SpliceBio has received FDA clearance for its investigational new drug (IND) application of SB-007, its lead therapeutic program intended to address the root genetic cause of Stargardt disease (SD).
First, a rundown on this company.
The Barcelona, Spain-based genetic medicine company is developing next-generation gene therapies to treat genetic diseases via a proprietary protein splicing platform (we’ll get to that in a moment).
While SpliceBio’s lead program is focused on SD, its pipeline also extends to other gene therapy therapeutics with ophthalmic and central nervous system (CNS) indications:
- SB-008 (monogenic inherited retinal disease [IRD])
- SB-009 (monogenic IRD)
- In partnership with Spark Therapeutics (see our coverage on this)
- SB-011 (monogenic CNS)
Circle back to this proprietary platform.
The basis for the platform is protein splicing, a multi-step biochemical reaction that leads to the formation of peptide bonds as well as a process typically carried out by a family of auto-processing-domain proteins called “inteins”.
- In relation to SpliceBio: A next-gen version of these proteins (engineered inteins) is currently in development for therapeutic use and is at the center of SpliceBio’s protein splicing platform.
The platform was developed with the potential to address diseases that currently cannot be treated with gene therapy because the necessary gene is too large to be delivered by adeno-associated virus (AAV) vectors, the company previously reported.
Now let’s talk about SB-009.
Before we do: It’s important to note that SD is usually caused by changes (mutations) in the ATP-binding cassette subfamily A, member 4 (ABCA4) gene—which, with its large size, poses a major challenge for the development of gene therapies.
- Because of this, there are no approved therapies currently available.
About this therapeutic: As a protein splicing dual AAV gene therapy, SB-007 is designed to deliver the full-length ABCA4 gene and restore expression of the native ABCA4 protein located within the retina.
- Its potential: Aside from targeting the root cause of SD, SB-007 also reportedly has the potential to treat “all patients across all ABCA4 mutations.”
Any clinical data on it yet?
Yes … according to SpliceBio, SB-007 has previously demonstrated “robust pharmacological activity” in SD-based animal models as well as “durable expression and safety” in non-human primates.
On a regulatory note: SB-007 was previously granted Orphan Drug Designation (ODD) by the FDA as well as by the European Commission.
- On the human-based clinical trial front: While no human-based data has been reported so far, the company launched the POLARIS study in March 2024.
Talk about that study.
This is an observational study of SD Type 1 caused by two or more mutations in the ABCA4 gene among participants aged 12 to 65.
The goal: Identifying “the right patients and the right tests to measure for future clinical trials of (SB-007) to treat (SD),” according to SpliceBio.
The POLARIS study is referred to as a “company-sponsored natural history study of (SD) designed to evaluate disease progression, refine endpoints, and streamline eligibility criteria for accelerated enrollment into the phase 1/2 ASTRA study.”
About this ASTRA study …
With enrollment initiation expected in H1 2025, this trial is expected to analyze the safety and efficacy of a single SB-007 dose when administered subretinally in SD patients.
- Its purpose: To enable a more precise diagnosis, rigorous disease monitoring, and (potentially) faster access to “innovative therapies” for SD patients.
So what’s the overarching significance of this?
In regards to this IND clearance: As SpliceBio CEO and Co-Founder Miquel Vila-Perelló, PhD, noted, this is the “first-ever IND for a protein splicing gene therapy” that is “a huge step forward to demonstrate the potential of this new therapeutic modality to address diseases caused by mutations in large genes such as ABCA4.”