Developing RNA therapeutics for rare and, so far, incurable Genetic Skeletal Disorders.

SiSaf is focused on developing innovative drugs for diseases with a genetic basis, characterized by the overproduction of one or more proteins. The depth and versatility of RNA coupled with our next-generation silicon stabilized hybrid lipid nanoparticle (sshLNP) technology enables us to address conditions in virtually any therapeutic area and pursue disease targets that are not otherwise treatable by small molecules and biologics.

Pipeline development strategy

We focus on rare, and as yet, incurable diseases to provide the first in class therapeutic within an expedited time frame, under the orphan drug designation program.

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 further accelerates the process of making safe and effective drugs available to patients.

Our in-house pipeline is focused on the rare Genetic Skeletal Disorders, Osteopetrosis, and Achondroplasia which requires:

• repeated systemic administration to target multiple organs in the body

• the ability to target the mutant gene without affecting the healthy gene

• safety and efficacy at any age, without accumulation over time

Our in vitro and in vivo studies to date indicate our BIO-COURIER siRNA constructs can achieve these exacting demands and similar strategies could be applied to other autosomal-dominant bone diseases, opening an avenue for wider use of RNA interference therapy in rare genetic disorders.

We also partner with a leader in ophthalmic genetic disease, Avellino Labs USA, to develop the world’s 1st eye drop RNA interference therapy and CRISPR cas 9 gene editing cure for Corneal Dystrophy.

SIS-101-ADO

SIS-101-ADO is a systemic BIO-COURIER siRNA designed to inhibit the dominant-negative mutations of the Clcn7 gene and rescue the phenotype of 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.

SIS-102-ACH

SIS-102-ACH is a systemic BIO-COURIER siRNA designed to inhibit mutated Fibroblast Growth Factor Receptor 3 gene (FGFR3), a negative regulator of bone growth, and rescue the phenotype of patients with Achondroplasia. 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, 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-201-CD

SIS-201-CD is a topical BIO-COURIER siRNA designed to inhibit the mutated Transforming Growth Factor Beta I (TGFBI) to prevent the overproduction and aggregation TGFBI protein in patients with 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-202-CDC

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 permanently stop the overproduction and aggregation TGFBI protein in patients with type II Corneal Dystrophy.

New Therapeutic Entities through drug repurposing. 505(b)(2) streamlined NDA process

A 505(b)(2) NDA contains full safety and effectiveness reports but allows at least some of the information required for NDA approval, such as safety and efficacy information on the active ingredient, to come from studies not conducted by or for the applicant. This can result in a much less expensive and much faster route to approval, compared with a traditional development path [such as 505(b)(1)], while creating new, differentiated products with tremendous commercial value.

SIS-022

SIS-022 is a topical BIO-COURIER 5-FU designed to block angiogenesis, fibroblast proliferation, and collagen type I expression occurring in hypertrophic scars and keloids. The anti-angiogenetic properties of 5-FU also contribute to its anti-inflammatory effect in the scar.  SiSaf’s BIO-COURIER technology facilitates localized skin absorption of 5-FU by penetrating the body of the hypertrophic scar. In addition, SIS-022 is expected to protect the superficial skin from the destructive effects of 5-FU, reduce the adverse events at the application site (such as erosions, ulcer and burning), to increase accessibility and patient compliance with treatment regimens.

Hypertrophic and keloid scars are commonly encountered complaints in dermatological practice. These abnormal lesions are clinically challenging to treat and can be a source of significant distress to both patients and providers. Reports suggest that around 40-70% of post-operative scars may become hypertrophic. In the developed world, up to 100 million problematic scars occur each year from 55 million elective operations and 25 million operations after; other insults to the dermis including burns, lacerations, tattoos, piercings, acne vulgaris, or vaccinations can also result in unsightly scars.