On
November 14, 2022, Daré issued a press release announcing positive topline results of its Phase 1/2 clinical study of DARE-VVA1.
Daré is developing DARE-VVA1 for the treatment of moderate to severe vulvar and vaginal atrophy (“VVA”). The randomized,
multi-center, double-blind, parallel-arm, placebo-controlled, dose ranging study enrolled 17 postmenopausal women with VVA and evaluated
the safety, tolerability, plasma pharmacokinetics (“PK”) and pharmacodynamics (“PD”) of DARE VVA1. The age of
the 17 study participants ranged from 49 to 68 years, with an average age of 60.9 years. Participants were randomly allocated to one
of five treatment groups (approximately four participants per group) that evaluated four dose levels of DARE-VVA1 (1 mg, 5 mg, 10 mg,
and 20 mg tamoxifen) and a placebo. Following a screening visit, DARE VVA1 was self-administered by study participants intravaginally
once a day for the first two weeks, and then twice a week for the following six weeks for a total treatment period of 56 days. In each
treatment group, participants had serial blood sampling for PK analysis and underwent safety evaluations and preliminary assessments
of effectiveness. Following the completion of the treatment period, participants attended a safety follow-up visit. Fourteen participants
completed the study.
The
primary endpoints of the study evaluated the safety and tolerability of DARE-VVA1 by vaginal administration and determined the plasma
PK of DARE-VVA1 after intravaginal application. Secondary endpoints evaluated preliminary efficacy and PD of DARE-VVA1 in terms of most
bothersome vaginal symptom and changes in vaginal cytology and pH.
Intravaginal
administration of DARE-VVA1 was well tolerated in the study and all treatment emergent adverse events were mild or moderate and equally
distributed between participants randomized to study drug treatment versus placebo. Concentration of tamoxifen in plasma samples collected
over the course of the study did not exceed 10 ng/mL, even in participants in the highest dose group (20 mg tamoxifen).
Participants
who received study drug treatment had improvements in the assessments and symptoms associated with VVA. Specifically, they had decreases
in vaginal pH, increases in the percentage of vaginal superficial cells, significant decreases in the percentage of vaginal parabasal
cells (p=0.04), and reduction in their self-assessed most bothersome vaginal symptom reported. Regarding the most bothersome vaginal
symptom reported, of the participants randomized to receive study drug treatment, 39% (5/13) reported that vaginal dryness and 62% (8/13)
reported that pain with intercourse (dyspareunia) was their most bothersome vaginal symptom at baseline. At the end of the treatment
period, among the participants randomized to receive study drug treatment who reported vaginal dryness as their most bothersome symptom
at baseline (n=5) (moderate or severe), all those who completed the study reported that vaginal dryness was either absent (n=1) or mild
(n=3). Among the participants randomized to receive study drug treatment who reported dyspareunia as their most bothersome symptom at
baseline (n=8) (moderate or severe), at the end of the treatment period, four reported no longer experiencing dyspareunia, one reported
mild dyspareunia, two had no change in this symptom, and one did not complete the study. Of the four participants randomized to the placebo
group, two reported vaginal dryness and two reported dyspareunia as their most bothersome symptom at baseline. At the end of the treatment
period, the participants randomized to the placebo group who reported vaginal dryness as their most bothersome symptom at baseline (n=2)
(moderate or severe), reported that vaginal dryness was either absent (n=1) or mild (n=1), and among the participants randomized to the
placebo group who reported dyspareunia as their most bothersome symptom at baseline (n=2), one reported no longer experiencing dyspareunia
and one did not complete the study.
Daré
believes the topline results of the Phase 1/2 clinical study support ongoing development of DARE-VVA1 as a treatment for moderate to
severe VVA, and that DARE-VVA1 has the potential to be the first therapeutic specifically approved for the treatment of VVA in U.S. patients
with, or at risk of recurrence of, hormone receptor-positive breast cancer.
Forward-Looking
Statements
Daré
cautions you that all statements, other than statements of historical facts, contained in this report are forward-looking statements.
Forward-looking statements, in some cases, can be identified by terms such as “believe,” “may,” “will,”
“estimate,” “continue,” “anticipate,” “design,” “intend,” “expect,”
“could,” “plan,” “potential,” “predict,” “seek,” “should,” “would,”
“contemplate,” “project,” “target,” “objective,” or the negative version of these words
and similar expressions. In this press release, forward-looking statements include, but are not limited to, statements relating to DARE-VVA1’s
potential as a safe and effective therapy for VVA, DARE-VVA1’s potential to become a new standard of care as the first FDA-approved
product for the treatment of VVA specifically in an HR+ breast cancer patient population, the importance of the Phase 1/2 clinical study
results to Daré and DARE-VVA1, and the anticipated regulatory approval pathway for DARE-VVA1. Forward-looking statements involve
known and unknown risks, uncertainties and other factors that may cause Daré’s actual results, performance or achievements
to be materially different from those expressed or implied by the forward-looking statements, including, without limitation: the risk
that positive findings in early clinical and/or nonclinical studies of a product candidate may not be predictive of success in subsequent
clinical and/or nonclinical studies of that candidate; Daré’s ability to develop, obtain FDA or foreign regulatory approval
for, and commercialize its product candidates and to do so on communicated timelines; failure or delay in starting, conducting and completing
clinical trials of a product candidate; Daré’s ability to design and conduct successful clinical trials, to enroll a sufficient
number of patients, to meet established clinical endpoints, to avoid undesirable side effects and other safety concerns, and to demonstrate
sufficient safety and efficacy of its product candidates; Daré’s dependence on third parties to conduct clinical trials
and manufacture and supply clinical trial material and commercial product; Daré’s ability to raise additional capital when
and as needed to advance its product candidates, execute its business strategy and continue as a going concern; the loss of, or inability
to attract, key personnel; the effects of the COVID-19 pandemic, macroeconomic conditions and geopolitical events on Daré’s
operations, financial results and condition, and ability to achieve current plans and objectives, including the potential impact of the
pandemic on Daré’s ability to timely enroll, conduct and report results of its clinical trials and on the ability of third
parties on which Daré relies to assist in the conduct of its business to fulfill their contractual obligations to Daré;
the risk that developments by competitors make Daré’s product or product candidates less competitive or obsolete; difficulties
establishing and sustaining relationships with development and/or commercial collaborators; failure of Daré’s product or
product candidates, if approved, to gain market acceptance or obtain adequate coverage or reimbursement from third-party payers; Daré’s
ability to retain its licensed rights to develop and commercialize a product or product candidate; Daré’s ability to satisfy
the monetary obligations and other requirements in connection with its exclusive, in-license agreements covering the critical patents
and related intellectual property related to its product and product candidates; Daré’s ability to adequately protect or
enforce its, or its licensor’s, intellectual property rights; the lack of patent protection for the active ingredients in certain
of Daré’s product candidates which could expose its products to competition from other formulations using the same active
ingredients; product liability claims; governmental investigations or actions relating to Daré’s product or product candidates
or the business activities of Daré, its commercial collaborators or other third parties on which Daré relies; the impact
of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health
care cost containment; cyber attacks, security breaches or similar events that compromise Daré’s technology systems or those
of third parties on which it relies and/or significantly disrupt Daré’s business; and disputes or other developments concerning
Daré’s intellectual property rights. Daré’s forward-looking statements are based upon its current expectations
and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified
in their entirety by these cautionary statements. For a detailed description of Daré’s risks and uncertainties, you are
encouraged to review its documents filed with the SEC including Daré’s recent filings on Form 8-K, Form 10-K and Form 10-Q.
You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made.
Daré undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date
on which they were made, except as required by law.