SB-007 update: dose-expansion portion of SpliceBio’s phase 1/2 trial underway with first participant dosed at Oxford

What is 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. Due to this mechanism, SB-007 has the potential to treat all individuals with an ABCA4 mutation leading to Stargardt disease.

ASTRA trial:

In early 2025, we reported that SB-007 had been authorised by the U.S. Food and Drug Administration (FDA) to progress to a phase 1/2 clinical trial, known as ASTRA. This phase 1/2 study aims to evaluate the safety, tolerability, and preliminary efficacy of single subretinal SB-007 administration to determine dose selection.

ASTRA is a multicentre, global clinical trial enrolling 57 participants aged 12-65 with Stargardt disease. Part A of ASTRA evaluated 3 dose levels of subretinal SB-007 in an open-label, dose escalation study. This means that both the participants and researchers knew which treatment was delivered and looked to establish the recommended dose to investigate in further trials.

Part B will evaluate 2 dose levels of subretinal SB-007 compared to an untreated control group through a randomized controlled and masked trial. This means that participants are randomly assigned to receive either the treatment or a placebo and will not be told which one they have received. Part B of the trial will evaluate findings over a 96-week follow-up period, assessing safety and tolerability of different doses of SB-007 as its primary endpoint.

“The use of 2 viral vectors that recombine once inside retinal cells is a unique approach to restoring the large gene needed in Stargardt disease, and dual vectors might have implications for treating other retinal degeneration. This unique gene therapy modality has the potential to slow or even halt progression of this debilitating disease, which is the most common cause of inherited blindness in children. We are delighted to have treated the first patient here in Oxford, in the critical second phase of the trial.” – Robert MacLaren, MD, PhD, professor of ophthalmology at the University of Oxford and National Health Service gene and cell therapy research lead at Oxford University Hospitals NHS Foundation Trust

ASTRA is running alongside the ongoing POLARIS natural history study sponsored by the company. POLARIS hopes to evaluate disease progression in Stargardt’s, tackle problems around endpoints in 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.

To read more about SpliceBio please visit their website here, or to learn more about the trial itself please follow this link. To register interest in SpliceBio’s clinical studies, please complete a simple form that can be found here: https://splice.bio/clinical/