Bio-Thera Solutions Publishes Phase I Clinical Study Results for BAT4406F, an ADCC-Enhanced Fully Humanized Anti-CD20 Monoclonal Antibody, in Patients with Neuromyelitis Optica Spectrum Disorders

GUANGZHOU, China, Jan. 14, 2025 /PRNewswire/ -- Bio-Thera Solutions, Ltd. today announced the publication of the Phase I clinical study results for BAT4406F, an ADCC-enhanced fully humanized anti-CD20 monoclonal antibody in Chinese patients with neuromyelitis optica spectrum disorders (NMOSD) in the journal CNS Neuroscience & Therapeutics.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare immune-mediated central nervous system (CNS) inflammatory demyelinating disease with high recurrence and disability, primarily characterized by severe optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM). ON might result in a decrease in visual acuity, visual field defects, and even blindness. Spinal cord inflammation will also cause paralysis and bladder rectal damage. B-cell depletion therapy by monoclonal antibody (mAb) against CD20 can reduce the recurrence of NMOSD and slow the progression of neurological dysfunction and has a significant therapeutic effect.

BAT4406F, a Class 1 innovative drugs developed by Bio-Thera, is a glycosylation-optimized fully anti-CD20 human mAb of IgG1 subclass with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) effect. In preclinical studies, BAT4406F has showed stronger B-cell depletion activity than the marketed anti-CD20 monoclonal antibodies including rituximab. In this first-in-human, open-label, dose-escalation Phase I clinical study of BAT4406F injection in Chinese NMOSD patients, the overall objective was to assess the tolerability, safety, pharmacokinetics (PK), pharmacodynamics, and immunogenicity of BAT4406F in NMOSD patients. The efficacy of BAT4406F in NMOSD was also preliminarily explored (ClinicalTrials.gov identifier: NCT04146285). Five fixed dose groups ranging from 20 mg to 750 mg were set. Fifteen eligible patients were enrolled in this trial and administered with a single intravenous infusion of BAT4406F followed by a 6-month observation period.

No subjects experienced DLT at the studied doses. BAT4406F injection has shown favorable safety, with most of the adverse events (AE) of CTCAE Grade 1 or 2 in severity, and no Grade ≥3 adverse drug reactions (ADR) or serious adverse reactions occurred in any subjects. With the dose increase of BAT4406F, C_max, AUC_0-t and AUC_0-inf showed an increasing trend, whereas the CL, l_Z, and V_d decreased. The mean elimination half-life (T_1/2) ranged from 9.0-16.4 days. PK profile of BAT4406F was generally nonlinear. BAT4406F led to a rapid and significant B-cell depletion in all dose groups. Single dose of BAT4406F administration maintains B lymphocyte at a low level, and the duration of B lymphocyte suppression and depletion depends on the dose. During the observation period, 13 (86.7%) subjects remained relapse free and 2 (13.3%) subjects relapsed. On day 180 postdose, 100 mg, 500 mg, and 750 mg groups had decreased expanded disability status scale (EDSS) scores compared to baseline. Three subjects were antidrug antibody (ADA) positive and all were neutralizing antibody (NAb)-negative. No obvious effects of ADA positivity on PK, safety, pharmacodynamics, or efficacy were observed.

In this study, BAT4406F was well tolerated and showed an expected pharmacodynamic effect of significant and long-term depletion of CD19⁺ B lymphocytes. BAT4406F also demonstrated preliminary evidence of activity as a NMOSD maintenance treatment. Based on this Phase I study, a Phase II/III multicenter, randomized, double-blind, placebo-controlled trial of BAT4406F in Chinese NMOSD patients is currently undergoing (NCT06044350).

About Bio-Thera Solutions
Bio-Thera Solutions, Ltd., a leading innovative, global biopharmaceutical company in Guangzhou, China, is dedicated to researching and developing novel therapeutics for the treatment of cancer, autoimmune, cardiovascular, eye diseases, and other severe unmet medical needs, as well as biosimilars for existing, branded biologics to treat a range of cancer and autoimmune diseases. As a leader in next generation antibody discovery and engineering, the company has advanced multiple candidates into late-stage development, including four approved products: QLETLI® and BETAGRIN®(Bevifibatide Citrate Injection) in China, and TOFIDENCE / BAT1806 and Avzivi® / Pobevcy® in the US, EU and China. In addition, the company has more than 20 promising candidates in clinical trials, focusing on immuno-oncology in the post-PD-1 era and targeted therapies such as ADCs. For more information, please visit www.bio-thera.com/en/ or follow us on Twitter (@bio_thera_sol) and WeChat (Bio-Thera).

Bio-Thera Cautionary Note Regarding Forward-Looking Statements
This news release contains certain forward-looking statements relating to BAT4406, or the product pipelines in general of Bio-Thera Solutions. Readers are strongly cautioned that reliance on any forward-looking statements involves known and unknown risks and uncertainties. The forward-looking statements include, among others, those containing "could," "may," "should," "will," "would," "anticipate," "believe," "plan," "promising," "potentially," or similar expressions. They reflect the company's current views with respect to future events that are based on what the company believes are reasonable assumptions in view of information currently available to Bio-Thera Solutions, and are not a guarantee of future performance or developments. Actual results and events may differ materially from information contained in the forward-looking statements as a result of a number of factors, including, but not limited to, risks and uncertainties inherent in pharmaceutical research and development, such as the uncertainties of pre-clinical and clinical studies. Other risks and uncertainties include challenges in obtaining regulatory approvals, manufacturing, marketing, competition, intellectual property, product efficacy or safety, changes in global healthcare situation, changes in the company's financial conditions, and changes to applicable laws and regulations, etc. Forward-looking statements contained herein are made only as of the date of their initial publication. Unless required by laws or regulations, Bio-Thera Solutions undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, changes in the company's views or otherwise.

1. QLETLI^® is a registered trademark of Bio-Thera Solutions, Ltd.
2. POBEVCY^® is a registered trademark of Bio-Thera Solutions, Ltd.
3. BETAGRIN^® is a registered trademark of Bio-Thera Solutions, Ltd.
4. Avzivi^® is a registered trademark of Sandoz AG
5. TOFIDENCE^™ is a trademark of Biogen

Contact
Bio-Thera Solutions, Ltd.:
Bert E. Thomas IV  +1.410.627.1734

SOURCE Bio-Thera Solutions, Ltd