In a significant move to advance rare disease therapeutics, Ligand Pharmaceuticals (Nasdaq: LGND) has closed a $75 million royalty financing agreement with Castle Creek Biosciences to fund the Phase 3 clinical trial of D-Fi, a promising gene therapy for dystrophic epidermolysis bullosa (DEB).
The financing structure includes a $50 million investment from Ligand, complemented by $25 million from a syndicate of co-investors including Paragon Biosciences, Valor Equity Partners, and XOMA Royalty Corporation. In return, the investors will receive a high-single digit royalty on worldwide sales of D-Fi.
Innovative Gene Therapy Approach
D-Fi (FCX-007) represents a novel approach to treating DEB, a progressive genetic skin disorder characterized by painful blistering and impaired wound healing. The therapy utilizes patients' own dermal fibroblasts, which undergo genetic modification using a self-inactivating lentiviral vector containing the COL7A1 gene. This modification enables the cells to produce type VII collagen protein, crucial for maintaining skin integrity.
The treatment is administered through local intradermal injections into chronic wounds, where the expressed COL7 protein supports the formation of anchoring fibrils in the skin. Clinical studies have shown D-Fi to be generally well-tolerated, with primarily mild injection site reactions reported as adverse events.
Regulatory Recognition and Clinical Progress
The therapeutic potential of D-Fi has been recognized through multiple FDA designations, including:
- Orphan Drug Designation for DEB treatment
- Rare Pediatric Disease designation
- Fast Track status
- Regenerative Medicine Advanced Therapy designation for RDEB
"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."
Strategic Impact and Market Potential
Matthew Gantz, president and CEO of Castle Creek, emphasized the significance of securing sophisticated investors for the Phase 3 trial: "Having a sophisticated investor like Ligand work closely with our extremely supportive equity partners made this transaction to support our Phase 3 clinical trial possible."
The investment underscores growing confidence in gene therapy approaches for rare diseases and represents a strategic expansion of Ligand's portfolio of revenue-generating assets. The agreement aligns with Ligand's business model of supporting clinical development of high-value medicines while maintaining a diversified approach to biotech investment.
