Abstract 4063: Oral small-molecule condensate modulator (c-mod) inhibits MYC activity and demonstrates robust anti-tumor activity across diverse tumor models

Abstract MYC is a key oncogenic driver that is commonly overexpressed or amplified across a wide spectrum of human cancers. Despite its therapeutic relevance, MYC has remained difficult to target pharmacologically due to its intrinsically disordered structure and dependence on dynamic biomolecular interactions. MYC forms transcriptional condensates to drive oncogene expression, suggesting that it might be inhibited by this mechanism. Using a condensate-focused screening approach, we previously identified first-generation MYC condensate modulators (c-mods) capable of disrupting MYC condensates and suppressing MYC-dependent transcription. Here we describe the profile of our orally bioavailable MYC Development Candidate (DC) with improved pharmacological properties, potency, and selectivity. This compound reduces MYC condensates, represses MYC-driven gene expression, and selectively inhibits the growth of MYC-addicted cancer cells by inducing apoptosis and cell-cycle arrest. Broad in vitro activity has been observed across multiple solid tumor types. In animal models, oral administration of our DC produces robust anti-tumor responses with an emerging tolerability profile supportive of continued development. Preclinical biomarker studies further demonstrate modulation of MYC pathway activity in vivo. Together, these findings position MYC condensate modulation as a promising therapeutic strategy for MYC-driven cancers. Citation Format: Jian-Guo Ren, Doug Baumann, Adam Talbot, Thomas Durand-Reville, Isaac Klein, Ann Boija. Oral small-molecule condensate modulator (c-mod) inhibits MYC activity and demonstrates robust anti-tumor activity across diverse tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4063.