When it comes to the health and wellbeing of a child, parents will do just about anything. Paul Bresge started a biotech company.
Bresge’s middle daughter, Tamar, was young when her eye problems started. She describes her vision as a tunnel that slowly gets tighter. At 15, she was diagnosed with retinitis pigmentosa, a rare inherited eye disease that causes the retina to slowly deteriorate, leading to a progressive loss of vision. Bresge took Tamar to several doctors. They all said the same thing: She will eventually go blind and nothing can be done.
“I decided I had no choice but to take matters into my own hands, and that’s how I got into the field, by necessity,” said Bresge, co-founder and CEO of Ray Therapeutics.
San Francisco-based Ray is developing a novel gene therapy for retinitis pigmentosa. While the startup’s approach builds on earlier gene therapies, Bresge says Ray aims to accomplish what none of them have done. So far, gene therapies for eye diseases only slow vision loss. Bresge’s goal is to restore sight. His company recently closed $100 million in financing to take its lead program into its first test in humans.
Retinitis pigmentosa stems from genetic mutations that affect the function and structure of photoreceptors, the retinal cells that detect light. The disease is typically first noticed as the loss of night vision in childhood. The vision problems progress to tunnel vision that affects reading, driving, and the ability to recognize faces.
Ray is the second biotech Bresge started to pursue a treatment for retinitis pigmentosa. The first one, Newport Beach, California-based jCyte, is developing a cell therapy that releases proteins intended to reduce photoreceptor death and support the function of the surviving photoreceptors. While Bresge was jCyte’s CEO, the company achieved positive mid-stage clinical data, catching the attention of Santen Pharmaceutical. In 2020, the Japanese drug company licensed rights to the therapy in Japan, Asia, and Europe. The jCyte cell therapy is currently in Phase 3 clinical testing.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
The gene therapy research of Ray and others in inherited retinal diseases stands on the shoulders of Spark Therapeutics. That biotech blazed a path with the 2017 FDA approval of Luxturna, a treatment for vision loss caused by mutations to the RPE65 gene. Luxturna delivers to retinal cells a normal copy of that gene. But there are so many mutations associated with vision disorders, including retinitis pigmentosa, it’s almost impossible to address them one by one, Bresge said.
Ray’s approach is not gene specific. Rather than replace a mutated gene, the biotech aims to restore the ability of retinal cells to respond to light. The science is called visual optogenetics—introducing into retinal cells a gene that codes for a light-sensitive protein. Another company, GenSight Biologics, has already reached Phase 1/2 testing with such a gene therapy for retinitis pigmentosa. In test results in a blind patient, the Paris-based biotech’s therapy led to partial recovery of vision. Results were published in 2021 in Nature Medicine. But in order to see, patients treated with the GenSight gene therapy must also wear goggles that amplify light and stimulate their retinal cells.
Bringing both a gene therapy and an accompanying medical device through regulatory review and commercialization would be challenging, Bresge said. Ray’s one-time treatment, RTx-015, also employs a light-sensitive protein. But Bresge said that by bioengineering the gene therapy to address the complexities of vision, such as visual acuity and contrast sensitivity, no light-amplifying goggles will be required. Ray’s therapy is based on research from Zhuo-Hua Pan, a professor of ophthalmology at Wayne State University. According to preclinical research results published in 2019 in Molecular Therapy, treating mice born blind without functioning photoreceptors led to vision restoration under ambient light levels.
Bresge said that when his daughter was diagnosed with retinitis pigmentosa in 2010, testing was more limited. The doctors could not even identify the genetic mutation driving her disease. That makes it important to develop solutions that are independent of genetic mutations. While jCyte’s research may restore some vision, Bresge said the cell therapy will mainly slow the progression of vision loss in those in early stages of the disease.
“We’re trying to restore vision to patients that are already or almost blind,” Bresge said of Ray’s research. “These are patients that are left behind.”
Ray formed in 2021, raising a $6 million seed round from 4BIO Capital. The startup has also received $4 million to date in grant funding from the California Institute for Regenerative Medicine. The Series A round was led by Novo Holdings. Other investors in the round include Deerfield Management, Norwest Venture Partners, Platanus, MRL Ventures Fund, and the venture fund of Merck & Co. 4BIO Capital also participated.
The Series A cash is enough to support RTx-015 all the way through pivotal testing in retinitis pigmentosa, Bresge said. A Phase 1 study is on track to start soon. The startup’s next disease target is Stargardt disease, a rare inherited form of macular degeneration with no FDA-approved therapies. Biopharmaceutical companies large and small are pursuing Stargardt with various genetic medicine approaches.
If all goes well with Ray’s rare eye disease research, Bresge said the company will expand to more prevalent vision-loss disorders, such as diabetic macular edema and geographic atrophy. Ray’s gene therapy represents a pipeline in a product opportunity. While the cell type targeted by the therapy will change depending on the indication, the genetic cargo will be the same across all of them.
Today, Tamar Bresge is 27. She is an artist and writer with a master’s degree in fine arts. Paul Bresge said Tamar still has good functional vision, but then adds that he’s in a race against time. The father has a deal with his daughter.
“You go on with your life, and I worry about your disease,” he said.
Photo by Ray Therapeutics
