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Loretto Callaghan, Vzarii Therapeutics

Developing innovative platform gene therapies targeting mitochondrial dysfunction, a hallmark of many neurodegenerative diseases.

What problem are you solving and what is innovative about your approach?

Age-related macular degeneration (AMD) is a neurodegenerative retinal disease affecting up to 10% of adults over 65 years and is the leading cause of irreversible vision loss in this age group. Age is the primary risk factor, although smoking, high blood pressure, a diet high in saturated fat and a family history of AMD also increase the risk of developing AMD.

AMD impacts the macula, the part of the retina responsible for clear vision, colour vision and much of the high-resolution vision we use daily. AMD progresses slowly over three stages: early, intermediate, and late-stage or advanced AMD. There are two forms of late-stage AMD; when central vision is lost; late-stage dry AMD (known as geographic atrophy or GA) and wet AMD (known as neovascular AMD).

There are treatments approved for wet AMD.

However, there are NO treatments for dry AMD or GA.

The initial symptom of GA may be experienced during reading, when one or several letters in a word are ‘missing’. As the disease progresses and central vision is lost, the ability to drive, read, recognize faces, and do close-up tasks is also lost.

The underlying cause of GA is multifactorial, involving multiple converging pathways including mitochondrial dysfunction.

Mitochondria are the site of the cell’s energy production and other metabolic functions. Cells that are high energy users, such as retinal cells, are more susceptible to mitochondrial dysfunction which in AMD contributes to progressive cell atrophy leading to vision loss.

Vzarii Therapeutics is developing innovative platform gene therapies that target mitochondrial dysfunction.

Vzarii’s lead program, aimed at treating GA, has demonstrated robust preclinical proof of concept, with benefits in multiple models of dry AMD, notably providing the first evidence that directly targeting mitochondrial dysfunction in retinal cells can enhance cellular bioenergetics, and provide benefit and improve visual function in dry AMD.

The Vzarii gene therapy technologies are the result of pioneering research from the Farrar team at the School of Genetics and Microbiology, Trinity College Dublin.

How is this idea commercially attractive?

There are currently NO approved treatments for the 5 million people globally (>1 million in the US) impacted by GA. Management focuses on risk factor reduction, use of dietary supplements and assistive technology. A recent economic study estimated the impact of GA in the US at €19.2 billion and in Germany at €3.7 billion and confirmed the significant burden of GA on the individual, those who provide care and support, and wider society.

Vzarii’s lead program aims to address this significant unmet medical need.

What do you hope to achieve by participating in Big Ideas?

The Enterprise Ireland Commercialisation Fund has supported the early-stage pre-clinical development providing pivotal bridging finance for the development of the Vzarii technology.

The team at Vzarii are preparing for spin-out from TCD. Vzarii are excited to be participating in Big Ideas and hopes to connect with potential investors to partner with and support the next stages of development of the Company’s innovative technologies.