The EG-501 Program
The EG-501 program represents Evergreen Therapeutics’ first end-to-end closed-loop validation of its proprietary AI platform, from drug discovery to achieving positive clinical outcomes. This breakthrough confirms AI’s practical value in drug development and offers a streamlined, reproducible R&D model.
Our AI platform utilizes a rigorous technical workflow, applying innovative methodologies such as Phenome-Wide Association Study (PheWAS) and machine learning algorithms for precise target mining and disease association.The platform’s efficiency is built on a robust data foundation：
- Integrates large-scale, high-quality data from top U.S. academic medical centers
- Includes whole-exome sequencing (WES) data from over 12,000 individuals and 250,000 coding variants
- Includes a de-identified electronic health record (EHR) database covering 35,000 participants and approximately 1,600 distinct disease phenotypes
From these extensive datasets, the platform identified 12 target-associated disease phenotypes. Neuropsychiatric Systemic Lupus Erythematosus (NPSLE)-related cognitive impairment was then selected based on strategic evaluation for Phase II clinical trials. This complete data-to-clinic technical loop underscores our AI platform as a validated asset-generating platform, effectively driving drug development.
Clinical Progress
The EG-501 program has successfully completed its Phase II clinical trial, a multicenter, randomized, placebo-controlled, double-blind study. This trial evaluated EG-501’s efficacy in treating NPSLE-related cognitive impairment, conducted at Vanderbilt University Medical Center, Cleveland Clinic, and the University of Texas Health Science Center at Houston. The positive results establish a strong foundation for the program’s advancement.
During the 12-week trial, 56 eligible patients were randomized. Among the 43 completers in the pre-specified primary analysis:
- Cognitive Improvement: The EG-501 group demonstrated a statistically significant improvement in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale score (mean change: +10.4) compared to the placebo group (mean change: +4.2) (p=0.032), providing objective evidence of cognitive enhancement.
- Domain-Specific Benefits: EG-501 also showed significant advantages in multiple cognitive function subdomains.
- Responder Rates: A notable 78% of EG-501 patients achieved a clinically meaningful response (RBANS Thresholds of ≥5) compared to 56% in the placebo group. Furthermore, 67% of EG-501 patients achieved a more substantial response (RBANS Thresholds of ≥8), supporting the compound’s pharmacological activity.
The EG-301 program
As a functional inhibitor of acid sphingomyelinase (ASM), EG-301 primary mechanism of action involves modulating lipid metabolism dysregulation in retinal pigment epithelium (RPE) cells, offering a novel therapeutic approach for Dry Age-related Macular Degeneration (AMD) in patients exhibiting high-risk characteristics for progression to Geographic Atrophy (GA). GA is the advanced, blinding form of dry AMD that currently has limited treatment options. This addresses an unmet clinical need and validates the transformative potential of AI across the drug development continuum.
The EG-301 program exemplifies Evergreen Therapeutics’ reverse translational medicine model for AI-enabled indication discovery.Under the reverse translational medicine framework, the program employs two key strategies:
- Integration of clinical and genomic phenotypic data with differential gene expression profiling in human ocular tissues, combined with AI-enabled Phenome-Wide Association Study (PheWAS) and pathway analysis, to identify lipid metabolism dysregulation as a core pathogenic driver.
- Divergence from conventional approaches by progressing from human epidemiological studies and tissue analyses to preclinical validation.
Clinical Progress
Evergreen Therapeutics announced on February 4, 2022, that the U.S. FDA approved the Investigational New Drug (IND) application for EG-301, an oral therapeutic for the treatment of dry age-related macular degeneration. This clearance initiated the Phase II clinical trial.
Leveraging the company’s AI platform, EG-301’s trial design was optimized through:
- Integration of sensitive functional endpoints (e.g., BCVA) for early efficacy detection
- Implementation of enhanced patient retention protocols
These measures aim to reduce costs, improve trial efficiency, and ensure data integrity to accelerate clinical development.
No therapies are currently approved for the treatment of dry AMD. Evergreen Therapeutics’ program is among the most advanced clinical-stage development efforts for this indication globally.
The EG-101 program
EG-101 is an investigational injectable therapeutic developed for preeclampsia. It addresses the unmet clinical need for this life-threatening pregnancy-specific disorder, offering a novel therapeutic strategy to improve maternal and perinatal outcomes while demonstrating the value of precision intervention for complex gestational conditions.
Preeclampsia is a serious obstetrical complication affecting 3–5% of pregnancies worldwide and represents a leading cause of maternal mortality and perinatal morbidity. Its hallmark features include new-onset hypertension and proteinuria, frequently accompanied by multisystem organ dysfunction—particularly hepatic and renal impairment. The condition’s complex etiology remains incompletely defined, with evidence suggesting vascular endothelial dysfunction contributes to its pathogenesis. Currently, no approved disease-modifying therapies exist for preeclampsia treatment or prevention, creating a substantial therapeutic gap.
In preclinical studies, EG-101 demonstrated therapeutic efficacy in preeclampsia models:
- Significant improvement in hypertension
- Substantial reduction in proteinuria
These effects target the disorder’s core pathophysiological features, providing a foundation for clinical development and a potential therapeutic solution for this unmet medical need.
Clinical Progress
In April 2025, the U.S. FDA authorized Evergreen Therapeutics’ Investigational New Drug (IND) application for EG-101, permitting initiation of clinical trials.
