Castle Creek Biosciences Raises $75 Million to Advance DEB Gene Therapy

Rare Daily Staff

Castle Creek Biosciences closed a $75 million royalty financing led by Ligand Pharmaceuticals to support the phase 3 clinical study Castle Creek’s experimental gene therapy for patients with the rare connective tissue disorder dystrophic epidermolysis bullosa.

Ligand originated, structured, and invested $50 million in Castle Creek and led a syndicate of co-investors who invested $25 million in exchange for a high single-digit royalty on worldwide sales of the gene therapy known as D-Fi. The syndicate includes existing Castle Creek investors Paragon Biosciences and Valor Equity Partners, and new investor XOMA Royalty Corporation.

“Partnering with Castle Creek is an exciting opportunity to advance an orphan drug-designated gene therapy for a serious unmet medical need through phase 3 development,” said Todd Davis, CEO of Ligand. “This collaboration reflects our commitment to invest in groundbreaking de-risked treatments that can transform patients’ lives and expand our diversified portfolio of revenue-generating assets.”

For Castle Creek, the deal provides critical financing while it gives Ligand a derisked innovative treatment that will help expand its revenue sources.

Dystrophic epidermolysis bullosa (DEB) is a rare and serious disease that affects the skin and mucosal tissues caused by one or more mutations in the COL7A1 gene. The COL7A1 gene is responsible for the production of functional COL7 protein that forms anchoring fibrils necessary to bind the inner layer of the skin, known as the dermis, to the outer layer of the skin, known as the epidermis. The lack of functional anchoring fibrils in DEB patients leads to extremely fragile skin that blisters and tears with minor friction or trauma. DEB patients suffer from open wounds, which lead to recurrent skin infections and fibrosis that can cause fusion of fingers and toes, and ultimately increase the risk of developing an aggressive form of skin cancer.

D-Fi is an injectable autologous gene-modified cell therapy candidate for the treatment of DEB. DEB is caused by a mutation in the COL7A1 gene, leading to a deficiency of normal COL7 protein, impairing the connection between the epidermis and the dermis. D-Fi is comprised of a patient’s own dermal fibroblasts, which are genetically modified ex vivo with a self-inactivating lentiviral vector containing the COL7A1 gene to express COL7. D-Fi is locally administered by intradermal injection into chronic wounds where the COL7 protein can support the formation of anchoring fibrils in the skin.

In clinical studies, D-Fi has been generally well tolerated, with injection site reactions being the primarily reported adverse drug reactions. The U.S. Food and Drug Administration granted D-Fi Orphan Drug designation for the treatment of DEB and granted Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations for the treatment of recessive dystrophic epidermolysis bullosa.