YourChoice Therapeutics has announced the publication of groundbreaking research in Communications Medicine, a Nature Portfolio journal, detailing the discovery and development of YCT-529, a first-in-class hormone-free male contraceptive pill that has shown remarkable efficacy in preclinical studies.
The research, led by Dr. Nadja Mannowetz, Chief Science Officer and co-founder of YourChoice Therapeutics, demonstrated that YCT-529 achieved 99% effectiveness in preventing pregnancies in mice within four weeks of oral administration. The contraceptive effect was fully reversible, with fertility returning within six weeks after discontinuation of the drug.
"There's a unique demand for contraceptives that are hormone-free," said Dr. Mannowetz. "With an unintentional pregnancy rate at nearly 50 percent in the U.S. and globally, we need more contraceptive options, particularly for men who have only condoms and vasectomy."
Novel Mechanism of Action
YCT-529 operates through a distinctive mechanism that targets the retinoic acid receptor-alpha (RAR-α) pathway. The drug prevents sperm production by interfering with vitamin A metabolism in the testes, specifically inhibiting the binding of retinoic acid—a vitamin A metabolite—to its receptor. This pathway has been validated by nearly a century of research as essential for sperm cell production.
In non-human primates, YCT-529 demonstrated rapid efficacy, inhibiting sperm production within just two weeks of oral dosing. Full reversal of the contraceptive effect occurred within 10-15 weeks after treatment cessation. Importantly, researchers detected no side effects in either mice or non-human primates during the studies.
Clinical Development Progress
Following successful preclinical studies, YCT-529 has advanced to human clinical trials. The company completed a Phase 1a safety study in June 2024 and is currently conducting a Phase 1b/2a clinical trial in New Zealand. This ongoing study will evaluate multiple ascending doses of the once-daily oral pill in up to 50 participants to assess safety, tolerability, and effects on sperm count.
"As the first hormone-free male pill candidate, YCT-529 is a trailblazer," said Akash Bakshi, CEO of YourChoice Therapeutics. "We made history when we completed the first human study of a hormone-free contraceptive pill in June 2024. A Nature publication in quick succession offers powerful validation that we can build upon with our second human study, which is currently underway and progressing well."
Addressing an Unmet Need
The development of YCT-529 addresses a significant gap in contraceptive options for men. According to research cited by YourChoice Therapeutics, 80% of men feel sole or shared responsibility for pregnancy prevention, yet their options remain limited to condoms and vasectomy. Studies have shown declining condom use, highlighting the need for additional male contraceptive methods.
Recent research also indicates strong demand for novel male contraceptives, with female partners expressing trust in men to use such options. This suggests a potential market readiness for innovations like YCT-529.
Collaborative Development
YourChoice Therapeutics developed YCT-529 in collaboration with Dr. Gunda Georg, a renowned medicinal chemist from the University of Minnesota College of Pharmacy. Dr. Georg leads one of the largest NIH-funded Contraceptive Centers. The Male Contraceptive Initiative (MCI) has provided funding for the early research and YCT-529's Phase 1 clinical trials.
The University of Minnesota's involvement has been instrumental in advancing this research. Their College of Pharmacy released findings that laid the groundwork for YCT-529 to become the first hormone-free male birth control pill to enter clinical trials.
Future Directions
Beyond YCT-529, YourChoice Therapeutics plans to leverage its patented therapeutic platform to develop additional hormone-free family planning products, including options for women. The San Francisco-based company, established in 2018, received a $15 million Series A investment in 2022 to support these efforts.
If successful in clinical trials, YCT-529 could represent a paradigm shift in contraceptive responsibility and options, potentially addressing the high rate of unintended pregnancies while offering men greater reproductive autonomy.
