Development of A Non-Hormonal Male Oral Contraceptive

Eppin Pharma Inc. of Chapel Hill, North Carolina, is in the process of creating a male oral contraceptive. We are currently optimizing the development of our lead compounds in preparation for an IND filing with the FDA.

 
Overview

Our lead male contraceptive candidate is a small organic compound that binds to EPPIN (SPINLW1; epididymal protease inhibitor), a protein on the surface of human sperm, resulting in the loss of sperm motility. Preclinical studies conducted by the O'Rand Laboratory and reported in Science (O'Rand et al., 2004. 306:1189) demonstrated compelling "proof of principle" that EPPIN is a key target for male contraception. 

The goal of EPPIN PHARMA INC is to develop a non-hormonal male contraceptive drug that targets EPPIN. EPPIN (SPINLW1; epididymal protease inhibitor) coats the surface of human testicular, epididymal and ejaculate spermatozoa in an EPPIN protein complex (EPC) containing lactotransferrin and clusterin [1,2]. During ejaculation semenogelin (SEMG1) binds to EPPIN in the complex [1,3] inhibiting the progressive motility of ejaculate spermatozoa. Subsequently SEMG1 is hydrolyzed by the serine protease PSA (prostate specific antigen) [4] and EPPIN modulates PSA hydrolysis of SEMG1 on the sperm surface, resulting in forwardly motile spermatozoa [5,6]. Based on our publication in Science in 2004 [7] demonstrating the “proof of principle” that anti-EPPIN antibodies, binding EPPIN on the sperm surface, resulted in the complete and reversible contraception of male monkeys immunized with EPPIN, we are currently optimizing a small organic lead molecule for the development of a sperm contraceptive.

 

 

Couple Hugging - Male Oral Contraceptive

Immunocontraception is not considered a viable option for a marketable product for efficacy, safety, and economic reasons, therefore Eppin Pharma has developed a series of small organic compounds that will mimic the effect of anti-EPPIN binding EPPIN (i.e. compounds that bind EPPIN and thereby inhibit sperm motility). The development of a non-hormonal male contraceptive will enhance family planning throughout the world and give men and women additional contraceptive choices. Currently men are limited in their options for contraception to condoms and vasectomy. In recent surveys the satisfaction rate for women on contraception is less than 60% for every method except tubal ligation and men want access to better contraceptives [8,9,10]. Therefore, a non-hormonal male contraceptive will fill an unmet need in contraception. We envision that our product will comprise a small organic compound that inhibits sperm motility by fitting into the EPPIN-SEMG1 binding site on the surface of spermatozoa. Further we envision that the drug will be administered orally and be taken on-demand a relatively short time before sexual activity and ejaculation.
 
References Cited
1. Wang Z, Widgren EE, Richardson RT O’Rand MG. 2007. Characterization of an eppin protein complex from human semen and spermatozoa. Biol Reprod 77: 476-484. PMID 1756961
2. Richardson RT, Sivashanmugam P, Hall SH, Hamil KG, Moore PA, Ruben SM, French FS, O'Rand MG. 2001. Cloning and sequencing of human Eppin: A novel family of protease inhibitors expressed in the epididymis and testis. Gene 270: 93-102 18.
3. O’Rand MG, Widgren EE, Wang Z, Richardson RT. 2006. Eppin: an effective target for male contraception. Molecular and Cellular Endocrinology 250: 157-162. PMID 16423450 17. 
4. Robert M, Gibbs BF, Jacobson E, Gagnon C. 1997. Characterization of prostate-specific antigen proteolytic activity on its major physiological substrate, the sperm motility inhibitor precursor/semenogelin I. Biochem 36: 3811-3819 19.
5. O’Rand MG, Widgren EE, Hamil KG, Silva EJ, Richardson RT. 2011. Functional studies of eppin. Biochem Soc Trans 39(5): 1447-1449. PMID: 21936831
6. O’Rand MG, Widgren EE, Hamil KG, Silva EJ, Richardson RT. 2011. Epididymal Protein Targets: A Brief History of the Development of Epididymal Protease Inhibitor as a Contraceptive. J Andrology 32 (6): 698-704. PMID: 21441428
7. O'Rand MG, Widgren EE, Sivashanmugam P, Richardson RT, Hall SH, French FS, VandeVoort CA, Ramachandra SG, Ramesh V, Rao AJ. 2004. Reversible Immunocontraception in Male Monkeys Immunized with Eppin. Science 306: 1189-1190
8. Rosenfeld JA, Zahorik PM, Saint W, Murphy G. 1993. Women's satisfaction with birth control. J Fam Pract Feb 36(2):169-73
9. Brooks M. 1998. Men's views on male hormonal contraception-a survey of the views of attenders at a fitness centre in Bristol, UK. Br J Fam Plann Apr;24(1):7-175.
10. Heinemann K, Saad F, Wiesemes M, White S, Heinemann L. 2005. Attitudes toward male fertility control: results of a multinational survey on four continents. Hum Reprod 20:(2) 549-556

Contact us today for further details about our goal to develop the first male oral contraceptive.