Reflecting on the INTEGRIS-PSC Phase 2a trial, can you elaborate on the safety profile of PLN-74809 observed over the 12-week period, especially concerning its tolerability in patients with suspected moderate to severe liver fibrosis?

How does the observed reduction in liver fibrosis markers ELF and PRO-C3 with PLN-74809 administration contribute to our understanding of its antifibrotic efficacy in PSC patients?

Based on MRI imaging results from the trial, can you discuss the implications of improved hepatocyte function and bile flow in patients treated with PLN-74809?

In comparison with existing treatment options for PSC, where does PLN-74809 stand in terms of effectiveness and patient outcomes, particularly in light of the trial results?

The trial noted a significant reduction in itch severity with PLN-74809. How important is this finding for the overall quality of life and symptom management in PSC patients?

Considering the varied dosages tested in the trial, how might PLN-74809 enable more personalized treatment strategies for PSC patients?

With the ongoing trial set to continue for a 24-week period, what are your expectations regarding the long-term efficacy and safety of PLN-74809 in PSC treatment?

Following these promising trial results, what are the anticipated next steps in the clinical development and regulatory process for PLN-74809, and how might this influence its accessibility to patients?

How does the use of single nuclei RNA sequencing (snRNA-seq) combined with the precision-cut liver slice (PCLivS) platform enhance our understanding of bexotegrast’s cell-specific effects in treating biliary fibrosis?

The study indicates that bexotegrast had an attenuated effect on immune cell gene expression compared to ALK5i. What are the potential clinical implications of this finding for patients with PSC?

Can you discuss the specific response profiles of key pathologic cell types, such as myofibroblasts and cholangiocytes, to bexotegrast treatment? How does this compare to their response to ALK5i?

What were the most significant differentially expressed genes (DEGs) and pathways identified in the study for bexotegrast-treated cells, and how do these contribute to its antifibrotic effects?