2023 World Conference on Lung Cancer (Posters)-P1.02. HRA00129-C004, a Novel c-Met ADC with Promising Preclinical Anti-tumor Activity and Expanded Therapeutic Window

P1.02. HRA00129-C004, a Novel c-Met ADC with Promising Preclinical Anti-tumor Activity and Expanded Therapeutic Window - PDF(Abstract)

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HRA00129-C004 is a novel c-Met targeted Antibody Drug Conjugate (ADC) that has shown promising preclinical anti-tumor activity and an expanded therapeutic window. C-Met is a protein that is highly expressed in various solid tumor types, making it an attractive target for ADC development. HRA00129-C004 consists of a topoisomerase I inhibitor conjugated to a c-Met monoclonal antibody via a cleavable linker. The ADC demonstrated strong binding affinity to c-Met in human and cynomolgus monkey models but not in rodents.<br /><br />In in vitro studies, HRA00129-C004 showed efficient internalization and quicker internalization compared to a Teliso-V analogue in lung cancer cells. It significantly inhibited the growth of c-Met expressing lung cancer, gastric cancer, and colorectal cancer cell lines with sub nanomolar IC50 values. Additionally, the ADC was able to kill both c-Met positive and negative cells when co-cultured, suggesting robust anti-tumor efficacy.<br /><br />In in vivo models, treatment with HRA00129-C004 demonstrated dose-dependent anti-tumor efficacy in gastric cancer, colorectal cancer, and lung cancer models. The ADC showed superior activity compared to the Teliso-V analogue in gastric cancer models. Pharmacokinetic studies in cynomolgus monkeys showed a half-life of 4.7 to 7.3 days, supporting more flexible dosing in clinical settings. The toxicology study established a highest non-severely toxic dose of 40 mg/kg in monkeys.<br /><br />Overall, the preclinical data for HRA00129-C004 suggest it is a promising c-Met targeted ADC with strong anti-tumor activity. The authors have submitted an Investigational New Drug (IND) application to the National Medical Products Administration (NMPA) for clinical testing.

Asset Subtitle

Yunan Tian

Meta Tag

Speaker Yunan Tian

Topic Tumor Biology: Preclinical Biology - Molecular Therapeutic Targets

Keywords

HRA00129-C004

c-Met targeted Antibody Drug Conjugate

preclinical anti-tumor activity

solid tumor types

ADC development

binding affinity

lung cancer cells

anti-tumor efficacy

Pharmacokinetic studies

clinical testing