New clinical data on Krystal Biotech Inc.'s investigational gene therapy for dystrophic epidermolysis bullosa (DEB), KB-103, found five of six wounds treated with the topical candidate closed completely during a phase II trial and, along with wounds investigators treated in phase I, have stayed closed so far. Krystal's shares (NASDAQ:KRYS) climbed 41.3% to $41.20 Monday as the company advanced plans to launch a pivotal study of the candidate by year-end, work aided by a recently awarded FDA regenerative medicine advanced therapy designation and EMA priority medicines status.

Results of treatment with KB-103, also known as bercolagene telserpavec, contrasted sharply with outcomes in three placebo-treated wounds that remained fully open at a prespecified 90-day checkpoint during the trial. The outcomes also showed that the experimental therapy effectively closed wounds sized up to 20 cm square, twice the size of those tested in the phase I portion of the study, GEM-1. (See BioWorld, Oct. 16, 2018.)

The randomized GEM-2 study was designed to enroll four patients in whom Krystal sought to demonstrate the safety and efficacy of KB-103 while building on earlier results from GEM-1. The four new patients – two adults and two teens – were dosed with KB-103 in the second half of December 2018. Each participant had three wounds treated, one with a placebo and two with KB-103.

Out of a total of 12 wounds treated, only nine were included in Krystal's analysis of the study because one patient dropped out after 30 days, primarily due to a hardship of traveling to the study site. Out of the nine remaining wounds analyzed, two chronic and four recurring wounds were treated with KB-103. Chronic wounds are those that remain open for 12 weeks or more while recurring wounds heal but easily open.

Five out of six wounds treated with KB-103 in GEM-2 closed 100% during the trial, with the wound that did not close completely being a chronic deep wound that has remained open for more than four years according to the trial participant.

The average time to 100% wound closure on all KB-103-treated wounds in GEM-2 was 23.4 days, about twice the amount of time it took to reach 100% wound closure in the smaller wounds treated in phase I. The average duration of wound closure on all recurring wounds in the phase II trial was 71 days, though investigators are continuing to monitor the ongoing duration of closure.

Safety data from all patients show that KB-103 was well-tolerated with no adverse events reported.

Peter Marinkovich, an associate professor of dermatology at Stanford University and the principal investigator in the GEM study, called the results "a really significant milestone" in development of the medicine, a replication-defective, non-integrating viral vector that delivers functional human COL7A1 genes directly to the patients' dividing and nondividing skin cells.

Suma Krishnan, founder and chief operations officer of the Pittsburgh-based company, said insights gleaned from GEM-2 will allow her team to design a robust pivotal program that will include both chronic and recurring wounds. Meetings with the FDA and EMA in the coming months will aim to sync up the company's MAA and BLA filings, while manufacturing progress has prepared it to produce clinical trial supplies of KB-103.

Krish Krishnan, CEO and chairman of Krystal, was unavailable for an interview Monday.

DEB, a genetic condition, is caused by one or more mutations in gene COL7A1. The gene is responsible for the formation of protein type VII collagen, or COL7, that forms anchoring fibrils that bind the dermis, or inner layer of the skin, to the epidermis, or outer layer of the skin. Mutations in the gene lead to a condition in which the skin can tear and blister easily, even in response to minor contacts. Though signs and symptoms of the disorder vary widely, it can lead to blistering on hands, knees, feet and elbows, and can even lead to vision loss or squamous cell carcinoma. Krystal estimates about 10,000 individuals worldwide currently live with DEB, split equally among the U.S., Europe and the rest of the world.

There is no FDA- or EMA-approved treatment for the condition. Day-to-day management typically consists of preventing mechanical forces that produce new blisters, wound care, nutritional support and infection control.

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