Krystal Biotech doses first patient in EMERALD-1 phase 1/2 trial for neurotrophic keratitis

Krystal Biotech announced the first patient has been dosed in EMERALD-1, its phase 1/2 clinical trial evaluating KB801 for the treatment of neurotrophic keratitis (NK), a degenerative corneal disease characterized by damage or loss of function in the neurons innervating the eye, leading to corneal epithelial defects, ulcers, and perforation.

According to the company,¹ while NK is a rare disease with an estimated prevalence in the range of 10 to 50 cases per 100,000, data suggests diagnosis rates are on the rise. An estimated 68,000 patients in the United States had an NK claim in 2024, up over 115% from 31,000 patients with an NK claim in 2020.

EMERALD-1 (NCT06999733) is a double-masked, multicenter, placebo-controlled study. Patients will be randomized 2:1 to receive KB801 at a concentration of 10¹⁰ PFU/mL or vehicle topically to the study eye twice weekly for 8 weeks. Patients will return for follow-up visits at 2 and 12 weeks after finishing treatment to monitor for safety and durability of corneal healing. Up to 27 adults with stage 2 or stage 3 NK, as defined by the Mackie criteria, will be enrolled.²

The primary objective of EMERALD-1 is to evaluate the safety and tolerability of topical ocular administration of KB801 in patients with NK, while the secondary objective is evaluation of efficacy based on the proportion of patients with complete durable healing of corneal epithelium at 8 weeks. Complete durable healing of corneal epithelium is defined by the company as 0 mm corneal fluorescein staining in the area of the corneal lesion at both week 8 and 0 mm corneal fluorescein staining in the same area at week 10, as assessed by a masked reader.

Suma Krishnan, president of R&D at Krystal Biotech, commented on the trial in a press release from the company.

“Until now, rapid protein clearance rates and high cell turnover in the front of the eye have severely limited the therapeutic potential of biologics and gene therapies for the treatment of corneal epithelial defects and other front of the eye diseases. We now have an opportunity to drive sustained expression and repeat administration of therapeutic biologic payloads with a simple eye drop application and look forward to delivering meaningful benefit to NK patients in need,” said Krishnan.

KB801 is a redosable eye drop gene therapy designed to enable sustained, localized expression and secretion of nerve growth factor (NGF) by epithelial cells in the front of the eye for the treatment of NK. The company noted that while recombinant NGF eye drops have been shown to significantly improve corneal healing and are approved for the treatment of NK in multiple jurisdictions worldwide, rapid clearance from the eye requires administration 6 times a day. Krystal notes that KB801 has the potential to significantly reduce the treatment burden for patients while also maintaining more consistent NGF levels in the front of the eye.

The company also recently announced the first patient was dosed in IOLITE,³ its phase 3 clinical trial evaluating KB803 for the treatment and prevention of corneal abrasions in dystrophic epidermolysis bullosa (DEB) patients. KB803 is a redosable eye drop gene therapy designed to deliver 2 copies of the COL7A1 transgene to the epithelial cells in a patient’s eye for the treatment and prevention of corneal abrasions in DEB patients.

References:

1. Krystal Biotech announces first patient dosed in phase 1/2 trial of KB801 for the treatment of neurotrophic keratitis. Published July 9, 2025. Accessed July 14, 2025. https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-first-patient-dosed-phase-12-trial

2. A study assessing KB801 for the treatment of stage 2 or 3 neurotrophic keratitis (EMERALD-1). NCT06999733. Accessed July 14, 2025. https://clinicaltrials.gov/study/NCT06999733?tab=table

3. Harp MD. Krystal Biotech doses first patient in phase 3 trial IOLITE. Published June 27, 2025. Accessed July 14, 2025. https://www.ophthalmologytimes.com/view/krystal-biotech-doses-first-patient-in-phase-3-trial-iolite