ABBV-CLS-628: An Investigational Therapeutic for Kidney Diseases

1. Executive Summary

ABBV-CLS-628 is an investigational therapeutic agent emerging from a collaborative effort between AbbVie and Calico Life Sciences LLC.[1] The primary clinical focus for ABBV-CLS-628 is kidney diseases, with Autosomal Dominant Polycystic Kidney Disease (ADPKD) being the lead indication for its later-stage clinical development.[3] While the precise mechanism of action for ABBV-CLS-628 is not officially disclosed in all public databases, which often list it as "undefined" [1], a significant body of evidence from patent filings and preclinical research by the developing entities strongly indicates that ABBV-CLS-628 is likely an inhibitor of Pregnancy-Associated Plasma Protein A (PAPP-A). This proteinase plays a crucial role in modulating the local bioavailability of Insulin-like Growth Factor 1 (IGF-1).[6]

The development of ABBV-CLS-628 follows a structured path, characteristic of pharmaceutical collaborations. Calico Life Sciences LLC sponsored and completed a Phase 1 first-in-human clinical trial (ACTRN12622001550796) in healthy adult volunteers, assessing the safety, tolerability, and pharmacokinetics of single and multiple ascending doses administered intravenously and subcutaneously.[8] Initial safety and tolerability data from this Phase 1 study were slated for presentation at the ERA Congress in 2025.[10] Building on these early findings, AbbVie is planning to initiate a global Phase 2 clinical trial (NCT06902558; M25-147) in May 2025. This trial will evaluate the safety and efficacy of ABBV-CLS-628 in adult patients with ADPKD over an extended treatment period.[3]