Startup Ocunova tests new use for overdose drug

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The firm, Ocunova, formed around research by scientists at Penn State University College of Medicine on uses of the drug naltrexone. The drug is mostly known for helping addicts fight off opioid and alcohol dependencies, but researchers at the university found it could also help diabetics with dry eyes, a common yet persistent symptom of the disease.

Ocunova recently received a $500,000 joint investment from Life Sciences Greenhouse of Central Pennsylvania and Ben Franklin Technology Partners. The investment is meant to help the company pursue clinical trials in humans later this year in pursuit of approval by the Food and Drug Administration.

Dr. Ron Thiboutot, executive vice president of Life Sciences Greenhouse, said the Harrisburg-based economic development entity usually stays with a company like Ocunova through the FDA approval process and up to acquisition.

One of the lead reasons the company was attractive to Life Sciences Greenhouse is the potential market for its use of naltrexone on people with diabetes. According to a report issued last summer by the Centers for Disease Control and Prevention, over 30 million Americans currently have diabetes.

“When they came to us, it seemed like this is a tremendous opportunity. It’s for a big unmet need because dry eye is a very, very, very big disease in the U.S.,” said Thiboutot.

Those with diabetes frequently develop a chronic form of dry eye syndrome, or DES. The disorder leads to pain, itchiness, discomfort and blurred vision. According to a 2008 study published in the journal BMC Ophthalmology, 54 percent of people with Type 2 diabetes — the most prevalent form of the disease — suffer from dry eye syndrome.

Current methods of treatment include over-the-counter eye drops and expensive anti-inflammatories that offer only temporary relief. Naltrexone, as used by Ocunova, could reverse dry eye symptoms altogether.

Researchers first explored naltrexone as a way to encourage wound healing in diabetics, particularly wounds to the cornea on the very front of the eyeball.

“The skin of the eyeball is only about five cells thick and it sticks down onto the cornea, the clear part of the eye. In diabetics, [the skin] can wipe away very easily and it heals very poorly. So we were looking initially to heal those abrasions,” said Dr. Joseph Sassani, a professor of ophthalmology at Penn State.

Sassani is one of a trio of Penn State researchers who have been investigating several symptoms of diabetes, including wound healing, for the last 20 years. Alongside him are Patricia McLaughlin and Ian S. Zagon, both professors at the College of Medicine in Derry Township.

In 2008, the team was conducting trials on diabetic rats when they noticed eye drops of naltrexone were helping the animals create more tears and reduce their dry eyes.

“We were adding it to the rats at eight in the morning, noontime, four in the afternoon, that kind of regimen. The reversal of the dry eye — or the normal tear production — lasted up to a few days,” said Patricia McLaughlin.

It wasn’t until 2016 that the use of naltrexone to treat dry eye in humans entered its first clinical trial with human subjects, known as phase I testing. The initial trial, known as a “tolerability test,” was not conducted on subjects with diabetes.

“They put on accelerating doses of the naltrexone formation, and simply saw the people were able to tolerate it. Their eyes didn’t turn red, there wasn’t excess tearing,” said McLaughlin

The clinical trials, however, were not conducted by any of the original three researchers. Because they are the inventors on the patent for naltrexone, their involvement in the clinical trials would have represented a conflict of interest, said Sassani.

To mitigate that risk, the university sought out a fourth researcher — assistant professor of ophthalmology Dr. David Liang — for phase I trials. Ocunova is currently looking for another independent researcher to conduct phase II trials.

The researcher needs to be someone without “an intellectual or a financial interest in seeing this be successful,” said Sassani.

In December 2016, the trio was presenting the results of their research at conference in Philadelphia when they came to the attention of Mike Shine, a veteran of the pharmaceutical industry who has developed a number of companies based on university research.

“I offer my services for academics who are looking to advance their technology in the commercial marketplace,” said Shine, now CEO of Ocunova.

One of the drugs Shine had worked with at a previous company was methylnaltrexone, a compound roughly similar to the naltrexone used in research by the Penn State team. Shine believed his experience with the drug made him a perfect fit for the technology.

After speaking with the researchers and Penn State, Shine formed Ocunova LLC in February 2017, licensing the patented use of naltrexone from Penn State.

According to Erika Swift, associate director at the Center for Medical Innovation at Penn State College of Medicine, a licensing agreement with the university typically shifts the financial burden of the intellectual property to the company.

“If there are any patenting costs, it’s their burden to pay,” said Swift.

The company could also be responsible for milestone payments to the university, made once the technology passes certain trials of its value, such as successful clinical trials.

In June last year, Life Sciences Greenhouse and Ben Franklin Technology Partners submitted a term sheet to cover the grounds for its investment, including the use of the funds for clinical trials.

According to Thiboutot, it’s rare for a venture capital firm to invest in a company like Ocunova at this point in its development. During the clinical trial process, investors have no guarantee the company will ever bring the drug to market and little idea how long they’ll have to wait until it can.

Life Sciences felt much of the risk was offset by the efficacy of the drug, said Thiboutot. Since naltrexone is already FDA-approved for its use against addiction disorders, Ocunova needs only to show it is effective and safe as a treatment for dry eye.

Combined with the relative low cost compared to other treatments for dry eye, Thiboutot feels the company has a relatively secure future.

“These are extremely expensive drugs. The active ingredient, naltrexone, that’s in here is a commodity almost. This would be a tremendous price reduction,” said Thiboutot.

The next step for Ocunova is to take the drug to phase II clinical trials, expected to begin this year. Whereas the initial phase I trial only observed healthy patients for one day for side effects, the phase II trial will observe diabetic patients with dry eye for a month.

Shine estimated the testing and approval process could take between three or four years, but emphasized a number of factors could get in the way.

“It’s caveated with a lot of stipulations related not only to efficacy and safety of the drug, but a lot of other dynamics such as our ability to progress it as a startup company, whether or not we develop partnerships with industry or raise funding for additional rounds on our own,” said Shine.