Core Viewpoint - Kezar Life Sciences has received a Type C meeting from the FDA to discuss the development of zetomipzomib for autoimmune hepatitis, indicating progress in its clinical development and potential for addressing unmet medical needs in this area [1][2][3] Group 1: Company Overview - Kezar Life Sciences is a clinical-stage biotechnology company focused on developing small molecule therapeutics for immune-mediated diseases [4] - Zetomipzomib is a selective immunoproteasome inhibitor being evaluated for autoimmune hepatitis and has potential applications in multiple chronic immune-mediated diseases [5] Group 2: Clinical Development - The Type C meeting will review a proposed global, randomized Phase 2b clinical study of zetomipzomib in patients with relapsed and refractory autoimmune hepatitis [2] - Kezar submitted pharmacokinetic and hepatic safety data from previous trials to support its proposal for parallel studies in autoimmune hepatitis and hepatic impairment [2] Group 3: Market Need - Autoimmune hepatitis is a rare chronic disease affecting approximately 100,000 individuals in the U.S., with a significant unmet medical need for effective treatments [6] - Current standard treatments involve chronic immunosuppressive therapies that can lead to severe side effects, highlighting the need for alternatives that minimize or eliminate the use of corticosteroids [6] Group 4: Strategic Initiatives - The company is undergoing a strategic review process to maximize shareholder value, which includes workforce reductions and cost-containment measures [3] - Kezar has engaged TD Cowen to assist in this strategic review, indicating a focus on enhancing shareholder returns [3]

Zetomipzomib in Autoimmune Hepatitis (AIH) - The PORTOLA Phase 2 study evaluated zetomipzomib in AIH patients with relapsed disease or inadequate response to prior therapy [16] - In a pre-specified subgroup of patients on steroid-based therapy (n=21), 36% (5/14) of zetomipzomib-treated patients achieved a steroid-sparing complete biochemical remission (CR) by Week 24, compared to 0% (0/7) in the placebo arm [18] - In the Intent to Treat (ITT) population (n=24), 31.3% (5/16) of zetomipzomib-treated patients achieved a steroid-sparing CR by Week 24 versus 12.5% (1/8) in the placebo arm [18] - The PORTOLA results support a registrational program in AIH, a disease affecting approximately 100,000 patients in the US [17, 21] - The company plans to present PORTOLA results at a major medical conference in the second half of 2025 [43] Zetomipzomib in Lupus Nephritis (LN) - In the MISSION Phase 2 study, 35% of LN patients achieved a complete renal response (CRR) following 25 weeks of treatment without induction therapy [48, 50] - In the PALIZADE Phase 2 study, over 40% of patients achieved a UPCR ≤0.5 at Week 25 in the 60 mg zetomipzomib dose group [48] - The MISSION Phase 2 study showed an 83% median reduction in UPCR from baseline to Week 29 (4 weeks post-EOT) [50] - In the PALIZADE trial, the median percent change in UPCR from baseline at Week 25 was -67% in the Zetomipzomib 60mg group [54] Safety and Tolerability - In the PORTOLA study, the most common treatment emergent adverse events (TEAEs) were injection site reactions (ISRs) and systemic injection reactions (SIRs), all of which were Grade 1 or Grade 2 [18]