Y-mAbs Therapeutics has an expanding portfolio that features accelerated FDA approval for naxitamab and pivotal-stage investigational omburtamab. Both were granted breakthrough therapy designation to expedite their development and review.
The safety and efficacy of the investigational products have not been established by health authorities, or approved for use in the United States or globally.
This antibody—radiolabeled monoclonal antibody 8H9 (131I-8H9)—is being developed to target B7-H3–expressing cells in human solid tumors, including embryonal tumors, carcinomas, sarcomas, and brain tumors. In vitro/ex vivo modeling has shown omburtamab binds to an FG loop-dependent conformation on the B7-H3 molecule, a domain critical for its biologic function.
Omburtamab is a promising investigational agent for radioimmunotherapy of leptomeningeal metastases, Diffuse Intrinsic Pontine Glioma (DIPG), and malignant ascites.
Neuroectoderm-derived tumors, sarcomas, and embryonal tumors are difficult to cure when they have metastasized. These cancers include neuroblastoma, retinoblastoma, melanoma, small cell lung cancer, brain tumors, osteosarcoma, rhabdomyosarcoma, Ewing’s sarcoma, liposarcoma, fibrosarcoma, leiomyosarcoma, and other soft-tissue sarcomas in adults. One of the common tumor antigens on the cell surface of all of these tumors is called disialoganglioside or GD2. Numerous research laboratories have recently discovered that, in addition, surface GD2 is present on breast cancer stem cells, neuroectodermal, and mesenchymal stem cells.
Our humanized monoclonal antibody has been granted Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD).
Neuroectoderm-derived tumors, including neuroblastoma and sarcomas, have high expression of tumor antigens GD2 and GD3. Our investigational bivalent GD2-GD3 vaccine is being studied by scientists at MSKCC for the immunization of high-risk neuroblastoma patients previously treated with naxitamab. The vaccine, in combination with adjuvants, is being studied to induce patients to produce their own anti-GD2 and anti-GD3 serum titers, with the goal of preventing subsequent relapse. Our investigational GD2-GD3 vaccine is currently in an ongoing Phase II study at MSKCC.
To further build upon our investigational anti-GD2 immunotherapy, scientists at MSKCC are studying a GD2 x CD3 bispecific antibody (nivatrotamab), with the goal of bringing highly potent T cells to directly kill GD2-expressing tumor cells. Nivatrotamab is the first T-cell–engaging antibody utilizing the BiClone format to enter human clinical trials. The BiClone format utilizes an IgG-scFv format to maximize tumor binding and T-cell recruitment and minimize risk of non-specific T-cell engagement. In pre-clinical studies, nivatrotamab demonstrated >1000-fold greater potency than conventional anti-GD2 IgG antibodies. Our investigational nivatrotamab is currently in a Phase I/II study at MSKCC.
Patients with refractory or relapsed acute myeloid leukemia (AML) have a poor prognosis, and there is a clinical need for new therapies in these patients. CD33 is a clinically validated target in AML based on the data from gemtuzumab ozogamicin therapy. The BiClone format utilizes an IgG-scFv format to maximize tumor binding and T-cell engagement by bivalent binding to both CD33 and CD3 and to minimize the risk of non-specific T-cell engagement. CD33xCD3 BsAb brings T cells into close proximity of CD33-expressing tumor cells leading to the cytotoxic destruction of these tumor cells by T cells as demonstrated in vitro.
This cytotoxic concept is being investigated in the first-in-human (FiH) trial in children and adolescents with refractory or relapsed AML. The primary aim of the FiH trial is to evaluate the safety of the CD33xCD3 BsAb and establish a Maximum Tolerated Dose (MTD) and recommended phase 2 dose (RP2D) for further clinical development.