click To Hide/Show 3 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.30 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)	0.37 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)	1.10 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

HER2 KSP-ADC 1.4 [Investigative]

ADC Info

Revealed Based on the Cell Line Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.20 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Drug-to-antibody ratios (DARs) and potency of the ADCs in the HER-2 positive breast cancer cell line KPL-4.
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310

References

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.