Kezar Life Sciences, Inc.

SOUTH SAN FRANCISCO, CA, USA I July 15, 2025 I Kezar Life Sciences, Inc . (Nasdaq: KZR), a clinical-stage biotechnology company developing novel small molecule therapeutics to treat unmet needs in immune-mediated diseases, today announced that the Division of Hepatology and Nutrition of the U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on the completed PORTOLA Phase 2a clinical trial evaluating zetomipzomib, a first-in-class selective immunoproteasome inhibitor, in patients with autoimmune hepatitis (AIH). “We are pleased that the FDA has lifted the partial clinical hold on zetomipzomib in AIH after their review of our comprehensive safety assessment of the zetomipzomib program,” said Chris Kirk, PhD, CEO and co-founder of Kezar. “We continue to believe that zetomipzomib has the potential to positively transform the lives of patients living with AIH. We look forward to engaging with the FDA to align on the design of the next clinical trial of zetomipzomib in AIH.” Although Kezar has suspended development of zetomipzomib in lupus nephritis (LN) to focus on AIH, the company met with the Independent Data Monitoring Committee (IDMC) for the previously terminated PALIZADE clinical trial to review the safety profile of zetomipzomib. The IDMC has provided Kezar with recommendations for conducting future clinical trials in LN. Based on this feedback and internal analysis of safety data across all clinical studies involving zetomipzomib, Kezar plans to respond to the FDA Division of Rheumatology and Transplant Medicine with a request to lift the clinical hold on zetomipzomib in LN. About Zetomipzomib Zetomipzomib is a novel, first-in-class, selective immunoproteasome inhibitor with broad therapeutic potential across multiple autoimmune diseases. Preclinical research demonstrates that selective immunoproteasome inhibition results in a broad anti-inflammatory response in animal models of several autoimmune diseases, while avoiding immunosuppression. Data generated from completed clinical trials provide evidence that zetomipzomib exhibits a favorable safety and tolerability profile for development in severe, chronic autoimmune diseases. About Autoimmune Hepatitis Autoimmune hepatitis (AIH) is a rare chronic disease in which the immune system attacks the liver and causes inflammation and tissue damage, severely impacting patients’ physical health and quality of life. Lifelong maintenance therapy is required to avoid relapse and burdensome adverse effects. If left untreated, AIH can lead to cirrhosis, liver failure and hepatocellular carcinoma. In the United States, AIH affects approximately 100,000 individuals, with incidence rates increasing. The cause of this condition remains unclear, with females affected four times as often as males. Currently, standard of care treatment for AIH is chronic, immunosuppressive treatment with corticosteroids that frequently cause life-altering side effects, including diabetes, osteoporotic fractures and cataracts. There is a significant need for treatment regimens that reduce or remove the need for chronic immunosuppression from use of corticosteroids. About Kezar Life Sciences Kezar Life Sciences is a clinical-stage biopharmaceutical company developing novel small molecule therapeutics to treat unmet needs in immune-mediated diseases. Zetomipzomib, a selective immunoproteasome inhibitor, is currently being evaluated for autoimmune hepatitis. This product candidate also has the potential to address multiple chronic immune-mediated diseases. For more information, visit www.kezarlifesciences.com , and follow us on LinkedIn , Facebook , Twitter and Instagram . SOURCE: Kezar Life Sciences

Kezar said it plans to request to lift the clinical hold on zetomipzomib in lupus nephritis.\n The FDA has lifted one of the two clinical holds placed on Kezar Life Sciences’ zetomipzomib, leading the biotech to speculate on whether to reignite another program for the same drug that remains under hold.The company announced Wednesday that the FDA has lifted the partial hold on Kezar’s phase 2a Portola trial evaluating the selective immunoproteasome inhibitor in autoimmune hepatitis. When the hold was implemented in November 2024, analysts explained that it was related to “potential concerns of some placebo patients among the four patients yet to roll over in the [open-label extension], who could be subject to safety risk upon initiating zetomipzomib treatment.”Since then, a topline readout from the trial has tied zetomipzomib to a 36% rate of complete biochemical response and a “favorable safety profile.”Kezar’s CEO, Chris Kirk, Ph.D., explained in this morning’s release that the FDA has now lifted the hold after “their review of our comprehensive safety assessment of the zetomipzomib program.”“We continue to believe that zetomipzomib has the potential to positively transform the lives of patients living with AIH,” Kirk added. “We look forward to engaging with the FDA to align on the design of the next clinical trial of zetomipzomib in AIH.” A separate hold on zetomipzomib in lupus nephritis remains in place. That hold was instigated in October 2024 after a review of emerging safety data revealed the death of four patients in the Philippines and Argentina during the phase 2b Palizade trial.Kezar has since decided to suspend its lupus work to focus on zetomipzomib in AIH, but today’s release suggests that the company may be having second thoughts after receiving recommendations from Palizade’s independent data monitoring committee for conducting fresh trials in lupus nephritis.“Based on this feedback and internal analysis of safety data across all clinical studies involving zetomipzomib, Kezar plans to respond to the FDA Division of Rheumatology and Transplant Medicine with a request to lift the clinical hold on zetomipzomib in LN,” the company explained.

Kezar Life Sciences on Tuesday said the FDA has lifted the partial clinical hold on a mid-stage study of its investigational immunoproteasome inhibitor zetomipzomib (KZR-616) to treat autoimmune hepatitis (AIH).Zetomipzomib’s development was marred by a dual setback last year. In October, the FDA issued a full clinical hold on the drug’s lupus nephritis (LN) programme, just days after the Phase IIb PALIZADE study had to be paused owing to four fatal serious adverse events. This prompted Kezar to refocus development efforts on AIH, whilst suspending work in LN. After deliberation with an Independent Data Monitoring Committee (IDMC), the US regulator subsequently put a partial clinical hold on the Phase IIa PORTOLA study investigating zetomipzomib in AIH, preventing four remaining patients in the double-blind portion from proceeding to the open-label extension phase of the trial.“We continue to believe that zetomipzomib has the potential to positively transform the lives of patients living with AIH,” stated Kezar CEO Chris Kirk, adding that the company will soon engage with the FDA to finalise the next stage trial design in AIH.Kezar further noted that despite zetomipzomib’s LN programme being suspended, it plans to request the agency to also lift the hold on PALIZADE, based on the IDMC’s recommendations and its internal analysis.