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Spanish Regulator Approves First-In-Human Trial of AP-2 for ALS

The program targets TDP-43 pathology with CK1 inhibition, a strategy supported by orphan-drug status from the EMA.

Overview

  • AEMPS has authorized a Phase I study of AP-2 at Hospital Universitario de La Princesa in Madrid, with first dosing planned for April.
  • Approximately 70–72 healthy volunteers will receive escalating doses to assess safety and pharmacokinetics.
  • AP-2 inhibits CK1 to prevent pathological phosphorylation of TDP-43 and aims to restore its nuclear function, with preclinical data showing reversal of TDP-43 anomalies in cell and transgenic animal models.
  • Patient dosing is planned to begin in January 2027 in a Phase Ib study if early safety results permit.
  • The trial is funded by Molefy Pharma, a CSIC spin-off majority-backed by Grupo Arquimea, and the candidate holds EMA orphan designation granted in October 2025.