The IND’s approval would allow a Phase 1/2 clinical trial to move forward to assess KB103’s safety, tolerability, and efficacy. The trial already has been approved by the National Institutes of Health (NIH)’s Recombinant DNA Advisory Committee to ensure that the trial’s proposed protocol follows all safety guidelines required to test gene therapies in humans.
Dystrophic epidermolysis bullosa is an inherited disease characterized by defective production of collagen fiber in the skin. The condition is caused by genetic mutations in the COL7A1 genes. Krystal is developing KB103 to specifically correct this genetic defect.
KB103 was designed based on the herpes virus structure and the company’s proprietary STAR-D gene therapy platform to deliver the correct, functional version of human COL7A1 genes directly to skin cells.
Recently, the U. S. Patent and Trademark Office issued a patent covering Krystal’s herpes viral delivery vectors and related gene therapies to be used for the treatment of wounds and skin disorders.
In November 2017, the U.S. Food and Drug Administration granted orphan drug designation to KB103 as a treatment for dystrophic epidermolysis bullosa.
The investigative gene therapy has demonstrated to effectively target fibroblasts and keratinocytes, two subsets of cells present in the skin, and to control the production of collagen. Transformation of these cells to have the correct version of the COL7A1 gene was shown to efficiently reverse their abnormal behavior while enhancing the production of collagen protein. These positive effects were seen in both laboratory experiments and mice models.
These preliminary preclinical data were the subject of a presentation at the 5th World Conference of EB Research held last September in Salzburg, Austria. The presentation was titled “HSV-1 Mediated COL7A1 (KB103) Delivery To Keratinocytes And Fibroblasts For Recessive Dystrophic Epidermolysis Bullosa (RDEB) Therapy: Preparations For Phase-I Clinical Trials.”
“2018 promises to be a productive and exciting year for Krystal,” Krystal Biotech CEO Krish S. Krishnan said in a press release. “Our immediate focus is to execute on our planned Phase 1/2 clinical study for our lead product candidate KB103 for treatment of dystrophic epidermolysis bullosa. … In parallel, we are building out our infrastructure with the goal of establishing a GMP [good manufacturing practice] facility in Pittsburgh, PA in the next 12 months for the production of our pipeline products.”
Last year, Krystal received a $700,000 equity-based award from the Epidermolysis Bullosa Research Partnership (EBRP) and the Epidermolysis Bullosa Medical Research Foundation (EBMRF) to continue developing a treatment for dystrophic epidermolysis bullosa.