Y-mAbs Therapeutics has an expanding portfolio that features accelerated FDA approval for naxitamab and investigational GD2-SADA.
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.
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).
The GD2-SADA construct was created using our SADA technology, which was licensed by the Company from Memorial Sloan Kettering Cancer Center and Massachusetts Institute of Technology. The SADA technology utilizes a pre-targeted payload delivery method where antibody constructs assemble in tetramers and bind to the tumor target. Unbound constructs predictably disassemble into smaller antibody fragments and are excreted through the kidneys within hours after administration. In a second infusion, a radioactive payload binds to the antibody constructs attached to the tumor target in order to radiate the tumor. This provides the possibility of targeting tumors with precision while minimizing radiation of normal tissues. We believe that the SADA technology platform can deliver a variety of payloads and could potentially be developed against multiple tumor targets, as well as for theragnostic purposes.
In the first in human clinical phase 1 trial (Study 1001) for the treatment of SCLC, melanoma and sarcomas, GD2-SADA is administered at various timepoints before administration of 177Lu-DOTA payload. The trial will be composed of three parts. The first part addresses optimization of protein doses and spacing between SADA protein administration and payload administration. Second part addresses optimal, safe levels of the payload delivery. In the third part, repeated exposures are investigated in order to try mapping out long-term safety signals.
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 investigational agent for radioimmunotherapy of leptomeningeal metastases, Diffuse Intrinsic Pontine Glioma (DIPG), and malignant ascites.
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.