MTX-241F / Mekanistic Therap - LARVOL DELTA

Identification of molecularly targeted therapy-induced immunopeptidome in diffuse midline glioma (DMG). (PubMed, Neoplasia) - "MTX-241F changes the glioma immunopeptidome, unveiling H2B1K, brain-enriched, and treatment-induced immunopeptides as immunologically visible targets. These findings provide a rationale for integrating molecularly targeted therapy with immunotherapeutic approaches to enhance tumor recognition and treatment efficacy in DMG and GBM."

IO biomarker • Journal • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Oncology • Pediatrics • Solid Tumor • HLA-A

Identification of a chromatin-remodeling peptide in diffuse midline glioma by immunopeptidomics (AACR 2025) - "The distinct peptide profiles of DMG and U87 and their different responses to MTX-241F suggest potential therapeutic avenues for precision immunotherapy targeting DMG. In addition, the identification of a shared immunopeptidome presents an opportunity to develop a therapeutic for both pediatric and adult glioma."

Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioblastoma • Glioma • Oncology • Solid Tumor • EGFR • HLA-B • NCOA4

Targeted inhibition of DNA repair and survival signaling in diffuse intrinsic pontine gliomas (SNO 2023) - "Our data provide proof-of-concept evidence to support advanced development of MTX-241F for the treatment of DIPG. Future studies will be designed to inform rapid clinical translation to ultimately impact patients diagnosed with this devastating disease."

Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Pediatrics • Solid Tumor • EGFR

Targeting DNA Repair and Survival Signaling in Diffuse Intrinsic Pontine Gliomas to Prevent Tumor Recurrence. (PubMed, Mol Cancer Ther) - "Our data provide proof-of-concept evidence to support advanced development of MTX-241F for the treatment of DIPG. Future studies will be designed to inform rapid clinical translation to ultimately impact patients diagnosed with this devastating disease."

Journal • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Pediatrics • Solid Tumor • EGFR

CYTOMEGALOVIRUS REACTIVATION AFTER MATCHED UNRELATED DONOR AND HAPLOIDENTICAL HEMATOPOIETIC CELL TRANSPLANTATION (EBMT 2023) - "In the multivariate regression model, CMV seropositive recipients as compared to seronegative recipients (OR 11.4, 95% CI 2.7-48.7, p<0.001) independently predicted the risk of CMV disease.CharacteristicsTotal (n=452)CMV viremia (n=181)P valueCMV disease(n=32)P valueAge, median years (range)57 (18-77)56 (18-77)0.28655 (25-74)0.724Male, n (%)277 (61.3%)105 (37.9%)0.24319 (6.9%)0.818Caucasians, n (%)381 (84.3%)134 (35.2%)<0.00124 (6.3%)0.025HCT-CI ≥3, n (%)251 (55.5%)95 (37.8%)0.28717 (6.8%)0.776Recipient CMV status, n (%)Negative185 (40.9%)7 (3.8%)<0.0012 (1.1%)<0.001Positive267 (59.1%)174 (65.2%)30 (11.2%)Donor CMV status, n (%)Negative218 (48.2%)67 (30.7%)<0.00113 (6%)0.372Positive234 (51.8%)114 (48.7%)19 (8.1%)Letermovir aYes176 (65.9%)113 (64.2%)0.64620 (11.4%)0.927No91 (34.1%)61 (67%)10 (11%)Conditioning, n (%)Myeloablative169 (37.4%)65 (38.5%)0.59613 (7.7%)0.695Reduced intensity283 (62.6%)116 (41%)19 (6.7%)Graft source, n (%)PBSC224 (49.6%)87..."

Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Disorders • Immunology • Transplantation

Co-inhibition of kinase signaling pathways and epigenetic regulators overcomes compensatory effects in pediatric high-grade gliomas (SNO 2022) - "Pharmacologically relevant catalytic LSD1 inhibitors were assessed using the alamarBlue viability assay and demonstrated wide ranges of IC₅₀ values with ORY-1001(19 μM to > 150 μM), ORY-2001( > 50 μM), GSK-LSD1(134 μM to > 500 μM), and IMG-7289(1.6 μM-179 μM) in the SU-DIPG lines...To overcome kinase activation from LSD1 inhibition, MEK or PI3K inhibitors, including selumetinib, trametinib, and BKM120, were tested. A novel dual kinase inhibitor directed against EGFR and PI3K, MTX-241F, was also assessed...Overall, the combination enhanced in vitro efficacy in contrast to single-agent inhibition supporting an interplay between LSD1 and kinase signaling in pHGG. Future studies will assess this combination utilizing orthotopic xenograft models of DIPG"

Clinical • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Pediatrics • Solid Tumor • EGFR • KDM1A