Everest Medicines (1952) Study Update summary

Study background and rationale

• EVER001 is a novel, highly selective, reversible covalent BTK inhibitor developed for autoimmune renal diseases, with primary membranous nephropathy (PMN/pMN) as the first indication.

• PMN is a significant unmet medical need globally, with no approved therapies and high prevalence in China and Asia.

• Current treatments are off-label, have substantial side effects, and high relapse or non-response rates.

• BTK inhibition targets multiple immune pathways implicated in PMN pathogenesis, offering a differentiated mechanism from anti-CD20 therapies.

• EVER001 is positioned for global development, targeting multiple renal autoimmune diseases.

Study design and patient population

• Phase I-B/II-A trial enrolled 31 Chinese patients with biopsy-proven PMN and high anti-PLA2R antibody levels.

• Two dosing cohorts: 100 mg QD escalating to 100 mg BID, and 200 mg BID, with up to 104 weeks of follow-up.

• Primary endpoint: safety and tolerability; secondary endpoints: proteinuria, anti-PLA2R, UPCR, eGFR, and remission rates.

• Included both newly diagnosed and relapsed/refractory patients.

• Data cutoff was September 13, 2024.

Efficacy results

• EVER001 induced nearly 100% reduction in anti-PLA2R autoantibody in both dose arms, maintained up to 52 weeks off-treatment in Cohort 1.

• Immunological complete remission (ICR) achieved in over 90% of low-dose patients by week 36 and 100% of high-dose patients by week 24.

• Proteinuria reduction reached 78% at week 36 (low dose) and 74% at week 24 (high dose), with >50% reduction as early as week 16 in Cohort 2.

• Proteinuria remission rates were 82% (low dose, week 36) and 86% (high dose, week 24); median time to remission was 19.7 weeks (Cohort 1) and 16.1 weeks (Cohort 2).

• Serum albumin normalized or near-normal by week 36 (Cohort 1) and week 24 (Cohort 2); eGFR remained stable.