The Population Council, Inc.

YCT-529 is the first contraceptive of its kind to be tested in humans. Women have long shouldered the burden of birth control. Now, men may soon have an option that is not only hormone-free, but also allows space between doses.  YourChoice Therapeutics on June 4 at the BIO International Conference in San Diego will share phase 1a data on 16 subjects showing that doses of their drug YCT-529 are safe for men. The figures also hinted at the possibility that the drug’s half-life might make it possible to spread doses out by as much as two weeks—an attractive idea given that some in the industry have expressed doubt that men would be willing to take daily pills, co-founder Akash Bakshi told Fierce Biotech Research. “I think one clear ‘aha moment’ for us is that we might have an extended half-life at each dose, that compliance might not necessarily be an issue,” he said. “Therefore, this is something that improves the health and well-being of women, too.” Bakshi and Nadja Mannowetz, Ph.D., started YourChoice in 2018 with the goal of giving women a hormone-free way to prevent pregnancy. After licensing a drug called niclosamide from the University of Minnesota, they shopped their idea around to investors to get it off the ground. But there was little interest.  Then the pandemic hit—and niclosamide, which also happened to have antiviral activity, turned out to be a better fit for COVID-19 than contraception, at least in the eyes of would-be financiers. They repackaged it under a spinout, ANA Therapeutics.  “[ANA] outraised the contraceptive company four-fold in less than three weeks,” Bakshi recalled. “It was the same team, the same drug, just a different indication.” ANA was acquired by NeuroBo Pharmaceuticals in 2020, leaving Bakshi and Mannowetz back where they started. Given how challenging it was to raise money for a new contraceptive for women, they decided to pivot to a different solution: a nonhormonal, reversible, oral contraceptive for men developed by the same University of Minnesota scientist who’d created niclosamide, Gunda Georg, Ph.D. It's a busy time in the world of male contraceptive drugs, which after decades of development have begun to make serious strides in the clinic thanks to investments from institutions like the National Institutes of Health's Contraceptive Development Program and nonprofits like the Male Contraceptive Initiative. Just a day before YourChoice presented its data at BIO, Population Council researchers shared that a hormone-based male birth control gel called Nesterone was safe and effective in a 222-subject phase 2 trial.  Nesterone works like most birth control drugs under development for men: It reduces sperm production by altering testosterone levels. While an effective approach, adverse effects have stopped earlier trials of testosterone-based contraceptives before they make it to large-scale studies.   YCT-529, in contrast, doesn’t act on hormones at all. It blocks retinoic acid receptors in the testes that are involved in sperm production and thus has a lower likelihood of side effects.  “Men need more birth control options, and they need more than one … we won’t clearly know the advantages of hormone-free versus hormone-based options until we have large-scale clinical studies,” Bakshi said in a follow-up email to FBR. “What’s fundamental is that we deliver several new options for men. Women have borne the burden of hormonal birth control for too long." An opportunity for options   Though it's still too early to say whether YCT-529 has efficacy in humans, preclinical data in mice, dogs and primates showed that the drug was safe, up to 99% effective and reversible. YourChoice is now in the process of launching a phase 1b trial, which will look at the safety and pharmacokinetics of multiple doses, and plans to complete it by early 2025.  The company has enough runway to get through 2026, which takes YCT-529  through early safety studies and perhaps initial efficacy tests as well, according to Bakshi. The team in 2022 closed a $15 million series A led by Future Ventures. New funds raised will be spent on commercializing the drug.  They might also go toward Bakshi and Mannowetz’s original vision of a non-hormonal female contraceptive. Though YCT-529 does ultimately help ameliorate the problem they set out to solve, there’s enough room in the market for both, Bakshi said. If successful, the drug might even drum up interest in non-hormonal female birth control.  “I think male contraception seems to be one mechanism to suggest to the market that this is an opportunity by which we can change the contraceptive landscape,” he said. “And I hope it also poses a question: If men get a non-hormonal pill before women do it, where's the hormone-free pill for women?” Editor's note: YourChoice first presented its data at BIO, not at the Endocrine Society's meeting as an earlier version of this article stated.