December 12, 2023 – Skyline Therapeutics, an innovation-driven gene therapy company committed to developing unique and novel solutions for rare and severe diseases, today announced that the China National Medical Products Administration (NMPA) has approved its Investigational New Drug (IND) application for the Phase I clinical trial of SKG0201, an SMN1 gene replacement therapy for Type 1 Spinal Muscular Atrophy (SMA).
SKG0201 is a novel adeno-associated virus (AAV)-mediated gene replacement therapy which innovatively comprises a codon-optimized human SMN1 cDNA under the control of a unique central nervous system (CNS)-selective promoter and specific regulatory elements, which drive high expression of SMN1 protein in the central and appropriate expression in the peripheral tissues. Every element in the vector genome has been meticulously designed and optimized.
Data from the comprehensive and rigorous preclinical study demonstrated that a single intravenous administration of SKG0201 not only rapidly and persistently resulted in long-lasting correction of functional SMN protein levels, but also significantly increased the body weight of SMNΔ7 mice (SMA disease animal model) and effectively extended their life span at low doses. No acute hepatotoxicity was observed in the livers of mice treated with high dose of SKG0201. The long-term durability and toxicity study in neonatal cynomolgus monkeys showed that a single intravenous administration of SKG0201 induced a high expression level of hSMN in the central nervous system (CNS), indicating robust and prolonged transgene expression. Importantly, the vector demonstrated safety and excellent tolerability in the study.
In a clinical study initiated by researchers at Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine for the treatment of Type I SMA patients using SKG0201, patients have been enrolled into multiple dose cohorts. SKG0201 demonstrated favorable tolerability and initial therapeutic effect in the follow-up assessments.
The approval of the Investigational New Drug (IND) for SKG0201 marks a significant milestone in Skyline’s unwavering efforts to advance gene therapy solutions for patients affected by the devastating Type 1 SMA.
SMA is a severe genetic neuromuscular disorder caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene, which results in insufficient production of functional motor neuron proteins. This deficiency adversely affects the muscle functions, including compromised motor, respiratory, and swallowing functions, and progressive muscle deterioration. SMA can be classified into several subtypes based on disease onset and the degree of SMN protein deficiency, with Type I SMA being the most severe form, which can lead to in premature mortality or the need for permanent ventilatory support in untreated infants.
Investigational SKG0201 is a novel AAV-mediated gene therapy comprising an optimized human SMN1 cDNA under the control of a unique promoter. The innovative design of SKG0201 is to fully attain restoration of SMN in the target cells and achieve maximal therapeutic effect in the central-nerve-system (CNS), while providing a functional copy of the human SMN1 gene to address the root cause of SMA. In the comprehensive and rigorous preclinical study, SKG0201 demonstrated a strong potency, CNS transduction efficiency, long-term durable SMN expression in target tissues and a safety profile with no liver toxicity at one-time intravenously administered low dose. SKG0201 has received IND approval from China NMPA of Phase I clinical trial for Type 1 SMA.
About Skyline Therapeutics
Skyline Therapeutics is an innovation-driven, clinical-stage gene therapy company dedicated to developing unique and novel solutions to address unmet needs in rare and severe diseases. Our cutting-edge adeno-associated virus (AAV) platform comprises multiple proprietary technologies for capsid discovery, transgene design, and vector engineering. Combining our AAV expertise with robust in-house process and analytical development, as well as GMP manufacturing for clinical-grade plasmid and viral vector production, we are advancing a diverse pipeline of gene therapies for ocular, neurological, cardiovascular and metabolic disorders. Our lead programs are currently in clinical trials with regulatory approvals from the US FDA and China NMPA, bringing us closer to providing life-changing therapies to patients in need. Skyline Therapeutics has established a global presence for research, development, regulatory, and manufacturing in Shanghai and Hangzhou, China, and Boston, MA, USA. www.skytx.com
1 Farrar MA, Park SB, Vucic S, et al. Emerging therapies and challenges in spinal muscular atrophy. Ann Neurol. 2017; 81(3):355-368.
2 Finkel RS, McDermott MP, Kaufmann P. et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014;83(9):810-7.