May 3, 2023 – Skyline Therapeutics, an innovation-driven gene therapy company dedicated to developing unique and novel solutions to address unmet needs in rare and severe diseases, today announced multiple data presentations at the American Society of Gene and Cell Therapy (ASGCT) 26th Annual Meeting in Los Angeles, CA, May 16-20, 2023.
Among the exciting findings from several innovative AAV gene therapy programs that the Skyline team will present at ASGCT are SKG0106, a novel recombinant adeno-associated virus (rAAV) vector developed for the treatment of neovascular age-related macular degeneration (nAMD) via intravitreal (IVT) administration, and SKG0201, an innovative next generation SMN1 gene therapy for spinal muscular atrophy (SMA).
SKG0106 is a proprietary AAV vector carrying a transgene genome encoding a novel anti-VEGF protein. Upon delivery, SKG0106 effectively and specifically suppresses the action of human VEGF, a key factor contributing to the pathological angiogenesis in the eyes of nAMD patients. Comprehensive pharmacological studies were conducted to thoroughly evaluate the efficacy of SKG0106 using a DL-α-AAA induced rabbit model of chronic retinal neovascularization (RNV) and a laser photocoagulation induced non-human primate (NHP) model of choroidal neovascularization (CNV). SKG0106 was administered via a single IVT injection.
Single treatment of SKG0106 via intravitreal delivery effectively reduced fluorescein leakage area and grade 4 lesion percentage in a dose dependent manner; strong efficacy was observed at low dose level
SKG0106 showed complete and durable inhibition of fluorescein leakage and significant reduction in subretinal hyperreflective material thickness in the 26-week long term study in NHP, suggesting the strong and durable efficacy of the vector in repressing the activity of VEGF
SKG0106 was well tolerated, and no significant adverse effect observed in ocular nor peripheral tissues
In comprehensive studies, SKG0106 demonstrated strong dose-dependent efficacy against vascular leakage in rabbit RNV and NHP CNV models, durable efficacy in NHP studies, and excellent local tolerance profiles and systemic safety. Further supported with positive outcome from long-term toxicity studies, SKG0106 is currently in clinical trial.
SKG0201 is a novel AAV-mediated gene replacement therapy comprising an optimized human SMN1 cDNA under the control of a unique promoter. Every element in the vector genome was carefully optimized to fully attain restoration of SMN in the target cells to achieve maximal therapeutic effect in the CNS while maintaining appropriate expression in peripheral tissues. The preclinical data demonstrated that a single intravenous administration of SKG0201 resulted in a rapid and long-lasting correction of functional SMN protein levels, which led to a significant improvement in the gain of body weight, extension in the lifespan, and restoration of motor functions of SMNΔ7 mice (SMA disease animal model) at low doses.
SKG0201 treatment exhibited a significantly reduced acute expression of SMN protein in the liver. In addition, the vector displayed a much stronger potency and superior safety profile with no liver toxicity compared to the reference vector (scAAV9-CMVen/CB-hSMN1), suggesting a significantly lower therapeutic dose in the clinical setting, further enhancing the safety profile of the vector
SKG0201-treated SMNΔ7 mice exhibited a lasting efficacy in improving deficit of motor functions, preventing neuromuscular junction (NMJ) breakdown, and increasing the axon conductivity in six-month durability studies
These results strongly suggest that this novel vector, with a potentially superior efficacy and safety profile, represents a highly promising new generation of AAV gene therapy to treat SMA.
In addition to SKG0106 and SKG0201, the Skyline team is rapidly advancing a number of innovative AAV gene therapy programs with high unmet medical needs through rigorous pre-clinical studies, targeting additional indications in ocular, neurological, cardiovascular, and metabolic disorders.
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, and 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, with significant therapeutic potential as validated by rigorous preclinical studies, are now in first-in-human clinical trials, bringing us closer to providing life-changing therapies to patients in need. Skyline Therapeutics has established global presence for research, development, regulatory, and manufacturing in Shanghai and Hangzhou, China, and Boston, MA, USA. www.skytx.com
The American Society of Gene & Cell Therapy (ASGCT) is a professional non-profit medical and scientific organization dedicated to the understanding, development and application of gene, related cell and nucleic acid therapies, as well as promotion of professional and public education in the field. With more than 5,000 members in the US and worldwide, ASGCT is the largest association of individuals involved in gene and cell therapy research. To learn more about ASGCT, visit its official website www.asgct.org