Everest Medicines (1952) Study update summary

Study design and mechanism

• Ongoing Phase Ib/IIa trial enrolled 31 Chinese patients with biopsy-proven, anti-PLA2R-positive PMN; primary endpoint was safety and tolerability, with efficacy endpoints including proteinuria, antibody levels and remission.

• Cohort 1 received 100 mg QD for 4 weeks then 100 mg BID for 32 weeks; cohort 2 received 200 mg BID for 36 weeks, followed by 16 weeks off treatment.

• At the March 21, 2025 cutoff, 11 cohort 1 patients had completed week 52 and 12 cohort 2 patients had completed 36 weeks of treatment.

• EVER001 is a reversible covalent BTK inhibitor; preclinical studies showed BTK potency similar to ibrutinib and greater selectivity against EGFR, ITK and Tec-family kinases.

Immunological response

• Anti-PLA2R antibodies fell by more than 60% in both cohorts by week 12 and more than 93% by week 24; reductions remained 89%–96% during off-treatment follow-up.

• Immunological complete remission appeared as early as weeks 4–8, reaching 76.9% in cohort 1 by weeks 24–36 and 100% in cohort 2 from week 36 through follow-up.

Clinical outcomes

• 24-hour proteinuria fell 37% in cohort 1 and 80% in cohort 2 at week 36; reductions deepened off treatment to 78% at week 44 in cohort 1 and 83% at week 52 in cohort 2.

• Geometric mean 24-hour proteinuria decreased by more than 50% at week 24 and ~80% at week 36 in both cohorts.

• Week-36 clinical remission was 69.2% in cohort 1, including two complete remissions, and 91.7% in cohort 2, including five complete remissions; all seven cohort 2 patients followed to week 52 were in remission.

• Serum albumin returned to normal by week 36 in both cohorts, while eGFR remained stable.