Founded in 2014, Eppin Pharma Inc. could soon revolutionize the pharmaceutical industry with an investigational non-hormonal male birth control.

Dr. Michael O’Rand, a retired professor from the University of North Carolina at Chapel Hill School of Medicine and reproductive biologist, created Eppin Pharma after 35 years of experience of studying human fertilization and sperm function.

O’Rand established the in vitro fertilization laboratory in the UNC School of Medicine’s North Carolina Memorial Hospital and created the first “test tube” baby in North Carolina.

O’Rand also spent a large part of his career attempting to create a long term vaccine that would prevent pregnancy. While his team did not find a permanent vaccine, they discovered the importance of a sperm protein that may play a role in the next generation of birth control – EPPIN.

EPPIN and anti-EPPIN, its antibody, are proteins found only in the testis that, when combined, allow sperm to be motile. In 2010, O’Rand and his team created a 3D model of EPPIN to find an organic molecule that could prevent the pairing of EPPIN and anti-EPPIN. The result was an organic molecule compound, called EP055, that replaces anti-EPPIN and prevents sperm motility.

“We designed a molecule that would, in fact, replace the antibody so it sits in the same binding area the antibody binds to,” O’Rand said. “But as a result of that binding, you get the same effect. That is, the sperm stops swimming forward.”

In April 2018, O’Rand and his team published a proof-of-concept study examining the effect of EP055 in male macaques in PLOS. They found that the macaques showed no indications of normal sperm motility 30 hours after receiving a high dose of EP055 through intravenous infusion. The primates showed full recovery in sperm motility in 18 days with no side effects.

Birth Control on Demand

Eppin Pharma is currently creating an oral formulation of the drug to make the non-hormonal birth control more commercially accessible.

“This is sort of a routine drug development situation, but it nevertheless takes time to get that oral formulation just perfectly aligned to what you want and to deliver the dose that you want,” O’Rand said.

Although it will depend on the final version of the oral formulation, according to O’Rand, the team’s goal is that men will be able to take the pill whenever they feel they need it.

“Our goal is that they could take it every day if they wanted to,” he said. “Just like a female contraceptive, just take one every day and then you’re safe. But on the other hand, perhaps a different individual might only want to take it when he felt like he needed it, you know, an on demand sort of thing.”

The responsibility of birth control has traditionally fallen on women, but recent surveys have shown that men, particularly younger generations and those in committed relationships, are willing to try new forms of contraception.

A 2017 study from Zava, for example, showed that 70 percent of men would be willing to take birth control despite potential side effects. Eighty-one percent of men believed that both partners are responsible for birth control.

“Our findings are that most young men, particularly if they’re in a committed relationship, are more than happy to take birth control pills and be supportive of family planning in that situation,” O’Rand said.

Looking to the Future

Once the oral formulation is finalized, Eppin Pharma will have to perform safety pharmacology testing to ensure that the drug is pure and safe for future clinical trials.

“There are different phases of a clinical trial, but to get approved for human trials, you need to prove that it is safe and that there is some kind of suggestion that it might be effective,” said Benjamin Oglesby, a project coordinator at IQVIA.

The company will then have to fill out an Investigational New Drug application, and if approved by the U.S. Food and Drug Administration, it will move on to the first phase of human clinical trials, where O’Rand and his team will test for potential side effects of the non-hormonal birth control.

After testing for side effects in healthy subjects, the drug will move to the second phase of trials. According to the FDA, Phase II is a pilot study that tests the preliminary effectiveness of the drug in the target population. Phase III studies then test the drug with different dosages and larger populations and uses the drug in combination with other drugs.

The clinical trial process is not only timely, but costly.

“It just depends on our funding how fast we can get permission to actually start a trial,” O’Rand said. “And most of that funding that we need is for the safety pharmacology [testing]. It’s very expensive to do this.”

Eppin Pharma has been funded in the past with various grants and loans, including a startup grant from UNC’s KickStart Award Program and a research loan from the Biotech Center, but timelines and expenses in drug trials can be unpredictable.

“Taking a drug to market costs between 2 and 3 billion from start to finish,” Oglesby said.

The cost to bring a new drug to market, from preclinical research to final FDA approval, increased 145 percent from 2003 to 2014, according to a study from the Tufts Center for the Study of Drug Development.

Startups often rely on larger pharmaceutical companies to fund their projects, but contraceptives are treated differently, according to O’Rand.

Small companies like Eppin Pharma often have trouble garnering interest from pharmaceutical giants O’Rand said. Therefore, they rely primarily on grants and loans from private and government organizations.

“Years ago, many of the pharmaceutical companies were doing research in contraception, but as time went along and the market settled into a number of either long acting patch or injection, or the normal, everyday oral birth control, then there was no real money to be made in investing in new research,” O’Rand said.

Despite the lack of investment from the industry, there are a number of organizations that fund research for male contraceptives, including The Gates Foundation and the Male Contraceptive Initiative, a nonprofit that raises money to fund new contraceptives.

Eppin Pharma does not have a clear timeline for the release of its non-hormonal male birth control, but O’Rand continues to look toward the future.

“Hopefully before five years, we’d like to be in in the clinical trial,” O’Rand said. “… It just depends on us getting enough funding to get there. We are always looking for investors and partners to help us get there.”