Everest Medicines Announces Updated Positive Results in Preliminary Analysis of Phase 1b/2a Clinical Trial of EVER001, a Novel BTK Inhibitor for the Treatment of Primary Membranous Nephropathy
- As of March 21st, 2025, longer follow-up data was collected from the ongoing Ph1b/2a study of EVER001: in Cohort 1, 11 patients completed 52 weeks of follow-up. In Cohort 2, 7 patients completed 52 weeks of follow-up.
- The updated data showed that EVER001 was well-tolerated and efficacious in patients with pMN. These results support the potential of EVER001 as a treatment for proteinuric autoimmune glomerular diseases.
- Compared to baseline, the geometirc least square mean of anti-PLA2R antibody levels decreased by 62.2% in Cohort 1 and 87.3% in Cohort 2 at week 12. The reductions in both cohorts reached more than 93% at week 24; the reductions in both cohorts were sustained through Week 52.
- Geometric LS mean of 24hr proteinuria levels in cohorts 1 and 2 decreased by 57.0% and 67.6% at Week 24, respectively; and further deepened to 76.7% and 80.6% at Week 36, respectively; the reductions in both cohorts were sustained through Week 52.
- Consistent with prior results, EVER001 was generally safe and well tolerated. No clinically significant adverse events commonly associated with BTK inhibitors were observed.
SHANGHAI, July 2, 2025 /PRNewswire/ -- Everest Medicines (HKEX 1952.HK, "Everest", or the "Company"), a biopharmaceutical company focused on the discovery, clinical development, manufacturing, and commercialization of innovative therapeutics, today announced updated positive results in the ongoing Phase 1b/2a clinical trial for the treatment of primary membranous nephropathy (pMN) with EVER001 (previously known as XNW1011), a next-generation covalent reversible Bruton's tyrosine kinase (BTK) inhibitor with potentially best-in-class characteristics for the treatment of autoimmune renal diseases. Compared to covalent irreversible BTK inhibitors, EVER001 offers improved selectivity while maintaining high potency, thereby potentially avoiding many of the side effects associated with earlier-generation BTK inhibitors. Everest Medicines holds global rights to EVER001 for the treatment of renal diseases.
The Phase 1b/2a clinical trial of EVER001 for the treatment of pMN is an ongoing open-label trial conducted in China. The study is designed to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of EVER001 in Chinese patients with glomerular diseases characterized by proteinuria. A total of 31 patients with biopsy-proven pMN who tested positive for anti-PLA2R autoantibodies were enrolled into two cohorts. The total treatment duration was 36 weeks.
The trial results, based on data analysis as of March 21st, 2025, include longer follow-up data (11 patients in Cohort 1 completed 52 weeks of follow-up. In Cohort 2, 16 patients completed 24 weeks of treatment, 12 patients completed 36 weeks of treatment, and 7 patients completed 52 weeks of follow-up). The results demonstrated that EVER001 was generally safe and well tolerated, with the most common Treatment-Related Adverse Events (TRAEs) categorized as Grade 1-2. No clinically significant adverse events commonly associated with covalent irreversible BTK inhibitors, such as bleeding, arrhythmia, severe infections, or severe liver function impairment were observed.
Compared to baseline, anti-PLA2R autoantibody levels showed an early and significant decrease in both cohorts. The geometric least squares (LS) mean levels of anti-PLA2R autoantibodies decreased by 62.2% in Cohort 1 and 87.3% in Cohort 2 at week 12. The reductions in both cohorts reached more than 93% at week 24. 76.9% of patients in cohort 1 and 88.2% in Cohort 2 achieved immunological complete remission at week 24.
At Week 24, geometric LS mean of 24hr proteinuria levels in cohorts 1 and 2 decreased by 57.0% and 67.6%, respectively; and further reduction to 76.7% and 80.6% by Week 36, respectively; the reductions in both cohorts were sustained through Week 52. 38.5% of patients in Cohort 1 and 70.6% of patients in Cohort 2 reached clinical remission at Week 24 and the remission rate improved to 69.2% and 91.7% by Week 36. The average serum albumin levels of patients in both cohorts reached the normal range during the treatment period, while maintaining the stable eGFR.
"We are pleased to see the encouraging new results in this preliminary analysis of our Phase 1b/2a clinical proof-of-concept trial of EVER001. There are approximately 2 million patients with pMN in China, and nearly 220,000 patients in the United States, Europe and Japan. To date, no drug has been approved globally for the treatment of pMN." Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines, said: "As a potential best-in-class therapy, EVER001 holds promise to offer more treatment options for over 10 million patients worldwide affected by pMN, IgA nephropathy (IgAN), minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and lupus nephritis (LN). EVER001's robust interim performance underscores its potential as a best-in-class candidate. The latest results validate the efficacy and safety of EVER001. We will continue to drive the global clinical development of EVER001, to meet patients' urgent clinical needs."
Sandra Zeng, Chief Medical Officer of Everest Medicines, said: "EVER001 is an effective covalent reversible BTK inhibitor that combines high potency with improved selectivity. Compared to traditional covalent irreversible BTK inhibitors, it has the potential to become a best-in-class therapy. EVER001 induces early and high rates of both immunological response and clinical remission, offering the promise to address unmet needs in current treatment options.
In terms of efficacy, EVER001 demonstrates a rapid onset of action, along with deep and durable responses across both immunological and clinical endpoints. The latest data show that the geometric least squares (LS) mean of anti-PLA2R autoantibodies levels decreased significantly at an early stage. The reductions in both cohorts reached more than 93% at Week 24. In addition, the 24hr proteinuria level decreased during treatment and further reduction was shown during the off-treatment follow up period, accompanied by increased serum albumin and stable eGFR levels.
Moreover, EVER001 was generally safe and well tolerated, with the most common Treatment-Related Adverse Events (TRAEs) categorized as Grade 1-2. Based on the encouraging clinical data to date, experts recommend initiating communication with the U.S. Food and Drug Administration (FDA) to launch a Phase III clinical trial, while also engaging with China's National Medical Products Administration (NMPA) in parallel."
pMN is a common pathological type of nephrotic syndrome in adults, and its prevalence in China has been increasing, ranking second only to IgA nephropathy 1. There are no approved drugs for this indication worldwide. The current treatments (such as cyclophosphamide, calcineurin inhibitors, and CD20 monoclonal antibodies) are used off-label. More than one-third of pMN patients still progress to end-stage renal disease under current standards of care.
This Phase 1b/2a clinical trial was approved by the Center for Drug Evaluation of the National Medical Products Administration in September 2022 to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of EVER001 in Chinese patients with glomerular diseases characterized by proteinuria.
About EVER001
EVER001 (previously known as XNW1011) is a next-generation covalent reversible Bruton's tyrosine kinase (BTK) inhibitor in development globally for the treatment of renal diseases. BTK is an essential component of the B-cell receptor signaling pathways that regulate the survival, activation, proliferation, and differentiation of B lymphocytes. Targeting BTK with small molecule inhibitors has been demonstrated to be an effective treatment option for B-cell lymphomas and autoimmune diseases.
Under an exclusive licensing agreement with Sinovent Pharmaceuticals and SinoMab BioScience, Everest owns global rights to develop, produce and commercialize EVER001 for the treatment of renal diseases.
About Everest Medicines
Everest Medicines is a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing transformative pharmaceutical products and vaccines that address critical unmet medical needs for patients in Asian markets. The management team of Everest Medicines has deep expertise and an extensive track record from both leading global pharmaceutical companies and local Chinese pharmaceutical companies in high-quality discovery, clinical development, regulatory affairs, CMC, business development and operations. Everest Medicines has built a portfolio of potentially global first-in-class or best-in-class molecules in the company's core therapeutic areas of renal diseases, infectious diseases and autoimmune disorders. For more information, please visit its website at www.everestmedicines.com.
Forward-Looking Statements:
This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law.
References:
- Overall clinical remission (complete remission or partial remission): 24h proteinuria complete remission (CR): 24h proteinuria < 0.3g/24 h; 24h proteinuria partial remission (PR): 24h proteinuria < 3.5g/24h, but ≥0.3g/24 h, and reduction > 50%, regardless of eGFR or the serum albumin level from baseline.
- Immunological complete remission (ICR): anti-PLA2R titer < 20RU/ml (negative).
- Expert consensus on the application of rituximab in the treatment of membranous nephropathy, Chin J Intern Med, March 2022, Vol. 61, No. 3.
SOURCE Everest Medicines
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