Focus | Overview

Overview

Our goal is to make a meaningful difference in the lives of underserved patient populations suffering from debilitating skin diseases. We work to accomplish this goal through scientific innovation and operational excellence, believing that “nature operates in the shortest way possible” (Aristotle).

Krystal Biotech, Inc. is a clinical-stage gene therapy company using its proprietary Skin TARgeted Delivery (STAR-D) platform to develop effective and innovative treatments for skin diseases. While we are initially developing topical and intradermal “off-the-shelf” novel therapies for rare and orphan dermatological indications, we are expanding the use of our pioneering STAR-D technology to target and treat other skin conditions as well.

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. Beremagene geperpavec (“B-VEC”, previously “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 evaluated in humans and is the subject of a planned phase III clinical trial. B-VEC 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 marked 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 is being tested in an ongoing phase I/II clinical trial. 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

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.

Construction of Ancoris, a new state-of-the-art Good Manufacturing Practice (GMP) facility located near the company’s headquarters in Pittsburgh, is complete. The 4,500-square-foot facility has been designed to satisfy the necessary manufacturing requirements for commercial development of B-VEC and the highest current GMP standards governing commercial production for biopharmaceutical use. The Ancoris facility will be the primary production site to meet projected commercial demand for B-VEC.

A groundbreaking ceremony for our second commercial gene therapy facility, named ASTRA, was held on January 24, 2020, in Findley-Township, Pennsylvania. The Findley-based facility is being designed as a state-of-the-art current Good Manufacturing Practice (cGMP) manufacturing facility that, beyond expanding Krystal’s current production platform, will allow the in-house incorporation of raw material preparation, excipient manufacturing, testing, packaging, labeling, and distribution, fully-integrating all components of the supply chain from starting materials to patient experience. The ASTRA facility will initially be used as a commercial backup facility for B-VEC, which is being developed for the treatment of dystrophic epidermolysis bullosa, a rare and devastating skin disorder, and expand to produce investigational and commercial material for our pipeline products.