Anti-PAPP-A antibody shows preclinical promise for autosomal dominant polycystic kidney disease

Pregnancy-associated plasma protein-A (PAPP-A) is involved in the development of autosomal dominant polycystic kidney disease. In preclinical mouse models, the anti-PAPP-A monoclonal antibody ABBV-CLS-628 was shown to reduce kidney volume and improve eGFR.

Dr Georgios Koukos (Calico Life Sciences, CA, USA) presented data on ABBV-CLS-628 in 3 different mouse models, including a fast-progressing non-orthologous disease model, an inducible and fast-progressing disease model, and a slow-progressing orthologous disease model [1]. Mice in the 3 models were treated weekly with either ABBV-CLS-628 or an isotype control antibody for a total of 22, 12, and 62 weeks, respectively, and plasma and kidney tissues were collected for analysis.

In the fast-progressing non-orthologous disease model, ABBV-CLS-628 led to a 52% decrease in total kidney volume (P<0.001) after 21 weeks of treatment, as well as an improvement in eGFR after 18 weeks of treatment (P=0.005), and in the probability of survival (P=0.0017), compared with control. Similarly, in the second model, the antibody induced a significant reduction in total kidney volume after weeks 5 and 8 of therapy, improved eGFR after 9 weeks, and led to significantly improved survival. Improvements in kidney total volume and function were also seen in the third model after up to 60 weeks of treatment. Transcriptomics analysis of mouse kidneys showed modulation of various pathways involved in autosomal dominant polycystic kidney disease, including epithelial-mesenchymal transition, inflammatory response pathways, oxidative phosphorylation, and TGF-β signalling.

In summary, ABBV-CLS-628 inhibited disease progression in mouse models of autosomal dominant polycystic kidney disease. “With this data, we felt confident to move to clinical trials,” concluded Dr Koukos. “We recently finished phase 1 and are soon moving to phase 2 studies, and we are excited to see that data.”

1. Koukos G, et al. A novel monoclonal antibody against PAPP-A significantly inhibits disease progression in three mouse models of autosomal dominant polycystic kidney disease. 62nd ERA Congress, 4–7 June 2025, Vienna, Austria.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 11 June 2025