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[en] Depletion of the sensitive volume for semiconductor based detectors is a key to achieve high performance. It is for instance required for charged particle detection in highly radiative environment and for X-ray spectroscopy.PIPPER-2 is a CMOS pixel sensor featuring an architecture that allows the application of the reverse bias of the pn junction from the frontside (cathode), on the electronic side, without process modification. Biasing voltages up to 45 V have been applied to sensor prototypes fabricated on two different high resistivity substrates: a thin epitaxial layer (1 kΩ cm) and a 40 μm thick bulk substrate (600 Ω cm).Calculations from a simplified analytical model and 3D-TCAD simulations were conducted to predict the evolution of the depletion depth with the bias voltage. These expectations were compared to measurements of PIPPER-2 illuminated with two X-ray energies.We conclude that the frontside biasing method allows the full-depletion of the thin epitaxial layer. In contrast, depletion of the bulk substrate reaches about half-depth but X-rays are still detected over the full depth.