Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0ZPLMN
ADC Name
C4.4A-EC4
Synonyms
C4.4a EC4; C4.4aEC4
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Drug Status
Investigative
Indication
In total 2 Indication(s)
Breast cancer [ICD11:2C60-2C65]
Investigative
Lung cancer [ICD11:2C25]
Investigative
Drug-to-Antibody Ratio
6.4
Structure
Antibody Name
Anti-human LYPD3 mAb
  Antibody Info 
Antigen Name
Ly6/PLAUR domain-containing protein 3 (LYPD3)
  Antigen Info 
Payload Name
NAMPT inhibitor 5
  Payload Info 
Therapeutic Target
Nicotinamide phosphoribosyltransferase (NAMPT)
  Target Info 
Linker Name
Open-chain glycine maleimide
  Linker Info 
Conjugate Type
Glycine maleimide was used for Michael addition reactions with the thiol groups of the antibody that were generated through the reduction of interchain disulfide bonds. Basic opening of the resulting succinimide at pH 8 to obtain an open-chain succinic amide.
General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 60.7
%
Breast cancer cells
Breast cancer
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
1.3
nM
A549-C4.4a cells
Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
58
nM
MDA-MB-453 cells
Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
> 10
uM
THP-1 cells
Childhood acute monocytic leukemia
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Cell Line-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) ≈ 60.70% (Day 80) High LYPD3 expression (LYPD3+++)
Method Description
The in vivo antitumor efficacy and tolerability of the selected NAMPTi-ADCs were evaluated in the cell line-derived MDA-MB-453 human breast cancer xenograft models. Treatment with the C4.4a-EC4 (10 mg/kg,iv,Q7Dx7).
In Vivo Model Breast cancer CDX model
In Vitro Model Breast cancer Breast cancer cells Homo sapiens
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) 1.30 nM High CD276 expression (CD276+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

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In Vitro Model Lung adenocarcinoma A549-C4.4a cells CVCL_0023
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 58.00 nM High LYPD3 expression (LYPD3+++); High HER2 expression (HER2+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

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In Vitro Model Breast adenocarcinoma MDA-MB-453 cells CVCL_0418
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 uM High LYPD3 expression (LYPD3+++); High HER2 expression (HER2+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

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In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
References
Ref 1 A Novel NAMPT Inhibitor-Based Antibody-Drug Conjugate Payload Class for Cancer Therapy. Bioconjug Chem. 2022 Jun 15;33(6):1210-1221.

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