SiSaf is developing siRNA treatments for autosomal dominant disorders and has recently added RNA therapeutics for oncological applications to its R&D pipeline. These therapies utilize the fundamental features of SiSaf’s proprietary Bio-Courier delivery platform: durable stabilization of RNA, non-immunogenic, efficient transfection, and no accumulation.
We work in close collaboration with renowned academic experts to generate in vivo validated therapeutic sequences. This removes the heavy lifting of internal sequence discovery and combined with the accelerated time frames of orphan drugs, it fast tracks the process of making safe and effective drugs available to patients.
Autosomal Dominant Osteopetrosis (ADO2)
ADO2 is a genetic bone disease affecting 5.5 in 100,000 people. The mutated gene causes a defect in bone reabsorption by osteoclasts resulting in increased bone density. This leads to an accumulation of bone with a defective architecture, making them brittle and susceptible to fracture. In the most severe forms, patients present with extensive osteosclerosis, especially of the skull base, pelvis, and vertebrae, and experience multiple fractures, osteomyelitis, hematologic failure, and sensorial symptoms, including impaired vision and hearing.
Currently, there is no cure for ADO2 and SIS-101-ADO represents a first-in-class treatment to reverse the bone phenotype to normal.
About one in 25,000 people are born with Achondroplasia, a disorder of bone growth that prevents the changing of cartilage (particularly in the long bones of the arms and legs) to bone. It is characterized by dwarfism, limited range of motion at the elbows, large head size (macrocephaly), and small fingers. Achondroplasia can cause health complications such as interruption of breathing (apnea), obesity, recurrent ear infections, and an exaggerated inward curve of the lumbar spine (lordosis). More serious problems include a narrowing of the spinal canal that can pinch (compress) the upper part of the spinal cord (spinal stenosis) and a build-up of fluid in the brain.
SIS-102-ACH will be the first RNA therapeutic that addresses the root cause of Achondroplasia, directly inhibiting the mutated FGFR3 gene without affecting its healthy copy.
Type II Corneal Dystrophy
Corneal Dystrophies are a group of genetic, often progressive, eye disorders in which abnormal material accumulates in the clear (transparent) outer layer of the eye (cornea). Corneal dystrophy can cause watery eyes, dry eyes, sensitivity to light, pain, corneal erosion, and significant visual impairment, but to date there is no cure and treatment focuses on alleviating symptoms.
SIS-201-CD represents a first-in-class treatment to target the mutated TGFBI gene and inhibit protein accumulation in the cornea with the ease and convince of eye drop administration.
SIS-202-CDC is a topical Bio-Courier CRISPR-Cas 9 designed to permanently edit the mutated Transforming Growth Factor Beta I (TGFBI) gene using double-cut CRISPR Cas 9 and stop the overproduction and aggregation of TGFBI protein in patients with type II Corneal Dystrophy.
SIS-202-CDC represents the first-in-class cure for patients with type II Corneal Dystrophy with the ease and convince of eye drop administration.