PROTEOGENOMIC DISCOVERY ENGINE FOR EXPOSING THE EXPOSED: SPLICE SURFACE THERAPEUTIC TARGETS

About This Grant

ABSTRACT A central barrier to next-generation immunotherapies is the scarcity of disease-specific extracellular targets. A major untapped source of targets arises from alternative splicing, which generates thousands of aberrant isoforms across many complex diseases. Many of these isoforms alter extracellular domains of transmembrane proteins, producing “splice surface antigens” (SSAs)—a novel class of epitopes with immense therapeutic potential. Despite strong biology rationale, no scalable, end-to-end platform exists to systematically discover, prioritize, and validate SSAs for drug development. This STTR Phase I will translate recent academic advances into the NeoSplice Discovery Engine™, a modular, disease-agnostic platform that 1) resolves full-length isoforms in heterogeneous samples, 2) scores candidates for surface exposure, safety, and tractability, and 3) confirms stable surface expression with targeted protein assays. Aim 1 will generate a ranked catalog of SSA candidates in a defined disease model, producing concise, partner-ready target dossiers. Aim 2 will establish a targeted validation workflow to verify isoform-specific surface expression across prioritized candidates and scale to larger panels. Phase I deliverables include a versioned scoring framework, prioritized SSA lists with per-target summaries, and validated assay panels suitable for therapeutic programs. This project lays the foundation to expand the actionable target space beyond canonical proteins. It will position us for Phase II lead generation, partnerships, and co-development of safer, more precise isoform-resolved therapies across multiple indications.