Programs & Pipeline
SalioGen aims to develop durable, safe and accessible genetic medicines for the treatment of a broad range of inherited disorders. With its ability to deliver DNA sequences of any length to defined genomic locations, SalioGen is in a unique position to address diseases that have a well-understood genetic basis but that have not been within the reach of today’s gene therapy or gene editing approaches. A modular therapeutic platform empowers SalioGen to conduct rapid, scalable candidate development in parallel across multiple target indications affecting different organs and tissue types, for high-velocity progress toward proof-of-concept in each indication.
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Familial hypercholesterolemia (FH) is a genetic disease that impairs the ability to remove excess low-density lipoprotein (LDL) from the blood, leading to LDL accumulation and significantly increasing the risk of early-onset cardiovascular disease and heart attacks. FH can be caused by any of over 1,000 mutations, in genes involved in LDL metabolism most often in the LDL receptor (LDLR) gene. Depending on whether an affected individual inherits 1 or 2 mutant copies of the gene, he or she may have heterozygous FH (HeFH) or homozygous FH (HoFH), respectively. Of the nearly 30 million people estimated to be affected by FH worldwide, about 43,000 are believed to have HoFH.
HoFH patients have severely high cholesterol from a young age, which leads to atherosclerosis—or fat and cholesterol build-up on the artery walls—including atherosclerosis of the coronary arteries, with a concomitant risk of heart attacks as early as childhood. Most patients with HoFH do not survive beyond young adulthood unless they are able to secure a liver transplant. HeFH patients tend to have significant albeit less severe complications, with moderately elevated cholesterol and high rates of premature cardiovascular disease.
Managing FH is a lifelong burden that involves permanent diet and lifestyle changes in combination with medications that reduce LDL, with variable outcomes. HoFH patients and patients with severe HeFH may also need periodic LDL apheresis procedures, in which the patient’s blood is passed through an apparatus outside the body that filters out LDL. Liver transplants are currently the only curative measure for FH and are often reserved for the most severe HoFH cases.
SalioGen is developing a non-viral gene therapy candidate for both HoFH and HeFH designed to reduce levels of LDL in the blood in a durable manner. SalioGen’s candidate leverages the unlimited cargo capacity afforded by its gene coding platform to deliver the large (6 kb) Very Low-Density Lipoprotein Receptor (VLDLR) gene directly to liver cells for integration into the genome and thus sustained receptor expression in the liver, where the receptor can remove excess LDL from the blood. The VLDLR gene was selected for this therapeutic candidate as the gene has previously demonstrated promise as a safe, potentially curative correction for LDLR mutations in FH. SalioGen’s gene coding platform is uniquely poised to deliver a gene of VLDLR’s size in a single therapy that can address any of FH’s pathogenic mutations and can be scaled up to serve the substantial FH patient population.
Inherited Macular Degeneration
Inherited macular degeneration (IMD) is a rare genetic disease of the macula, the part of the light-sensing tissue called the retina, found in an estimated 800,000 people worldwide, at the back of the eye that results in is responsible for sharp, straight-ahead vision. Degeneration of the macula over time manifests as progressive, irreversible vision loss. , which patients may begin noticing as early as childhood. Patients may slowly lose much of their straight-ahead vision, and with it, their ability to distinguish details and shapes; they may also develop difficulties with color vision or with seeing in low light.
While there are more than 900 known mutations that can cause the disease, the most commonly mutated gene in IMD is ABCA4, a gene expressed almost exclusively in the retina related to transporting molecules across cell membranes to support vision. IMD is found in an estimated 800,000 people worldwide, and there are currently no available treatments that can reverse, stop or even slow the progression of IMD.
SalioGen is developing a non-viral gene therapy candidate for the treatment of the diseaseIMD that delivers the large (7.3 kb) ABCA4 gene directly to the cells in the retina construct directly to the cells in the retina, where ABCA4 can be integrated into the genome. By restoring durable expression of healthy, functional ABCA4 in the eye, the candidate has the potential to mitigate vision loss in people living with IMD. SalioGen’s gene coding platform enables the candidate to address any of hundreds of genetic mutations causing IMD with a single, scalable product.