On
January 9, 2023, Daré issued a press release announcing topline pharmacokinetic (“PK”) results of its Phase 1/2 clinical
study of DARE-HRT1. Previously, on October 17, 2022, Daré reported topline efficacy data from the study. Topline results from
the study support continued clinical development of DARE-HRT1 and Daré plans to advance DARE-HRT1 into a Phase 3 clinical trial.
Following clinical development, Daré plans to seek marketing approval of DARE-HRT1 for the treatment of moderate to severe vasomotor
symptoms (“VMS”) due to menopause in women with intact uteri. Daré believes U.S. Food and Drug Administration (“FDA”)
approval of DARE-HRT1 for that indication is achievable via the FDA’s 505(b)(2) pathway supported by a single, placebo-controlled,
Phase 3 clinical trial of DARE-HRT1 and a scientifically justified PK “bridge” (via a relative bioavailability trial) between
DARE-HRT1 and the selected listed estradiol and progesterone drugs.
The
randomized, open-label, two-arm, parallel group Phase 1/2 study of DARE-HRT1 was designed to evaluate the PK of two versions of DARE-HRT1
(estradiol 80 µg/progesterone 4 mg IVR and estradiol 160 µg/progesterone 8 mg IVR) in approximately 20 healthy, post-menopausal
women over approximately three consecutive months of use. The study also collected safety, usability, acceptability and symptom-relief
data, including VMS as well as the vaginal symptoms of menopause.
Topline
data from the study demonstrate that DARE-HRT1 successfully delivered estradiol and progesterone over the 12-week evaluation period.
The baseline-corrected steady state release of estradiol and progesterone from both the lower (IVR1) and higher (IVR2) dose versions
of DARE-HRT1 evaluated in the study demonstrated steady state release levels in month 3 of the 12-week study as shown in the table below:
|
|
Steady
State Cavg
(standard deviation) |
DARE-HRT1
IVR1 (n=11) |
|
|
Estradiol
|
|
22.17
(4.47) pg/mL |
Progesterone |
|
1.25
(0.34) ng/mL |
DARE-HRT1
IVR2 (n=10) |
|
|
Estradiol |
|
38.97
(10.79) pg/mL |
Progesterone |
|
1.80
(0.28) ng/mL |
The
levels of estradiol released from both the lower and higher dose formulation of DARE-HRT1 evaluated in the study achieved or exceeded
the levels that were targeted for hormone therapy. Target levels of estradiol for hormone treatment for either the VMS or vaginal symptoms
of menopause were established by reviewing PK levels published for FDA-approved products for both the treatment of VMS as well as the
genitourinary symptoms of menopause. Based on the estradiol PK data in the DARE-HRT1 Phase 1/2 study, the results support the potential
of DARE-HRT1 as an effective hormone therapy for both VMS and vaginal symptoms associated with menopause. The levels of progesterone
released from both versions of DARE-HRT1 evaluated in the study met the objectives of releasing progesterone. Progesterone is used in
hormone therapy to reduce the impact of estrogen on nontarget sites, such as the endometrium, to prevent estrogen-induced endometrial
hyperplasia.
The
levels of estradiol released from both the lower and higher dose formulation of DARE-HRT1 evaluated in the study achieved statistically
significant improvement in VMS as well as the genitourinary symptoms of menopause, and vaginal pH and maturation index.
Menopausal
symptoms, including hot flashes and night sweats, were reduced compared with baseline in both DARE-HRT1 dose groups (p<0.01). Participants
also showed significant improvement from baseline in all measures surveyed on The Menopausal Quality of Life Survey (MENQOL), which surveys
not only parameters of VMS, but also physical, psychosocial and sexual symptoms (p<0.01 on all domains). With DARE-HRT1 use, vaginal
pH significantly decreased compared to baseline (p<0.01) and cytologic tests of the vaginal epithelium (vaginal maturation index)
showed significant normalization (all p values <0.01 for increases in superficial cells, increases in intermediate cells and decreases
in parabasal cells from baseline) among all participants. The most common genitourinary symptom, vaginal dryness, which was reported
by 70% of participants at baseline, showed significant improvement in both DARE-HRT1 groups (p<0.01) and this subset also experienced
significant decreases in vaginal pain with DARE-HRT1 use (p<0.01).
The
study treatment was well tolerated with the types of most common adverse events consistent with other vaginal products. There were only
two early discontinuations due to an adverse event, and no serious adverse events were reported.
DARE-HRT1
had a high level of acceptability in the study, with 100% of subjects reporting that the IVR was comfortable to wear, and there were
no reports of the IVR being expelled from the vagina during use. Additionally, over 95% of subjects stated they would be either somewhat
or very likely to use the IVR for a women’s health condition or unrelated disease if needed.
Included
as Exhibit 99.2 to this report is a presentation about Daré and its product and product candidates, dated January 9, 2023, which
is incorporated herein by reference. Daré intends to use the presentation and its contents in various meetings with investors,
securities analysts and others, commencing on January 9, 2023.
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. Forward-looking statements include, but are not limited to, statements relating to DARE-HRT1’s potential
as a safe and effective hormone therapy for symptoms of menopause, DARE-HRT1’s potential to be the first FDA-approved monthly IVR
product delivering both estrogen and progestogen hormone therapy for symptoms of menopause, the importance of the Phase 1/2 clinical
study results to Daré and DARE-HRT1, the anticipated regulatory approval pathway for DARE-HRT1, and the potential for FDA approval
of DARE-HRT1 for the treatment of moderate to severe VMS due to menopause in women with intact uteri based on a single Phase 3 clinical
trial together with study data that establishes a scientific bridge to the selected listed drugs. 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; the risk that development of a product candidate requires
more clinical or nonclinical studies than Daré anticipates, or that the duration of a study or number of study subjects must be
significantly greater than anticipated; 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 such as inflation, rising interest rates 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 commence, 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 impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; 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.