On December 23, 2025, GC801 Injection, an IgG (Immunoglobulin G)-degrading enzyme drug independently developed by Beijing Genecradle Therapeutics Co., Ltd. (hereinafter referred to as "Genecradle Therapeutics"), was accepted by the National Medical Products Administration (NMPA) for clinical trial registration review. Classified as a Class 1 Therapeutic Biological Product, this marks the fifth new drug clinical trial application submitted by Genecradle Therapeutics.
Center for Drug Evaluation, NMPA
| Serial No. | Acceptance No. | Drug Name | Drug Type | Application Type | Registration Classification | Company Name | Acceptance Date |
|---|---|---|---|---|---|---|---|
| 1 | CXSL2501108 | GC801 Injection | Therapeutic Biological Product | New Drug | 1 | Beijing Genecradle Therapeutics Co., Ltd. | December 23, 2025 |
▲ Source from the official website of CDE
Previously, Genecradle Therapeutics' IND-approved products—GC101 Injection (for Spinal Muscular Atrophy), GC301 Injection (for Pompe Disease), GC304 Injection (for Hypertriglyceridemia), and GC310 Injection (for Wilson's Disease)—are all AAV vector-based gene therapy drugs. In contrast, the newly applied GC801 Injection is a protease-based drug, which is expected to break through the therapeutic limitations caused by pre-existing antibodies in vector-mediated gene therapy, effectively expand the scope of AAV gene therapy, and provide advanced treatment opportunities for patients who were previously ineligible for gene therapy due to high titers of pre-existing AAV antibodies in their bodies. Additionally, it enables repeated administration of AAV gene therapy.
GC801 Injection
GC801 Injection is an engineered IgG antibody-degrading enzyme designed to address the therapeutic dilemma caused by the obstruction of pre-existing AAV antibodies in gene therapy. Based on the engineering modification of the natural IdeS enzyme, GC801 exhibits highly specific IgG-degrading activity, with vitality far exceeding that of the wild-type IdeS. After administration, GC801 can catalyze the cleavage of the lower hinge region of the heavy chain of all human IgG subclasses. The cleaved IgG antibodies lose most of their effector functions and are rapidly degraded by the body, thereby reducing or eliminating pre-existing AAV antibodies in vivo and opening the window for AAV gene therapy in populations with high levels of pre-existing AAV antibodies.
Pre-existing Antibodies in Gene Therapy Severely Hinder Patient Benefits
Gene therapy refers to a therapeutic strategy that corrects pathogenic genetic defects by introducing therapeutic genes to modify or replace the expression of missing or defective genes in the body. Due to its safety advantages, the AAV vector has become the most widely approved and applied viral vector system in current in vivo gene therapy, regarded as one of the most promising gene delivery tools. It typically achieves in vivo delivery of therapeutic genes through intravenous infusion or local injection.
In AAV-mediated gene therapy, pre-existing antibodies are one of the key factors affecting efficacy and safety. Particularly, neutralizing antibodies can recognize and bind to AAV capsid proteins, preventing the virus from entering target cells and thereby significantly reducing gene transduction efficiency. Epidemiological studies show that approximately 30%-60% of the general population has pre-existing neutralizing antibodies against different AAV serotypes. The presence of such antibodies not only limits the scope of eligible patient populations but also may restrict repeated administration strategies in treatment.