Epidermolysis Bullosa (EB) is a genetic condition that causes skin fragility leading to chronic wounds, skin cancers, and gastrointestinal (GI) ulcerations. EB wounds are often complicated by infection, fibrosis and scarring, and their nutritional uptake is severely limited, all of which impacts on the length and quality of the lives of patients. We are developing systemically-acting neutralising antibodies that target a novel protein called Flightless – I that negatively affects wound healing. In addition to the lead indication of EB, this treatment modality could also be used for other indications including IBD, skin cancer, and wound-healing applications such as diabetic foot ulcers.
Technology Features, Specifications and Advantages
The technology is a panel of antibodies targeting the protein Flightless – I, which is secreted in response to tissue damage and is a negative regulator of wound repair.
The Flii neutralizing antibodies (FnAb) have been extensively been validated in vitro and in vivo with strong wound healing properties identified including:
- Improved healing of acute wounds in vivo.
- Improved healing of blistered skin.
- Prolonged lifespan of RDEB mice.
- Improved healing of burn wounds in vivo.
- Improved healing of diabetic wounds in vivo.
- Improved angiogenesis in vivo.
- Promotion of angiogenesis in vitro.
- Increased cellular proliferation and migration in vitro.
This Flightless - I antibodies can be used to target several conditions that present with tissue damage, wounding and blistering. The lead indication is EB, which is a set of rare genetic disorders caused by mutations to genes that express structural proteins such as collagen and laminin that hold the epidermal layers of skin together. In EB, the aforementioned mutations cause the structural robustness of the skin is compromised leading to chronic wounding and blistering, with a related increase in Flii expression levels. Our antibodies neutralize Flii, promoting better wound repair and could improve patient outcomes.
Other indications include - Inflammatory Bowel Disease - Flii therapy has been shown to reduce the symptoms of IBD in animal models.
Skin cancer - Flii therapy slows the progression of cutaneous squamous cell carcinomas, which are a key complication of EB.
Diabetic foot ulcers - Flii therapy could be used to improve the healing of wounds in diabetic foot ulcers.
The global EB market size is estimated to be ~ US$ 2b. There are approximately 500,000 patients globally and the annual costs of wound management are estimated to be $400,000.
Currently, there are no approved treatments for EB. The standard of care is reliant on wound management through bandaging, treatment of infection and sepsis by the administration of antimicrobials and surgery for skin grafting, as well as to place feeding tubes to improve the nutritional intake of patients, which is highly compromised due to lesions in the GI tract of EB patients.
Flii therapy offers the key advantages of being able to improve both external and internal wounds, through systemic administration of the antibodies. It is also at a lower price point relative to gene/cell therapies, and targets a larger addressable market. Moreover, EB is a set of genetic conditions and current pipeline treatments focusing on cell/gene therapies for the disease are only effective on external wounds and are specific for particular mutations unlike the Flii therapy, which can work on all subtypes of EB.