MC-339 / Novartis - LARVOL DELTA

Discovery and preclinical characterization of ETN029, a novel radiotherapeutic agent for the treatment of DLL3-expressing cancers (EANM 2025) - "ETN029 (also known as MC339) is a novel macrocyclic peptide that binds to DLL3 (Fig 4) designed to achieve high, rapid uptake and retention in tumor tissue and fast clearance of the unbound compound via the renal route...Chemotherapy was administered for a total of three days (cisplatin 2.5 mg/kg IP on Day 13; etoposide 3.5 mg/kg IP on Days 13, 14, and 15)...Additionally, in a re-challenge study using a syngeneic CT26.DLL3 mouse model, mice that had achieved complete tumor regression following treatment with 225 Ac-ETN029 (1 µCi) or a low dose of 225 Ac-ETN029 (0.25 µCi) combined with anti-PD-L1 did not develop tumors upon re-exposure to tumor cells, indicating the establishment of long-term anti-tumor immunity (Fig 9). Conclusion Taken together, these studies support the use of 225 Ac-ETN029 either as single agent treatment or in combination with standard-of-care chemotherapy and/or immunotherapy in patients with SCLC and potentially..."

IO biomarker • Preclinical • Endocrine Cancer • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

ETN029: Discovery and development of a DLL3-targeting radioligand therapy for the treatment of SCLC and beyond (ACS-Fall 2025) - "Structural insights from co-crystal analysis guided additional refinements, ultimately leading to the development candidate ETN029 (also known as MC339). In CDX models (NCI-H69, SHP-77), a single dose of [225Ac]Ac-ETN029 (0.35-1.4 µCi) resulted in robust tumor regression and prolonged survival. These studies support further investigation of the novel therapeutic ETN029 as a treatment for patients with DLL3-expressing solid tumors."

Endocrine Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

MC339, a novel radiopharmaceutical, targets DLL3-expressing cancers of different tissue origins (EORTC-NCI-AACR 2024) - "Taken together, these studies support further investigation of the radiolabeled MC339 as a novel therapeutic for patients with DLL3-expressing solid tumors."

Endocrine Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

Preclinical characterization of MC339: A novel radiotherapeutic agent for DLL3 expressing cancers (ESMO 2024) - "Taken together, these studies support further investigation of the novel therapeutic MC339 as a treatment for patients with DLL3-expressing solid tumors."

Preclinical • Endocrine Cancer • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

Mariana Oncology to be Acquired by Novartis to Advance Precision Radiopharmaceuticals to Treat Cancer (Businesswire) - "Mariana Oncology...announced it will be acquired by Novartis for $1 billion upfront and up to $750 million in potential milestone payments. The acquisition brings together Mariana Oncology’s innovative radiopharmaceutical pipeline and platform with the proven clinical development and commercialization expertise of Novartis....The company’s lead program, MC-339, is a novel radioligand therapy (RLT) designed to target small cell lung cancer."

M&A • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Mariana Oncology Announces $175 Million Series B Financing (Businesswire) - "Mariana Oncology Inc...today announced the closing of an oversubscribed $175 million Series B financing co-led by Deep Track Capital and Forbion....Proceeds from the financing will support the advancement of Mariana Oncology’s novel portfolio of precision, next-generation radiopharmaceuticals including its lead candidate, MC-339, as the company transitions into a clinical-stage organization....'The proceeds from this financing support the advancement of our pipeline and the initial development of our lead candidate, MC-339, which we anticipate will enter the clinic in 2024 in small cell lung cancer, supported by our own GMP radiopharmaceutical manufacturing.'"

Financing • New trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer