Supplementary Figures 1-15 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways
Authors: Venneti Sriram , Kawakibi Abed Rahman , Ji Sunjong , Waszak Sebastian M. , Sweha Stefan R. , Mota Mateus , Pun Matthew , Deogharkar Akash , Chung Chan , Tarapore Rohinton S. , Ramage Samuel , Chi Andrew , Wen Patrick Y. , Arrillaga-Romany Isabel , Batchelor Tracy T. , Butowski Nicholas A. , Sumrall Ashley , Shonka Nicole , Harrison Rebecca A. , de Groot John , Mehta Minesh , Hall Matthew D. , Daghistani Doured , Cloughesy Timothy F. , Ellingson Benjamin M. , Beccaria Kevin , Varlet Pascale , Kim Michelle M. , Umemura Yoshie , Garton Hugh , Franson Andrea , Schwartz Jonathan , Jain Rajan , Kachman Maureen , Baum Heidi , Burant Charles F. , Mottl Sophie L. , Cartaxo Rodrigo T. , John Vishal , Messinger Dana , Qin Tingting , Peterson Erik , Sajjakulnukit Peter , Ravi Karthik , Waugh Alyssa , Walling Dustin , Ding Yujie , Xia Ziyun , Schwendeman Anna , Hawes Debra , Yang Fusheng , Judkins Alexander R. , Wahl Daniel , Lyssiotis Costas A. , de la Nava Daniel , Alonso Marta M. , Eze Augustine , Spitzer Jasper , Schmidt Susanne V. , Duchatel Ryan J. , Dun Matthew D. , Cain Jason E. , Jiang Li , Stopka Sylwia A. , Baquer Gerard , Regan Michael S. , Filbin Mariella G. , Agar Nathalie Y.R. , Zhao Lili , Kumar-Sinha Chandan , Mody Rajen , Chinnaiyan Arul , Kurokawa Ryo , Pratt Drew , Yadav Viveka N. , Grill Jacques , Kline Cassie , Mueller Sabine , Resnick Adam , Nazarian Javad , Allen Joshua E. , Odia Yazmin , Gardner Sharon L. , Koschmann Carl 
Published: February 2025

<p>Contains supplementary data and table titles and as well as supplementary figures with associated titles and legends.Fig. S1. Selection method for planned efficacy analysis of ONC201 in patients with H3K27MDMG.Fig. S2. Progression-free survival from diagnosis of trial patients with non-recurrent H3K27MDMG treated with ONC201.Fig. S3. Swimmers’ plot of ONC201 response by recurrence status, tumor location, and ONC201 trial.Fig. S4. ONC201 efficacy is independent of TP53 mutation status and chromosomal instability.Fig. S5. Cox proportional hazard regression to assess the effect of ONC201 after adjusting for confounders.Fig. S6. Survival of patients with H3K27M-DMG treated with ONC201 versus ONC201untreated historical controls.Fig. S7. Survival of patients with H3K27M-DMG treated with ONC201 versus ONC201untreated patients (PNOC003 or HERBY Phase II trials).Fig. S8. Molecular attributes of patients with H3K27M-DMG treated with ONC201.Fig. S9: Survival of H3K27M-DMG mice models treated with ONC201.Fig. S10. Integrative analysis of in vitro and human tumor metabolic gene expression in response to ONC201.Fig. S11. ONC201-mediated L2HG production increases H3K27me3 in H3K27M-DMG cells.Fig. S12. ONC201-induced increase in H3K27me3 is mediated by lactate dehydrogenase.Fig. S13. ONC201 alters genomic chromatin accessibility and H3K27ac distribution in H3K27M-DMG cells.Fig. S14. ONC201 increases global H3K27me3 in patient samples.Fig. S15. ONC201 does not cause hypermethylation leading to a glioma CpG island methylator phenotype.</p>