Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)

ADC ID	DRG0RSLVL
ADC Name	JP2025011033A Ab6
Synonyms	Ab6 Click to Show/Hide
Organization	ELI LILLY AND COMPANY
Drug Status	Investigative
Antibody Name	Ab6	Antibody Info
Antigen Name	Nectin-4 (NECTIN4)	Antigen Info
Payload Name	Undisclosed
Therapeutic Target	Stimulator of interferon genes protein (STING1)	Target Info
Linker Name	Undisclosed

ADC-specific functional property(2027 Update)

Binding Affinity

Click To Hide/Show 2 ADC-specific functional property Data

Dissocation Constant (Kd)	Binding Target	Description	Reference
91.8±25.5 nM	Human Nectin-4	In each analysis cycle, a different ADC was captured on flow cell 2 of each channel by injecting it at 5 ug/mL and 10 uL/min. After capture, the same analyte was injected on flow cells 1 and 2 in all 8 channels for 2 minutes at 30 uL/n and dissociation was monitored for 10 minutes. After dissociation, all surfaces were regenerated with three 1-minute injections of 5 mM phosphoric acid at 10 uL/min. ADC capture and analyte cycles were repeated to obtain analyte binding of each ADC at concentrations of 0, 2.5, 7.4, 22, 67, 200 and 600 nM nectin-4. Click to Show/Hide	[1]
114 nM	Rat Nectin-4	In each analysis cycle, a different ADC was captured on flow cell 2 of each channel by injecting it at 5 ug/mL and 10 uL/min. After capture, the same analyte was injected on flow cells 1 and 2 in all 8 channels for 2 minutes at 30 uL/n and dissociation was monitored for 10 minutes. After dissociation, all surfaces were regenerated with three 1-minute injections of 5 mM phosphoric acid at 10 uL/min. ADC capture and analyte cycles were repeated to obtain analyte binding of each ADC at concentrations of 0, 2.5, 7.4, 22, 67, 200 and 600 nM nectin-4. Click to Show/Hide	[1]

Bystander Killing Effect

Click To Hide/Show 1 ADC-specific functional property Data

Bystander Killing Effect	Description	Reference
yes	Nectin-4 Ab6 of this disclosure showed similar potency and magnitude of bystander effect to the enfortumab antibody in the same Ab6 format on T24 mScarlet clone 5 nectin-4 negative cells.	[1]

General Information of The Activity Data Related to This ADC

Discovered Using Cell Line-derived Xenograft Model

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

Standard Type	Value	Units	Cell Line	Disease Model
Mean tumor colume&#177SEM	304.9&#17727.25	mm³	Undisclosed	Undisclosed
Mean tumor colume&#177SEM	866.94&#177119.56	mm³	Undisclosed	Undisclosed

Revealed Based on the Cell Line Data

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

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal inhibitory Concentration (lC50)	0.0608	nM	CVCL_1494	Minimally invasive lung adenocarcinoma
Half Maximal inhibitory Concentration (lC50)	0.0783	nM	CVCL_0554	Bladder carcinoma

Full List of Activity Data of This Antibody-drug Conjugate

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	Mean tumor colume&#177SEM	304.9&#17727.25 mm³	Moderate nectin-4 expression (nectin-4++)
Method Description	Female NSG mice between 5-6 weeks of age were injected subcutaneously withMDA-MB-468 cells with moderate nectin-4 expression, when tumors reached appproximately 150-250 mm^3, animals were matched by tumor volume into treatment or controls groups and dosing initiated (Day 0, n=8 per group). The test articles were given at a single dose (2 mg/kg) formulated with 5% dextrose. Tumors were measured biweekly until Day 71. Click to Show/Hide
In Vivo Model	MDAMB468 xenograft model
Experiment 2 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Mean tumor colume&#177SEM	866.94&#177119.56 mm³	High nectin-4 expression (nectin-4 +++)
Method Description	Immune compromised female mice between 5-8 weeks of age with weight 18-20 grams were implanted unilaterally on the right flank with UM-UC-3 Nectin4 clone F7 cells with high nectin-4 expression, when tumors reached appproximately 150-250 mm^3, animals were matched by tumor volume into treatment or controls groups and dosing initiated (Day 0, n=8 per group). The test articles were given at a single dose (2 mg/kg) formulated with 5% dextrose. Tumors were measured biweekly until Day 40. Click to Show/Hide
In Vivo Model	UMUC3 Nectin-4 clone F7 xenograft model

Revealed Based on the Cell Line Data

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

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	0.0608 nM	Positive nectin-4 expression (nectin-4+++/++)
Method Description	ADCs were tested in NCI H1781 cells, and were added at final working concentration from 200 nM, 1:4 serially diluted in culture medium for 5 days.
In Vitro Model	Minimally invasive lung adenocarcinoma	NCI-H1781 cells		CVCL_1494
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	0.0783 nM	Positive nectin-4 expression (nectin-4+++/++)
Method Description	ADCs were tested in T24-human nectin-4 clone 108 cells, and were added at final working concentration from 200 nM, 1:4 serially diluted in culture medium for 5 days.
In Vitro Model	Bladder carcinoma	T24-human nectin-4 clone cells		CVCL_0554

References

Ref 1	Nectin-4 antibodies and antibody-drug conjugates