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(Slides)

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Researchers at Jiangsu Hengrui Pharmaceuticals have developed a novel antibody-drug conjugate (ADC) called HRA00129-C004, targeting the c-Met protein. C-Met is known to drive tumor growth and resistance to targeted therapies. The ADC consists of a topoisomerase I inhibitor (SHR9265) conjugated to a c-Met monoclonal antibody (mAb) through a cleavable linker, with an optimized drug-to-antibody ratio (DAR) of 6.0. <br /><br />In preclinical studies, HRA00129-C004 showed strong binding affinity to tumor cells and selective tumor cell-killing effects, while showing weaker activity against non-tumor cells, indicating an improved safety profile. It also demonstrated efficient internalization and bystander killing effects. In vitro and in vivo studies demonstrated potent anti-tumor activity against various cancer cell lines, including lung cancer, gastric cancer, and colorectal cancer. It exhibited superior efficacy in mouse models of lung cancer, gastric cancer, and colorectal cancer. Additionally, pharmacokinetic studies showed favorable stability and a wide therapeutic index. <br /><br />Toxicology studies in cynomolgus monkeys showed that HRA00129-C004 was well-tolerated with no mortality and no significant adverse effects on clinical signs, body weight, or hematology. The ADC exhibited a favorable safety profile in these studies.<br /><br />Based on these promising preclinical results, an Investigational New Drug (IND) application has been filed with the Chinese National Medical Products Administration, and a first-in-human study is planned to begin in the third quarter of 2023.<br /><br />Overall, HRA00129-C004, a novel c-Met-targeted ADC, has shown promising preclinical anti-tumor activity, improved safety profile, and a wide therapeutic index. It has the potential to be an effective treatment option for various solid tumor types expressing high levels of c-Met.

Asset Subtitle

Yunan Tian

Meta Tag

Speaker Yunan Tian

Topic Tumor Biology: Preclinical Biology - Molecular Therapeutic Targets

Keywords

antibody-drug conjugate

HRA00129-C004

c-Met protein

tumor growth

targeted therapies

topoisomerase I inhibitor

SHR9265

monoclonal antibody

preclinical studies

anti-tumor activity