Almost half of pregnancy in the world is unexpected, so the need for effective, reversible male birth control pills remains urgent. Despite decades of research, men still rarely choose birth control options, mainly condoms or irreversible surgery to prevent sperm from reaching the egg. Hormonal and non-hormonal treatments tested for men in the past have not yet brought it to the market, partly due to adverse side effects. For nearly a century, dietary vitamin A metabolites have played an important role in sperm production. Building on this knowledge, a group of researchers created a new compound that targets this pathway in a very specific way. This approach provides a promising new avenue for male birth control pills without affecting their hormones.
Professor Gunda Georg leads a team from the University of Minnesota, working with investigators from the Columbia University School of Physicians and Surgeons (Professor Debra Wolgemuth and Dr. Sanny Chung) and your Choice Therapeutics (Dr. Nadja Mannowetz and Mr. Akash Bakshi), a combination that has developed and tested a COMP-YCT-529. Their findings, now published in the Natural Portfolio Science Journal Communication Medicine, describe how YCT-529 blocks a protein called retinoic acid receptor alpha, which helps the body use the metabolite retinoic acid vitamin to support sperm development.
The team found that within one month of oral administration with YCT-529, male mice were temporarily infertile because they stopped making sperm, but otherwise it was normal. For possible contraceptive applications, mice recovered fertility a few weeks after discontinuation of treatment. In male monkeys, the drug showed a similar effect: shortly after the start of treatment, sperm levels decreased and there was no negative effect in the animals, including behavior or male sex hormone testosterone levels. After treatment, sperm production returns to normal within a few months.
“Our study describes the development of YCT-529, a highly selective retinoic acid receptor-Alpha blocker, which only blocks proteins associated with sperm production, which temporarily reduces sperm count in male mice and male monkeys,” said Professor Georg. She noted that the drug does not interfere with hormones such as testosterone, a major obstacle to previous efforts to develop male birth control.
This success represents an important step in finding reliable and reversible methods of male contraception that do not affect hormone levels. Professor Wolgemuth’s lab has studied the molecular genetic mechanisms of retinoid signaling in sperm production for more than 20 years, highlighting the “importance of basic research in identifying possible pharmacological interventions and ultimately clinical applications”. The study shows that YCT-529 works by blocking the specific signals needed to produce sperm (in this case, the signals associated with vitamin A, but does not interfere with other body functions. The drug was found to be well tolerated, easily absorbed by the human body, and has no harmful side effects, making it a strong candidate for clinical testing for men.
Professor Georg and colleagues believe their findings confirm that the protein retinoic acid receptor alpha, which is associated with sperm production, is an important goal in developing male birth control strategies. They suggest YCT-529 may be the earliest oral, non-hormonal contraceptive pill and potentially used as a “male pill.”
Journal Reference
Manowitz (N. Communication Medicine, 2025. doi:
About the Author
Dr. Nadja Mannowetz It’s YourChoice Therapeutics, Inc. co-founder and serves as its Chief Science Officer (CSO). She is a sperm biologist with extensive experience in microscopy, imaging and sperm patch clips, studying the molecular mechanisms that regulate sperm movement. In her role as CSO, she has extensive experience in designing preclinical research and preparing clinical research protocols and other documents related to clinical trial applications. Currently, she is providing men with the first hormone-free birth control pill, and with her comprehensive skills, she will further develop novel birth control pills to shape the future of modern family planning. Dr. Mannowetz received his PhD from Biology at Eberhard Karls University in Germany.
Dr. Sanny SW is an associate research scientist at Columbia University’s School of Physicians and Surgeons. She led research on germ cell development and differentiation, using a knockout mouse model of Professor Debra Wolgemuth with an infertile phenotype. Dr. Chung is internationally recognized for his expertise in morphological assessment of testicular defects in these models. Together with Professor Wolgemuth, she made an important contribution to characterizing and establishing retinin signaling mediated in physiological processes mediated by the retinoic acid receptor α (RARα). These studies, published in peer-reviewed research journals, have defined the critical role of nuclear transcription regulators at multiple stages of male germ cell development. It is worth noting that their pioneering work was one of the first to study oral pan-antagonists as potential non-hormonal male birth control pills, in which case laying the foundation for current research on RARα-specific antagonists. Dr. Chung received his PhD in Molecular and Cell Biology from the University of Hong Kong. Her doctoral research was conducted under the guidance of Professor Will Lee from the University of Hong Kong and Dr. C. Yan Cheng from the Population Committee on the Rockefeller University campus.
Dr. Soma Maitra She received her undergraduate degree in India before transferring us to pursue her PhD. At the University of Kansas, she works in the synthesis of natural products. She conducted postdoctoral research at the University of Minnesota in George’s Laboratory, where she made significant contributions to the discovery and synthesis of YCT-529. She joined Biogen’s medicinal chemistry group in 2021, where she contributed to several CNS small molecule programs. She currently serves as a senior research scientist at Vertex Pharmaceuticals.
MD Abdullah Al Noman The School of Medicinal Chemistry at the University of Minnesota conducted a doctoral study under the supervision of Dr. Gunda Georg, focusing on the development of non-hormonal male birth control pills targeting the retinoformate receptor alpha (RARα). He is currently a postdoctoral fellow at Stanford University, working at the interface of medicinal chemistry and chemical biology to promote small-molecular therapies for oncology, neurodegenerative, infectious diseases and rare diseases. Noman is driving several drug discovery programs, drawing on his expertise in medicinal chemistry, project management and cross-functional collaboration. He remains committed to transforming academic innovation into influential real-world therapies.
Huang Shi graduate Cum Excellent received a bachelor’s degree in biology from Brooklyn College (New York City) and a PhD in biology/immunology from Case Western Reserve University and Cleveland Clinic. He completed a postdoctoral fellowship at the Hoffman-Laroche/Roche Institute of Nutley, Nutley, NJ with a focus on cytokine biology and drug discovery. He then left the industry for five years at the National Institutes of Health (NIH), exploring the macrophage regulation of immune responses. After returning to the biotech industry, Dr. Wong focuses on proprietary oncology and immunology/inflammatory drug discovery programs, both as members of a multidisciplinary project team and as leaders. This allows him to participate in all aspects of drug development from target identification, screening, lead optimization, proof of concept, efficacy, PK/PD, mechanism of action, biomarker development to planning of phase I clinical strategies. Some of the successes have been made including being a member of the original former preclinical development team, approved by the regulatory authority for the proteasome inhibitor bortezomib (Velcade), and a member of the team responsible for the anti-anti-angiogenic antibody antibody pegdinetanib (Agiocept) BLA. Currently, Dr. Wong is the core director of pharmacology at the Institute of Drug Discovery and Development (ITDD) at the University of Minnesota, where he provides drug discovery/development expertise and introduces translation methods to the Intramural and Diplomatic Basic Research Program.
Dr. Narsihmulu Cheryala He is an Assistant Professor of Research and Senior Chief Scientist in the Department of Medicinal Chemistry at the University of Minnesota. He has 20 years of experience in medicinal chemistry, and studies have covered drug discoveries for antiviral, anticancer, antigastric and antipsychotic and non-hormonal male birth control pills. Dr. Cheryala is committed to designing small molecules to solve challenging biological problems and meet unmet clinical needs. Dr. Cheryala also has previous industry experience, which strengthens his translation methods for early drug discovery. He received his Ph.D. In the synthetic organic chemistry of the Indian Institute of Chemical Technology (IICT), he specializes in the total synthesis of biologically active natural products and the development of novel synthetic methods.
Akash Bakshi It’s YourChoice Therapeutics, Inc. co-founder and serves as CEO. He is a serial biotech entrepreneur with a record of converting academic science into first-tier medicines, including his former tenure as CEO of ANA Therapeutics, and CEO of Neurobo Pharmaceuticals, where he led the rapid development of Covid-19 treatment. Mr. Bakshi received his bachelor’s degree in biochemistry and cell biology from the University of California, San Diego, and a master’s degree in biotechnology from the University of Queensland, Australia, and is an alumnus of the Y Combinator Winter 2019 Cohort.
Dr. Debra J. Wolgemuth He is a professor of genetics and development at Columbia University’s School of Physicians and Surgeons. She is an internationally recognized leader in the field of genetic control for mammalian germ cell development and differentiation. Her lab made a pioneering contribution to understanding the role of mitotic and meiotic cell cycle control, the role of BBD-containing bacterial specific domain proteins, and through the retinal localization signaling pathway in mouse models. She collaborated with colleague assistant research scientist Dr. Sanny Chung, PhD, to show that the nuclear transcription regulator retinoic acid receptor alpha (RARα) is needed at several stages of male germ cell differentiation. These studies involve a wide range of morphological and biochemical characterization of sterile phenotypes Lala- / – Knockout mice, germ cell stem cell transplantation and more recently pharmacological inhibitory effects of RARα on pan-antagonists in vivo. They showed that orally available RARα antagonists inhibit spermatogenesis and cause male-specific sterility, which is reversible after discontinuation of treatment. These combined studies provide the rationale for the current study, developing RARα-specific antagonists to target RARα function in male birth control pills. Dr. Wolgemuth received his PhD in Human Genetics and Developmental Biology from Columbia University, and conducted a postdoctoral training after tumorigenesis in Memorial of Molecular Biology at Sloan Sloan Kettering Institute and Rockefeller University. Gynecology, Institute of Human Nutrition and Herbert Irving Comprehensive Cancer Center.
