Making a Difference
MAKING A DIFFERENCE
IN THE LIVES OF WOMEN
Daré Bioscience, Inc. (“Daré”) is a healthcare company committed to the development and commercialization of innovative products in women’s reproductive health. We believe there is an unmet need globally for new product candidates that expand options, improve outcomes and are easy to use. By advancing these products, we seek to expand choices and to make a difference in the lives of women worldwide.
Implementing a unique and synergistic approach
The problem isn’t early innovation. The global donor community of foundations and governments has invested in early research to expand options, improve outcomes and advance global women’s health. Yet, promising candidates often fail to advance.
The problem isn’t commercialization. Pharmaceutical companies with established sales and marketing franchises in women’s health exist; however, many of these companies prefer to get involved in later stages of development, e.g., in pivotal trials or following an application for regulatory approval.
The problem is the gap. We believe there is a gap between early innovation and commercialization in women’s health that creates a potential opportunity for Daré. Our business model is to license the rights to promising product candidates (many with clinical proof-of-concept data), advance their clinical development, and if successful, implement a comprehensive global commercialization strategy in combination with established pharmaceutical partners and regional distributors. We believe this approach is efficient in both its use of time and financial resources.
Our strategy for filling the gap. We intend to drive efficiencies by leveraging the existing product candidates and development expertise of non-profit developers and private company innovators. We have the potential to multiply the impact of our shareholder dollars by working with researchers, developers and members of the donor community who share our commitment to expand options and improve outcomes.
OUR FIRST PRODUCT CANDIDATE
Filling The Void In The Contraceptive Method Mix
The contraceptive market represents a particularly interesting segment for Daré given the size of the opportunity coupled with identified unmet needs.
A large yet untapped market: An estimated 40 million women (62% of women of reproductive age) in the United States use some type of contraceptive method, and worldwide, usage was estimated at 64% in 2015. While many women currently use birth control, these figures also imply that nearly 35% are not using any method. Surveys have revealed that 40% of women using contraception are not satisfied with their current method, reporting difficulty of use, problems with side effects, and concerns about effectiveness and reduced sexual pleasure. Opportunities exist to provide women with new and improved options that better suit their specific needs.
Since the early 1960s when oral contraceptive pills and intrauterine devices were first introduced in the United States, most advances in contraception have focused on the use of hormones. Many new hormonal contraceptive products have become available including implants, injectables, vaginal rings, patches and hormonal intrauterine systems. Research has focused on new hormones, different hormone combinations and lower doses of hormones. Numerous examples exist of successful commercial contraceptive brands including the hormonal vaginal ring, NuvaRing®, from Merck ($777 million in revenue in 2016) and the hormonal intrauterine system, Mirena®, a family of products from Bayer ($1.13 billion in revenues in 2016).
Despite the many advances in hormonal contraception, current contraceptive options fail to meet the needs of the many women who can’t, or don’t want to, use hormones:
- Some women cannot tolerate hormones and experience breast tenderness, bloating, mood swings or other side effects.
- Other women should not use hormones for health reasons, and
- Many women simply want to take a break from hormones.
Advances in non-hormonal methods have failed to provide better effectiveness and convenience. Female condoms, new designs of male condoms, spermicides and novel diaphragms have been introduced, but all must be used at the time of intercourse and most have “typical use” effectiveness ranging between 72-82%. We believe there is a need for something better.
Our initial efforts will focus on addressing a clear gap in the contraceptive method mix – an effective, non-hormonal reversible method that does not require intervention at the time of intercourse. To fill this gap, we selected Ovaprene®, a non-hormonal contraceptive intravaginal ring intended to provide protection over multiple weeks of use. If approved, Ovaprene® would represent a new category of birth control.
In a pilot clinical study conducted in 21 women, Ovaprene® demonstrated the ability to immobilize sperm and prevent their progression into the cervical mucus. The study also demonstrated the acceptability of the device to both partners. No serious adverse events were reported. The pilot study was not designed to be utilized as part of a regulatory submission, so we plan to run a postcoital test (PCT ) clinical trial in approximately 15-30 women. Assuming a successful outcome, it is our intention to progress to a pivotal contraceptive study to support marketing approvals of Ovaprene® in the United States, Europe and other countries worldwide.
Regulatory endpoints in contraception
Unlike many therapeutic areas where trial endpoints may be impacted by subjectivity or ambiguity, the clinical endpoints in contraceptive trials are straightforward and based on pregnancy outcomes. In addition, for products with a barrier component such as Ovaprene®, PCT clinical trials provide a preliminary indication of potential efficacy with a relatively small sample (typically 15-30 women). In three studies of similar size conducted with three other products, those products with no motile sperm in the cervical mucus in their PCT assessments later demonstrated “typical use” contraceptive effectiveness of 88% in pivotal contraceptive studies evaluating pregnancy rates over time. By way of comparison, the typical use effectiveness of other short acting hormonal methods (oral contraceptive pills, patches, and intravaginal rings) is approximately 91%.
We believe that a non-hormonal monthly contraceptive ring that is convenient (inserted and worn for multiple weeks), safe and demonstrates typical use effectiveness comparable to diaphragms, pills, patches and hormonal rings (which have 88-91% contraceptive effectiveness in “typical use” ) has an opportunity to capture market share across the broad spectrum of short-acting methods, primarily from non-hormonal contraceptive users and current non-users of any form of contraception, but also from a small segment of hormonal contraceptive users.
Clinical development path
We intend to work closely with developers who have clinical and regulatory expertise in reproductive health and have a proven track record of FDA success. Non-profit developers, such as Population Council and Medicines360, were responsible for the clinical development of some of today’s popular contraceptive brands, and Daré believes working with an experienced development partner will provide for the efficient use of capital and time to advance Ovaprene®; and any other future product candidates. Daré intends to conduct the PCT clinical trial of Ovaprene® with CONRAD, a non-profit organization established to improve reproductive health globally under a cooperative agreement between Eastern Virginia Medical School and the U. S. Agency for International Development (USAID). CONRAD oversaw the successful recent development and FDA approval of the Caya® diaphragm, the most recently approved barrier contraceptive device in combination with a locally-acting spermiostatic agent.
There are benefits of working with non-profit researchers and developers. The donor community that funds research and development shares our commitment to expanding options and improving outcomes for women. Thus, there may be funding opportunities, such as grants, which are not dilutive, as well as opportunities for us to work or partner with non-profit organizations on development and distribution efforts to ensure the innovations reach women worldwide.
“Typical use” refers to effectiveness experienced among all couples who use the method, including inconsistent and incorrect use, as compared with “perfect use” which denotes effectiveness among couples who use the method both consistently and correctly.
The Postcoital test clinical trial (PCT) was originally developed to assess infertility in couples. The PCT is performed near the time of ovulation and within hours of intercourse. Cervical mucus is isolated and analyzed for the quantity and quality of motile sperm. The PCT has since evolved into the industry standard test of initial contraceptive efficacy for vaginal chemical (spermicide) and barrier devices. The quantity and quality of motile sperm able to reach the cervical mucus serve as a proxy for determining potential, or preliminary, contraceptive efficacy. Contraceptive success is demonstrated by the prevention of viable sperm from reaching the cervical mucus.
Center for Devices and Radiological Health (CDRH). Within the U.S. Food and Drug Administration (FDA), CDRH is responsible for advancing regulatory science, providing industry with predictable, consistent, transparent, and efficient regulatory pathways, and assuring consumer confidence in devices marketed in the U.S.
OUR second PRODUCT CANDIDATE
Addressing an unmet need for female sexual arousal disorder (FSAD) therapies
Female sexual arousal disorder (FSAD) is characterized primarily by an inability to attain or maintain sufficient physical sexual arousal that causes distress or interpersonal difficulty.1 As many as thirty-three percent of women in the U.S. (21 to 60 years old) experience symptoms of low or no sexual arousal.2 Up to an estimated ten million women in the U.S. are affected and/or distressed by this condition and seek a solution to improve their condition.3
There are currently no approved products in the U.S. that specifically address the symptoms or underlying pathology of FSAD. If approved, we believe Sildenafil
Cream, 3.6%, would be the first FDA approved treatment for FSAD.
Sildenafil Cream, 3.6%, incorporates sildenafil, the same active ingredient in Viagra®, in a proprietary cream formulation that is specifically designed to locally increase blood flow to the vulvar-vaginal tissue in women, leading to a potential improvement in genital arousal response and overall sexual experience. Based on known biological pathways for the molecule, topical sildenafil is expected to increase local blood flow to the genital tissue, which we believe will lead to an improvement in genital response and overall sexual experience.
More specifically, studies of women have demonstrated that an improvement in genital blood flow is linked to increased arousal and improved sexual experience.4 Sildenafil is known to inhibit PDE5, leading to an increase in smooth muscle relaxation and improved blood flow.5 Our investigational Sildenafil Cream, 3.6% formulation is expected to exhibit similar PDE5 inhibitor effects on female genital tissue. In a Phase 2a trial in women with FSAD, Sildenafil Cream, 3.6% demonstrated an increase in blood flow to the vaginal tissue in both pre- and postmenopausal women with FSAD when compared to placebo.6
We held a Type C meeting with the FDA to discuss the Phase 2 and 3 trial designs for Sildenafil Cream, 3.6% in FSAD patients in summer 2018. The Phase 2 and 3 trials should establish the efficacy and safety of Sildenafil Cream, 3.6% for this proposed use and support future regulatory applications to bring an important new treatment for women to commercial markets. We plan to pursue the 505(b)(2) regulatory pathway for Sildenafil Cream, 3.6% in the U.S. and leverage the existing data and established safety profile of the Viagra® brand.
1Human Sexuality and Its Problems (Third Edition), 2009
2Ad Hoc Market Research: FSAD Prevalence Report (Oct 2015) conducted for SST LLC.
316% of women are distressed per Ad Hoc Market Research: FSAD Prevalence Report (Oct 2015) conducted for SST LLC. Based on US Census projections for 2016 this equates to 10 million women.
4Safety and Efficacy of Sildenafil Citrate for the Treatment of FSAD: A Double-Blind, Placebo Controlled Study. The Journal of Urology. Vol 170, 2333-2338, December 2003.
5Viagra® prescribing information, Mechanism of Action Section 12.1, https://www.viagra.com, https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/20895s039s042lbl.pdf
6Date on file.