Gene Therapy Pioneer Reflects Opus Genetics Career and Goals

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01 October 2021

5 minutes to read

Source / Disclosures

Source: Healio Interviews

Disclosures: Bennett claims to have stakes in Opus Genetics.


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Jean Bennett, MD, Ph.D., inventor and co-developer of Luxturna, the first gene therapy approved by the FDA, is now scientific co-founder and sits on the board of directors of Opus Genetics, founded to study gene therapies for rare diseases of the retina.

Bennett aims to use gene therapies to treat ultra-rare diseases with the aim of ultimately targeting diseases with the highest prevalence in the population.

Healio / OSN spoke with Bennett about her career investigating gene therapy and what she sees for the future of Opus Genetics.

Healio / OSN: How did you start to study gene therapies?

Bennett: I got interested long before gene therapy was actually tested in an approved clinical trial. When I was doing my training right after my PhD, it was an exciting time when the technology was starting to be developed to be able to isolate genes and move them, clone them and be able to express them in cells and eventually in animals. So, it was only natural that I and many others had a light bulb that went out saying, “Aha! If you can move these genes, you may be able to move them to treat the disease. It had not been shown that it was possible to pass genes to cells in a living animal at that time. There were a lot of hurdles to jump through, including ways to safely pass genes to target cells, to be able to measure if they’re active, if they’re producing an effect, etc.

That was about 40 years ago, and when I got my first job at the University of Pennsylvania, that’s when I seriously started trying to overcome these various obstacles with my associates. .

Healio / OSN: How has your path taken you from the research and invention of Luxturna (voretigene neparvovec-rzyl, Spark Therapeutics) to where you are now, co-founder and board member of Opus Genetics?

Bennett: Much of my work has revolved around the eye and, in particular, the retina. From my earliest days, I was trying to find ways to pass genes to the retina in living animals with the goal of ultimately using them to treat blindness.

We had our first big success around 2000 when we applied what we had discovered about how to pass genes to the retina. We had cloned them, and we had developed the recombinant viral vectors, which we used to deliver these genes, and showed that they were safe for animals. My collaborators had three dogs born with congenital blindness similar to Leber congenital amaurosis in children. We had isolated the normal version of the gene that, when mutated, caused this disease in the puppies. We decided “let’s try this on these three animals” and lo and behold, there were dramatic improvements in vision in these puppies. It was so exciting to see these blind dogs see, and of course the natural question was, “Wouldn’t it be great to see blind children see?”

This led to various phases of clinical trials by our group, and there were a few others who were doing contemporary clinical trials for the same disease. We ended up going through the different phases of clinical trials and then getting FDA approval for Luxturna in 2017. We developed the path of gene therapy for blindness because there was no path before. We had to develop this ourselves using the advice of the FDA. It is now natural to say, “How can we use our experience to develop treatments for other blinding diseases?” “

Healio / OSN: Can you break down the goal of Opus Genetics?

Bennett: If I had to sum it up, it would be to develop a simplified way of developing interventions for genetic blindness. To expand further, we are selecting some of the more overlooked forms of inherited blindness that large pharmaceutical companies would not traditionally touch because they are ultra-orphan (extraordinarily rare), while also creating new orphan scales and manufacturing efficiencies. We aim to conduct these studies, hopefully helping people with congenital Leber 5 amaurosis, but also in the process of derisking this type of approach so that we can treat many more people with primary illnesses. photoreceptors.

Healio / OSN: Can you explain the importance of researching therapies for these rare but devastating diseases?

Bennett: These are devastating illnesses, and we want to help patients and their families, who are living a normal day. Helping families is a major objective; However, we also want to be able to use this experience to develop therapies for other blinding diseases more quickly. The diseases we aim to target are among the most serious because they affect babies and young children. There are many other forms of blindness which are not as serious but which rob people of their vision. Perhaps even worse, they deprive them of their vision after enjoying the vision and become addicted to it, which is therefore psychologically damaging as well. I am thinking in particular of retinitis pigmentosa. If we can show that we can tackle the problem in one of the more serious diseases, I think it will pave the way for the fight against blindness caused in much more prevalent conditions such as retinitis pigmentosa.

Healio / OSN: Two currently announced therapies are in development and should enter clinical practice. Can you detail how they work?

Bennett: Like the target we initially worked on, these diseases all have a common denominator that mutations prevent the production and / or proper functioning of the protein encoded by the gene. So, there is a missing protein or a defective protein that causes the disease. We use the simpler approach to gene therapy in that we deliver a normal copy of the gene responsible for the disease in the hope of replacing the missing function. There are more complex approaches to gene therapy, some of which are currently being tackled by other groups, for example, gene editing, in which the goal is to enter and splice the correct DNA sequence to a specific location. We selected our target diseases because it is clear that the lack of function of that particular gene or protein is the cause. We think this is a logical solution.

Healio / OSN: What are the next steps in your research?

Bennett: I continue to try to develop a pipeline that will allow us to move forward and gradually abandon other strategies for gene therapy. We are thinking about metabolic diseases that affect the retina and how we could intervene with them and also about strategies that could be generic, where we do not have to deliver a specific gene for each disease. For example, maybe there is a gene that controls a metabolic pathway that could ameliorate disease in a multitude of conditions caused by different genes.

Healio / OSN: What are the next steps for Opus Genetics?

Bennett: Now that Opus Genetics is formed, the real work begins. We will team up and establish timelines to move forward efficiently and safely to launch and execute our clinical trials quickly, and perform natural history studies in complementary ways to support potential future regulatory submissions. We basically put all of these parts together and make them work together.

Healio / OSN: Do you have anything to add?

Bennett: I am grateful to the Foundation Fighting Blindness, the RD Fund, and the funders and partners of this new venture for making this possible. Opus is the first spin-off company designed and launched in-house by the RD Fund, and led by industry and business experts Dr. Ben Yerxa, Dr. Rusty Kelley, Peter Ginsberg and Jason Menzo to advance the mission of the foundation. They are trying to stimulate the development of therapies for these rare diseases, and this is a new approach built by and for patients. I think they should be accredited pioneers in this space to move the accelerator forward to develop treatments for these devastating conditions.


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