SalioGen Therapeutics announced it is clinically advancing SGT-1001, its one-time, non-viral investigational therapy currently in clinical development for the treatment of Stargardt disease.
Refresh me on this company.
Headquartered in Lexington, Massachusetts, the next-generation genetic medicine company is focused on developing gene coding-based therapies to treat inherited disorders—including inherited retinal diseases (IRDs) such as Usher syndrome, retinitis pigmentosa (RP), and Stargardt disease to name a few.
How it’s doing this: via novel Gene Coding technology
Explain this technology.
SalioGen’s proprietary Gene Coding technology is designed as a non-viral method of integrating large or multiple whole genes into the genome at specific locations (via transposition, ie: exchanging the position of two things).
The key: The method has no reliance on double-standard breaks or ribonucleic acid (RNA) as guides.
How does it do this?
Per the company, the technology uses “a mammal-derived bioengineered enzyme, Saliogas enzyme, that can seamlessly insert large pieces of DNA (up to 100 kb) into specific locations in the genome.”
Its background: This Saliogas enzyme is based on enzymes that move discrete segments of DNA (called transposons) from one location in the genome to a new site, all without the need for RNA intermediates or creating double-stranded breaks.
- These “transposases” are engineered to target specific sequences within the human genome with high efficiency.
- Watch a video of this process by clicking here.
So this enzyme requires no additional guide strand?
Nope! No other guide strand or elements are needed due to the targeting system’s ability to connect directly to the transposases.
Even better: Following the gene’s insertion, the host cell can recycle the Saliogas enzyme.
What’s the benefit of this mechanism vs others?
SalioGen stated that this technology “has the potential to overcome the safety risks and limitations” often associated with other genetic therapy approaches.
Gotcha. So why focus on Stargardt?
As an inherited retinal disease (IRD), Stargardt disease is typically caused by mutations (potentially over 1,000 different types with two copies inherited from parents [one each]) in both copies of a patient’s ABCA4 gene.
Note: The ABCA4 gene is a large gene with the purpose of generating a protein involved in transporting toxins (such as Vitamin A molecules) out of the cell.
The issue: When the ABCA4 gene has a defect, this protein isn’t produced or doesn’t operate properly, leading to potential retina cell death and progressive central vision loss.
And this investigational therapy?
As SalioGen’s first development candidate to utilize its Gene Coding technology, SGT-1001 includes a “full-length ABCA4 gene construct and mRNA (messenger RNA) coding for the Saliogase enzyme.”
Its mechanism of action: utilizes a proprietary lipid nanoparticle delivered by subretinal injection via one single doseAnd its purpose: to address the underlying genetic cause of Stargardt disease
Any clinical data on it?
Yes… preclinical data, that is.
Preclinical studies were reported to show “promising gene integration in photoreceptors and retinal pigment epithelium cells (RPE), as well as sufficient expression of ABCA4 to reduce levels of lipofuscin A2E [click here to read up on that] associated with macular degeneration in a validated animal efficacy model,” according to the company.
Note: This tolerability (measured via optical coherence tomography [OCT]) was also reported to be consistent with a “commercially available gene therapy administered through subretinal injection.”
- No specifics on this comparative gene therapy were given.
So what’s next for this candidate?
According to SalioGen CEO Jason Cole, the company is looking to complete investigational new drug (IND)-enabling studies for SGT-1001 within the second half (H2) of 2024.
The goal: to “bring this potential one-time therapy to the clinic in the first half of 2025,” Cole stated.
And the significance?
With no treatment currently approved for Stargardt disease, SGT-1001 has the potential to become the first to treat the disease’s underlying genetic causes.