Focus | Our Approach

Our Approach

Platform

Viral gene therapy platform for dermatology

We are leveraging the advantageous properties of type 1 herpes simplex virus (HSV-1), including the virus’s natural affinity for skin cells, to develop a safe viral gene therapy platform adapted for dermatology. Our engineered HSV-1-based system is suited for a topical route of administration, allowing for non-invasive therapeutic applications when treating the skin.

Programs

Initial focus on orphan diseases

Our initial products are directed to the treatment of monogenic and congenital skin diseases, including dystrophic epidermolysis bullosa (DEB) and autosomal recessive congenital ichthyosis (ARCI).

DEB is an incurable, often fatal skin blistering condition caused by mutations in the gene encoding type VII collagen, or COL7, a protein that provides critical structural adhesion between skin layers in a normal individual. KB103, a replication-defective, non-integrating HSV-1 that is based on the company’s viral gene therapy platform, is Krystal’s lead product candidate currently being tested in a phase I/II clinical trial. KB103 has been engineered to deliver wild-type human type VII collagen genes (and thus, functional COL7 protein) directly to a DEB patient’s dividing and non-dividing skin cells, providing molecular correction of the underlying genetic deficiency to stabilize the patient’s otherwise extremely fragile skin.

ARCI is a life-long, severe genetic skin disease that often results in pronounced scaling of the skin and disruption to the epidermal barrier, leading to pronounced dehydration, transepidermal exposure to unwanted toxins and surface microorganisms, and a greatly increased risk of infection. While a number of genetic mutations have been associated with the development of ARCI, the most common cause of ARCI is an inactivating mutation in the TGM1 gene encoding transglutaminase-1, a protein that is essential for the proper formation of the skin barrier. KB105 is Krystal’s second product candidate that has been extensively validated in pre-clinical animal models. This product is engineered to deliver wild-type human TGM1 genes into the skin of ARCI patients, allowing for the treatment of the skin barrier defects observed in this patient population.

Expansion

Expanding beyond rare and orphan diseases

In addition to our work developing novel treatments for rare, orphan skin diseases, we are currently leveraging our expertise and viral gene therapy platform to explore new therapeutic approaches for additional dermatological indications, including non-monogenic diseases and diseases not caused by inherited genetic defects.

Manufacturing

Bring manufacturing in-house

Bringing all stages of the manufacturing process in-house affords us a number of unique opportunities, including: ensuring robust virus production and the highest quality of purified drug product; reducing lot-to-lot variability between virus batches; being able to rapidly institute process improvements identified by our Process Development (PD) and Chemistry, Manufacturing, and Controls (CMC) teams; optimizing our internal processes to meet all necessary regulatory requirements; and avoiding the high demand for gene therapy services from third party Contract Manufacturing Organizations (CMOs), safeguarding against delays.

We have begun construction of a Good Manufacturing Practice (GMP) facility that will support all clinical and commercial production of our gene therapy formulations. Completion of the GMP facility and initiation of GMP manufacturing is expected in Q4 2018.