In the summer of 1960, the FDA made a decision that would forever change family planning conversations. Enovid, the first oral contraceptive, was approved for sale.
Since then, research has led to the manufacturing of other options like the IUD, NuvaRing and Nexplanon. All of those options are made for women.
When it comes to birth control methods for men, there are really only two options: a condom or a vasectomy.
For nearly a decade, Michael O’Rand’s company Eppin Pharma Inc. has been traveling the long and expensive path of developing a drug that would change all that: a male birth control pill.
O’Rand explained the research that kickstarted it all happened back in 2001, when he was a cell biology and physiology professor at the University of North Carolina at Chapel Hill.
“We published a paper in Science Magazine about immunizing male monkeys with antigen that we had found, called Eppin, which is a protein on the surface of human sperm. When we did that, the monkeys made antibodies to it and it affected the ability of their sperm to swim,” O’Rand said. “We tested their fertility, and they were infertile. When we stopped immunizing the monkeys with the protein Eppin, their titer dropped, the number of antibodies in their system went down, and they regained their fertility.”
Out of that research, O’Rand said they learned antibodies wouldn’t make a good contraceptive because different people have varying responses to immunization. Instead, Eppin Pharma has worked to find a molecule that would replace the antibody so it could be more widely effective.
“Instead of the antibody binding to the sperm, and binding to Eppin which is on the sperm, and stopping the sperm from functioning, we decided to replace that with a small molecule. We spent a long time looking for through hundreds of thousands of compounds that would substitute for an antibody,” said O’Rand.
The ultimate goal is to develop a non-hormonal pill for men.
“It costs hundreds of millions of dollars to get a drug to market,” said O’Rand. “As you go down the rabbit hole of developing a contraceptive, it gets darker and darker, and the only thing that brings light is money.”
He said, “It’s not easy to convince somebody that there will be a big market for a male contraceptive. Our feeling is that once we have demonstrated in the phase one clinical trial that it works, there’ll be a lot more interest.”
O’Rand believes younger generations will be more accepting of trying the new birth control method.
“The high prevalence of unintended pregnancies is a significant problem to be solved, and one way to do that is to make family planning a more equal situation in which both men and women can participate,” said O’Rand.
According to Center for Disease Control and Prevention’s National Center for Health Statistics, more than 5.5 million unplanned pregnancies occur in the U.S. every year. According to the United Nations’s sexual and reproductive health agency UNFPA, there were 121 million unplanned pregnancies worldwide in 2021.
The development of a contraceptive for men could have a huge economic impact globally. U.S. federal and state expenditures on unintended pregnancies are estimated at tens of billions of dollars annually. Beyond the wider economics, unwanted pregnancies can also strain personal and family relationships, while interrupting educational and career plans.
In a statement, Planned Parenthood South Atlantic told WRAL, “We support any effort to make birth control more available and equitable so that people of all genders can exercise bodily autonomy and fully participate in family planning. Every person should have the opportunity to control their sexual and reproductive health and choose a birth control method that works best for them.”
A male version of ‘the pill,’ minus hormones and side effects
O’Rand said, “Females have lots of choices, but they’re all basically hormonal of one sort or another. Lots of women cannot take the hormonal contraceptive, or they don’t want to take it. So, having a non hormonal contraceptive would alleviate some of those problems, and it would also make men part of family planning.”
With no pharmaceutical birth control options for men that parallel “the pill,” women currently shoulder a greater degree of responsibility in avoiding unplanned pregnancies, explained O’Rand. Yet, Eppin Pharma’s lead drug candidate—a safe, non-hormonal oral male contraceptive pill—could bring greater balance, options and flexibility for everyone.
“For us, that’s an important point because having a couple in a stable relationship, they could both take part in family planning,” O’Rand said.
The drug’s non-hormonal makeup has significant advantages over other hormonal male contraceptive technologies, including topical gels or creams, that are also being developed. “Giving excess testosterone or some combination of progestin to men may have implications for their long-term health,” said O’Rand.
“If you’re going to use hormonal contraception on men, then you have to stop sperm from being made, which takes several months to halt the process. And, if you change your mind and want to restart, you have to wait another month or more to get the engine back up and working—to get spermatogenesis turned on again. So, in addition to the hormonal side effects that may occur, there are drawbacks to stopping spermatogenesis that may not be attractive to people.”
Unlike hormonal options, Eppin Pharma’s drug candidate is designed to act rapidly and be readily reversible with little-to-no side effects because it works on mature sperm. O’Rand said that, based on initial primate studies, data shows that the drug goes into effect within six hours or sooner and only lasts for one or two days, which could offer greater flexibility for short- and long-term use. “This could be an on-demand contraceptive, where one day you choose to take a pill or not,” he said. “But we think that the market will be men who find it easier to just take a pill every day, whether they need it or not. Just like women have a wheel of pills, men could have the same option of taking a pill as part of their daily routine.”
Groundbreaking research sparks go-to-market plans
O’Rand, a pioneer in reproductive biology who established the in vitro fertilization laboratory at UNC Hospital and led efforts with the first “test tube” baby conceived in North Carolina, launched Eppin Pharma when his lab at the medical school became interested in exploring the effects of drugs on male fertility.
“As a faculty member at the School of Medicine, our lab research was funded by NIH grant money, and I wanted to start exploring problems that dealt with how drugs influenced fertilization or activated a particular pathway, for example,” said O’Rand. “These were not, as NIH considered, basic science problems but rather more practical problems. We had good ideas about contraception but needed to fund our laboratory. So, we formed a company that could apply for NIH SBIR and STTR grants. So, it was funding for the research that prompted the formation of a company.”
O’Rand’s lab identified a class of compounds that could serve as potential contraceptive drugs. The company worked with the UNC Office of Technology Commercialization to file a patent on its compounds, taking advantage of the Carolina Express License Agreement. The license agreement is designed to help make the licensing process for faculty- and employee-founded startup companies more efficient by shortening the negotiation timeline and minimizing legal costs for young ventures.
“The key thing in dealing with UNC was the Carolina Express License Agreement,” said O’Rand, who said that the University owns the patent on the intellectual property, which is licensed to Eppin Pharma. “When Carolina does an express license, there’s a lot of money saved by the company, so we got a special deal with the express license agreement.” O’Rand said that the technology is protected by patents in the U.S., Canada, Europe, and India. Patent protection in China may be next, he said.
By 2018, Eppin Pharma had gained enough traction with grants that it used one of its STTR grants and funding from the North Carolina Biotechnology Center to conduct a study in conjunction with the Oregon National Primate Research Center.
“We gave monkeys some of our drug and then collected sperm and looked at them. Sure enough, we noticed the motility change,” said O’Rand. “That study was the main impetus to go ahead and develop this drug, because once we realized that it would have this effect in primates, then we could chart our course to the market.”
Path to impact: Lessons from Eppin Pharma’s entrepreneurial journey
Some of Eppin Pharma’s earliest funding came from the KickStart Commercialization Grant-Award Program, funds issued by Innovate Carolina’s KickStart Venture Services team. Innovate Carolina is UNC-Chapel Hill’s central team for innovation, entrepreneurship and economic development, and the awards granted by its KickStart team help early-stage companies meet early commercial milestones. Following the KickStart grant, Eppin Pharma focused on the federal SBIR/STTR grants programs, which fund small businesses focused on scientific and technological innovation.
Eppin has received SBIR Phase 1 and 2 grants as well as STTR Phase 1 and 2 grants. SBIR grants are for small businesses to engage in federal research and development, while STTR grants require collaboration between small businesses and research institutions. The company also participated in the One North Carolina Small Business Program, which awards matching funds to North Carolina businesses that receive federal SBIR or STTR grants. In 2019, Eppin Pharma also received a $75,000 Small Business Research Loan from the NCBiotech.
In 2023, Eppin Pharma received an investment of up to $800,000 investment from the Male Contraceptive Initiative (MCI) to fund a proof-of-concept study of its drug candidate. The startup previously received a $300,000 grant from MCI in late 2019. “The grant system is great, but eventually you need more money than a grant can give you. And that’s where MCI comes in, because they were willing to make some investments that were over and above what we could get from an NIH grant,” said O’Rand. “MCI is a very important vehicle for the development of male contraception, and their investment has enabled us to move further toward our goal.”
Eppin Pharma has a few more FDA requirements to fulfill before it is ready to begin a phase one clinical trial. The larger concern is finding the necessary funding. O’Rand estimates it will take a few million to get a clinical trial up and running. If the company receives the funding it needs, it says it is possible a clinical trial could begin by the end of 2025.
Note: This story includes reporting from UNC’s Innovate Carolina publication.