Pediatric Low-Grade Glioma Drug Pipeline — PatSnap Eureka
Pediatric Low-Grade Glioma Drug Pipeline: BRAF, MEK & Tovorafenib
pLGG is the most common brain tumor in children — approximately 15,500 new US diagnoses annually. MAPK pathway alterations dominate the molecular landscape, making BRAF and MEK inhibition the central therapeutic strategy. Explore the patent and literature signals shaping this pipeline.
BRAF: The Central Oncogenic Driver in Pediatric Low-Grade Glioma
Pediatric low-grade glioma is the most common brain tumor in children, and its molecular biology is dominated by MAPK pathway alterations — particularly BRAF fusions, rearrangements, and point mutations. According to patent filings retrieved via PatSnap Eureka, the Day One Biopharmaceuticals WO patent explicitly bifurcates the molecular landscape: BRAF fusion or rearrangement (the predominant alteration in pilocytic astrocytomas) and BRAF V600 point mutation (more common in pleomorphic xanthoastrocytoma and ganglioglioma).
Beyond BRAF, secondary genomic targets include the MYB-QKI fusion gene — identified by Dana-Farber Cancer Institute as the driver of angiocentric glioma — and CXCL10 signaling, highlighted as a mediator of the low-grade glioma tumor microenvironment. Research from the University of Bonn Medical Center further demonstrates that co-activation of the PI3K/mTOR pathway with BRAF V600E is required for benign neoplasm formation, with TP53 loss and PI3K/mTOR signaling state determining tumor biology.
The relapsed or refractory pLGG population — specifically addressed in the tovorafenib patent — represents a subset with limited standard-of-care options, making targeted innovation particularly impactful. For a broader view of life sciences patent intelligence, PatSnap's platform covers the full translational pipeline from discovery to commercialization.
Patent Activity & Development Stage Across pLGG Modalities
Derived from patent and literature records retrieved via PatSnap Eureka. All values reflect dataset signals only.
Key Patent Assignees in pLGG Targeted Therapy
Innovation activity is concentrated among a small number of focused organizations, with Day One Biopharmaceuticals holding the only patent specifically claiming tovorafenib in pLGG.
pLGG Therapeutic Modalities by Development Stage
Tovorafenib (Type II pan-RAF) is the most advanced modality in the dataset, with preclinical and discovery-stage approaches addressing non-BRAF targets.
Five Targeted Approaches Shaping the pLGG Pipeline
From clinical-stage pan-RAF inhibition to preclinical MYB-QKI suppression — a modality-by-modality breakdown from patent and literature signals.
Tovorafenib — Type II / Pan-RAF Inhibitor
Day One Biopharmaceuticals holds the only retrieved patent specifically claiming tovorafenib for pLGG, covering patients ≥6 months old with relapsed or refractory disease. Administered orally on a once-weekly schedule, tovorafenib is a Type II RAF inhibitor that binds the DFG-out inactive conformation — providing activity against both BRAF fusion-driven (Class 1) and BRAF V600 mutation-driven (Class 2) tumors. This dual-class activity is a key differentiator from first-generation BRAF inhibitors that paradoxically activate MAPK signaling in fusion-driven tumors. The patent's dose titration scheme (starting dose with provision for reduced doses) suggests tolerability data from clinical evaluation has been incorporated.
Clinical-Stage · WO Patent · Day One BiopharmaceuticalsBRAF V600E Inhibitors (Type I, Selective)
Array BioPharma (now part of Pfizer) holds active patent claims for substituted 3,4-dihydroquinazolin-4-one derivatives treating BRAF-associated diseases including cancer. Quest Diagnostics patents list specific approved BRAF inhibitors relevant to intracranial neoplasm management — including GDC-0879, Encorafenib, Dabrafenib (GSK2118436), Vemurafenib, and SB590885 — for patient selection. A Chinese patent from Capital Medical University Beijing Tiantan Hospital discloses an acquired dabrafenib-resistant human primary glioma cell line (CGMCC No. 45631), signaling active interest in overcoming BRAF inhibitor resistance in glioma.
Clinical Translation · CL, EP, CN, CA PatentsMEK Inhibitors (Trametinib & Combinations)
Novartis AG holds a retrieved patent covering biomarker use for predicting response to BRAF- and/or MEK-targeted agents, specifically listing dabrafenib + trametinib combinations. MEK inhibition provides an indirect downstream strategy to block MAPK pathway output from both BRAF V600 mutations and BRAF fusions, which activate MEK/ERK constitutively. The University of Bonn academic paper on PI3K/mTOR-BRAF V600E interaction in developmental brain tumors provides mechanistic grounding for MEK-directed therapy. Trametinib is in active clinical investigation in pLGG per retrieved signals. Learn more about patent landscape analytics for oncology combinations.
Active Clinical Investigation · CN Patent · Novartis AGERK5 Inhibitors (ERK5-IN-1, TG02)
University of Pittsburgh holds two WO patent applications — one claiming ERK5 inhibitors (specifically ERK5-IN-1) for treating pediatric glioma including DIPG with H3K27M mutation, and a related patent disclosing TG02 (a CDK/ERK5 inhibitor) for pediatric glioma treatment. These modalities address MAPK pathway components downstream of or parallel to MEK. Though their primary retrieved application is to high-grade pediatric glioma, their mechanism intersects with MAPK signaling biology relevant to pLGG. Both filings are preclinical-stage.
Preclinical · WO Patents · University of PittsburghNon-BRAF Targets: MYB-QKI & CXCL10
Dana-Farber Cancer Institute patents address angiocentric glioma — a molecularly distinct pLGG subtype — driven by MYB-QKI rearrangement. The therapeutic strategy involves suppressing MYB-QKI fusion gene expression or activity, providing a non-MAPK target for BRAF-wild-type pLGG. A separate US patent from inventor Anastasaki describes engineered Cxcl10-deficient animal models for growing LGG patient-derived xenografts — a key translational tool for preclinical drug testing. The NCI classifies angiocentric glioma as a distinct WHO entity, underscoring the clinical relevance of this non-BRAF subtype.
Preclinical/Discovery · WO, US Patents · Dana-Farber, AnastasakiBRAF + PI3K/mTOR Co-inhibition & Immuno-Oncology
The University of Bonn paper demonstrates that PI3K/mTOR co-activation is a key determinant of BRAF V600E tumor behavior — suggesting combination strategies targeting both RAF and PI3K/mTOR pathways may be necessary for complete tumor suppression. The Novartis biomarker patent also documents interest in combining dabrafenib + trametinib with anti-PD-1 therapy (spartalizumab), signaling immuno-oncology combination interest, though the pediatric pLGG immune microenvironment would require specific investigation. This emerging mechanistic rationale is not yet reflected in dedicated patent claims in this dataset. Explore how biopharma teams use PatSnap to track combination therapy IP.
Emerging · Mechanistic Rationale Only · No Dedicated Patents YetWho Holds the Key IP in pLGG Targeted Therapy?
Innovation activity in pLGG-specific BRAF/MEK/tovorafenib approaches is concentrated among a small number of highly focused organizations.
What the Patent Signals Mean for R&D Strategy
Derived from patent claim structures, filing timing and specificity, and retrieved academic literature in this dataset.
Tovorafenib: Defensible IP in an Orphan Indication
Day One Biopharmaceuticals holds the only retrieved patent specifically claiming tovorafenib in pLGG, covering a broad pediatric age range (≥6 months), both major BRAF alteration classes (fusion and V600), and a refined dose titration scheme — suggesting strong, defensible IP positioning in this orphan pediatric indication.
PI3K/mTOR Co-Activation Creates Combination Trial Rationale
The mechanistic insight that BRAF V600E alone is insufficient for pLGG tumor formation (PI3K/mTOR co-activation required) creates a scientific rationale for combination trials, representing a potential opportunity for companies developing PI3K/mTOR/AKT pathway inhibitors to pursue pLGG indications alongside BRAF inhibitor partners.
Key Molecular Findings from the Retrieved Dataset
BRAF (V600E and fusion/rearrangement): In this dataset, BRAF is the central molecular target for pLGG. The Day One Biopharmaceuticals WO patent explicitly bifurcates the molecular landscape into BRAF fusion/rearrangement (the predominant pLGG alteration, estimated in the majority of pilocytic astrocytomas) and BRAF V600 point mutation (more common in pleomorphic xanthoastrocytoma and ganglioglioma). Tovorafenib is claimed to address both classes — an important distinction from first-generation BRAF inhibitors that paradoxically activate MAPK signaling in fusion-driven tumors.
PI3K/mTOR co-activation with BRAF V600E: The University of Bonn Medical Center academic paper demonstrates that BRAF V600E alone is insufficient for tumor formation in murine neural progenitors — co-activation of PI3K/mTOR signaling (constitutively phosphorylated Akt) is required. TP53 loss and PI3K/mTOR signaling state determine tumor biology and functional properties, including neural excitability. This has direct implications for combination therapeutic strategies.
MYB-QKI fusion: Dana-Farber Cancer Institute patents identify the MYB-QKI rearrangement as the driver of angiocentric glioma, a distinct pLGG entity. The therapeutic approach of suppressing MYB-QKI fusion gene expression provides a non-MAPK target for a BRAF-wild-type pLGG subtype. The WHO classifies angiocentric glioma as a distinct central nervous system tumor entity in its 2021 CNS tumor classification.
CXCL10 / tumor microenvironment: The Anastasaki patent positions CXCL10 as a microenvironmental regulator in LGG, with Cxcl10-deficient animal models enabling patient-derived xenograft (PDX) growth — a key translational tool for preclinical drug testing. PatSnap's life sciences intelligence platform supports teams tracking tumor microenvironment IP across oncology indications.
ERK5: University of Pittsburgh patents position ERK5 as a druggable MAPK family kinase in pediatric glioma, noting its relevance in H3K27M-mutant DIPG contexts. Overlap with pLGG is indirect but mechanistically relevant given shared MAPK pathway biology. The European Bioinformatics Institute maintains curated kinase target data supporting ERK5 pathway research.
Pediatric Low-Grade Glioma Drug Pipeline — key questions answered
Pediatric low-grade glioma (pLGG) is the most common brain tumor in children, with approximately 15,500 new diagnoses annually in the United States and 300,000 globally.
pLGG is highly driven by MAPK pathway alterations — particularly BRAF fusions, rearrangements, and point mutations. BRAF fusions (such as KIAA1549-BRAF) represent the majority of molecular alterations in pLGG, particularly in pilocytic astrocytomas. BRAF V600E point mutations are more common in pleomorphic xanthoastrocytoma and ganglioglioma.
Tovorafenib is a Type II RAF inhibitor administered orally on a once-weekly schedule. It binds the DFG-out inactive conformation, providing activity against both BRAF fusion-driven (Class 1) and BRAF V600 mutation-driven (Class 2) tumors, which is particularly relevant for pLGG where both alteration classes coexist. Day One Biopharmaceuticals holds the only retrieved patent specifically claiming tovorafenib in pLGG, covering patients 6 months of age or older with relapsed or refractory disease.
Research from the University of Bonn Medical Center demonstrates that BRAF V600E alone is insufficient for tumor formation in murine neural progenitors — co-activation of PI3K/mTOR signaling (constitutively phosphorylated Akt) is required. This finding suggests that single-agent BRAF inhibition may be insufficient in tumors where PI3K/mTOR is co-activated, providing a rationale for combination therapeutic strategies targeting both RAF and PI3K/mTOR pathways.
Key patent holders in this dataset include Day One Biopharmaceuticals (tovorafenib for pLGG), Dana-Farber Cancer Institute (MYB-QKI suppression for angiocentric glioma), Array BioPharma/Pfizer (BRAF-associated disease treatment), Quest Diagnostics (companion diagnostics for BRAF inhibitor patient selection), Novartis AG (BRAF/MEK biomarker strategy), and University of Pittsburgh (ERK5 inhibitors for pediatric glioma).
Dana-Farber Cancer Institute patents identify the MYB-QKI rearrangement as the driver of angiocentric glioma, a distinct pLGG subtype. The therapeutic approach of suppressing MYB-QKI fusion gene expression or activity provides a non-MAPK target for a BRAF-wild-type pLGG subtype — representing an emerging strategy for patients whose tumors lack BRAF alterations.
Still have questions about pLGG patent intelligence? Let PatSnap Eureka answer them for you.
Ask Eureka About pLGG PatentsAccelerate Your pLGG Drug Discovery Intelligence
Join 18,000+ innovators already using PatSnap Eureka to accelerate their R&D. Map the BRAF, MEK, and tovorafenib patent landscape in minutes — not weeks.
References
- Methods of treating pediatric low-grade glioma — Day One Biopharmaceuticals, Inc., 2025, WO [Patent]
- Heterogeneity and excitability of BRAF V600E-induced tumors is determined by PI3K/mTOR-signaling state and Trp53-loss — Section for Translational Epilepsy Research, University of Bonn Medical Center, 2021 [Paper]
- Substituted 3,4-dihydroquinazolin-4-one derivative compounds and their use in the treatment of BRAF-associated diseases and disorders — Array BioPharma Inc., 2023, CL [Patent]
- Methods for detecting craniopharyngioma and for selecting medicaments and patients for treatment — Quest Diagnostics Investments LLC, 2024, EP [Patent]
- Compositions and methods for screening pediatric gliomas and methods of treatment thereof — Dana-Farber Cancer Institute, Inc., 2017, WO [Patent]
- Compositions and methods for screening pediatric gliomas and methods of treatment thereof — Dana-Farber Cancer Institute, Inc., 2019, US [Patent]
- Engineered cells, animal models, and uses thereof for modeling low grade glioma (LGG) — Anastasaki, Corina, 2023, US [Patent]
- Use of ERK5 inhibitors for treating gliomas in pediatric subjects — University of Pittsburgh, 2020, WO [Patent]
- Use of TG02 for treating gliomas in pediatric subjects — University of Pittsburgh, 2020, WO [Patent]
- Cancer Biomarkers — Novartis AG, 2023, CN [Patent]
- Human primary glioblastoma acquired resistance cell line and application thereof — Capital Medical University Beijing Tiantan Hospital, 2024, CN [Patent]
- Methods for detecting intracranial neoplasms — Quest Diagnostics Investments LLC, 2018, CA [Patent]
- National Center for Biotechnology Information (NCBI) — PubMed literature database
- National Cancer Institute (NCI) — Pediatric brain tumor classification and treatment resources
- World Health Organization (WHO) — 2021 Classification of Tumors of the Central Nervous System
- European Bioinformatics Institute (EMBL-EBI) — Kinase target and pathway databases
All data and statistics on this page are sourced from the references above and from PatSnap's proprietary innovation intelligence platform. This report is derived from a limited set of patent and literature records retrieved across targeted searches and represents a snapshot of innovation signals within this dataset only.
PatSnap Eureka searches patents and research to answer instantly.