Eppin Pharma Developing Male Birth Control Pill

As a professor studying fertilization at the University of North Carolina at Chapel Hill in the early 1980s, Michael O’Rand, Ph.D., was involved in producing the first test-tube baby conceived in North Carolina through the then-new technique of in vitro fertilization, the joining of sperm and egg in a glass container.

Now, almost four decades later, he may be on track to make reproductive history again, this time as an entrepreneur who is developing what would be the world’s first non-hormonal male contraceptive pill.

As founder, president and chief executive officer of Durham-based Eppin Pharma, O’Rand is pursuing a contraceptive that he says would be “a brand new choice for men and also very helpful for family planning, for men and women.”

Men currently have only three options for contraception – condoms, vasectomies and withdrawal – and all have downsides. The burden of contraception often falls on women, who have more options but all with drawbacks too.

Drug candidate disables sperm

Eppin, a spinout of UNC, is developing a small organic compound called EP055. The molecule binds to a protein called EPPIN – an abbreviation for epididymal protease inhibitor – that’s found on the surface of sperm cells and is essential to sperm’s motility. EP055 electrically hyper-polarizes a sperm cell membrane, disabling the sperm’s normal functions. 

“The sperm can’t swim forward, and it can’t capacitate, and it can’t undergo the acrosome reaction, so it can’t fertilize (an egg), O’Rand explains. 

Capacitation refers to the physiological changes sperm must undergo in the female reproductive tract so they can penetrate and fertilize an egg. The acrosome reaction is the fusion of sperm membranes, allowing the sperm to join with the egg and the genetic material of both cells to combine, resulting in fertilization.

Proof of concept demonstrated

A recent study of EP055 in male rhesus macaques – a species of Old World monkeys – demonstrated the compound’s proof of concept. Thirty hours after receiving a high-dose intravenous infusion of EP055, the animals showed no indications of normal sperm motility. Eighteen days after the treatment, all of the monkeys completely recovered their sperm motility, suggesting that EP055 is reversible. No side effects were apparent throughout the study.

The research confirmed that EP055 stays in the bloodstream for only 10 to 12 minutes and “goes right to the target and sticks there” for about three days, O’Rand says. “That’s why we say this could be a possibility for an on-demand contraceptive. It could also be a contraceptive that a man could take daily and simply build up a reservoir of blocked target.”

The monkey research, funded by the National Institutes of Health and in part by a loan from the North Carolina Biotechnology Center, was conducted by O’Rand and collaborators in the Oregon National Primate Research Center of Oregon Health and Science University. The results were published April 19 in PLOS ONE, an open-access, peer-reviewed science journal.

Further R&D needed

Despite the encouraging study results, Eppin must complete “a very long list” of tests and development milestones before men might begin taking EP055 as a contraceptive one day, O’Rand says.

First is the technical challenge of developing a pill or capsule formulation of the compound that can be taken orally and that can survive the stomach’s acidic environment. The formulation must be able to deliver the drug intact to the small intestine, where it can be absorbed into the bloodstream and find its way to sperm in the epididymis, the coiled tube where sperm are stored, and in the testes, where sperm are produced.

“Once we have our oral formulation work done, we will again test it in monkeys and this time ask the question, is there a contraceptive effect, by actually mating the monkeys who are on the pill,” O’Rand says.
Eppin must also complete a litany of toxicology, dosing and safety tests.

“We have to raise money in order to go through all these events,” O’Rand says. 

Grants, loans fund work

Thus far, the 4-year-old company has relied on state and federal grants and loans to advance its research and product development. In addition to receiving two Small Business Technology Transfer grants from the National Institutes of Health, Eppin has scored a matching grant from the One North Carolina Small Business Program, a startup grant from UNC’s KickStart Award Program and a Small Business Research Loan from the Biotech Center.

“I think it’s important that NCBiotech gets credit for helping us get started,” O’Rand says. “Their research loan was critical for us to get going . . . before we got our NIH money.”

To continue advancing EP055, O’Rand says Eppin will need additional funding and likely collaborations with other companies involved in reproductive health.

“We just have to look at anything that’s out there and at people who are interested in male contraception,” he says. “It just takes time, and we’re going as fast as we can go given our funding.”

If successful, the company’s preclinical work would likely qualify EP055 for Investigational New Drug (IND) status with the U.S. Food and Drug Administration, the company’s main goal. Approval of an IND application would authorize clinical trials for determining the drug’s safety and effectiveness in humans.

If all goes well, a commercial launch would likely be five to 10 years away, O’Rand estimates.

Relocation to Durham

Eppin recently moved from leased labs at UNC to BioLabs North Carolina, a co-working facility for life science startup companies, in downtown Durham.

“It’s a really nice place, very supportive of startups,” O’Rand says. “They have a lot of shared equipment and help for finding investors and things like that. I have to give them credit for allowing us to relocate there.”
O’Rand, who retired from UNC when he started Eppin Pharma in 2014, is joined in the enterprise by Jeff Handler, Ph.D., chief operations officer and board member; board member Zahed Subhan, Ph.D., M.B.A., J.D., a professor of entrepreneurship and innovation at Drexel University; and Katherine Hamil, senior director of operations.