A team of University of Iowa researchers has formed S5G Therapeutics Inc., a startup company designed to move years of research on the antioxidant ubiquinol beyond the laboratory and toward patients. The company, which recently received a Small Business Innovation Research award from the National Institutes of Health, creates a pathway for the researchers to further develop their technology, pursue regulatory approval and, ultimately, manufacture it at a scale that could make it widely available.

For Mark Greiner, MD, Professor of Ophthalmology and Beulah and Florence Usher Chair in Cornea/External Disease and Refractive Surgery, the creation of S5G represents a natural extension of the team's work at Iowa.

"S5G formed because the university said, ‘Okay, you guys have this intellectual property here as investigators on faculty at the university. You've got great idea to bring that to market, now you need to spin off a company,’" Greiner said.

The company brings together Greiner; Jessica Skeie, PhD; Christine Sindt, OD, FAAO; Aliasger Salem, PhD; Greg Schmidt, MBA, CEBT; and former UI graduate student Sanjib Saha, PhD. Together, the group is working to translate a deceptively simple idea, protecting cells from oxidative stress, into therapies that could eventually address several eye diseases.

A discovery in donor corneas

The story behind S5G stretches back years and began not with eye drops, but with donated corneal tissue.

Greiner's laboratory at the Iowa Lions Eye Bank had been studying why some donor corneas were more susceptible to damage than others. That work helped reveal the sensitivity of corneal endothelial cells, which line the inner surface of the cornea, to oxidative stress. Unlike many cells in the body, human corneal endothelial cells do not normally regenerate, so protecting the cells a person has is particularly important.

 In 2016, Skeie and her team received a small grant from Eversight to investigate whether adding an antioxidant to cornea storage media could protect donor tissue during the period between donation and transplantation.

The researchers tested several antioxidants. When they compared donor corneas with ubiquinol added to the storage solution to the standard storage solution, the difference caught her attention immediately.

"The difference was like night and day," Skeie said. "I didn't believe it, so we repeated the whole thing, and it happened again. And that's when I knew this was very important."

Ubiquinol is an antioxidant that can help protect cells from oxidative damage. The team's subsequent research has shown its potential to reduce oxidative stress and maintain the health and function of corneal endothelial cells.

But identifying the molecule was only part of the problem. Ubiquinol is difficult to formulate in liquid. The researchers initially had to use ethanol and heat to make it soluble.  That was an impractical approach for routine eye bank use and an obvious obstacle to putting it directly into a person's eye.

Working with Salem and colleagues in the UI College of Pharmacy, the team developed an aqueous delivery system. The stable, soluble formulation opened possibilities well beyond donor tissue storage.

From the eye bank to the patient's eye

The next leap came from a conversation with Sindt, whose clinical work includes patients who wear contact lenses.

After learning about the antioxidant work, Sindt saw another potential application: Could a soluble antioxidant help protect the ocular surface of contact lens wearers experiencing irritation, dry eye and oxidative stress? The question changed the trajectory of the project.

"We need to make this into drops," Skeie recalls Sindt saying.

Suddenly, a technology developed to protect donor tissue outside the body had the potential to protect corneal cells in patients.

That possibility ultimately helped spur the formation of S5G Therapeutics. The company is pursuing the use of intellectual property developed at the University of Iowa. Currently, Skeie said, S5G has an option agreement with the university while the team works to secure funding and complete pre-investigational new drug research. A future licensing agreement would allow the company to bring the technology to market under terms established with the university.

For the researchers, creating a company provides a mechanism to continue shepherding a discovery they have spent years developing rather than waiting for an outside company to take an interest in the technology.

It also required the scientists to learn an entirely different side of innovation.

Skeie participated in programs through UI Ventures and the university's entrepreneurship ecosystem, including pitch competitions and the National Science Foundation's I-Corps program. As part of that process, she and Schmidt interviewed approximately 100 people to better understand potential customers and where the technology could have the greatest impact.

The experience gave Skeie a new perspective that she now brings back to the laboratory: "Don't make a really cool thing people won't want to buy."

Treating more than symptoms

One of S5G's first potential markets is dry eye disease.

Current approaches to dry eye frequently focus on managing symptoms through artificial tears, gels, warm compresses, and other therapies. The Iowa team's approach is different. Because oxidative stress and inflammation can contribute to the disease process, the researchers hope an antioxidant therapy could intervene in that process rather than simply provide temporary relief.

"If you can fight the inflammation, by reducing the oxidative stress response, you can prevent these symptoms from being persistent," Skeie said. The goal, she added, is to reduce the burden of continually treating symptoms and ultimately improve patients' day-to-day quality of life.

Dry eye is only one potential application.

At Iowa, the researchers are also studying ubiquinol as a potential therapy for Fuchs endothelial corneal dystrophy, an inherited disease in which oxidative damage contributes to the death of corneal endothelial cells.

Skeie said the team's work may ultimately have applications at multiple points along the spectrum of corneal care, including donor tissue, transplantation, dry eye and diseases such as Fuchs dystrophy.

Building a public-private partnership

Now, S5G Therapeutics is adding another source of momentum.

The company has received a six-month Small Business Innovation Research award from the National Institutes of Health. Skeie said the federal award is just over $313,000, with an additional $50,000 in matching support expected through BioConnect Iowa, an economic development program. The project will further help develop a Fuchs-specific delivery system designed to increase uptake of ubiquinol in endothelial cells.

The award also creates a bridge between S5G and the university. Greiner and Salem are supporting the work on the UI side through a subcontract, while Skeie is splitting her time between the university and S5G during the six-month project.

Greiner sees that arrangement as an example of the role public-private partnerships can play in moving discoveries from academic research toward products that can benefit patients.

"This is a commercialization effort, and that’s more nimble on the private side," Greiner said.

The distinction matters because proving that a molecule works in a laboratory is far removed from producing a medicine. Before a therapy can reach patients, researchers must refine its formulation and delivery, conduct additional preclinical testing, navigate the regulatory process, manufacture it consistently and eventually demonstrate its safety and effectiveness in clinical trials.

S5G gives the Iowa team a vehicle for taking on those next steps.

For some applications, such as dry eye, Skeie believes the startup may be able to move development forward itself. Other potential therapies, particularly those designed to deliver antioxidants to cells inside the eye, could ultimately require partnership with a larger pharmaceutical company capable of handling large-scale manufacturing and distribution.

Either way, the objective is the same: turn a discovery made in an Iowa laboratory into something patients can actually use.

For Greiner, that is what makes the creation of S5G significant. It isn't separate from the research taking place at the University of Iowa. It is a potential pathway for that research to make the final journey from discovery to treatment.

"This is public-private partnership at its finest," Greiner said.

And the project still traces back to the same question the team began asking years ago: How can we keep vulnerable corneal cells alive and healthy?

The answer first led them to donor corneas, then to ubiquinol, then to a soluble formulation and potential eye drops. With S5G Therapeutics, the team is now working on the next challenge: figuring out how to turn that science into a treatment that can be manufactured, distributed and, one day, placed into the hands of patients.