Evergreen Medicines Announces Positive Phase II ClearMEMory Trial Results for EG-501, an AI-Driven Therapy for Cognitive Impairment in Neuropsychiatric Lupus

Oct 27, 2025 09:38 CST Updated 09:38

Evergreen Therapeutics

Innovative Drug Developer

Preface

Recently, Evergreen Therapeutics announced the Phase II clinical study data of its investigational drug EG-501, which has been deeply developed using artificial intelligence (AI) technology. EG-501 is used to treat cognitive impairment caused by neuropsychiatric systemic lupus erythematosus (NPSLE). As an AI-powered, first-in-disease innovative drug targeting this indication, EG-501 has shown rapid clinical progress, having previously received U.S. FDA approval to enter Phase II clinical trials in just 18 months.As a representative pipeline in China's AI pharmaceuticals field,EG-501 has been receiving continuous attention, and the research achievements this time further confirm the enormous potential of the "AI + Drug Development" model.。

Dr. Li Changqing Releases Phase II Clinical Trial Data of EG-501 at the Conference

01 Research Background

Systemic Lupus Erythematosus (SLE) is a complex, autoimmune-mediated diffuse connective tissue disease. It affects millions of people worldwide, with an increasing incidence rate. Cognitive Impairment (CI) is one of the most common clinical manifestations of SLE, significantly impacting patients' daily functioning and social participation. In patients with NPSLE, the prevalence of cognitive impairment ranges from 57% to 80%, often presenting symptoms such as "brain fog," memory deficits, and reduced executive function. Currently, the FDA has not approved any specific drugs for this condition, and clinical treatment primarily relies on symptomatic medications like corticosteroids and hydroxychloroquine, which cannot effectively address glutamate excitotoxicity. After diagnosis, patients face a significantly higher risk of unemployment, a severe decline in quality of life, and impose a heavy socioeconomic burden (with annual related expenses in the U.S. alone reaching approximately $20 billion).

EG-501 is a small molecule oral tablet for the treatment of cognitive impairment caused by NPSLE. It can reduce neuroinflammation in the brain and provide neuroprotective effects through NMDA receptor antagonism. This Phase II clinical trial is being conducted at three renowned academic centers in the United States: Vanderbilt University Medical Center, Cleveland Clinic, and The University of Texas Health Science Center at Houston. The trial aims to evaluate the efficacy of EG-501 in improving objective neuropsychological function in patients with systemic lupus erythematosus (SLE).

02 Research Methods

The ClearMEMory study (Clinical Trial Registration Number: NCT03527472) is a Phase II, multi-center, randomized, double-blind, placebo-controlled trial.First, potential subjects who meet the pre-screening criteria will be screened for objective neuropsychological dysfunction using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). If a subject's RBANS score is one age-adjusted standard deviation below the population norm, they will meet the inclusion criteria and will be stratified according to their NMDA receptor antibody status, then randomly assigned to the EG-501 group or the placebo group. Subjects will gradually increase their dose on a weekly basis to determine the maximum tolerated dose (range 10-40mg/day). The primary endpoint of the study is the change in RBANS score from baseline to the end of the study (Week 12); other endpoints include scores on each RBANS subscale, lupus disease activity, fibromyalgia, depression/anxiety scores, and Patient Global Impression of Change (PGIC) scores.

03 Research Conclusions

·EG-501 significantly improved the objective neuropsychological functions of patients

(RBANS Total Score Comparison Table, Placebo Group on the Left, EG-501 Group on the Right)

Among 258 pre-screened subjects and 131 formally screened subjects, 56 were ultimately randomized to the EG-501 group (n=26) or the placebo group (n=30). Of the screening failures, 93% were due to not meeting the qualifying threshold on the RBANS (Repeatable Battery for the Assessment of Neuropsychological Status). After randomization, the dropout rates due to adverse events (AEs) were identical in both groups (five subjects each), butA lower proportion of patients in the EG-501 group tolerated the maximum dose (42% vs. 70%), indicating that EG-501 has good safety.。

The study observed that the improvement in the total RBANS score was significantly greater in the EG-501 group compared to the placebo group (EG501: +10.4; Placebo: +4.2; p=0.032).The proportion of responders in the EG-501 group was higher than that in the placebo group (an 8-point increase: 67% vs. 36%, NNT=3.2; achieving the Minimal Clinically Important Difference (MCID) with a 5-point increase: 78% vs. 56%, NNT=4.6). Significant improvement was also observed in the RBANS Immediate Memory subscale (P=0.023). Additionally,More subjects who took EG-501 were rated as "Improved" or "Significantly Improved" on the Patient Global Impression of Change (PGIC) scale.No significant intergroup differences were observed in other outcome measures.

Dr. Changqing Li, Co-founder and Chief Medical Officer of Evergreen Therapeutics"We are excited about the Phase II clinical data of EG-501, which represents a significant achievement resulting from our team's years of dedication to leveraging AI-driven clinical technologies in drug development. We are highly optimistic about EG-501’s potential to improve the quality of life for patients with cognitive impairment associated with systemic lupus erythematosus. Furthermore, the drug’s core mechanism of modulating neuroinflammation holds great promise for expansion into other therapeutic areas, such as the treatment of cognitive impairments associated with rheumatoid arthritis (RA), Sjögren's syndrome, and Parkinson’s disease, offering hope to even more patients."

The EG-501 project will accelerate the advancement of its regulatory strategy in the United States, including applications for Orphan Drug Designation, Fast Track Designation, or Breakthrough Therapy Designation. It also plans to hold an End-of-Phase II meeting with the FDA to initiate pivotal clinical trials.

Notably, in the development of EG-501, both the research on SLE phenotypes related to cognitive impairment and drug repurposing studies originated from Evergreen Therapeutics' self-developed AI platform. During the drug development process, "dry lab" predictions via AI were closely integrated with clinical "wet lab" experiments.Evergreen Therapeutics Further Deepens the Understanding of GRIN2A's Role in Neurological and Immune Diseases. The Evergreen AI model successfully identified correlations that traditional models struggle to capture, fully demonstrating the feasibility of this AI platform in drug repurposing for rare central nervous system (CNS) disorders.By adopting this drug repositioning method, the cost of drug discovery can be significantly reduced from the conventional $2-3 billion to approximately $50 million, while the R&D cycle can be shortened from 10 years to 2-3 years. This approach greatly enhances R&D efficiency, reduces R&D risks, and paves a new path for pharmaceutical innovation.

About Evergreen Therapeutics

Evergreen Therapeutics is an innovative pharmaceutical company focusing on the development and application of AI technologies in biology and clinical fields. With branches in Shenzhen and Yantai in China, and Maryland in the United States, its international team brings together top talents from AI drug-related fields such as clinical medicine, international regulatory laws, chemistry, and computational science. The company always prioritizes addressing diseases with "urgent clinical needs" and is committed to developing first-in-disease global innovative drugs. Currently, six of Evergreen Therapeutics' proprietary pipelines have been approved by the U.S. FDA to enter clinical trials, with over 60 patent applications covering major pharmaceutical markets worldwide, including China, the U.S., Europe, and Japan.

The company adopts a "self-research + service" dual business model. On one hand, it focuses on the development of differentiated "in-house" drugs in the fields of ophthalmology, cardiovascular, and autoimmune diseases. In other therapeutic areas, it relies on its unique AI drug discovery platform and comprehensive capabilities and professional experience in pharmaceutical regulations and clinical trials to provide clients and partners with "one-stop" solutions that address challenges from drug discovery to the clinical process. It offers flexible and efficient R&D solutions and optimal regulatory submission pathway planning services tailored to specific needs.

About EvergreenAI Platform

Evergreen Therapeutics Integrates Multi-Omics, Clinical, and Real-World Data Using AI Technology to Enhance Scientific Design from the Outset, Building a Comprehensive and Efficient AI Platform Spanning the Entire Drug Development Cycle. The platform's functions include: Mechanism of Action (MOA) and Indication Identification, Pathway Analysis and Mechanism Elucidation, Multi-Omics and Patient Stratification, Clinical Trial Protocol Writing, Drug Repositioning, as well as Clinical Trial Prediction and Optimization. By innovatively constructing the "Three Major Engines"—Cross-Species Translation Prediction Engine, Mechanism Prioritization Engine, and "Target-Population-Disease" Mapping Engine—the platform effectively addresses long-standing challenges in the clinical stage, significantly improving the success rate of candidate drugs entering clinical trials while reducing R&D costs and shortening timelines. Evergreen Therapeutics plans to productize its proprietary AI platform and actively seeks global partners to empower more innovative pharmaceutical companies, jointly advancing this highly efficient innovation model to maximize commercialization and return on investment.