On April 11, CDE’s official website revealed that the application for an Investigational New Drug, the new first-in-class [TAA06 Injection] by PersonGen BioTherapeutics (Suzhou) Co., Ltd. was accepted. Based on public information, TAA06 is an independently developed B7-H3-targeted CAR-T therapy of PersonGen. The drug was granted the Orphan Drug Designation (ODD) for treating neuroblastoma by the FDA (Food and Drug Administration) in March of this year.
![The application of the new first-in-class [TAA06 Injection] by PersonGen BioTherapeutics (Suzhou) Co., Ltd. was accepted](https://eimg.pharmasources.com/upload/image/20220523/R3StUWVJDxC2CPmtMpSXV6BWw0hid3HGpx13uXnF.png "The application of the new first-in-class [TAA06 Injection] by PersonGen BioTherapeutics (Suzhou) Co., Ltd. was accepted")
B7-H3 (CD276) is a type I transmembrane protein and a member of the B7 immune co-stimulation and co-suppression family. It is overexpressed in solid tumors such as bladder cancer, prostate cancer, and melanoma, but its expression is limited in normal tissues. The early discovery of B7-H3 was mainly demonstrated to function as a co-stimulatory receptor, promoting the proliferation of CD4+ and CD8+ T cells, inducing cytotoxic T cells, and producing immunostimulatory functions by selectively stimulating interferon γ (IFN-γ) in the context of T cell receptor signaling. As the research progressed, there is increasing evidence showing that B7-H3 plays a major role in immune cells as a co-inhibitor, facilitating the evasion of tumor cells from immune surveillance. Therefore, the overexpression of B7-H3 is related to the poor prognosis of tumor patients and the invasion and metastatic potential of tumor in vitro models.
B7-H3 is an emerging target for immunotherapy. Among all the products, omburtamab by Y-mAbs Therapeutics progresses the fastest and has resubmitted the BLA (Biologics License Application) for the treatment of pediatric patients with the central nervous system (CNS) or leptomeningeal metastasis neuroblastoma to the FDA in early April. Omburtamab is a radionuclide iodine-131-labeled B7-H3-targeted monoclonal antibody that targets B7-H3-expressing cells in solid tumors and binds to the FG loop-dependent conformation, a critical region of biological function in the B7-H3 molecule. In December 2020, SciClone Pharmaceuticals reached an agreement with Y-mAbs Therapeutics and obtained exclusive rights to the co-development, registration, and commercialization of the drug and GD2 targeted monoclonal antibody-Danyelza (naxitamab-gqgk) in Greater China (including Chinese mainland and Hong Kong/Macau/Taiwan Regions of China). Moreover, Y-mAbs Therapeutics has developed 177Lu-omburtamab-DTPA radiolabeled by lutetium-177 for the treatment of pediatric patients with relapsed or refractory medulloblastoma and adult patients with positive CNS tumors or leptomeningeal metastasis, among which the medulloblastoma indication was granted rare pediatric disease designation (RPDD) by the FDA.
And the B7-H3-targeted monoclonal antibody enoblituzumab developed by MacroGenics also sees good progress, now in Phase II clinical trials. Enoblituzumab is an immune optimized anti-B7-H3 monoclonal antibody. It combines the exclusive Fc optimization technology platform of MacroGenics, with unique antibody advantages and therapeutic potential. The published interim analysis results of Phase I clinical trials of enoblituzumab for refractory solid tumors show that: the drug can be tolerated up to 15 mg/kg without maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). In July 2019, I-Mab Biopharma reached an agreement with MacroGenics to obtain the exclusive development and commercialization rights of the drug in Greater China (including the Chinese mainland, Hong Kong/Macau/Taiwan Regions of China).
In addition to monoclonal antibodies, pharmaceutical companies have also developed bispecific antibodies, antibody-drug conjugates (ADC), and CAR-T therapies around B7-H3 targets, as shown in the table below.
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