Krystal Biotech announces interim results from Phase 1/2 trial of KB103
Krystal Biotech announced interim results from its ongoing placebo-controlled Phase 1/2 clinical trial of KB103. Two adult Recessive Dystrophic Epidermolysis Bullosa, or RDEB, NC1 patients aged 35 and 28 years old have completed treatment with topical KB103 to date. The patients were re-dosed during the study. In each patient, two wounds with an approximate surface area of 10 cm were randomized to receive either topical KB103 or placebo. KB103 was also injected intradermally in both patients to intact skin to evaluate the mechanism of action of KB103 and validate molecular correction. Both KB103-treated wounds and intradermally injected intact skin were biopsied to assess functional COL7 expression and anchoring fibril formation. KB103-treated wounds were also evaluated for clinically relevant healing compared to placebo-treated wounds and to baseline. They were also monitored for general and recombinant viral infection and autoimmune response at each evaluation. Analysis of KB103-treated wounds demonstrates clearly detectable robust functional COL7 expression by immunofluorescence in the biopsy samples from the two treated patients as early as day 2 of treatment. Functional COL7 was determined by staining the tissue samples with NP185 and LH24 antibodies that bind to NC1 and NC2 domains of the COL7 protein respectively. Both of the patients were NC1 positive at baseline. The tissues from the skin biopsies show the presence of both the NC1 and NC2 domains demonstrating production of functional COL7 that has linearly deposited along the basement membrane zone, or BMZ. NC1 and NC2 reactive anchoring fibrils were observed by immunoelectron microscopy, or IEM, as early as day 14 and up to the last biopsy for both patients. Safety data from both patients show that KB103 was well tolerated. No serious adverse events, and no product-related adverse events were reported. No inflammation or irritation was observed at KB103-treated wounds. In addition, no antibody response was noted for type VII collagen. Repeat administration of KB103 in both patients demonstrated continued expression of COL7 expression with no immune or safety concerns. In Patient 1, the wounds administered with KB103 closed in 2 weeks while wounds administered with placebo closed in 10 weeks. In Patient 2, the wounds administered with KB103 closed in 2 weeks also demonstrating a faster rate of wound closure on KB103-administered wounds to date compared to placebo. Patient 2's placebo-administered wound did not fully close throughout the study. To date, both of the patient's KB103-treated wounds remain closed, representing 4.5 months of total closure for Patient 1 and 3.5 months of total closure for Patient 2. Patient 1 has chosen to discontinue bandaging on the KB103-treated wound that previously required regular bandaging. Analysis of KB103-treated intact skin revealed clearly detectable functional COL7 expression by immunofluorescence in biopsy samples collected from the intradermal injection sites. Clinical data from two patients were submitted to the FDA. FDA acknowledges molecular correction as evidenced by expression of COL7 and anchoring fibrils. Consequently, the protocol has been amended to remove the intradermal arm for patients in the Phase 1/2 trial going forward. Per discussion with the FDA, the amended protocol will now enroll pediatric patients and will focus on evaluating durability of wound closure in preparation for selecting endpoints for Phase 3 clinical trial. With safety and molecular correction established, the revised Phase 1/2 protocol allows for increased dosing and KB103 administration to larger wound areas.