University of North Carolina at Chapel Hill: Breakthrough gene therapies in sight

Patients with genetic lysosomal storage diseases – particularly children – are living longer because of better treatments. But with promising advances and longer lives comes complications, the loss of eyesight as these rare diseases take their toll over time.

Lysosomal storage diseases are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body’s cells as a result of enzyme deficiencies, according to the National Organization for Rare Disorders. With these diseases, patients are missing the mucopolysaccharidosis type 1 (MPS1) gene. Current therapies that allow patients to live longer don’t address corneal clouding caused by these diseases. However, one Carolina-affiliated startup, RainBio, is developing a novel gene therapy for MPSI corneal blindness, giving patients a chance not only for longer lives but better ones.

The company’s treatment, RBIO-1, is poised to meet a large unmet medical need in ophthalmology. Co-founded by Matt Hirsch, associate professor of ophthalmology at the UNC Gene Therapy Center, RainBio is the only ocular gene therapy pioneer focused on blindness in the cornea. The company’s adeno-associated virus vector gene therapy can directly correct cornea cellular function to maintain or restore vision in patients at risk of blindness. The company’s first candidate is a groundbreaking, first-in-class lead program for corneal clouding in MPS1 patients who have vision loss.

“As we look at what is being done in the ophthalmology space, we see that most [adeno-associated virus] therapeutics are focused on the back of the eye – the retina, but nobody seems to be looking at the front of the eye – the cornea,” says Fran Martin, RainBio president. “If we can provide those affected with lysosomal storage diseases a mechanism where they can see, they’d be able to have a better quality of life.”

The idea for RainBio’s treatment started less than five years ago, when Dr. Joanne Kurtzberg, a pediatric bone marrow transplant specialist, who conducts stem cell transplants in children with lysosomal storage diseases at Duke, met with Hirsch and Samulski to figure out how to potentially address the blindness that comes with lysosomal storage disease. Kurtzberg works with stem cell therapies that can extend the longevity of life for kids affected but don’t address the loss of sight. Hirsch realized if he could replace the missing gene in the cornea, those kids could regain their sight.

“With our product, you inject the missing gene right into the cornea,” says Martin. “This allows for prevention of corneal clouding or blindness, and can even reverse the blindness or cornea clouding if the treatment is given early enough.”

For kids who are losing their sight, another option is to have a cornea transplant. But those transplants don’t come without risk.

“Corneal transplants can sometimes result in high rejection rates and potential infection,” adds Martin. “We can offer an additional treatment that patients can try before moving to a transplant.”

The RainBio team often collaborates with colleagues at local universities as well as Joseph Muenzer, a professor of pediatric genetics and metabolism at the School of Medicine, who treats children affected by lysosomal storage diseases. Jude Samulski, professor of pharmacology at the Gene Therapy Center in the UNC School of Medicine and a pioneer in gene therapy, also contributed to the patents for the product.

“A lot of expertise in gene therapy was developed over the past few decades at UNC,” says Martin. “That expertise has benefited RainBio, and we’ve benefited from the input into the science around our product as well.”

To make the best use of resources, the RainBio team benefits from collaborating with KickStart Venture Services as well as Carolina’s Office of Technology Commercialization. KickStart supports faculty startup formation, business development and growth by providing coaching and mentoring, early-stage funding, connection with key service providers, management, investors and space. Both KickStart and the Office of Technology Commercialization. are part of Innovate Carolina, the University-wide initiative for innovation and entrepreneurship.

“It’s been a pleasure to work with KickStart and OTC to really get the guidance and resources needed as we’ve grown as a company,” says Martin. “They helped us work through the Carolina Express License and have been very supportive in helping us to understand the process as well as in providing resources as we think through our strategy as a growing company.”

The Carolina Express license assists Carolina startups by streamlining and speeding the path for UNC-Chapel Hill faculty, students or staff startup founders to translate new discoveries into useful products.

Alongside Epigenos Bioscience, the RainBio team also had the opportunity in fall 2020 to present to approximately 20 advisors who gave them advice on how to continue commercializing their technology and growing their business, even in the midst of a pandemic. This is one of the programs that Kickstart adapted online to continue providing support for startups. Advice and guidance offered at advisory meetings includes anything from R&D to fundraising and strategy. Other startup companies that would like to present can get in touch with KickStart to be considered for a future meeting.

In addition, RainBio received a $100,000 loan from NCBiotech as well as support from the MPS Society, which funded a key rabbit toxicology study. RainBio also collaborated with NC State University through co-founder Brian Gilger, who has conducted the toxicology studies at the NC State School of Veterinary Medicine.

And for patients who are ready to try RainBio’s RBIO-1 treatment, Martin says the idea of a one-time dose is promising.

“Although we are still testing the product, what’s also unique about this treatment is that only one dose may be required. In addition, a very small amount of product – around 250 times less – will be needed compared to other treatments on the market for retinal blindness,” she adds.

Although the company only launched in June 2020, RainBio already has pre-clinical efficacy and safety data and is poised to meet with the US Food and Drug Administration.

“Even though we’re not even a year old, we have orphan drug designation and rare pediatric disease designation that was granted to us by the FDA,” says Martin. “We have pre-clinical efficacy in the MPS1 canine model, and 100 percent prevention and reversal of cornea blindness.”

RainBio is developing a platform for additional treatments for blinding corneal diseases.

“There are several Lysosomal storage diseases that have the same cornea blindness issue,” says Martin. “Although it’s a different gene that is missing, we believe as we prove this concept in MPS1 patients, then it will be translatable to other lysosomal storage diseases.”