— First investigational therapy to demonstrate statistically significant improvement in objective cognitive function for patients with neuropsychiatric SLE —
BETHESDA, MD. and NASHVILLE, TN. – April 21, 2026 – Evergreen Therapeutics, Inc., a biopharmaceutical company focused on neuroimmune disorders, and Vanderbilt University Medical Center (VUMC) today announced positive results from a randomized, double-blind, placebo-controlled Phase 2 clinical trial evaluating EG-501, an investigational drug candidate for the treatment of cognitive impairment in adults with systemic lupus erythematosus (SLE).
The study, known as ClearMEMory, met its primary endpoint. Participants treated with EG-501 demonstrated significantly greater improvement in objective cognitive performance compared with placebo, as measured by the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS®) Total Scale Index Score from baseline to week 12. EG-501 was well tolerated, with no treatment-related serious adverse events (SAEs) and a discontinuation rate comparable to placebo.
Full findings will be presented at the American Academy of Neurology (AAN) annual meeting in Chicago, IL, and at the European Alliance of Associations for Rheumatology (EULAR) 2026 annual congress in London, UK.
From Genetic Discovery to Targeted Therapy
The development of EG-501 was guided by pioneering genetic research conducted at VUMC. Using advanced phenome-wide association studies (PheWAS) of Vanderbilt’s BioVU biobank, researchers identified a specific genetic variation linked to cognitive symptoms in SLE patients. This variation is associated with increased activity of the NMDA receptor in the brain, a key regulator of learning and memory.
That discovery provided the scientific rationale for investigating NMDA receptor antagonism as a targeted treatment for lupus-related cognitive dysfunction. EG-501, a selective antagonist, was subsequently advanced into the Phase 2 ClearMEMory trial, translating foundational genetic insight into a promising clinical candidate.
Addressing a Critical Unmet Need
Cognitive impairment — often described as “brain fog” — is a prevalent and disabling manifestation of lupus, affecting at least 38% of patients. Currently, no FDA-approved therapies exist specifically indicated to improve objective cognitive impairment in SLE.
“Cognitive dysfunction is a debilitating manifestation of lupus for which there is currently no approved treatment option,” said Dr. Leslie Crofford, former director of the VUMC Division of Rheumatology and Immunology and the study’s principal investigator. “I am very optimistic about these results and hope that additional testing will bring a new therapeutic option to market for this population.”
Dr. James Jackson, a director at the VUMC Critical Illness, Brain Dysfunction, and Survivorship Center and study co-investigator, added: “These findings represent a meaningful step forward in addressing the ‘silent’ burden of cognitive impairment in lupus, where objective measures like RBANS can guide targeted interventions.”
ClearMEMory Trial Key Results
The ClearMEMory trial randomized 56 adults with lupus and objective cognitive impairment to receive either EG-501 (titrated up to 40 mg/day) or placebo for 12 weeks.
- Primary Endpoint: Median change in RBANS Total Scale Index score improved by +8 in the EG-501 group versus +5 in the placebo group (p=0.032).
- Immediate Memory: Median change in the RBANS Immediate Memory domain score was +18.5 with EG-501 versus +7 with placebo (p=0.023).
- Patient Stability: While 16% of placebo recipients reported worsening health at week 12, 0% of EG-501 recipients reported worsening.
- Tolerability: 42% of EG-501 recipients and 70% of placebo recipients were able to tolerate the maximum dose of 40 mg/day.
Management Commentary
“This Phase 2 clinical trial reinforces our conviction that cognitive dysfunction in lupus is a treatable, objective clinical problem,” said Dr. Charles Lee, MD, DrPH, Co-Founder and Chief Medical Officer of Evergreen Therapeutics. “The magnitude of improvement observed in Immediate Memory is especially notable. Furthermore, our shift plot analysis — which displays the quantiles of RBANS change scores for the placebo group against the treatment difference — demonstrates a consistent cognitive benefit across the entire spectrum of response. With data points consistently positioned above the zero line, it is clear that treated participants achieved better outcomes than placebo regardless of the baseline magnitude of change.”
About EG-501
EG-501 is a first-in-disease, targeted therapeutic candidate developed by Evergreen Therapeutics to address cognitive impairment in patients with SLE, with potential future expansion to other autoimmune diseases. It is a novel NMDAR antagonist that offers potential neuroprotective effects while preserving normal physiological function.
About Cognitive Impairment in Systemic Lupus Erythematosus (SLE)
Cognitive impairment — often described as “brain fog” — affects at least 38% of SLE patients, significantly impairing memory, verbal recall, concentration, and daily functioning. There are currently no FDA-approved therapies specifically indicated for objective cognitive impairment in SLE. The global SLE market was estimated at 2.83 billion dollars in 2023, with cognitive impairment treatment positioned to expand into other autoimmune diseases.
About Evergreen Therapeutics, Inc.
Headquartered in Bethesda, Maryland, Evergreen Therapeutics is a biopharmaceutical company focused on developing therapies for neuroimmune disorders. Using AI-powered technologies, Evergreen advances drug candidates for areas of high unmet medical need in chronic and disabling conditions.
About Vanderbilt University Medical Center
Vanderbilt University Medical Center is a leading academic medical center renowned for transformative research, including pioneering work in genomic medicine and drug repurposing. VUMC is committed to advancing science and translating discoveries into improved patient care.
Forward-Looking Statements
This press release contains forward-looking statements regarding the future development of EG-501, planned clinical activities, and potential therapeutic uses. These statements are subject to risks and uncertainties, including clinical trial outcomes and regulatory feedback, which could cause actual results to differ materially.
Media Contact:
james.diao@egmedai.com
Source: Evergreen Therapeutics, Inc. / Vanderbilt University Medical Center