Vedere Bio bypasses what’s broken to create light in vision loss

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Cyrus Mozayeni, President and CEO of Vedere Bio / Photo courtesy of Vedere Bio

Vedere Bio, a company developing next-generation eye gene therapies, officially debuted this morning with the goal of restoring vision in multiple underserved forms of blindness.

Officially Vedere Bio II, the new company is the successor to the first Vedere Bio, which was acquired through Novartis in September 2020. Novartis has decided to to expand its presence in ophthalmology and strengthen its leadership position in AAV-based gene therapy.

The solid $ 77 million Series A was led by Octagon Capital and the leadership and research team behind the first Vedere Bio.

The new Vedere aims not only to slow vision loss, as is the case with most current gene therapies, but also to restore it to a higher quality with new payloads delivered via adeno-associated virus capsids. (AAV) owners.

Vedere’s optogenetics platform, based on technology created by scientific founders Drs. Ehud Isacoff and John G. Flannery at UC Berkeley, and the improved delivery of ocular gene therapy developed with the School of Veterinary Medicine at the University of Pennsylvania is twofold.

A receptor coupled to a gene protein is expressed in the retina, which then binds permanently to the second component, a synthetic molecule. This small molecule then reacts to light, changes shape and leads to signaling through the receptor that lets the brain know what the eye sees.

The normal human eye contains a photoreceptor which admits light and transforms it into a neuroelectric signal. In most forms of vision loss, this cell dies. Vedere’s approach targets downstream cells which, thankfully, don’t suffer the same fate.

“The cells that are downstream of this defective photoreceptor can survive for many decades and be healthy and viable. They just don’t get any contribution. We use this approach to target surviving cells that do not normally respond to light, and we can convert them to a surrogate photosensitive cell type, a surrogate photoreceptor, ”said Cyrus Mozayeni, President and CEO of Vedere. “Essentially, we’re bypassing the broken part of the circuit and installing this feature where it wouldn’t normally be. “

In preclinical studies using an RD1 mouse, the gold standard for retinitis pigmentosa (RP), Vedere has demonstrated its ability to restore vision-based behaviors.

“We have robust data sets on several behavioral models in these blind mice where we have demonstrated the ability to restore visual function, to the point where at least in the tests we have used to date, they do not differ from wild type animals that have no blemishes, ”said Mozayeni.

Mozayeni has high hopes for translatability.

“Even though the exact architecture of the eye and retina is different from animal to animal, the wiring and fundamental cellular structures involved in vision are very similar from mammal to mammal. We therefore believe that there is a huge translational capacity of this animal model in terms of the likelihood of efficacy. The key is that because the structure is different, you must have capsids that can actually deliver to the target cell of interest. So that’s a big part of what we have, ”he explained.

Mozayeni added that the kinetic capacity of the therapies played a big role in attracting the enthusiasm of founding investors like Atlas Venture and new funders like Samsara BioCapital and Casdin Capital.

“What we have seen is that we are able to restore not only high acuity vision, but also high acuity vision in motion. This is extremely important when we think about the quality of life and the independence of patients. It is one thing to restore sight in a slow moving world or in a static snapshot. It’s already an amazing thing, but if it can do it and make it work in a rapidly changing world, then hopefully a patient can cross a busy street safely, ”he said. .

Vedere’s approach is also unique in that it can treat disease at a later stage of progression.

“With the gene replacement or correction approach that most others use, you’re just trying to change the shape of a decline curve. So you start with reduced vision and try to preserve that reduced vision instead of seeing it get worse. With our approach, we are actually adding a new function, so we are quickly adding a function gain. This means that we can treat the disease later, ”said Mozayeni.

While Vedere begins with RP, his mutation-agnostic approach is linked to a wide variety of inherited retinal diseases (IRDs) that arise from photoreceptor death, as well as other non-hereditary conditions.

A primary target is geographic atrophy, or age-related dry macular degeneration (AMD), which Mozayeni says affects around 5 million people worldwide.

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