Science
Moonwalk's AI-enabled discovery platform integrates large-scale human genetics, epigenomics and multi-omics with functional validation to identify and prioritize causal targets for cardiometabolic disease.
Our platform combines:
- Human genetic studies across metabolic diseases
- Epigenetic profiling of healthy and obese, subcutaneous and visceral, and white and brown adipose tissues
- Tissue-specific gene expression and other ‘omics analyses
- Functional validation in primary human adipocytes
- In vivo efficacy studies using proprietary adipose-targeted siRNA technology
This integrated approach enables the discovery of first-in-class therapeutic targets with strong human biological validation.
Moonwalk is combining advances in genomics medicine and AI to enable rational drug development
Target Identification
- High resolution, multimodal, tissue specific biological data + AI reasoning.
- Achieving >40% hit rate.
Drug Design
- Tissue specific (extrahepatic) siRNA modality to modulate gene targets.
- AI-enabled siRNA design and large scale screening.
Preclinical Validation
- Validate clinical candidates in disease models, and evaluate safety; data feeds Target ID AI model.
- Achieving novel Target ID to DC in less than a year.
Clinical Validation
- Validate clinical candidate safety and efficacy predictions in human.
- Identification of candidate biomarkers.
Purpose-Built for Adipose Tissue
Moonwalk’s proprietary adipose-targeted siRNA platform is designed to selectively deliver RNA therapeutics to adipose tissue while minimizing off-target exposure. The technology has demonstrated durable target knockdown in preclinical models and supports infrequent, quarterly or half-yearly dosing.
Comprehensive metabolic trait genetic analysis
Genes with human genetic support were identified through mapping genome-wide association study loci across a comprehensive panel of metabolic traits. Approaches used to map variants to genes include spatial proximity, colocalization with expression quantitative trait loci, identification of protein coding variants, and cross referencing with gene burden tests.
Comprehensive overlay of epigenetic view of adipose cell states through genome wide methylation
Primary human white adipose tissue-derived adipocytes and preadipocytes from healthy, overweight and obese BMI donors were subjected to whole-genome DNA methylation analysis. Brown adipocytes cultured from human supraclavicular brown adipose tissue depots were also analyzed. Differentially methylated regions were identified and catalogued.
Novel target prediction at the intersection and validation in disease relevant models to select causal targets
Screening campaigns to identify high-efficiency siRNA sequences to target these genes in rodents. Modification and conjugation of siRNA sequences to mediate adipose-tissue targeting was performed, and adipose-targeted siRNA constructs were tested for in vivo silencing efficacy and therapeutic activity in diet-induced obesity (DIO) models.
Targeting Novel Adipose Biology to Treat Obesity
Moonwalk's discovery platform combines human genetics, epigenetics and functional biology to identify and validate novel therapeutic targets in adipose tissue. By analyzing adipose samples from healthy, overweight and obese individuals, and different types of adipose tissues, we uncover disease-driving biological pathways that may enable differentiated treatments for obesity and metabolic disease.
Example: Differentially Methylated Region (DMR) and genetic evidence for a target implicated in lipolysis and lipid droplet formation
Biological pathways represented in novel Moonwalk targets
Moonwalk siRNAs show efficacy across diverse targets and adipose mechanisms; MW01 data shown
Representative DEXA scan of late-stage obesity mice treated with negative template control (NTC), MW01 or ALK7 comparator. Red color indicates adipose tissue.
