CT-179 / Curtana Pharma - LARVOL DELTA

In vitro and in vivo evaluation of CT-179 in combination with ONC201 and ONC206 in patient-derived models of diffuse midline glioma (SNO 2026) - No abstract available

Combination therapy • Preclinical • Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor

Targeting OPC transcriptional states enhances the effect of p53 reactivation in diffuse midline glioma (EANO 2026) - "Targeting the OPC-like program with the OLIG2-inhibitor CT-179 and navtemadlin enhanced apoptosis in DMG models, induced selective tumor cell death at nanomolar concentrations in organoid assembloids, and was validated in vivo in PDX models. Lineage-specific transcriptional states critically influence response to p53 reactivation in HGG. Adaptive accumulation of an OPC-like state drives resistance to MDM2 inhibition by modulating p53 signaling and blocking apoptosis. Targeting OLIG2-driven OPC programs enhances therapeutic benefits of p53 reactivation and provides rationale for combination strategies in HGG."

Brain Cancer • Diffuse Midline Glioma • Glioma • High Grade Glioma • Oncology • Solid Tumor • OLIG2

OPAL: OLIG2 Inhibitor CT-179 for Recurrent and Newly-diagnosed Glioblastoma (clinicaltrials.gov) - P1 | N=54 | Not yet recruiting | Sponsor: Olivia Newton-John Cancer Research Institute

First-in-human • Monotherapy • New P1 trial • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Solvent-free Nanoparticle Assembly Protocol (SNAP): one-pot formulation of drug loaded polyester nanoparticles and their vessel size-dependent perivascular transport in the brain. (PubMed, bioRxiv) - "We examined loading of multiple therapeutic compounds, including diclofenac, loperamide, bortezomib, CT179, panobinostat, docetaxel, methotrexate, and camptothecin. In sum, these studies present a new platform for facile production of polyester nanoparticles, demonstrate their ability to encapsulate a variety of hydrophobic small molecules, and expand our knowledge on the development of nanocarriers for intrathecal administration. Taken together, these data open new opportunities for development safer and more effective nanoparticle-based therapies."

Journal

Targeting Pediatric Glioblastomas by Combining OLIG2 Inhibitor CT-179 with Fractionated Radiation in a Panel of Patient-Derived Orthotopic Xenograft Mouse Models. (PubMed, Int J Mol Sci) - "Doses needed to eliminate OLIG2 expression in vitro varied from 0.3 to >1 µM in pGBM cells. In summary, our data showed that orally administered CT-179 penetrated the blood-brain barrier (BBB) and exhibited potential for inhibiting pGBM growth when combined with XRT."

Journal • Preclinical • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • OLIG2

Oligodendrocyte transcription factor 2 orchestrates glioblastoma immune evasion by suppressing CXCL10 and CD8+ T cell activation. (PubMed, J Clin Invest) - "OLIG2 inhibition by either genetic deficiency or pharmacological targeting with CT-179 sensitizes GBM tumors to anti-PD-L1 therapy, enhancing antitumor immune responses and prolonging survival. Our findings reveal OLIG2+ glioma stem-like cells as critical mediators of immune evasion and identify the OLIG2/HDAC7/CXCL10 axis as a potential therapeutic target to enhance immune checkpoint inhibitors efficacy and to improve immunotherapy outcomes in aggressive GBM."

IO biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CD8 • CXCL10 • HDAC7 • OLIG2 • STAT3

Suppressing recurrence in Sonic Hedgehog subgroup medulloblastoma using the OLIG2 inhibitor CT-179. (PubMed, Nat Commun) - "Consistent with CDK4 mediating CT-179 resistance, CT-179 combines effectively with the CDK4/6 inhibitor palbociclib, further prolonging survival in vivo. These data support therapeutic targeting of OLIG2+ tumor stem cells in regimens for SHH-driven MB, to improve response, delay recurrence and ultimately improve MB patient outcomes."

Journal • Brain Cancer • Medulloblastoma • Oncology • Solid Tumor • OLIG2

OLIG2 mediates a rare targetable stem cell fate transition in sonic hedgehog medulloblastoma. (PubMed, Nat Commun) - "Targeting this rare OLIG2-driven proliferative programme with a small molecule inhibitor, CT-179, dramatically attenuates early tumour formation and tumour regrowth post-therapy, and significantly increases median survival in vivo. We demonstrate that targeting transition from quiescence to proliferation at the level of the tumorigenic cell could be a pivotal medulloblastoma treatment strategy."

Journal • Brain Cancer • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • OLIG2 • SOX2

OLIG2 Is a Determinant for the Relapse of MYC-Amplified Medulloblastoma. (PubMed, Clin Cancer Res) - "Further studies demonstrated that OLIG2 was essential for recurrence, as OLIG2 disruption with CRISPR-mediated deletion or with the small molecule inhibitor CT-179 prevented recurrence from the residual radioresistant tumor cells. Our studies reveal that OLIG2 is a biomarker and an effective therapeutic target in a high-risk subset of MYC-amplified MB, and OLIG2 inhibitor combined with radiotherapy represents a novel effective approach for treating this devastating disease."

Journal • Brain Cancer • Medulloblastoma • Oncology • Solid Tumor • MYC

OLIG2 is a determinant for the relapse of MYC-amplified medulloblastoma. (PubMed, Clin Cancer Res) - "Our studies reveal that OLIG2 is a biomarker and an effective therapeutic target in a high-risk subset of MYC-amplified MB, and OLIG2 inhibitor combined with radiotherapy represents a novel effective approach for treating this devastating disease."

Journal • Brain Cancer • Medulloblastoma • Oncology • Solid Tumor • MYC

[VIRTUAL] Antibody Drug Conjugates for Non - small Cell Lung Cancer (IASLC-WCLC 2021) - "T-DXd, an ADC designed based on HER2-targeted trastzumab and deruxtecan, has shown promising results in early phase clinical trials in NSCLC with HER2 mutation and expression. In HER2-expressing NSCLC, the efficacy of T-DM1, which was already a standard treatment for HER2-positive breast cancer, has been investigated but did not show favorable clinical efficacy (1, 2)...In triple-negative breast cancer, Trop2-ADC, Sacituzumab govitecan, demonstrated definite efficacy comparing with standard chemotherapy in phase 3 trial. Datopotamab-DXd (Dato-DXd), other Trop2-ADC, showed promising efficacy and feasibility in phase I trial for advanced NSCLC, despite of relatively high frequency of ILD (14/175, 8%, including 3 G5) (8)...CEACAM5, also know as CEA, is detected in adenocarcinoma NSCLC(9) and CEACAM5-DM4 (SAR408701) is CEACAM5 targeted ADC, which preliminary efficacy and safety of phase I trial has been reported (10)...Telisotuzumab-vedotin (Teliso-V) is an anti–c-Met ADC of..."

Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Triple Negative Breast Cancer • CEACAM5 • EGFR • ERBB3 • HER-2 • MET • TROP2