SB-007, we’ve been expecting you
Introducing Splice Bio, a genetic medicines company with some exciting developments for Stargardt’s patients.
Introducing Splice Bio, a genetic medicines company with some exciting developments for Stargardt’s patients. In December 2024, Splice Bio announced that the U.S. Food & Drug Administration (FDA) had authorised treatment SB-007’s progression to phase 1/2 clinical trial, passing the investigative new drug stage. This clinical trial, known as ASTRA, will begin enrolment in early 2025 and aims to evaluate the safety and efficacy of SB-007, a revolutionary protein splicing therapy looking to “transform the lives of Stargardt disease patients”.
ASTRA is set to run alongside the ongoing POLARIS natural history study sponsored by the company, involving 75 Stargardt patients across several clinical sites throughout the US. POLARIS hopes to evaluate disease progression in Stargardt’s, tackle problems around endpoints in inherited retinal disease (IRD) clinical trials and streamline eligibility criteria for enrolment into the ASTRA trial. This should hopefully result in a better understanding of disease progression, improved patient experiences, and identification of the most appropriate outcome measures for the ASTRA trial to determine the effectiveness of SB-007.
What is Stargardt Disease?
Stargardt disease is caused by mutations in the ABCA4 gene, which provides the instructions needed to make a protein found in the retina’s light-sensing photoreceptor cells. This protein is responsible for transporting toxic byproducts, made by the regular visual cycle, away from photoreceptor cells. Mutations in this single ABCA4 gene can lead to fatty material, known as lipofuscin, accumulating on the macula, the tiny area of tightly packed photoreceptors in the middle of the retina, which we use for seeing fine detail in high definition. Over time, this fatty material destroys light-sensing cells and central vision. Stargardt disease currently has no treatment options and has long been a challenge for researchers developing gene therapies, due to the large size of the ABCA4 gene.
Splice Bio and SB-007.
SB-007 is a type of adeno-associated viral vector (AVV) gene therapy. This means that a small virus, that doesn’t cause illness in humans, is used as a delivery system to introduce or alter genetic material within cells. Most gene therapies for IRD’s work on the premise of delivering an entire new gene to replace the mutated one, however, the whole ABCA4 gene is too large to deliver in one viral vector. Splice Bio look to overcome this problem by delivering the ABCA4 gene in 2 halves, using dual viral vectors, through a one-time injection into the eye. Once in the cells, each half of the gene will make half of the desired protein. SB-007 then uses a process known as protein splicing to bond each half the protein together to make it functional.
SB-007 is the only clinical-stage therapeutic treatment addressing the genetic cause of Stargardt disease. As a result, SB-007 has the potential to help all Stargardt’s patients with a pathogenic variant in the ABCA4 gene. Splice Bio hope that protein splicing as a gene therapy approach can also be used to target other large Retinitis Pigmentosa (RP) genes.
Italian biotech company AAVantgarde are also looking to use this technique in treatment approaches for Stargardt’s and RP related to Usher 1B. AAVantgarde’s leading programmes have entered phase 1/2 clinical trials for their therapeutic approach for RP related to Usher 1B, however remain at pre-clinical stage for their Stargardt’s therapeutic approach. With Splice Bio and AAVantgarde leading the field with major milestones in protein splicing therapy treatments, we can surely expect some exciting developments from this research in the future!