亲合力公司是一家专注于肿瘤微环境激活（TMEA）药物的临床期生物制药及平台公司，通过感知肿瘤微环境状态递送和释放药物，降低药物毒性，提高药效。该公司宣布，将于2025年4月25日至30日在伊利诺伊州芝加哥举行的AACR年会上展示其最新的摘要和研究成果。 摘要涵盖了亲合力公司创新型的肿瘤微环境激活 (TMEA)  CTLA-4 抗体的临床前数据，和双负载 TMEA-ADC 平台的临床前数据。  

以下是摘要和海报展示的详细信息：  

Presentation Title: Dual-payload TME-activated ADC platform

Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Drug Delivery Technologies
Time: 4/28/2025 9:00:00 AM - 12:00:00 PM
Location: Poster Section 23, Board #24

Key Findings: For dual-payload TMEA-ADCs, each hydrophilic TMEA linker is paired with two insoluble payloads. Compared to GGFG linkers cleaved by lysosomal enzymes such as cathepsins B and K, the TMEA linkers exhibited superior stability in human plasma, higher cleavage efficiency in tumor homogenates, and strong safety profile in primate models. In various PBMCs-CDX models, dual-payload TMEA-ADCs such as IMD526 (HER2-Toxin-ISAC Dual Payload ADC) and IMD2113 (EGFR&TROP2- Dual Payload ADC) have  displayed significant dose-dependent antitumor activities and superior efficacy over two single-payload-ADCs with no observable toxicities. In tumor re-challenge studies, mice that were cured by IMD526 exhibited immune memory and were resistant to tumor re-inoculation.

Presentation Title: A novel chemical conjugated anti-CTLA-4 antibody with tumor microenvironment activation

Session Category: Clinical Research
Session Title: Therapeutic Antibodies, Including Engineered Antibodies 2
Time: 4/29/2025 2:00:00 PM - 5:00:00 PM
Location: Poster Section 35, Board #19

Key Findings: IMD-303 (CTLA-4 TMEAbody) demonstrated strong anti-tumor activities as single agent in MC38 murine colon cancer models and anti-PD-1 primary resistant EMT-6 models, and it displayed significant synergistic effects when combined with IMD101 (a TMEA-Cytokine releasing IL-2), in which IMD-303 can reduce the number of Treg cells in tumors that were slightly up-regulated by IMD101. Preclinical GLP toxicology studies showed that the MTD (maximum tolerated dose) was > 360 mg/kg for single-dose in SD rats, and the NOAEL (no-observed-adverse-effect level) was > 200mg/kg for 2-month repeat-dose in primate, which was over 8.7 times human equivalent dose of clinically effective dose.