Proteogenomic discovery engine for exposing the exposed: splice surface therapeutic targets

The National Center for Advancing Translational Sciences, part of the National Institutes of Health under the Department of Health and Human Services, awarded $321,316 to Neosplice Therapeutics, Inc. on July 20, 2026, under the NCATS program (Assistance Listing 93.350).

Neosplice Therapeutics will develop the NeoSplice Discovery Engine, a modular platform designed to systematically discover, prioritize, and validate splice surface antigens (SSAs)—a novel class of disease-specific therapeutic targets arising from alternative splicing. The platform integrates three core capabilities: resolving full-length isoforms in heterogeneous samples, scoring candidates for surface exposure, safety, and tractability, and confirming stable surface expression through targeted protein assays. Phase I deliverables include a versioned scoring framework, prioritized SSA candidate lists with per-target summaries, and validated assay panels suitable for therapeutic development. Aim 1 will generate a ranked catalog of SSA candidates in a defined disease model with partner-ready target dossiers. Aim 2 will establish and scale a targeted validation workflow to verify isoform-specific surface expression across prioritized candidates.

Performance occurs in New York, New York. The period of performance runs from July 20, 2026, through July 19, 2027. This Phase I effort lays groundwork for Phase II lead generation, partnerships, and co-development of isoform-resolved therapies across multiple indications.

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.