YCT-529: New Male Contraceptive Begins Human Trials, Reshaping Family Planning

Non-Hormonal Male Contraceptive Advances to Human Trials, Offering New Paradigm in Family Planning

LONDON, UK - A major milestone in male contraception development has been reached with the successful finish of the initial human trial for YCT-529, a novel non-hormonal oral drug designed to temporarily halt sperm production without affecting testosterone levels. This progress, detailed in Communications Medicine on July 22, 2025, represents a possible paradigm shift in a field long dominated by female-focused options and limited male choices.

The trial, carried out by YourChoice Therapeutics and registered as NCT06094283 on ClinicalTrials.gov, confirms the safety and tolerability of YCT-529, paving the way for larger efficacy studies. Akash Bakshi, CEO of YourChoice Therapeutics, highlighted the existing imbalance in contraceptive burdens, stating, "Studies and surveys continue to show that men want to share the burden of pregnancy prevention with their partners, but they have just one non-permanent contraceptive option-condoms-and it's 170 years old."

Mechanism of Action and Preclinical Success

YCT-529 works by blocking retinoic acid receptor-alpha (RARα), a protein essential for spermatogenesis, the process of sperm development. When RARα is inhibited, sperm production stops, mimicking a state of vitamin A deficiency but without the broader hormonal effects or systemic toxicity linked to earlier attempts at male contraception. This targeted strategy seeks to avoid the significant side effects that have plagued hormonal male contraceptive candidates, such as cardiovascular problems, liver injury, weight gain, and mood changes, as reported in a comprehensive 2020 review in Biology of Reproduction by Md Abdullah Al Noman et al.

Preclinical work showed strong efficacy and reversibility:

• Mouse models: Male mice rendered infertile within four weeks of YCT-529 administration regained full fertility 4-6 weeks after stopping treatment.
• Primate models: In non-human primates, infertility was induced within 10-15 weeks, with recovery thereafter.
• Safety margins: IND-enabling studies in rats and dogs confirmed efficacy, reversibility, and safety with substantial margins, ranging from 22 to 40 times the effective dose.

These animal investigations underscored the compound's selective action and its rapid reversibility, a critical attribute for a contraceptive.

First-in-Human Trial: Safety and Pharmacokinetics

The Phase 1a clinical trial involved 16 healthy, vasectomized male volunteers, aged 32-59, who received single oral doses of YCT-529 from 10 mg to 180 mg, both in fasted and fed states. The study's primary goals focused on assessing safety and tolerability, with secondary aims examining pharmacokinetics (PK) and pharmacodynamics (PD).

Key findings from the trial, published on July 22, 2025, include:

• Tolerability: YCT-529 was well tolerated across all tested doses.
• Adverse Events: No serious adverse events (SAEs) or dose-limiting toxicities were reported. Common temporary, mild, and self-limiting treatment-emergent adverse events (TEAEs) included headache and respiratory tract infection, which were generally not deemed related to the study drug.
• Specific Clinical Absence of Hormonal Impact: Single doses of YCT-529 up to 180 mg showed no clinically relevant effects on:
  • Heart rate (including QTc interval, PR interval, QRS duration)
  • Hormone levels (follicle-stimulating hormone, luteinizing hormone, testosterone)
  • Sex hormone-binding globulin
  • Inflammatory biomarkers (E-selectin, hsCRP, vWF), although sporadic, non-clinically relevant rises in IL-6 and TNF-alpha were observed in some subjects.
  • Sexual desire or mood, as recorded via psychosexual diaries.
• Pharmacokinetics: Peak plasma concentrations (Cmax) occurred between 4.03 and 8.00 hours post-dose, with terminal elimination half-lives (T½) spanning 51.41 to 75.72 hours.
• Food Effect: Administration with a high-fat, high-calorie breakfast modestly increased YCT-529 exposure (Cmax by 160.36 %, AUC0-t by 136.52 %, and AUCinf by 133.89 %), indicating that food intake influences absorption but did not raise safety concerns.

One isolated case of asymptomatic cardiac arrhythmia in a subject receiving a single 90 mg dose was classified as "possibly related" to YCT-529; however, a cardiology review concluded there was no evidence of cardiac disease or damage from the drug, and the event resolved without intervention.

Addressing an Unmet Need

Worldwide, nearly half of all pregnancies are unintended, highlighting a pressing demand for broader contraceptive options for both men and women. Current male contraceptive choices are largely limited to condoms, which have a 13 % failure rate, and vasectomy, a surgical procedure with uncertain reversibility. The emergence of YCT-529, if successfully developed, could provide a reversible, non-hormonal alternative that fills a longstanding gap in reproductive health.

The present results from this Phase 1a study lay the essential groundwork for ongoing and future clinical investigations. A 28-day and 90-day repeat-dose Phase 1b/2a trial (NCT06542237) is already in progress, further probing YCT-529's safety and its impact on sperm parameters over extended periods. This progression signals a committed effort to bring a novel, effective, and safe male contraceptive to market, potentially redefining shared responsibility in family planning within the dating generation like [Link to "dating apps" (https://www.forbes.com/health/healthy-sex/dating-apps/)].