ADC ID	DRG0IQHKX
ADC Name	Anti-DOG1-DM4-ADC
Synonyms	Anti DOG1 DM4 ADC; Anti-DOG1-DM4    Click to Show/Hide
Drug Status	Investigative
Indication	In total 4 Indication(s) Colon cancer [ICD11:2B90] Investigative Esophageal cancer [ICD11:2B70] Investigative Gastric cancer [ICD11:2B72] Investigative Hepatocellular carcinoma [ICD11:2C12] Investigative
Drug-to-Antibody Ratio	3.55
	3D MOL			2D MOL
Antibody Name	Anti-DOG1 mAb					Antibody Info
Antigen Name	Anoctamin-1 (ANO1)					Antigen Info
Payload Name	Mertansine DM4					Payload Info
Therapeutic Target	Microtubule (MT)					Target Info
Linker Name	N-succinimidyl 4-(2-pyridyldithio) butanoate (SPDB)					Linker Info
Conjugate Type	Random conjugation through nucleophilic lysines.
Combination Type	Ravtansine

Standard Type	Value	Units	Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI)	≈ 95.42	%	Gastrointestinal stromal tumor (GIST) PDX model
Tumor Growth Inhibition value (TGI)	≈ 99.9	%	Gastrointestinal stromal tumor (GIST) PDX model

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 69.69	%	KYSE-410 cells	Esophageal squamous cell carcinoma
Tumor Growth Inhibition value (TGI)	≈ 83.3	%	Hep-G2 cells	Hepatoblastoma
Tumor Growth Inhibition value (TGI)	≈ 89.32	%	HT-29 cells	Colon adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 92.04	%	Hep-G2 cells	Hepatoblastoma
Tumor Growth Inhibition value (TGI)	≈ 92.11	%	MGC-803 cells	Gastric cancer
Tumor Growth Inhibition value (TGI)	≈ 95.53	%	KYSE-410 cells	Esophageal squamous cell carcinoma
Tumor Growth Inhibition value (TGI)	≈ 96.24	%	MGC-803 cells	Gastric cancer
Tumor Growth Inhibition value (TGI)	≈ 98.67	%	HT-29 cells	Colon adenocarcinoma

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	8.37	nM	GIST882 cells	Gastrointestinal stromal tumor
Half Maximal Inhibitory Concentration (IC50)	8.87	nM	GIST882 cells (Imatinib resistant)	Gastrointestinal stromal tumor
Half Maximal Inhibitory Concentration (IC50)	9.91	nM	HT-29 cells	Colon adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	12.11	nM	KYSE-410 cells	Esophageal squamous cell carcinoma
Half Maximal Inhibitory Concentration (IC50)	17.92	nM	MGC-803 cells	Gastric cancer
Half Maximal Inhibitory Concentration (IC50)	24.56	nM	Hep-G2 cells	Hepatoblastoma
Half Maximal Inhibitory Concentration (IC50)	33.19	nM	HCCLM3 cells	Adult hepatocellular carcinoma
Half Maximal Inhibitory Concentration (IC50)	39.99	nM	HCT 116 cells	Colon carcinoma
Half Maximal Inhibitory Concentration (IC50)	> 200	nM	LoVo cells	Colon adenocarcinoma

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 95.42% (Day 50)	Positive DOG1 expression (DOG1 +++/++)
Method Description	5 mg/kg anti-DOG1 ADC and control (PBS) were administered Q3Dx3 via tail vein injection to mice once every three days for a total of three doses.
In Vivo Model	Gastrointestinal stromal tumor (GIST) PDX model
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.90% (Day 50)	Positive DOG1 expression (DOG1 +++/++)
Method Description	10 mg/kg anti-DOG1 ADC and control (PBS) were administered Q3Dx3 via tail vein injection to mice once every three days for a total of three doses.
In Vivo Model	Gastrointestinal stromal tumor (GIST) PDX model

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 69.69% (Day 17)	Positive DOG1 expression (DOG1 +++/++)
Method Description	Nude mice were used to establish cell line derived xenograft (CDX) models. After tumor inoculation, the tumor bearing mice were intravenously injected with naked anti-DOG1 antibody or a 5 mg/kg Q3Dx3 dose of the anti-DOG1 ADC.
In Vivo Model	Kyse-410 CDX model
In Vitro Model	Esophageal squamous cell carcinoma	KYSE-410 cells		CVCL_1352
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 83.30% (Day 25)	Positive DOG1 expression (DOG1 +++/++)
Method Description	Nude mice were used to establish cell line derived xenograft (CDX) models. After tumor inoculation, the tumor bearing mice were intravenously injected with naked anti-DOG1 antibody or a 5 mg/kg Q3Dx3 dose of the anti-DOG1 ADC.
In Vivo Model	HepG2 CDX model
In Vitro Model	Hepatoblastoma	Hep-G2 cells		CVCL_0027
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 89.32% (Day 25)	Positive DOG1 expression (DOG1 +++/++)
Method Description	Nude mice were used to establish cell line derived xenograft (CDX) models. After tumor inoculation, the tumor bearing mice were intravenously injected with naked anti-DOG1 antibody or a 5 mg/kg Q3Dx3 dose of the anti-DOG1 ADC.
In Vivo Model	HT-29 CDX model
In Vitro Model	Colon adenocarcinoma	HT-29 cells		CVCL_0320
Experiment 4 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 92.04% (Day 25)	Positive DOG1 expression (DOG1 +++/++)
Method Description	Nude mice were used to establish cell line derived xenograft (CDX) models. After tumor inoculation, the tumor bearing mice were intravenously injected with naked anti-DOG1 antibody or a 10 mg/kg Q3Dx3 dose of the anti-DOG1 ADC.
In Vivo Model	HepG2 CDX model
In Vitro Model	Hepatoblastoma	Hep-G2 cells		CVCL_0027
Experiment 5 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 92.11% (Day 21)	Positive DOG1 expression (DOG1 +++/++)
Method Description	Nude mice were used to establish cell line derived xenograft (CDX) models. After tumor inoculation, the tumor bearing mice were intravenously injected with naked anti-DOG1 antibody or a 5 mg/kg Q3Dx3 dose of the anti-DOG1 ADC.
In Vivo Model	MGC-803 CDX model
In Vitro Model	Gastric cancer	MGC-803 cells		CVCL_5334
Experiment 6 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 95.53% (Day 17)	Positive DOG1 expression (DOG1 +++/++)
Method Description	Nude mice were used to establish cell line derived xenograft (CDX) models. After tumor inoculation, the tumor bearing mice were intravenously injected with naked anti-DOG1 antibody or a 10 mg/kg Q3Dx3 dose of the anti-DOG1 ADC.
In Vivo Model	Kyse-410 CDX model
In Vitro Model	Esophageal squamous cell carcinoma	KYSE-410 cells		CVCL_1352
Experiment 7 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 96.24% (Day 21)	Positive DOG1 expression (DOG1 +++/++)
Method Description	Nude mice were used to establish cell line derived xenograft (CDX) models. After tumor inoculation, the tumor bearing mice were intravenously injected with naked anti-DOG1 antibody or a 10 mg/kg Q3Dx3 dose of the anti-DOG1 ADC.
In Vivo Model	MGC-803 CDX model
In Vitro Model	Gastric cancer	MGC-803 cells		CVCL_5334
Experiment 8 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.67% (Day 25)	Positive DOG1 expression (DOG1 +++/++)
Method Description	Nude mice were used to establish cell line derived xenograft (CDX) models. After tumor inoculation, the tumor bearing mice were intravenously injected with naked anti-DOG1 antibody or a 10 mg/kg Q3Dx3 dose of the anti-DOG1 ADC.
In Vivo Model	HT-29 CDX model
In Vitro Model	Colon adenocarcinoma	HT-29 cells		CVCL_0320

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	8.37 nM	Positive DOG1 expression (DOG1 +++/++)
Method Description	Cancer cells were treated with anti-DOG1-DM4-ADC or naked anti-DOG1 antibody (as control) at different concentrations for 72 hours.Viable cell counts were determined with RTCA assays and the IC 50 values were calculated.
In Vitro Model	Gastrointestinal stromal tumor	GIST882 cells		CVCL_7044
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	8.87 nM	Positive DOG1 expression (DOG1 +++/++)
Method Description	Cancer cells were treated with anti-DOG1-DM4-ADC or naked anti-DOG1 antibody (as control) at different concentrations for 72 hours.Viable cell counts were determined with RTCA assays and the IC 50 values were calculated.
In Vitro Model	Gastrointestinal stromal tumor	GIST882 cells (Imatinib resistant)		CVCL_7044
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	9.91 nM	Positive DOG1 expression (DOG1 +++/++)
Method Description	Cancer cells were treated with anti-DOG1-DM4-ADC or naked anti-DOG1 antibody (as control) at different concentrations for 72 hours.Viable cell counts were determined with RTCA assays and the IC 50 values were calculated.
In Vitro Model	Colon adenocarcinoma	HT-29 cells		CVCL_0320
Experiment 4 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	12.11 nM	Positive DOG1 expression (DOG1 +++/++)
Method Description	Cancer cells were treated with anti-DOG1-DM4-ADC or naked anti-DOG1 antibody (as control) at different concentrations for 72 hours.Viable cell counts were determined with RTCA assays and the IC 50 values were calculated.
In Vitro Model	Esophageal squamous cell carcinoma	KYSE-410 cells		CVCL_1352
Experiment 5 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	17.92 nM	Positive DOG1 expression (DOG1 +++/++)
Method Description	Cancer cells were treated with anti-DOG1-DM4-ADC or naked anti-DOG1 antibody (as control) at different concentrations for 72 hours.Viable cell counts were determined with RTCA assays and the IC 50 values were calculated.
In Vitro Model	Gastric cancer	MGC-803 cells		CVCL_5334
Experiment 6 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	24.56 nM	Positive DOG1 expression (DOG1 +++/++)
Method Description	Cancer cells were treated with anti-DOG1-DM4-ADC or naked anti-DOG1 antibody (as control) at different concentrations for 72 hours.Viable cell counts were determined with RTCA assays and the IC 50 values were calculated.
In Vitro Model	Hepatoblastoma	Hep-G2 cells		CVCL_0027
Experiment 7 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	33.19 nM	Positive DOG1 expression (DOG1 +++/++)
Method Description	Cancer cells were treated with anti-DOG1-DM4-ADC or naked anti-DOG1 antibody (as control) at different concentrations for 72 hours.Viable cell counts were determined with RTCA assays and the IC 50 values were calculated.
In Vitro Model	Adult hepatocellular carcinoma	HCCLM3 cells		CVCL_6832
Experiment 8 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	39.99 nM	Positive DOG1 expression (DOG1 +++/++)
Method Description	Cancer cells were treated with anti-DOG1-DM4-ADC or naked anti-DOG1 antibody (as control) at different concentrations for 72 hours.Viable cell counts were determined with RTCA assays and the IC 50 values were calculated.
In Vitro Model	Colon carcinoma	HCT 116 cells		CVCL_0291
Experiment 9 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 200 nM	Negative DOG1 expression (DOG1 -)
Method Description	Cancer cells were treated with anti-DOG1-DM4-ADC or naked anti-DOG1 antibody (as control) at different concentrations for 72 hours.Viable cell counts were determined with RTCA assays and the IC 50 values were calculated.
In Vitro Model	Colon adenocarcinoma	LoVo cells		CVCL_0399

Ref 1	DOG1 as a novel antibody-drug conjugate target for the treatment of multiple gastrointestinal tumors and liver metastasis. Front Immunol. 2023 Jan 26;14:1051506. doi: 10.3389/fimmu.2023.1051506. eCollection 2023.