BULLOSA (RDEB) and
Epidermolysis bullosa (EB) is a group of rare inherited skin disorders that cause the skin to become very fragile. Any trauma or friction to the skin can cause painful blisters.1
RDEB and JEB are the two main types of EB.
RDEB is caused by mutations in the COL7A1 gene that codes for COL7A1 protein. The COL7A1 gene is involved in coding for the collagen that helps attach the epidermis to underlying layers of skin. We are targeting nonsense mutations in COL7A1. These represent approximately 30-40% of all mutations in COL7A1.
JEB is most commonly caused by mutations in the LAMA3, LAMB3 and LAMC2 genes. The LAMA3, LAMB3, and LAMC2 genes are involved in coding for a protein that plays an important role in strengthening and stabilizing the skin. We are targeting nonsense mutations in LAMB3 genes that represent approximately 70% of all mutations.
Infants are typically born with widespread blistering and areas of missing skin, often caused by trauma during birth
Most RDEB patients develop skin cancer by age 35
Average mortality of patients with JEB is 18 months
Affects ~4,000 patients worldwide with nonsense mutations
There are no approved treatments; management is palliative
ZKN-013 is our lead TURBO-ZM™ based molecule in our program to address nonsense mutations in RDEB/JEB.
Existing data paved the way for clinical development
Supported by clinical results with gentamicin
Patients treated with gentamicin (vs those treated with placebo) had ~70% increase in wound closure and ~70% decrease in blistering events
COL7 IN TREATED RDEB PATIENT KERATINOCYTES*
Preclinical results support that RMAs can restore
functional collagen protein at levels comparable
to high-dose gentamicin
Preclinical results support that RMAs may be safely orally dosed at 300-400 mg QD
Reference: 1. Genetics home reference: dystrophic epidermolysis bullosa. National Institutes of Health: US National Library of Medicine. https://ghr.nlm.nih.gov/condition/dystrophic-epidermolysis-bullosa#genes. Accessed June 17, 2021.