Programs

Our Approach to Gene Therapy

Mother And Adult Daughter Relaxing In ParkAt Sio, we are in pursuit of long-lasting, transformative treatments that address the underlying biology of both rare and prevalent neurodegenerative diseases. Our understanding of the genetic basis of many diseases, developments in viral vector design, and progress in vector manufacturing methods places us on the cusp of a new era of gene therapies. Led by scientific experts and pioneers in gene therapy, we diligently optimize an approach tailored to the unique features of the disease, honing the mechanism, vector and route of administration to provide the maximum benefit.

Pipeline

Candidate

Indication

Vector

Phase

Research
Pre-clinical
Clinical
GM1 gangliosidosis
AAV9
Phase 1/2
Gene(s): GLB1
FDA designations: Orphan Drug Designation, Rare Pediatric Disease Designation
Geographic rights: Worldwide
Partners: Andelyn Biosciences, Auburn University, NIH, Viralgen
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Tay-Sachs / Sandhoff disease
AAVrh8
Phase 1/2
Gene(s): HEXA, HEXB
FDA designations: Orphan Drug Designation, Rare Pediatric Disease Designation
Geographic rights: Worldwide
Partners: Andelyn Biosciences, NIH, University of Massachusetts Medical School, Viralgen
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Parkinson’s disease
Lentivirus
Phase 2 – SUNRISE-PD
Gene(s): TH, CH1, AADC
Geographic rights: Worldwide
Partners: Oxford Biomedica
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GM1 Gangliosidosis: AXO-AAV-GM1

GM1 gangliosidosis is a rare and fatal pediatric lysosomal storage disorder (LSD) that progressively destroys neurons in the central nervous system and leads to a host of systemic manifestations. The underlying causes of GM1 gangliosidosis are mutations in the gene for beta-galactosidase (GLB1), a key enzyme responsible for the breakdown of toxic molecules known as gangliosides throughout the body, which results in rapidly progressing neurodegeneration. Despite an understanding of the underlying cause of the disorder and the systemic manifestations of the disease in multiple organs, there are currently no approved treatment options available for these children.

AXO-AAV-GM1 is the only IV-administered gene therapy validated through extensive preclinical studies in naturally occurring animal models. AXO-AAV-GM1’s systemic route of administration has the potential to restore beta-galactosidase function to the entire body, thereby halting disease progression in its tracks. AXO-AAV-GM1 is currently the most advanced GM1 therapy and has the potential to be the first approved treatment for this devastating disease. It is also the only gene therapy in development for both Type 1 and Type 2 forms of GM1 gangliosidosis. The U.S. Food & Drug Administration has granted Orphan Drug Designation and Rare Pediatric Disease Designation for AXO-AAV-GM1 for the treatment of GM1 gangliosidosis.

We are currently evaluating AXO-AAV-GM1 in a registrational clinical trial which consists of a Stage 1 dose-ranging study evaluating safety and exploratory measures of efficacy and a Stage 2 efficacy study. For more clinical trial information, click here or contact us at patients@siogtx.com.

Tay-Sachs/Sandhoff Disease: AXO-AAV-GM2

GM2 gangliosidosis, also known as Tay-Sachs and Sandhoff disease, is a rare and fatal pediatric neurodegenerative lysosomal storage disorder (LSD) resulting from mutations in beta-hexosaminidase, a key enzyme in the lysosome. These genetic defects lead to the toxic accumulation of gangliosides, resulting in neurodegeneration and life expectancy shortened to just two to four years of age.

AXO-AAV-GM2 is a gene therapy that delivers a functional beta-hexosaminidase enzyme through bilateral administration directly to the thalamus and spinal canal of patients using a surgically targeted approach. AXO-AAV-GM2 has the potential to be the first treatment approved for this devastating disease. The U.S. Food & Drug Administration has granted Orphan Drug Designation and Rare Pediatric Disease Designation for AXO-AAV-GM2 for the treatment of Tay-Sachs/Sandhoff disease.

We are currently evaluating AXO-AAV-GM2 in a potentially registrational clinical trial which consists of a Stage 1 dose-ranging study and a Stage 2 efficacy study. For more clinical trial information, contact us at patients@siogtx.com.

Parkinson’s Disease: AXO-Lenti-PD

Dopamine DiagramParkinson’s disease is a progressive neurodegenerative disorder that is caused by the loss of dopamine signaling in the brain and results in the continual decline of motor control and quality of life. While there is currently no cure for the disease, through dopaminergic strategies that temporarily increase dopamine levels in the brain, patients see a short-term improvement in symptoms which wanes with disease progression.

AXO-Lenti-PD is the only investigational gene therapy for Parkinson’s disease that delivers the three key genes (TH, CH1, and AADC) required for endogenous dopamine synthesis in a single lentiviral vector. The goal of this one-time infusion is to restore steady, tonic levels of dopamine, potentially reducing the need for daily L-dopa medication while stabilizing the disease to provide long-lasting benefits. Initial clinical data demonstrate that a single dose of AXO-Lenti-PD “turns back the clock” for patients by improving motor function and activities of daily living. AXO-Lenti-PD has been optimized from ProSavin, an earlier gene therapy for the treatment of Parkinson’s disease. 

SUNRISE-PD Design

We are currently evaluating AXO-Lenti-PD in a Phase 2 clinical trial (SUNRISE-PD) in patients with moderate to advanced Parkinson’s disease. For more information, click here or contact us at patients@siogtx.com.

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