CT-179 / Curtana Pharma - LARVOL DELTA

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