On January 30, 2023, the first clinical study of VGN-R09b injection, a gene therapy drug developed by Shanghai Vitalgen BioPharma Co., Ltd. (“Vitalgen BioPharma”) - “an open, dose-escalation early clinical study to evaluate the tolerability, safety and efficacy of intra-striatal injection of VGN-R09b in patients with AADC deficiency” was successfully started at Shanghai Children’s Medical Center (SCMC) affiliated to Shanghai Jiao Tong University School of Medcine. The project is also the clinical trial of gene therapy products conducted by the site as the leading unit for the first time.

The meeting was co-chaired by Jiwen Wang, Chief of Neurology/Principal Investigator of the project, and Xinyan Sun, Director of the Clinical Research Management Center, with Yunhai Song, Deputy Chief of Neurosurgery, Suzhen Dong, Chief of Medical Imaging, and other investigators, as well as the sponsor, and SMOs in attendance.

At the kick-off meeting, the clinical development department of Vitalgen BioPharma gave a full introduction of the study background, study protocol and trial process, serious adverse events, informed consent, monitoring plan and other points of the trial, laying a solid foundation for the scientific, standardized and smooth implementation of the project in the later stage. Director Jiwen Wang delivered a summary of the meeting and said that subsequent trials should be conducted in strict compliance with the study protocol and GCP requirements, hoping that the trials will go smooth and that they will put forward the advancement of gene therapy.

I. About AADC deficiency

AADC (aromatic aminoacid decarboxylase) deficiency is the result of a pathogenic mutation in the DDC gene encoding AADC, which is responsible for the decarboxylation of L-DOPA (levodopa) and 5-HTP (5-hydroxytryptophan) to form the neurotransmitters dopamine and 5-hydroxytryptamine, respectively. AADC deficiency impedes the synthesis of critical neurotransmitters that control the sympathetic nervous system, emotion, cognition and motor coordination, presenting clinical symptoms such as motor dysfunction, mental retardation and diminished alertness and sleep disturbances, with a risk of premature death in the first decade of life. There are no formal epidemiological studies of the disease in China except a newborn screening program for AADC deficiency in Taiwan, which showed a birth incidence of AADC deficiency of approximately 1/ 32,000.

II. About the investigational drug

VGN-R09b is a gene therapy product developed by Shanghai Vitalgen BioPharma Co., Ltd., which uses recombinant AAV as a gene therapy vector to restore dopamine production based on the delivery of functional AADC, thus achieving the potential therapeutic effects. By local striatal injection, the drug can be applied directly to the site of disease, reducing the dose administered systemically and correspondingly leading to a decrease in adverse effects such as immune reactions. Theoretically, gene therapy requires only one injection to have long-term therapeutic effects.

III. Patient recruitment requirements

1. Those who are ≥2 years to <8 years old at the time of signing informed consent, or those with a head circumference size determined by the investigator to be suitable for the operation;

2. A documented history of confirmed AADC deficiency with clinical signs complying with either 1) cerebrospinal fluid neurotransmitter testing showing reduced 5-HIAA and HVA levels and elevated L-Dopa or 2) plasma AADC activity ≤ 5 pmol/min/ml and genetic testing confirming the AADC diallele markers as a pathogenic mutation of IVS6+4A>T isozygoty or heterozygosis.

3. Motor development ≤ 3 months of age at baseline and poor efficacy of standard treatment regimens (dopamine receptor agonists, monoamine oxidase inhibitors, or vitamin B6 analogs) as judged by the investigator;

4. The subject’s parent/guardian understands the information about the trial as well as the purpose and risks of the trial as described in the informed consent form, consents to the subject’s enrollment in the trial, and authorizes the use of the subject’s health information by providing a signed and dated informed consent form.

IV. Contact information

Doctor: Feng Han

Tel: 18817821496

Address: Shanghai Children’s Medical Center (SCMC) affiliated to Shanghai Jiao Tong University School of Medcine, 1678 Dongfang Road, Pudong District, Shanghai