Intravaginal Ring (IVR) Technology Platform
Daré has an exclusive, global license to Juniper’s novel intravaginal ring technology that was developed by Dr. Robert Langer from the Massachusetts Institute of Technology and Dr. William Crowley from Massachusetts General Hospital and Harvard Medical School.
The Juniper intravaginal ring technology allows for sustained drug delivery over time periods ranging from weeks to months. Unlike other vaginal rings, the Juniper intravaginal rings release drugs in a solid ethylene vinyl acetate polymer matrix without the need for a membrane or reservoir to contain the active drug or control the release.
Current 505(b)(2) candidates under development by Juniper include JNP-0101, an oxybutynin ring for the treatment of overactive bladder; JNP-0201, a combination estradiol + progesterone ring for hormone replacement therapy; and JNP-0301, a natural progesterone ring for the prevention of preterm birth.
Daré’s exclusive license covers all three rings in development as well as additional applications of the intravaginal ring technology platform in other therapeutic areas.
PT-101 - A Proprietary Vaginal Formulation of Tamoxifen
In May 2018, we entered into a merger agreement with Pear Tree Pharmaceuticals, Inc., a development-stage women’s biopharmaceuticals company. Daré has entered into the merger agreement to secure the rights, currently owned by Pear Tree, to develop PT-101, a proprietary vaginal formulation of tamoxifen, as a potential treatment for vulvar and vaginal atrophy (VVA) in patients with hormone-receptor-positive breast cancer, including estrogen receptor-positive (ER-positive) and progesterone receptor-positive (PR-positive) breast cancer. Vulvar and vaginal atrophy (VVA) is a chronic medical condition characterized by thinning of the epithelial lining of the vagina and lower genitourinary tract and loss of vaginal elasticity with associated diminished vaginal lubrication. Physiological cellular changes in the vaginal wall epithelial lining include decreases in superficial cells and increases in parabasal and intermediate cells. There is also an increase in vaginal pH. VVA is associated with a constellation of symptoms that impact intimate relationships, daily activities, and quality of life. Primary symptoms include vaginal irritation (50%), dyspareunia (27%), and vaginal dryness (24%).Oral tamoxifen is already approved by the FDA as a treatment for hormone-receptor-positive breast cancer. PT-101 incorporates the active ingredient tamoxifen in a tablet formulation designed to deliver the drug vaginally.
Vulvar and Vaginal Atrophy in Postmenopausal Women: Findings from the REVIVE (REal Women’s VIews of Treatment Options for Menopausal Vaginal ChangEs) Survey. Sheryl A. Kingsberg, PhD, Susan Wysocki, WHNP, FAANP, Leslie Magnus, MD, and Michael L. Krychman, MD, FACOG
Orbis Biosciences, Inc. - ORB-204 and ORB-214
In March 2018 we entered into an agreement with Orbis Biosciences, Inc. for the development of an injectable etonogestrel contraceptive with 6- and 12-month durations (ORB-204 and ORB-214, respectively). The collaboration represents our first partnership that leverages funds and development work supported to date by investment from a donor and non-profit development community devoted to improving options in women’s reproductive health, positioning Daré as a committed industry partner to advance innovation that addresses global gaps in therapeutic options.
The initial development on Orbis’ long-acting injectable contraceptive program was carried out under a subcontract funded by Family Health International (FHI 360) through a grant from the Bill & Melinda Gates Foundation. Through its Contraceptive Technology Innovation (CTI) initiative, FHI 360 is developing new and strategically important contraceptives that are designed to fill gaps in the market, provide mid-to-long duration of action and have favorable usability profiles.
An injectable contraceptive is designed to provide discreet, non-implanted, protection over several months. Limitations of the currently marketed injectable contraceptive is that it provides contraceptive protection for only three months, and can delay the ability to get pregnant for up to ten months after receiving the injection. The target product profiles of ORB-204 and ORB-214 include prolonged duration (6 to 12 months), improved ease of use, with an improved side effect profile and predictable return to fertility.
Pre-clinical studies for the 6- and 12- month formulations have been completed to date, including establishing pharmacokinetics and pharmacodynamics profiles. The collaboration with Orbis will continue to advance the program through formulation optimization with the goal of achieving sustained release over the target time period.
The terms of the agreement with Orbis provide Daré with an option to enter into a license agreement for ORB-204 and ORB-214 should upcoming development efforts be successful.
CatSper – A Novel Approach to Male and Female Contraception
CatSper (Cation Channel of Sperm) is a well-studied target for contraception. The identification of the CatSper target represents the potential to develop a novel class of non-hormonal contraceptive products for both men and women and is based on the discovery made by David Clapham, M.D., Ph.D. The discovery of a sperm-specific ion channel, CatSper, was validated in animal models where it was demonstrated that male mice lacking CatSper have poor sperm motility.
CatSper proteins are ion channels expressed solely in the membranes of sperm flagellum and are essential to sperm motility. Specifically, pre-clinical research has demonstrated CatSper mediates hyperactive motility of sperm. Sperm hyperactivity is necessary to penetrate the physical barrier known as the zona pellucida which encloses the ovum and protects the egg.1 The contraceptive benefit of targeting CatSper is achieved by inhibiting sperm hyperactivity and preventing egg fertilization.
Pre-clinical research suggests that sperm cell development and female fertility are not adversely affected when CatSper is temporarily inhibited and resumption of full fertility should occur shortly after discontinuation. Since CatSper expression is confined to sperm, a drug targeting CatSper could potentially be delivered to males or females and a fast-acting formulation has the potential to be used immediately prior to intercourse.
This novel approach to pregnancy prevention is strongly aligned with the objectives of large non-profit foundations and government agencies that fund global contraceptive research. Daré will pursue non-dilutive funding opportunities to support the near-term research and development objectives for this program.