美国食品药品监督管理局(FDA)已授予 Ambrx 专有的抗 PSMA 抗体偶联物 (ADC) 研究疗法 ARX517 的快速通道称号,用于治疗转移性去势耐药患者雄激素受体途径抑制剂进展后出现前列腺癌 (mcRPC)。
Upon binding to PSMA on the surface of cancer cells, ARX517 is internalized and pAF-AS269, its cancer cell killing payload, is released following lysosomal metabolism. ARX517’s site-specific linkage, stable conjugation chemistry, ...
The serum stability of ARX517 should effectively deliver more payload to target tumor cells, and in multiple CDX and PDX prostate cancer models, ARX517 showed dose-dependent anti-tumor activity in both enzalutamide-sensitive and enzalutamide-resistant models. Repeat dose toxicokinetic studies in non-...
The main metabolite of ARX517 cytotoxic linker payload, pAF-AS269, was barely measurable (0.2 ng/mL) in the serum in repeat dosing study At the highest non-severely toxic dose (HNSTD), ARX517 serum exposure was greater than ARX517 exposure at a pharmacologically acti...
After the product binds to PSMA on the surface of cancer cells, the drug is internalized and its payload, referred to as pAF-AS269, is released after lysosomal metabolism. Notably, the agent is noted to display a homogenous drug-to-antibody ratio, as well as biophysical pro...
To enhance stability, the developers of ARX517 integrated several features into the drug, including a non-cell permeable payload, a noncleavable PEG linker, and a unique oxime conjugation chemistry facilitated by a genetically encoded and biosynthetically integrated synthetic amino acid. Notably, in ...