Everest Medicines Announces Positive Results in Preliminary Analysis of Phase 1b/2a Clinical Trial of EVER001, a Novel BTK Inhibitor for the Treatment of Primary Membranous Nephropathy

USA - English

• APAC - English
• USA - English
• APAC - Traditional Chinese

• Patients in the low-dose cohort who have completed 36 weeks of treatment, 9 out of 11 (81.8%) achieved overall clinical remission and 10 out of 11 (91%) achieved immunological complete remission.
• In the high dose cohort, 6 out of 7 (85.7%) patients achieved overall clinical remission and all patients achieved immunological complete remission by week 24.
• EVER001 was generally safe and well tolerated. No clinically significant adverse events typically associated with earlier-generation BTK inhibitors, such as bleeding, arrhythmia, severe infection, leukopenia, thrombocytopenia, or severe liver function impairment, were reported.

SHANGHAI, Dec. 4, 2024 /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 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. In an analysis of the data available as of September 13^th, 2024, results from the Phase 1b/2a clinical trial showed that for patients in the low-dose cohort who have completed 36 weeks of treatment, 9 out of 11 (81.8%) achieved overall clinical remission¹ and 10 out of 11 (91%) achieved immunological complete remission (ICR)². In the high dose cohort, 6 out of 7 (85.7%) patients achieved overall clinical remission and all patients achieved ICR by week 24.

EVER001 is a covalent reversible 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 trial conducted in China. 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. Based on the patient data collected by September 13^th, 2024, in the low-dose cohort, the geometric least squares mean 24-hour proteinuria decreased by 78.3% at week 36 compared to baseline, while the high-dose cohort achieved a 73.8% reduction by week 24. EVER001 treatment induced greater than 90% reductions in anti-PLA2R antibody as early as week 24 in the low-dose cohort and week 12 in the high-dose cohort. EVER001 was generally safe and well tolerated. No clinically significant adverse events typically associated with earlier-generation BTK inhibitors, such as bleeding, arrhythmia, severe infection, leukopenia, thrombocytopenia, or severe liver function impairment, were reported.

"We are excited to see the encouraging results in this preliminary analysis of our Phase 1b/2a clinical proof-of-concept trial of EVER001. This demonstrates the potential of EVER001 as a next-generation BTK inhibitor for the treatment of various autoimmune renal diseases, including pMN." Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines, said："This data release marks the first time Everest Medicines has disclosed results from its global pipeline. We look forward to completing this trial and sharing detailed data in future conferences and publications. Moving forward, we will continue to drive the global clinical development of EVER001, to meet patients' urgent clinical needs."

Membranous nephropathy is a common pathological type of nephrotic syndrome in adults, and its prevalence in China has been increasing, ranking second only to IgA nephropathy³. There are about 2 million patients with pMN in China, with an estimated 80,000 to 100,000 patients in the United States, 80,000 in Europe, and 40,000 in Japan. There are no approved drugs for this indication worldwide. The current treatment goal is to improve remission rates, reduce high relapse rates, and minimize the risk of chronic toxicity caused by currently available treatments. 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. The previously published results of a Phase 1 study conducted in healthy Chinese and Australian subjects conducted by SinoMab BioScience indicate that EVER001 has high selectivity, excellent pharmacokinetic properties, a good safety profile, and strong target binding.

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. Based in part on results from a completed phase 1 trial with healthy subjects conducted by SinoMab in China, EVER001 exhibited high selectivity, excellent pharmacokinetics properties, strong target binding and a safety profile that supports continued clinical development.

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.

Investor Calls Information

Everest Medicines will hold investor calls on the data results from EVER001 Phase 1b/2a clinical study in primary membranous nephropathy. EVER001 is a next-generation covalent reversible Bruton's tyrosine kinase (BTK) inhibitor, and Everest owns the global rights to develop EVER001 for the treatment of renal diseases.

The English session of the conference call will be held at 9:00 AM on Dec. 4, 2024, Beijing Time (8:00 PM U.S. Eastern Time on Dec. 3, 2024) and the Mandarin session of the conference call will be held at 10:30 AM Beijing Time on the same day (9:30 PM U.S. Eastern Time on Dec. 3, 2024).

The conference calls can be accessed by the following links:

For English Session:
Time: 9:00 AM Beijing Time, Wednesday, Dec. 4, 2024 (8:00 PM U.S. Eastern Time on Dec. 3, 2024)
Pre-Registration Link: https://www.acecamptech.com/eventDetail/60510700
Webcast Link: https://www.acecamptech.com/meeting_live/70512679/774680?event_id=60510700

Alternatively, participants may dial in to the conference call using below dial-in information:

United States:           +1-646-2543594 (EN)
Chinese Mainland:    +86-10-58084166 (EN)
                                  +86-10-58084199 (CN)
Hong Kong, China:    +852-30051313 (EN)
                                  +852-30051355 (CN)
United Kingdom:        +44-12-1368-0466 (EN)
International:             +1-866-6363243 (EN)
Password:                 842080

For Mandarin Session:
Time: 10:30 AM Beijing Time, Wednesday, Dec. 4, 2024 (9:30 PM U.S. Eastern Time on Dec. 3, 2024)
Webcast Link: https://s.comein.cn/n3arj55s

Alternatively, participants may dial into the conference call using below dial-in information:

United States:           +1-646-3578788
                                  +1-408-7093255
Chinese Mainland:    400-969-8928
                                  400-806-3263
Hong Kong, China:   +852-301-83602
Taiwan, China:          +886-226563394
                                  +886-277417882
Singapore:                +65-64075649
                                  +65-66220840
United Kingdom:       +44-2070970018
International:             +86-2362737123
Password:                 377570

The replay of English session will be available shortly after the call and can be accessed by visiting the Company's website at http://www.everestmedicines.com.

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:

1. 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.
2. Immunological complete remission (ICR): anti-PLA2R titer < 20RU/ml (negative).
3. Expert consensus on the application of rituximab in the treatment of membranous nephropathy, Chin J Intern Med, March 2022, Vol. 61, No. 3.