BAY 1135626 synthesizes BAY 1129980, an Auristatin-based anti-C4.4A (LYPD3) antibody–drug conjugate (ADC) used in non–small cell lung cancer (NSCLC) research and anti-tumor studies [1].

C4.4A (LYPD3), a protein expressed in non-small cell lung cancer (NSCLC) with minimal expression in normal tissues, can be targeted by BAY 1135626, which synthesizes into BAY 1129980 (C4.4A-ADC). BAY 1129980 exhibits a strong anti-proliferative effect on C4.4A-expressing cell lines, including A549 lung cancer cells transfected with C4.4A. In vitro studies show that BAY 1129980 (0.001-100 nM; 72 hours) has high and selective efficacy on hC4.4A:A549 cells, demonstrating high potency at a subnanomolar range with an IC50 value of 0.05 nM and over 1,000-fold selectivity compared to mock:A549 cells. Additionally, BAY 1129980 inhibits the growth of various cancer cell lines (NCI-H292, FaDu, NCI-H322, SCaBER, SCC-4) in a dose-dependent manner.

BAY 1129980, administered intravenously at doses ranging from 1.9 to 7.5 mg/kg over 20 days, effectively inhibits tumor growth in vivo in a C4.4A-positive NCI-H292 NSCLC xenograft mouse model. At a minimum effective dose (MED) of 1.9 mg/kg, the treatment halted tumor growth by day 20. With repeated dosing of 15 mg/kg for 21 days in the first cycle and 57 days in the second cycle, the compound reduced tumor volume and significantly delayed tumor growth. This regimen showed good tolerance without affecting the treatment sensitivity, even for regrown tumors.