SOUTH SAN FRANCISCO, Kezar Life Sciences, Inc., reported interim results from the Phase 2 portion of its MISSION clinical trial evaluating KZR-616, a first-in-class selective immunoproteasome inhibitor, in patients with active, proliferative lupus nephritis (LN).

“The MISSION Phase 2 interim results present a strong signal that KZR-616 is active and could be a meaningful therapy for patients with lupus nephritis, a long term and difficult to treat disease,” said Noreen R. Henig, M.D., Kezar’s Chief Medical Officer. “Reduction in proteinuria, as quickly as possible, is an important therapeutic goal for patients with lupus nephritis, and we observed meaningful reductions at 6 months as well as encouraging data at 3 months. KZR-616 continues to appear to be immunomodulatory rather than immunosuppressive, which we believe could offer advantages over current treatments available. Based on these interim findings, we look forward to reporting top-line data in the second quarter of 2022.”

Samir V. Parikh, M.D., Associate Professor of Medicine, Division of Nephrology, The Ohio State University Wexner Medical Center and an investigator in the MISSION study, added, “these interim results are important for patients living with lupus nephritis. One of the devastating consequences of the disease is kidney failure, so new immunomodulatory treatments that have the potential to protect kidney function would fulfill a substantial unmet need and could lead to better long-term outcomes.”

The MISSION Phase 2 clinical trial is an open-label study to demonstrate the responder rate of KZR-616 in patients with active lupus nephritis. During the 24 week treatment period, patients received 60 mg of KZR-616 subcutaneously once weekly (first dose of 30 mg) in addition to their background therapy. Patients in the MISSION Phase 2 trial do not receive KZR-616 as part of “induction” therapy, which represents a significant difference in comparison to other recently published trials in lupus nephritis. End of treatment assessments occurred at Week 25.

For the interim analysis, five patients had reached end of treatment, and ten patients had reached week 13 of treatment. The primary efficacy endpoint for the trial is the proportion of patients achieving a renal response measured by a 50% or greater reduction in urine protein to creatinine ratio (UPCR) at end of treatment. The secondary efficacy endpoint for the trial is the number of patients with a complete renal response (CRR) and partial renal response (PRR).

Key findings from the interim analysis of the MISSION Phase 2 are summarized below:

Clinically meaningful renal response was observed at end of treatment.

3 of 5 patients achieved a 50% or greater reduction in UPCR at week 25 compared to baseline, the primary efficacy endpoint of the clinical trial.

4 of the 5 patients who completed treatment at week 25 with KZR-616 demonstrated clinically meaningful reduction in proteinuria to less than 0.8 UPCR:

• 2 patients showed a CRR and had a reduction of absolute proteinuria values to equal to or less than 0.5 UPCR.

• 2 patients showed a PRR and had a reduction of absolute proteinuria values to between 0.5 and 0.8 UPCR.

Clinically meaningful reductions in UPCR were also observed in 5 of 10 patients at week 13 of KZR-616 and included improvements in key disease biomarkers.

KZR-616 was well tolerated over the six-month treatment period.

No new safety signals were observed in the Phase 2 portion of the MISSION trial.

Adverse events were generally mild-to-moderate (Grade 1 or 2).

There were no study discontinuations due to drug related adverse events. There was one temporary interruption of study drug due to a Grade 3 serious adverse event, the occurrence of a migraine, and one discontinuation unrelated to the study drug.

Top-line data from the Phase 2 MISSION trial in patients with lupus nephritis are expected in the second quarter of 2022.

Data from the MISSION Phase 2 clinical trial are preliminary and will require confirmation in additional patients as well as longer follow-up to draw any clinical conclusion. Interim top-line and preliminary data from Kezar’s clinical trials that it announces or publishes from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.