KB407 In-human Trial Expected After Gene Therapy Found Safe in Animals

Aisha I Abdullah PhD avatar

by Aisha I Abdullah PhD |

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Krystal Biotech is expecting to start a Phase 1 clinical trial by early fall to test KB407 for cystic fibrosis (CF), after the investigational inhaled gene therapy was found safe and well-tolerated in nonhuman primates.

According to Krystal, the positive results from a completed toxicology study will support a required investigational new drug application with the U.S. Food and Drug Administration (FDA). A go-ahead from the FDA will allow Krystal to conduct a first clinical trial of KB407. 

That trial is expected to launch sometime between July and September, the company said.

“Successful completion of this GLP [good laboratory practice] toxicology and biodistribution study is an important milestone not only for KB407, but also for our emerging pulmonary portfolio,”  Suma Krishnan, Krystal’s founder and chief operating officer, said in a press release. Notably, GLP refers to a set of quality and integrity standards for preclinical studies, while biodistribution examines the location of a given compound in the body.

An inheritable disease, CF results from mutations in the CFTR gene, which yield defective CFTR protein. The defective protein causes a build-up of thick mucus in tissues and organs, including the airways in the lungs. 

KB407 is an inhaled therapy that delivers two healthy copies of the CFTR gene directly to patients’ lung tissues using a modified version of the herpes simplex virus type 1 (HSV-1). The modified virus is safe for patients. 

The treatment was found to restore normal CFTR protein production in cultured lung cells in the lab. In studies in mice and primates, KB407 was safe and effective at delivering healthy CTFR

Based on this preclinical data, Krystal Biotech conducted a study in nonhuman primates, with KB407 given three times weekly. The study involved a total of 36 animals — 10 received a high dose of the therapy, 10 a low dose, and 10 an empty HSV-1 vector control. Six of the animals received air.

The repeat doses of KB407 were well-tolerated, with no adverse effects observed at the highest tested dose. 

Following treatment, tissue analysis detected KB407 throughout the lung tissue, including in the bronchioles — branched airways — and alveoli or air sacs. Little to no vector was found in other tissues. Further analysis found delivery specifically to the cells lining the lung airways.

Both vector and CFTR gene activity persisted in the lung tissue at least until 28 days after the last dose, suggesting the treatment’s effects are sustained.

According to the company, a Phase 1 study of KB407 should start in the third quarter of 2021.

Krystal also is developing KB408, a potential inhaled gene therapy for the treatment of alpha-1 antitrypsin deficiency.  The company will meet with the FDA this year to determine the next steps in KB408’s development.


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