Amryt Pharma plc: Positive results for novel non-viral gene therapy AP103

Amryt, a revenue generating orphan drug company focused on acquiring, developing and commercialising products that help improve the lives of patients where there is a high unmet medical need, today announces positive results from two pre-clinical studies which support the development of its novel non-viral gene therapy, AP103, as a potentially disease-modifying therapy for patients with Recessive Dystrophic Epidermolysis Bullosa (“RDEB”), a subset of Epidermolysis Bullosa (“EB”).

RDEB is a particularly severe form of EB and is caused by mutations in a single gene, COL7A1, which codes for the production of collagen VII, a structural protein vital for the elastic and structural integrity of the skin. Restoring production of collagen VII in skin cells could be transformative for these patients, potentially making their skin less fragile and more resistant to damage and blistering. As a result, the quality of life for patients with RDEB could be dramatically improved.

Pre-clinical studies sought to investigate the potential of AP103 as a topical gene therapy intervention to restore expression of the COL7A1 gene.

• In vitro tests on RDEB keratinocytes, the main cell type in the top layer of skin, showed that a single delivery of the human collagen VII gene, by AP103, restored collagen VII production to levels exceeding those produced by healthy human keratinocytes
• Topical application of AP103 onto a 3-D matrix of human RDEB skin restored collagen VII along the basement membrane to levels similar to those observed post delivery using a viral vector
• AP103 exhibited no evidence of cellular toxicity after repeated administration

AP103 is based on a new gene therapy delivery platform, in-licensed by Amryt in March 2018, that utilises a non-viral delivery vector, HPAE (Highly Branched Poly β-Amino Ester), designed to deliver the correct collagen VII gene into skin cells. It is topically applied to the skin.

Joe Wiley, CEO of Amryt Pharma, commented: “These results further support the potential of our novel gene therapy platform as a potentially transformative treatment for patients with RDEB, which is a particularly severe form of EB. If successful, this platform has potential in other genetic skin conditions and beyond. Unlike other gene therapies that rely on viral vectors, AP103 is a novel synthetic delivery technology, which provides a potential competitive advantage in the gene therapy field. Following the recently announced grant funding from the Irish Government, we look forward to progressing this exciting program in 2019. Today’s news also follows our recent encouraging results from the EASE Global Phase III study in EB. Both developments are significant milestones for Amryt and our shareholders as we build a global EB franchise and become a leader in rare and orphan diseases.”

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About Amryt

Amryt is a biopharmaceutical company focused on developing and delivering innovative new treatments to help improve the lives of patients with rare or orphan diseases.

Lojuxta is an approved treatment for adult patients with the rare cholesterol disorder - Homozygous Familial Hypercholesterolaemia (“HoFH”). This disorder impairs the body’s ability to remove low density lipoprotein (“LDL”) cholesterol (“bad” cholesterol) from the blood, typically leading to abnormally high blood LDL cholesterol levels in the body from before birth - often ten times more than people without HoFH - and subsequent aggressive and premature narrowing and blocking of blood vessels, heart attacks and strokes, even at a very young age if not properly diagnosed or receiving adequate treatment. Lojuxta is indicated as an adjunct to a low-fat diet and other lipid-lowering medicinal products with or without LDL apheresis in adult patients with HoFH.

Amryt is the marketing authorisation holder and has an exclusive licence to sell Lojuxta (lomitapide) across the European Economic Area, Middle East and North Africa, Switzerland, Turkey, Israel, Russia, the Commonwealth of Independent States and the non-EU Balkan states.

Amryt’s lead drug candidate, AP101, is a potential treatment for Epidermolysis Bullosa (“EB”), a rare and distressing genetic skin disorder affecting young children and adults for which there is currently no treatment. It is currently in Phase III clinical trials. The European and US market opportunity for EB is estimated to be in excess of €1 billion.

In March 2018, Amryt in-licenced a pre-clinical gene-therapy platform technology, AP103, which offers a potential treatment for patients with Recessive Dystrophic Epidermolysis Bullosa, a subset of EB, and is also potentially relevant to other genetic disorders.

For more information on Amryt, please visit amrytpharma.com.