Krystal Biotech Inc. announced updated results from the Phase 1/2 clinical trial evaluating topical administration of KB105 in patients with autosomal recessive congenital ichthyosis (ARCI) associated with mutations in the TGM1 gene. These data show that repeat doses of KB105 continue to be well tolerated with no adverse events and with no evidence of immune response, systemically or at the sites of application. Phenotypic improvement, based on the IGA scale, was observed at each KB105 dosing site at varying time points throughout the 30-day dosing period, with the maximum effect observed in the treatment areas that received the highest KB105 dose. These results build on previous data showing a dramatic increase in KB105-mediated TGM-1 expression and activity in 3 patients, which correlated with an improvement on the IGA scale after KB105 topical treatment, with or without pretreatment of the area through micro-needling. No drug-related adverse effects were reported. Initial Phase 2 Data: An adult subject, aged 63, was enrolled and four 100cm2 treatment areas were identified. Each treatment area was assigned to receive repeat doses of 4.0x109 PFU (n=2 treatment areas) or 1.0x1010 PFU (n=2 treatment areas). Each area was dosed on Day 1 and 3, after which dosing continued either every 3 days (n=2 treatment areas) or every 6 days (n=2 treatment areas) up to day 30. Treatment areas were clinically evaluated at pre- and post-KB105 application timepoints, using a 5-point IGA scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = very severe). Repeated topical doses of KB105 were well tolerated, and no drug-related adverse effects were reported. No vector shedding or systemic viral exposure was detected at any time point. Improvement on the IGA scale was observed in each treatment area, with the maximum effect observed in TA3 and TA4 that received the highest dose; at day 27, the investigator assigned an IGA score of 2, which was improved as compared to baseline score of 4 in each area. Variable 1-point improvements were observed at other time points and in the treatment areas that received the lowest dose. As in the Phase 1 portion of the trial, TGM1 turnover was observed to be variable but relatively rapid, and the observed IGA improvements were not sustained through day 60.