About the Innovation UnitWe have identified five therapeutic areas that show high potential for RNA based therapies including lung diseases, eye diseases, skin diseases, central nervous system diseases and neuromuscular diseases. We are employing our toolbox of RNA technologies to target severe genetic diseases and grow the company’s pipeline beyond cystic fibrosis and Leber’s congenital amaurosis. The efforts in the innovation unit have resulted in the current pipeline including programs for Usher syndrome, Fuchs corneal endothelial dystrophy, dystrophic epidermolysis bullosa, Alzheimer’s disease, Huntington’s disease, and Friedreich’s ataxia.
Besides our QR-010 program for cystic fibrosis (CF) caused by the F508del mutation we are working on other CFTR mutations that can potentially be treated using our RNA technologies. We could potentially target an additional 5% of the CF population with these programs.
Our ophthalmology group was founded on the basis that there are several severe genetic eye disorders that currently have very limited treatment options for which RNA based therapeutics have the potential to make a large impact. The eye is a well validated target for RNA based therapies given the approved RNA therapies for the eye, their long half-lives and potential for local delivery and therefore could be an important class of drugs for ophthalmic indications in the future. Besides the program in Leber’s congenital amaurosis, QR-110, that is currently being prepared for first clinical studies we are working on programs for other ophthalmic indications including QRX-411 for Usher syndrome and QRX-504 for Fuchs endothelial corneal dystrophy (FECD).
Usher syndrome & QRX-411What is Usher syndrome? Usher syndrome is the leading cause of combined deafness and blindness. Patients with this syndrome generally progress to a stage in which they have very limited central vision and moderate to severe deafness. What causes Usher syndrome? Usher syndrome type II is most commonly caused by mutations (or defects) in a gene in the DNA called the USH2A gene. In the specific mutation we are targeting, the so-called c.7595-2144A>G mutation, the genetic defect results in the lack of a functional USH2A protein. Similar to CEP290 protein that we target in our QR-110 program for Leber’s congenital amaurosis, the USH2A protein that is defective in Usher syndrome type II is responsible for the proper functioning of the light perceiving cells (rods and cones) in the retina. Treatment The moderate to severe deafness that patients experience with Usher syndrome type II is manageable with hearing aids or cochlear implants. However, there are currently no available treatment options for the vision loss associated with this disease. About QRX-411 With our program, QRX-411, we aim to treat the c.7595-2144A>G mutation in the USH2A gene that leads to vision loss. Our single stranded RNA oligonucleotide aims to repair the genetic defect in the RNA in the eye, such that it leads to a normal “wild-type” mRNA, which then translates into normal protein, thereby modifying the underlying disease. This treatment will target patients with Usher syndrome with this mutation and non-syndromic retinitis pigmentosa patients which have the visual issues but do not suffer from hearing loss.
Fuchs endothelial corneal dystrophy & QRX-504What is Fuchs endothelial corneal dystrophy (FECD)? FECD is a common inherited condition characterized by the dysfunction and degeneration of the corneal endothelium, a single cell layer on the inside of the cornea in the eye. There are different types of this disease and we focus on age-related FECD (FECD3). Some patients with age-related FECD develop advanced disease with corneal edema and corneal clouding. These symptoms can lead to complete vision loss and the need for surgery and a corneal transplant. What causes Fuchs endothelial corneal dystrophy? Most of age-related FECD is caused by a mutation (or defect) in the TCF4 gene. Treatment There are currently no other treatment options for any form of FECD patients with vision loss, apart from corneal transplantation or replacement of the corneal endothelial layer. This requires surgery where the damaged cornea is removed and replaced with a healthy donor cornea. However, transplantation has several limitations, including the availability of donors, risk of rejection, the inherent risk of an invasive procedure and is only available to patients with advanced FECD. About QRX-504 Our program, QRX-504, aims to prevent corneal dystrophy in patients with a mutation in the TCF4 gene by using a single stranded RNA oligonucleotide.
Dystrophic epidermolysis bullosa & QR-313What is dystrophic epidermolysis bullosa (DEB)? DEB is a severe genetic orphan disease that affects the connective tissues including the skin and mucosal tissues. Children with DEB are often called ‘Butterfly children’ due to their fragile skin; blistering and skin erosions occur upon the slightest touch or even spontaneously. Symptoms include open wounds, skin infections, fusion of fingers and toes (pseudosyndactyly), gastrointestinal tract problems and eventually patients develop lethal squamous cell carcinoma. What causes DEB? DEB is caused by mutation(s) (or defects) in a gene in the DNA called the COL7A1 gene. This gene is responsible for the formation of protein collagen type VII that forms anchoring fibrils that bind the different skin layers together. The defects can occur in different parts of the COL7A1 gene causing loss or dysmalfunctioning of the anchoring fibrils and fragile skin. Treatment Although there are treatment options that help the healing of wounds in DEB patients, there is no approved treatment available that target the underlying cause of for any type of DEB. About QRX-313 Our program, QRX-313, targets all DEB caused by defects in a specific part of the COL7A1 gene called exon 73. By excluding this exon 73 from the RNA that harbors the defect, we hope to restore functionality of the anchoring fibrils.
Central Nervous System diseases
In our CNS group we are working on product candidates for several disease targets, including QRX-203 for Alzheimer’s disease and QRX-704 for Huntington’s disease.
Within our neuromuscular group we are working on a program called QRX-604 that aims to increase Frataxin protein levels in people with Friedreich’s ataxia.