Krystal Biotech Doses First Patient in Phase 1/2 Trial Testing Gene Therapy Candidate KB103 for DEB

Inês Martins, PhD avatar

by Inês Martins, PhD |

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Krystal Biotech recently dosed the first patient in a Phase 1/2 clinical trial testing KB103, a topical gene therapy candidate for the treatment of dystrophic epidermolysis bullosa (DEB).

DEB is a progressive and painful form of epidermolysis bullosa characterized by blistering of the skin. The blistering happens because of a lack of type VII collagen (COL7) due to mutations in the COL7A1 gene. COL7 keeps the skin’s upper layer attached to its lower layer. A lack of COL7 causes the layers to separate, leading to blisters.

KB103 is designed to prevent blistering through topical application directly onto the skin.

It uses Krystal’s STAR-D gene therapy platform, made up of a genetically engineered virus and technology that enables the transfer of healthy genes to different types of skin cells. Krystal is using this approach to develop off-the-shelf therapies for skin diseases that currently have no treatment.

The gene therapy delivers a healthy and functional copy of the human COL7A1 gene directly to the patient’s skin cells in order to produce normal COL7 protein. The functional gene is delivered using the herpes simplex virus type 1 (HSV-1) modified to not cause the virus.

According to the company, the modified HSV-1 virus vector is able to penetrate skin cells with greater efficiency than other vectors and with a lower risk of inducing an immune response.

The open-label Phase 1/2 trial, being conducted at Stanford University, is evaluating the safety and tolerability of KB103 in people with the recessive type of DEB, the most severe form of the disease. The therapy’s effectiveness will also be evaluated through wound imaging and analysis of COL7 expression and anchoring collagen fibril formation in the basement membrane zone.

“This is an important milestone for us, as it brings us a step closer to offering a meaningful therapeutic option for patients with dystrophic epidermolysis bullosa who do not have a treatment option presently,” Suma Krishnan, founder and chief operating officer of Krystal, said in a press release.

“We are grateful to our clinical investigators and expert collaborators, who have supported Krystal Biotech and helped guide our efforts. Most of all, we are thankful to the patients and their families affected by DEB for their participation in our trial,” Krishnan said.

In January 2018, the U.S. Patent and Trademark Office issued a patent covering Krystal’s HSV vectors and related gene therapies for the treatment of wounds and skin diseases.

Recently the U.S. Food and Drug Administration cleared an investigational new drug application for KB103 as a topical gene therapy for DEB. The FDA’s decision followed a decision from the European Medicines Agency in April this year to grant KB103 orphan medicinal product designation for DEB treatment.

Even though the study has not yet been registered with, it has been approved by the National Institutes of Health’s Recombinant DNA Advisory Committee, which ensures that Krystal’s proposed protocol follows all safety guidelines required to test gene therapies in humans.