MODEYSO is the first treatment of its kind1

By targeting oncogenic pathways, MODEYSO reverses H3 K27me3 loss, the central hallmark of H3 K27M–mutant diffuse midline glioma2,3

MECHANISM OF MODEYSO

In preclinical studies, MODEYSO reversed H3 K27me3 loss using a targeted approach2

Protease activators are a class of small-molecule anticancer compounds that share a unique heterocyclic pharmacophore that targets specific GPCRs and mitochondrial ClpP, resulting in cancer cell death.1,4

As a CNS-penetrant protease activator, MODEYSO addresses the oncogenic expression and pathway activation in 2 ways1,2,4,5

  1. ClpP agonism: MODEYSO alters energy production in the mitochondria to induce a stress response and apoptosis.

  2. DRD2 antagonism: MODEYSO inhibits DRD2 intracellular signaling pathways.

Image of the perceived mechanism of action of MODEYSO

In cell-based assays and in vivo models of H3 K27M–mutant diffuse glioma, MODEYSO exhibited antitumor activity. Altered mitochondrial metabolism induced by MODEYSO impacts histone demethylases to reverse H3 K27me3 loss2

AKT, protein kinase B; ClpP, caseinolytic protease P; CNS, central nervous system; DRD2, dopamine receptor D2; ERK, extracellular signal-regulated kinase; GPCRs, G protein-coupled receptors; H3, histone 3; RAS, reticular activating system.

Explore efficacy results from the integrated analysis

References: 1. Allen JE, Kline CLB, Prabhu VV, et al. Discovery and clinical introduction of first-in-class imipridone ONC201. Oncotarget. 2016;7(45):74380-74392. doi:10.18632/oncotarget.11814 2. MODEYSO™. Package insert. Chimerix, Inc; 2025. 3. Saratsis AM, Knowles T, Petrovic A, Nazarian J. H3K27M mutant glioma: disease definition and biological underpinnings. Neuro Oncol. 2024;26(suppl 2):S92-S100. doi:10.1093/neuonc/noad164 4. Free RB, Cuoco CA, Xie B, et al. Pharmacological characterization of the imipridone anticancer drug ONC201 reveals a negative allosteric mechanism of action at the D2 dopamine receptor. Mol Pharmacol. 2021;100(4):372-387. doi:10.1124/molpharm.121.000336 5. Jackson ER, Persson ML, Fish CJ, et al. A review of current therapeutics targeting the mitochondrial protease ClpP in diffuse midline glioma, H3 K27-altered. Neuro Oncol. 2024;26(suppl 2):S136-S154. doi:10.1093/neuonc/noad144