Arousal Disorders in Women

• Female sexual arousal disorder (FSAD) FSAD, as described in the Diagnostic and Statistical Manual 4^th Edition (DSM-IV), is a condition characterized as a persistent or recurrent inability to attain or maintain sufficient genital arousal (an adequate lubrication-swelling response) during sexual activity, frequently resulting in distress or interpersonal difficulty. Of the various types of female sexual dysfunction disorders, FSAD is most analogous to erectile dysfunction (ED) in men.

There are currently no FDA-approved therapies for FSAD.

Market Opportunity

• A meta-analysis of 95 studies from 2000-2014 indicated prevalence of Female Sexual Dysfunction in premenopausal women worldwide is 41%, and difficulty with arousal alone is 23%.¹
• Market research estimates:
  • 33% of US women aged 21 to 60 (~ 20 million women), experience symptoms of low or no sexual arousal.^2,3
  • 10 million women in the US are considered distressed and actively seeking treatment.²
• To put the market opportunity for an FDA-approved FSAD treatment in context, a PDE5 inhibitor utilized in an ED medication for men – Viagra® — peaked at $2.05 billion in sales in 2012.⁴

Our Investigational Candidate, Sildenafil Cream, 3.6%

Orally administered sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, received FDA approval in 1998 for the treatment of erectile dysfunction in men and is marketed under the brand name Viagra®. Given the underlying pathophysiologic similarities of ED and FSAD, using sildenafil to direct blood to the genitals before sexual activity could provide a potential improvement in genital arousal response and overall sexual experience for women as it does in men.

Sildenafil Cream, 3.6% is an investigational proprietary topical formulation of sildenafil being developed as a first-in-category option for women for the treatment of FSAD. Unlike the oral formulations of PDE-5 inhibitors, Sildenafil Cream is applied locally to the vaginal tissue and is designed to facilitate vasodilation and increased blood flow directly to the genital tissue to improve the physical arousal response symptoms commonly associated with FSAD while avoiding systemic side effects observed with oral formulations of sildenafil.

Phase 1 and Phase 2a Clinical Studies, Previously Completed

In a Phase 1 clinical study in 20 healthy post-menopausal women, topical sildenafil cream was safe and well tolerated at clinically relevant doses, and study subjects reported favorable product characteristics: easy to use and readily absorbed.

In a Phase 2a study in women with FSAD (15 pre-menopausal and 16 post-menopausal), Sildenafil Cream increased measurable blood flow to the genital tissue compared to placebo cream. Further, data from a thermography study in healthy women demonstrated significantly greater increases in genital temperature after administration of Sildenafil Cream compared to placebo cream, indicating a positive impact on genital blood flow during the 30-minute testing session, with statistical separation from placebo within the first 15 minutes after dosing.

Content Validity Study, Previously Completed

We also completed a content validity study designed to identify and document the genital arousal symptoms that are the most important and relevant to women with FSAD. The findings of this study helped facilitate alignment with the FDA on acceptable efficacy endpoints for the Phase 2b RESPOND study and a future Phase 3 program.

Exploratory Phase 2b RESPOND Study, Completed in 2023

Phase 2b Study Design

• The Phase 2b study was an exploratory study to evaluate a number of primary endpoints and secondary endpoints as well as to identify a target patient population for Sildenafil Cream, 3.6%.
• The Phase 2b clinical study was designed as a multi-center, double-blind, placebo-controlled study to evaluate the efficacy and safety of Sildenafil Cream, 3.6% in premenopausal patients with female sexual arousal disorder (FSAD).
• Study participants used Sildenafil Cream and placebo cream over 12 weeks in their home setting, following both a non-drug and placebo cream run-in period.
• All participants had a main diagnosis of FSAD and may have also had concomitant sexual dysfunction diagnoses or symptoms including decreased desire, orgasmic dysfunction, and genital pain.

Phase 2b Study Highlights

Exploratory Phase 2b clinical study designed to evaluate Sildenafil Cream vs. placebo over 12 weeks of double-blinded dosing following both a non-drug and placebo run-in period:

• Compared Sildenafil Cream vs. placebo used in patients’ home setting.
• Co-primary endpoints: patient reported outcome (PRO) instruments measured improvement in localized genital sensations of arousal (Arousal-Sensation Domain of the Sexual Function Questionnaire) and reduction in FSAD related distress (Female Sexual Distress Scale).
• Secondary endpoint: measured change in the number of satisfactory sexual events
• Exploratory endpoints: Several efficacy endpoints measured and could be candidate endpoints in a Phase 3 study. Efficacy assessments were administered both on an electronic diary to be completed within 24 hours of a sexual event and via 28-day recall assessments.
• Sildenafil Cream-treated group showed meaningful improvement in the co‑primary endpoint assessment that evaluated change from baseline in the Arousal-Sensation Domain of the Sexual Function Questionnaire, although the endpoint did not achieve statistical significance.¹
• Post-hoc analyses showed that Sildenafil Cream met the Ph2b co-primary endpoint (SFQ28-arousal domain patient reported outcome (PRO)) and demonstrated clinically meaningful benefit in patients who have FSAD or FSAD with concomitant decreased desire.

• • Secondary and exploratory endpoints saw these patients report meaningful improvement in arousal sensation, desire, orgasm, as well as stress, guilt, and embarrassment about the sexual dysfunction.

(ClinicalTrials.gov Identifier: NCT04948151)

Read more about the Phase 2b clinical study here.

Regulatory Strategy for Sildenafil Cream, 3.6%: Next Steps

The Company is conducting an end-of-phase 2 meeting with the FDA in the 4^th quarter of 2023 to review the data accumulated during the Phase 2b RESPOND Study and to align with the FDA on the Phase 3 study design.

At the conclusion of the development program, if successful, Daré intends to leverage the existing safety and efficacy data for sildenafil to utilize the FDA’s 505(b)(2) pathway to obtain marketing approval of Sildenafil Cream, 3.6% for the treatment of women in the U.S.

*This page includes forward-looking statements subject to qualifications described in the Terms of Service, including Section 13.4, Forward-Looking Statements; Disclaimer.

Sildenafil Cream, 3.6% Footnotes

1. McCool et al. Sex Med Rev 2016;4:197-212. DOI: 10.1016/j.sxmr.2016.03.002
2. Ad Hoc Market Research: FSAD Prevalence Report (Oct 2015) conducted for SST LLC.
3. Based on US Census projections for 2016.
4. https://qz.com/quartzy/1238783/its-the-20th-anniversary-of-viagra-heres-how-its-changed-the-world