June 22, 2024

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Optogenetic Ophthalmic Gene Therapy: Preclinical Data Misses Expectations

Optogenetic Ophthalmic Gene Therapy: Preclinical Data Misses Expectations


Optogenetic Ophthalmic Gene Therapy: Preclinical Data Misses Expectations

Recently, Vedere Bio II , an American eye disease gene therapy start-up company , announced that it has decided to stop operations after comprehensive consideration because it failed to meet the predetermined test standards in preclinical trials.


Vedere Bio II chairman, Atlas Venture partner Kevin Bitterman , and company CEO Cyrus Mozayeni wrote, “We set a relatively high bar for treatment methods and conducted extensive preclinical efficacy studies to determine whether we can break through this. standard. Based on the results of the research we have obtained so far, we have made the difficult decision to cease operations.


This is a nearly 2-year-old biotech company headquartered in Cambridge, Massachusetts, focused on developing gene therapies for ophthalmology through optogenetics . At the same time as its official debut in May 2021, the company announced that it has received $77 million in financing from investors including Atlas Venture, Mission BioCapital, and Foundation Fighting Blindness. In September 2020, its predecessor, Vedere Bio, was acquired by Novartis with an upfront payment of $1.50 and a subsequent milestone payment of $130 million.


Optogenetic Ophthalmic Gene Therapy: Preclinical Data Misses ExpectationsSource: Vedere Bio II official website


Kevin Bitterman and Cyrus Mozayeni also mentioned in the statement that the team members believe that the decision based on the trial data is in the interests of patients and investors.


It is worth mentioning that Novartis’s spokesperson stated in an email to foreign media that Novartis is still advancing the preclinical gene therapy candidate pipeline and technology acquired from Vedere Bio in 2020, and the products under research are in the preclinical development stage.



UCB Professor Lianchuang, the predecessor was acquired by Novartis within 1 year after its establishment


Founded in 2019, Vedere Bio is focused on developing gene therapies to treat different types of blindness, including congenital and acquired blindness. Its underlying science is based on research in the labs of Ehud Isacoff and John Flannery at the University of California, Berkeley (UCB) .


Ehud Isacoff , professor of neurobiology in UCB’s Department of Molecular and Cellular Biology and director of the Helen Wells Institute for Neuroscience, has expertise in neuronal chemistry, electrical signaling, and the development of optical neurotechnology to observe and remotely regulate brain cell activity Deep; John G. Flannery is Professor of Optometry and Vision Sciences, Professor of Neurobiology in the Department of Molecular and Cellular Biology, and Deputy Director of the Helen Wills Neuroscience Institute. His research focuses on retinal degeneration, AAV gene treatment and for vision restoration by means of optogenetics.


Optogenetic Ophthalmic Gene Therapy: Preclinical Data Misses ExpectationsLeft: Prof. John G. Flannery, right: Prof. Ehud Isacoff (Source: UCB official website)



In 2019, Ehud Isacoff and John G. Flannery’s research group collaborated to deliver the photosensitive protein receptor gene into the vitreous humor of blind mice, successfully making 90% of the ganglion cells of blind mice sensitive to light, and helping blind mice return to normal level of mice.

Based on this research, the established start-up company Vedere Bio restores retinal vision through optogenetics. The specific working mechanism is to deliver naturally occurring light-sensitive proteins to specific retinal ganglion cells through AAV, stimulate target cells to perceive information and The information is transmitted to the visual processing center of the brain.

The approach could restore vision in patients by bypassing the loss of functioning photoreceptor cells in retinal degeneration, the loss of function of the photosensitive nerve layer at the back of the eye.


This way of restoring vision has attracted the attention of Novartis , which believes that the gene therapy method that helps mice see again is likely to have a similar effect in patients who are blind due to inherited retinal diseases.

At that time, Novartis invested a lot of money in the field of gene therapy and regarded Vedere Bio’s treatment as a potential method for the treatment of inherited retinal dystrophy (IRD) .


IRD is a group of inherited retinal diseases characterized by loss of photoreceptor function and progressive vision loss, with strong heritability and high clinical heterogeneity.

These diseases affect more than 2 million people worldwide and often result in complete blindness. At present, more than 270 genes have been associated with IRD, and the existing treatment methods are still relatively limited.


Optogenetic Ophthalmic Gene Therapy: Preclinical Data Misses ExpectationsSource: Journal of Medical Genetics


In 2020, Novartis announced the acquisition of Vedere Bio, which has been established for only one year, for US$280 million, with an upfront payment of US$150 million and subsequent milestone payments of US$130 million.

According to the acquisition agreement, Novartis acquired Vedere Bio’s main projects and novel delivery technologies at that time, including 2 preclinical optogenetics AAV gene therapy projects, light-sensitive proteins delivered to retinal cells and specific glands injected into the vitreous cavity for treatment Related viral AAV delivery vectors.


In addition, there are some technologies that are not included in this transaction. In May 2021, the original leadership team and investors re-formed a new company , Vedere Bio II , based on these technologies and a different preclinical pipeline. Indications to meet needs” and “Potential to overcome the limitations of traditional gene therapy”.

Incubated by Atlas Venture, the company was immediately led by Octagon Capital, and new investor Casdin Capital participated in the investment. The founding investor Atlas Venture also continued to bet, raising $77 million in the first round of financing.


Subsequently, Gabor Veres, head of gene therapy research at BioMarin, a rare disease listed company, joined Vedere Bio II as chief scientific officer. After joining, he was responsible for the development of the AAV platform.




It can target any mutated form of the gene and has shown clinical potential


Vedere Bio II is positioned as a “next generation” ophthalmic gene therapy startup with the goal of developing novel gene therapies that restore and preserve vision, not just slow vision loss, for patients with vision loss due to malfunctioning photoreceptor cells. Most current gene therapies target specific genetic mutations and only slow vision loss.


According to the official introduction, the company’s preferred indications are hereditary retinitis pigmentosa (RP) and geographic atrophy (GA) .

RP is the most common clinical form of inherited retinal disease, a complex group of inherited dystrophies that primarily affect photoreceptor and pigment epithelial function; GA is an advanced form of dry age-related macular degeneration (AMD) , Progressive and irreversible vision loss can result.


Based on the “mutation -agnostic ” optogenetics platform, the company plans to develop gene therapy methods for hereditary retinitis pigmentosa and geographic atrophy that are not restricted by specific genetic genes .

In the case of hereditary retinitis pigmentosa, a disease caused by mutations in more than 50 genes, the company’s approach works for many, if not all, mutated forms of hereditary retinitis pigmentosa.


As mentioned above, the preclinical product acquired by Novartis is a one-time gene therapy candidate pipeline relying on 11-cis-retinal (11-Cis-Retinal) , which works by delivering genes expressing light-sensitive proteins in the retina.

Vedere Bio II’s treatment project is an improved GPCR-based system, including gene therapy and small molecule drugs injected into the eye.

Officials claim that this treatment has the potential to restore vision more efficiently than previous projects.


Optogenetic Ophthalmic Gene Therapy: Preclinical Data Misses ExpectationsSource: UCB official website


Specifically, gene therapy delivers a G protein-coupled receptor (GPCR) that regulates cellular function and signaling into the vitreous humor of the eye, which itself is not responsive to light; however, when gene therapy is combined with small molecules Once the compound binds, the gene therapy becomes light-responsive, with the small molecule acting as a photoswitch and changing shape in response to light, which is then signaled through the GPCR.

This approach does not rely on light-sensitive proteins in the body, such as 11-cis-retinal, so this approach may be more effective in patients who lack this type of protein.


Cyrus Mozayeni pointed out that different small molecules respond to different wavelengths of light, and we can improve the treatment of small molecules through continuous optimization. In addition, patients can make adjustments according to the actual situation, stop or continue to take small molecules.


Initially, the treatment did show promising clinical potential. Vedere Bio II presented preclinical data on its AAV capsids at the 2022 annual meeting of the American Society for Gene and Cell Therapy, saying that these AAV capsids have “very high transfection efficiency” in the retina.

In a mouse model of retinitis pigmentosa, the company’s technology platform and therapies were able to restore visual function, helping blind mice return to the level of vision seen in normal, non-defective mice.


Cyrus Mozayeni said the data are very promising signs for the company’s science.

Not only does it increase the likelihood of success for a company-led project, but it also improves the ability to build a pipeline and prepare and produce high-quality vectors.


At that time, the company stated that it would use the A-round financing to promote the IND application of the leading product.

However, with the further advancement of preclinical trials, the candidate products did not meet the predetermined test standards, and the management team made the decision to shut down the company.







1. https://www.biopharmadive.com/news/vedere-bio-biotech-shut-down-optogenetics/646599/
2. https://www.reuters.com/article/us-vederebio-ma-novartis-idUKKBN27E0QW
3. https://news.berkeley.edu/2019/03/15/with-single-gene-insertion-blind-mice-regain-sight/
4. https://www.prnewswire.com/news-releases/vedere-bio-ii-presents-positive-new-data-supporting-its-proprietary-platform-at-the-25th-annual-asgct-meeting- 301550552.html

Optogenetic Ophthalmic Gene Therapy: Preclinical Data Misses Expectations

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