Japan-based PeptiDream Inc. (Tokyo Stock Exchange: 4587) has announced the first patient dosing in a first-in-human radiopharmaceutical clinical trial of 64Cu-PD-29875, a macrocyclic peptide conjugate targeting Claudin 18.2 (CLDN18.2) in patients with gastric or gastroesophageal junction (GEJ) cancer. The PeptiDream claudin18.2 radiopharmaceutical program is structured as a Phase 0 imaging study, using copper-64 (⁶⁴Cu) labelling to generate PET/CT imaging data on safety, pharmacokinetics, tumor uptake, and dosimetry. The study's diagnostic data are intended to inform the development of a companion ²²⁵Ac-labeled therapeutic, forming an integrated radiotheranostic pair.
Patient enrollment numbers and a projected completion date were not disclosed. Endpoints center on diagnostic performance characterization and dosimetry, with the imaging data expected to support the design of subsequent therapeutic trials. The program received funding from Japan's Agency for Medical Research and Development (AMED) under its Practical Research for Innovative Cancer Control initiative in 2024.
CLDN18.2 is a tight-junction transmembrane protein whose normal expression is tightly restricted to differentiated gastric epithelial cells, where it remains physically inaccessible to circulating agents. In gastric and GEJ cancer specifically, CLDN18.2 expression is retained through metastatic progression, making it relevant across disease stages rather than only at diagnosis. The clinical validation of this target arrived with the 2024 FDA approval of zolbetuximab-clzb (Vyloy), a CLDN18.2-directed monoclonal antibody from Astellas Pharma, in first-line HER2-negative, CLDN18.2-positive gastric/GEJ adenocarcinoma — the first approved therapy directed at this target.
PD-29875 is a macrocyclic peptide discovered using PeptiDream's proprietary Peptide Discovery Platform System (PDPS) technology and further optimized through in vivo imaging and efficacy studies at PDRadiopharma, PeptiDream's wholly owned subsidiary. In its diagnostic configuration, the peptide is conjugated to ⁶⁴Cu, a positron emitter with a 12.7-hour half-life suited to the timescale of peptide biodistribution and tumor accumulation. The claudin18.2 PET imaging data generated in this Phase 0 study are designed to confirm tumor uptake, establish dosimetry parameters, and identify patients most likely to benefit from the therapeutic counterpart — a ²²⁵Ac-labeled version of the same peptide scaffold delivering targeted alpha-particle radiation.