We developed photo-activatable-competition and chemoproteomic enrichment (PACCE) as global method for identifying RNA-binding sites on proteins. PACCE is complementary to existing RNA interactome capture methods and enables functional profiling of canonical RNA-binding domains as well as discovery of moonlighting RNA binding activity in the human proteome. Here, we provide an update on functional evaluation of non-canonical RBPs discovered using PACCE.

Lightning.AI, Anima’s groundbreaking TechBio platform, uses Visual Biology to transform target and drug discovery. With PathwayLight, it generates deep, large-scale disease biology data by imaging cellular pathways in healthy and diseased cells. This data trains neural networks to identify “disease signatures,” uncover novel targets, and discover small molecules that modulate mRNA biology. Validated through partnerships with Lilly, Takeda, and AbbVie, Lightning.AI now powers over 20 drug discovery programs.

Using orally bioavailable small molecules to modulate the function of messenger RNAs offers a promising strategy for developing new therapies that extend beyond currently druggable protein targets. Here, we discuss our structure-based approach to discovering mRNA-targeted small molecules, touching on unique challenges in building a broad and robust platform.

The viability of an emerging small molecule splicing program often depends on the ability to drive potency towards a particular target, while maintaining reasonable selectivity. This presentation highlights our hit-to-lead efforts towards the development of a splicing modifier of an undisclosed gene of high interest.

Rgenta Therapeutics has developed a proprietary, integrative RNA-targeting oral small molecule discovery platform to deliver first-in-class therapies. We are pursuing targets in the oncology and neurological diseases space, exemplified by the oncogenic transcription factor c-MYB and the PMS1 gene. In this presentation, we’ll share an overview of our platform and recent progress on selected targets.

Metabolite binding to RNA can modulate gene expression. We have developed a technology using LC/MS-based metabolomics and an endogenous metabolite library to systematically discover functional binding pockets on RNA. These pockets enable an efficient drug discovery campaign using AI/ML-enabled structure-based drug design. This process has been successfully executed on several RNA targets in multiple therapeutic areas. Our discovery of compounds that bind to the UTR of human SERPINA1, which is implicated in Alpha-1-Antitrypsin (A1AT) deficiency, will be presented.