The cornea is a densely innervated structure that accounts for over two-thirds of the eye’s total optical power and is the first ocular structure that light encounters as it enters the eye. Because of its vital role in visual quality, any disruption to the cornea’s metabolism or structure can have significant consequences for patients.
A single layer of basal cells overlaid by 4 to 5 layers of nonkeratinized stratified squamous epithelial cells. The corneal epithelium continuously regenerates, with cells migrating from the basement membrane to the surface over the course of about one week. Owing to their cell-to-cell connections via tight junctions, the corneal epithelium also functions as a barrier against fluid loss from the ocular surface and pathogen infiltration from the air.
Layer Thickness: 65–67 Microns
An acellular membrane that lies between the epithelial basement membrane and the anterior stroma.23 Because Bowman’s layer is unable to regenerate, any damage to it is of particular concern.
Layer Thickness: 8–12 Microns
A transparent tissue made of collagen structured in lamellae, sheets of collagen fibrils whose arrangement is critical to maintaining corneal transparency.
Layer Thickness: 478–500 microns
An acellular matrix separating the stroma from the endothelium. Descemet’s membrane is essential in maintaining corneal structure and clarity.24,25
Layer Thickness: 3–10 microns
A single, nonregenerative layer of cells that lies between the aqueous humor and Descemet’s membrane. The endothelium is responsible for maintaining the state of dehydration necessary for corneal transparency, acting as a pump to regulate stromal hydration and thus corneal transparency.
Layer Thickness: 0.1–10 microns
Claris is pioneering new innovations for a significant patient population struggling with the impacts of corneal scarring.
Hepatocyte growth factor (HGF) is a cytokine that stimulates epithelial cell proliferation, movement, structure, and the formation of blood vessels in several tissues throughout the body, including the cornea.17 Across these tissues, HGF is secreted by stromal and mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on T cells.18 HGF is a growth factor known to:
Additionally, the anti-fibrotic and healing properties seen with HGF has been demonstrated across many disease models and medical conditions.
Claris has identified that a deletion variant of hepatocyte growth factor (dHGF), in which five amino-acid residues are deleted, can accelerate corneal wound healing and prevent and reverse corneal scarring. dHGF has the potential to support restoration of both structural and functional corneal integrity resulting from disease, mechanical or chemical injury, and infection.
Initially named “Scatter Factor,” dHGF contains altered solubility and immunological properties while retaining the biological activities of the full sized protein.19
Claris is developing a human recombinant dHGF, CSB-001, for the treatment of NK and is administered topically as a 0.1% ophthalmic solution. The unique mechanism of action has demonstrated greater activity than a comparator molecule in the treatment of neurotrophic keratitis.
CSB-001 is a heterodimeric molecule consisting of a 69-kD α-chain and 34-kD β-chain that binds to c-MET, a receptor tyrosine kinase involved in wound healing that is unregulated in corneal disease.20,21
CSB-001 is stored at room temperature, dosed (1 drop) four times daily, and administered via an easy to handle sterile droptainer dispenser.
Corneal scars can follow corneal ulceration, perforation, or inflammation. HGF has previously demonstrated significant reduction of baseline expression of opacity-inducing α-SMA in corneal fibroblasts. HGF has also been shown to inhibit the expression of myofibroblast markers with potential to induce reversal of myofibroblast phenotype back to fibroblast phenotype.6,15
Studies have revealed HGF’s ability to advance corneal wound healing through various mechanisms. Normalization of corneal tissue structures and increased stratification of the epithelial cell layer were seen in HGF-treated corneas. Furthermore, HGF has been shown to inhibit tissue infiltration of inflammatory cells, which would otherwise lead to degradation of the extracellular matrix. Corneal transparency has been restored after injury involving corneal stroma due to inhibition of opacity-inducing myofibroblasts by HGF.6
Accelerate healing and nerve growth
Reduce the risk of and reverse corneal scarring
Repopulate the corneal endothelium
Neurotrophic Keratitis (NK) is a condition in which corneal nerves degenerate with time.
NK is often caused by the herpes keratitis virus but can stem from a number of other etiologies. Signs of NK include punctate keratopathy and significant epithelial irregularity (Stage 1 NK), persistent epithelial defects without stromal thinning or ulceration (Stage 2 NK), or corneal ulceration (Stage 3 NK). Current therapies for NK range from artificial tears in mild NK to matrix regenerating therapy and growth factor therapy in more severe NK.16
Currently, Claris is conducting a phase 1/2 clinical trial in patients with Stage 2 or 3 Neurotrophic Keratitis (NK). (NCT04909450) Patients will be randomized 1:1 to the CSB-001 investigational treatment arm or vehicle control arm.
During the controlled treatment phase, all patients will receive treatment 4 times daily, whether CSB-001 or vehicle for 8 weeks. During the controlled treatment phase, patients will return to the clinic weekly from Day 0 to Week 8, and again at Week 10. Patients randomized to the vehicle arm whose NK is not resolved by the end of the controlled treatment phase will have the opportunity to participate in an open-label, uncontrolled treatment phase. The study was initiated in August 2021, and its planned completion date is July 2024.22
In investigating the role and potential benefits of our innovative dHGF therapy, Claris aims to address the high unmet need for treating sight-threatening corneal disease, ultimately improving patient visual outcomes and quality of life.
