SBIR-STTR Award

The global contraceptives market was valued at $16.0 billion in 2011 and is expected to grow at a CAGR of 5.9% from 2013 to 2018, to reach an estimated value of $23.3 billion in 2018. The contraceptive market consists of short-term methods such as condoms and oral contraception, long-term methods including implants and IUDs, and permanent methods such as tubal ligations and vasectomies. Eppin Pharma's product has a unique set of characteristics, namely ease-of use, high efficacy, reversibility and no side-effects, that differentiates it favorably from all the other male contraceptive competitors. An important high impact driver of this market is the prevalence of unintended pregnancies. In the US there are 3.1 million unintended pregnancies annually through inconsistent or non-use of contraception. Eppin Pharma will be competing in the short-term contraception market. The goal of EPPIN PHARMA INC is to develop a non-hormonal male contraceptive drug that targets the protein EPPIN, which is present on the human sperm surface. Unlike hormonal contraception which inhibits spermatogenesis our therapeutic agent, EP055, is present in epididymal fluid and binds to EPPIN on the surface of sperm, inhibiting sperm motility. The target EPPIN is only present in the male; in testis, epididymis, and on sperm, thereby reducing non-specific binding concerns. The Specific Aims of this SBIR proposal are designed to complement STTR phase 2 data and initiate metabolic and transporter studies of EP055, which are needed before first-in-human studies can begin. It is crucial to determine if EP055 will have significant drug-drug interaction before proceeding further because the male contraceptive would be taken by a healthy population of men or women. Our goal in this SBIR phase I application is to collect additional pharmacology data that will support and facilitate the completion of an IND application to the FDA. Specific aim #1 will determine if EP055 is a substrate, inhibitor, or inducer of cytochrome P450. Specific Aim #2 will determine if EP055 is a substrate, or inhibitor of a transporter. This aim will evaluate transporters that are predominantly in the intestine, liver, kidneys and blood brain barrier. Specific aim 3 will analyze and document our drug manufacturing process; scale up for production of EP055 to support future nonclinical and clinical studies.

Public Health Relevance Statement:
Relevance to Public Health This research proposal is relevant to public health because it will develop a new male non- hormonal contraceptive that 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. Therefore a non-hormonal male contraceptive will fill an unmet need in contraception. This proposal is designed to develop a drug for male contraception that targets EPPIN and will initiate metabolic and transporter studies of EP055, which are needed before first-in-human studies can begin.

Project Terms:
Binding; Biological Assay; Blood - brain barrier anatomy; Characteristics; Clinical Research; Complement; condoms; Contraceptive Agents; Contraceptive methods; Cytochrome P450; Data; design; Development; Drug Interactions; Drug Targeting; Ejaculation; Enzymes; Epididymis; Family Planning; first-in-human; Formulation; Funding; Future; Goals; hormonal contraception; Human; Implant; In Vitro; in vivo; Infertility; inhibitor/antagonist; Intestines; Kidney; Lead; Liquid substance; Liver; male; Male Contraceptive Agents; man; manufacturing process; men; Metabolic; Methods; Monkeys; Oral; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; phase 1 study; phase 2 study; Population; Prevalence; Process; Production; Protease Inhibitor; Proteins; Public Health; public health research; Research Proposals; Safety; scale up; Seminal fluid; Seminal Vesicles; side effect; Small Business Innovation Research Grant; Small Business Technology Transfer Research; sperm cell; Sperm Motility; Spermatogenesis; Surface; Testing; Testis; Therapeutic Agents; Tubal Ligation; unintended pregnancy; Validation; Vasectomy; Woman; Work

The global contraceptives market was valued at $24BN in 2018 and is expected to grow at aCAGR of 6.9% from 2019 to 2027. The contraceptive market consists of short-term methodssuch as condoms, oral contraceptives, patches and rings, long-term methods including implantsand IUDs, and permanent methods such as tubal ligations and vasectomies. The global condommarket was expected to see $12BN in revenue in 2018 and is projected to grow at a CAGR of9% over the period 2019-2024. Condoms accounted for $200MM in the United States in 2018growing at a CAGR of 3.5% from 2017-2020. There are currently no commercially availableproducts in the category of non-hormonal male contraceptive technologies involving oral pillsand/or implantable devices which would compete in the short-term market. Eppin Pharma'sdrug will provide a significant pharmaceutical alternative to male condoms and should commanda significant share of the contraceptive market. Once commercially available, this new malecontraceptive technology has the potential to be disruptive to the traditional male contraceptivecondom market as well as the contraceptive market generally. Eppin Pharma's market reviewprojects that new male contraceptive technology entrants can feasibly capture 8-10% of thetraditional short-term male contraceptive market which is at least $550MM. Eppin Pharma'sproduct has a unique set of characteristics, namely ease-of use, reversibility and minimal side-effects that differentiates it favorably from all the other male contraceptive competitors. Animportant high impact driver of this market is the prevalence of unintended pregnancies; in theUS there are 3.1 million unintended pregnancies annually due to inconsistent or non-use ofcontraception. Eppin Pharma is an emerging pharmaceutical company focused on thedevelopment of a safe, non-hormonal male contraceptive that can be taken orally. Thecompany's contraceptive product candidate is a small organic compound that binds to EPPIN(epididymal protease inhibitor), a protein on the surface of human sperm, resulting in the loss ofsperm motility. The Specific Aims of this SBIR Phase 2 proposal are designed to build onSBIR phase 1 data and demonstrate that our lead compound, EP055, is safe and ready for aphase 1 clinical trial as an oral male contraceptive that targets EPPIN. The Specific aims are:1) Safety pharmacology; this aim is intended to evaluate the potential for EP055 to causeeffects on organ systems acutely critical for life: CNS, Respiratory and Cardiovascular. 2)Toxicology; repeat-dose GLP toxicology studies. 3) Manufacture of 2kg of EP055.

Public Health Relevance Statement:
Relevance to Public Health This research proposal is relevant to public health because it will develop a new male non- hormonal contraceptive that 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. Therefore a non-hormonal male contraceptive will fill an unmet need in contraception.

Project Terms: