In 1960, the US Food and Drug Administration (FDA) approved the birth control pill, a revolutionary development that enabled women to control their fertility. However more than 50 years on, women are still the ones risking the well-documented side effects of oral contraceptive use in order to avoid unwanted pregnancies.
The male contraceptive market is currently limited to condoms and vasectomies and users often find reason for dissatisfaction with both options. Eppin Pharma anticipates providing an additional option for both men and women who are unsatisfied with their current means of contraception with the availability of an oral, non-hormonal male contraceptive that can be taken as needed and has no material side effects. Eppin Pharma hopes to fill an unmet need, as well as expand into global markets where family planning is not a just a question of convenience, but a necessity.
EppinPharma’s lead male contraceptive candidate is a small compound that binds to EPPIN, a secreted male-specific protein found on the surface of human sperm, resulting in the loss of sperm motility. Extensive studies conducted by the O’Rand Laboratory at the University of North Carolina, Chapel Hill, USA, and reported in Science (O’Rand et al., 2004) demonstrated the complete and reversible contraception of male macaques immunized with EPPIN. This compelling “proof of principle” that EPPIN was an effective target for male contraception spurred the development of alternative methods for using EPPIN as a means for altering sperm function.
It is important that Eppin Pharma’s contraceptive candidates exert their activity via a direct pharmacological action that inhibits sperm motility. The molecular target EPPIN is only found in the male reproductive track making it a highly specific target and therefore, drugs with contraceptive potential can be expected to affect a minimum number of body systems. Such non-hormonal options for male contraception are preferable to hormonal treatments because they have no effect on sperm production or other male hormone dependent functions. Because our drugs targeting Eppin were developed and tested with human sperm samples, their potential for success outside of a laboratory setting greatly increases.
EPPIN (gene name EPPIN, previously known as WFDC7 or SPINLW1) is a small disulfide bonded extracellular protein containing both WAP and Kunitz protease inhibitor domains. It is secreted in the testis and epididymis and exists as a dimer and possibly as a tetramer, It coats the surface of sperm throughout the male reproductive tract
It is involved in the innate immune system by having antibacterial activity. It also is an inhibitor of PSA activity (prostate-specific antigen, a reproductively important serine protease), and is a binding partner of semenogelins , major components of semen critical for fertility.
The SEMG-Eppin binding is critical for sperm to acquire motility and the ability to fertilize an egg. By interfering with this interaction, our drug will keep sperm from becoming motile thereby acting as a contraceptive.
Our drug can inhibit motility of sperm by additional mechanisms. When bound to EPPIN, our lead compounds affect sperm function by interfering with important membrane channels including ones important for maintaining proper pH and calcium levels.
Eppin Pharma has developed a series of small organic compounds that will mimic the effect of anti-EPPIN binding to EPPIN (i.e. compounds that bind EPPIN and thereby inhibit sperm motility).
Once our contraceptive drug is present in the body, it will be distributed to various body fluids and tissues. The target EPPIN is only present in the male and only present in testis and epididymal tissues thereby reducing non-specific binding concerns. Following administration of the drug it will be present in epididymal fluid and bind to EPPIN on the surface of sperm, which are stored there prior to ejaculation. Any additional sperm stored in the vas would also have the drug bound to them.
Prior to ejaculation EPPIN will have coated all of the stored sperm. Upon ejaculation, sperm will move through the vas; seminal fluid, containing the protein semenogelin (SEMG1) and prostatic fluid will be added to the ejaculate.
SEMG1 is the natural binding partner for EPPIN and could compete with our drug for binding to EPPIN in the semen; however, SEMG1 bound to EPPIN inhibits sperm motility, making any competition moot.
During the first thirty minutes after ejaculation, the seminal clot is hydrolyzed by an enzyme in the prostatic fluid (PSA) and SEMG1 is removed from the sperm. Our drug would still be present in the semen, binding EPPIN and continuing to inhibit sperm motility. Because the sperm have been treated before ejaculation, while stored in the epididymis, they should be non-motile in the semen, depending upon the timing of drug administration.