Krystal Biotech (KRYS) Status Update summary

Clinical program updates

• KB408 and KB407 demonstrated positive interim safety and gene delivery results for rare respiratory diseases, with KB408 showing efficient, safe, and reusable HSV1-based gene delivery to the lung via inhalation and high transduction rates in airway epithelial cells.

• KB408 phase I SERPENTINE-1 study enrolled seven patients across two dose cohorts, showing no serious adverse events or dose-limiting toxicities, and plans to enroll two more in Cohort 2 and open Cohort 3 for higher dosing.

• KB407 phase I CORAL-1 study enrolled five patients, with positive safety data, no dose-limiting toxicities, and conditional protocol sanctioning by the CFF TDN.

• Both programs are supported by robust preclinical data and have received conditional sanctioning from relevant networks for clinical protocols.

• Data from Cohort 3 of CORAL-1, including CFTR gene delivery and expression, is expected in 1H 2025.

Molecular and functional data

• KB408 achieved high airway cell transduction (up to 39%) and significant increases in AAT levels in the lung, with over eight-fold rise post-dose in one patient not on IV augmentation.

• Functional AAT expression led to a >50% reduction in active neutrophil elastase in the lung after a single dose.

• All four Cohort 2 patients showed increased serum AAT levels post-KB408, with rises up to 5.3 µM in those not on IV augmentation.

• In patients on augmentation therapy, KB408 still showed robust gene delivery and expression, with quantifiable vector genomes and transcripts detected.

• Correlation between lung and serum AAT levels is being further explored to support biomarker-driven regulatory pathways.

Safety and tolerability

• Both KB408 and KB407 were well tolerated, with only mild to moderate, transient adverse events such as chills and fatigue, and no serious adverse events or dose-limiting toxicities reported.

• No evidence of neutralizing antibody response was observed, supporting potential for repeat dosing.

• Inflammatory reactions were transient and manageable, with no drug-induced cough or lung-specific adverse events reported.

• Nebulizer administration was straightforward, requiring minimal training and short administration times.

• No systemic vector distribution was observed in KB407 studies.