“Focused on Developing Treatments to Address Age-related and Retinal Diseases.”
Zimura® (avacincaptad pegol)
We are developing our product candidate Zimura for the treatment of geographic atrophy secondary to dry age-related macular degeneration and Stargardt disease.
Complement factor C5 is a central component of the complement cascade believed to be involved in the development of age-related macular degeneration and Stargardt disease. Zimura is designed to target and inhibit the cleavage of complement protein C5 and the formation of the terminal fragments, C5a and C5b. By inhibiting the formation of complement system terminal fragments, Zimura may decrease the activation of inflammasomes and decrease the formation of MAC (membrane attack complex), thereby potentially avoiding or slowing the degeneration of RPE (retinal pigment epithelial) cells and providing the rationale as a potential therapy for both geographic atrophy and Stargardt disease.
Geographic Atrophy Secondary to Dry Age-related Macular Degeneration
Dry age-related macular degeneration (AMD) is characterized by the development of yellow-white deposits under the retina, known as drusen, along with deterioration of the retinal tissue. Geographic atrophy (GA), an advanced form of dry AMD, is a disease characterized by atrophy of the retina that leads to central vision loss.
We estimate that there are approximately one million individuals in the United States with GA. There is currently no FDA or EMA approved therapy to treat GA.
Stargardt Disease (STGD1)
Stargardt disease, the most common inherited macular dystrophy in both children and adults, is an orphan inherited retinal disease that leads to the macular atrophy and loss of vision.
We estimate that there are approximately 62,000 to 77,000 individuals in the United States and the five major European markets on a combined basis with Stargardt disease.
The most common type of Stargardt disease is inherited in the autosomal recessive form, which is referred to as STGD1. STGD1 is caused by mutations in the ATP-binding cassette, subfamily A, number 4, or ABCA4 gene, which is responsible for making a protein that helps to clear byproducts resulting from the visual cycle from inside photoreceptor cells in the eye.
In an animal model of Stargardt disease, decreasing complement activation lead to rescue of photoreceptors with approximately a 30% increase in the number of photoreceptor nuclei in the transduced area (Lenis et al., 2017). These findings indicate that the inhibition of complement activation may potentially lead to healthier retinal cells which in turn are better capable of processing the visual cycle byproducts in Stargardt disease. There is currently no FDA or EMA approved therapy to treat autosomal recessive Stargardt disease.
Complement Inhibition Rescues Photoreceptors
(High Temperature Requirement A Serine Peptidase 1 Protein)
HtrA1 belongs to the family of serine proteases and is potentially implicated in a range of retinal diseases including geographic atrophy, an advanced form of dry age-related macular degeneration. There is a strong genetic link between HtrA1 and AMD. The overexpression of HtrA1 in retinal pigment epithelial (RPE) cells has been demonstrated in patients with AMD, potentially impacting both RPE cell structure and function. HtrA1 overexpression may impact the Bruch’s membrane and extracellular matrix underneath the RPE cells, as well as the RPE cells themselves, secondarily impacting the retinal cells that are crucial for vision.