In a highly refractory population, 35.7% of zetomipzomib-treated patients on steroid therapy at screening achieved complete biochemical remission (CR) and steroid taper to ≤5 mg/day. How significant is this for a field where durable steroid-sparing options are virtually nonexistent?

Notably, 18.8% of zetomipzomib-treated patients achieved both CR and full steroid withdrawal. From a clinical perspective, how transformative is this possibility for long-term disease management and quality of life in AIH patients?

Though the topline data focus on biochemical endpoints, biopsies were also taken pre- and post-treatment. How important is histologic improvement in confirming disease control in AIH, and what are your expectations for future biopsy data from PORTOLA?

Zetomipzomib targets the immunoproteasome, which differs from broad immunosuppression. Can you explain how this mechanism could offer targeted immune modulation without the systemic risks of steroids or traditional immunosuppressants?

Systemic injection reactions (SIRs) were frequent but low-grade, and infectious AEs were actually lower in the zetomipzomib arm than placebo. How would you assess the risk-benefit profile of zetomipzomib in light of these safety findings?

Given that PORTOLA is the first randomized trial to show success in treatment-refractory AIH, what are the key regulatory hurdles Kezar may face, and what trial design elements would you prioritize in a registrational study?

The PORTOLA trial used standard ALT, AST, and IgG normalization to define CR. Are there emerging biomarkers or immunologic signatures that could further refine response assessment or patient selection in future trials?

Given zetomipzomib’s mechanism and broad anti-inflammatory potential, how do you view its applicability to other autoimmune diseases with steroid-reliant treatment regimens—such as lupus nephritis, vasculitis, or Sjögren’s syndrome?