A First-in-Class vIRF3-Derived Peptide (VDP) Therapy Targeting the PKM2 Metabolic Axis for Tumor Regression and Metastasis Inhibition.

Cancer progression and metastasis are increasingly recognized as processes driven by metabolic and signaling reprogramming, rather than uncontrolled proliferation alone.
PKM2 (pyruvate kinase M2) functions as a structure-dependent signaling node, acting as a nuclear transcriptional co-factor in its dimeric state and as a metabolic–epigenetic signaling hub in its tetrameric state, thereby coordinating oncogenic programs that support tumor growth, survival, metabolic adaptation, and metastatic competence.
This technology introduces vIRF3-derived peptides (VDP) that selectively disrupt the vIRF3–PKM2 protein–protein interaction, identified as a critical regulatory switch governing PKM2-dependent pathological signaling.
Rather than directly inhibiting PKM2 enzymatic activity, VDP modulates pathological PKM2 structural signaling dynamics, thereby avoiding systemic metabolic disruption.
Mechanistically, VDP competitively interferes with the PKM2 interaction interface, disrupting pathological PKM2 structural signaling and suppressing tetramer-driven acetyl-CoA–dependent metabolic–epigenetic programs required for tumor invasion, EndoMT induction, and metastatic dissemination.
In vivo tumor models demonstrate significant tumor regression, strong inhibition of cancer cell migration and invasion, and effective suppression of metastatic spread, without significant body-weight loss or overt toxicity.
The platform supports peptide optimization, expansion into peptide–drug conjugates (PDCs), validation in patient-derived xenograft (PDX) models, and development of companion diagnostics (CDx) based on PKM2-dependent metabolic and signaling signatures.
Commercialization opportunities include global IP licensing (option or exclusive), strategic co-development, and clinical-stage partnerships targeting metabolically dependent cancers, encompassing both orphan indications and major solid tumor markets.