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Item 1. Business

2024-03-28 compared with 2023-03-30 · 332 added, 256 removed, 1051 unchanged (36% of the section changed)

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We are driven by a mission to identify, develop and bring to market a diverse portfolio of differentiated therapies that prioritize women's health and well-being, expand treatment options, and improve outcomes, primarily in the areas of contraception, vaginal health, reproductive health, menopause, sexual health and fertility.

Our first product, XACIATO [zah-she-AH-toe] (clindamycin phosphate) vaginal gel, 2%, was approved by the FDA in December 2021 as a single-dose prescription medication for the treatment of bacterial vaginosis in female patients 12 years of age and older.

In March 2022, we entered into an exclusive global license agreement with an affiliate of Organon & Co., Organon International GmbH, or Organon, to commercialize XACIATO, which became fully effective in June 2022.

Accordingly, our potential future revenue from the commercialization of XACIATO will consist of royalties based on net sales and milestone payments from Organon as discussed below.

We anticipate the first commercial sale of XACIATO in the U.S.

to occur in the first half of 2023.

Our business strategy is to in-license or otherwise acquire the rights to differentiated product candidates in our areas of focus, some of which have existing clinical proof-of-concept data, to take those candidates through mid to late-stage clinical development or regulatory approval, and to establish and leverage strategic collaborations to achieve commercialization.

We and our wholly-owned subsidiaries operate in one business segment.

The first FDA-approved product to emerge from our portfolio of women's health product candidates is XACIATO (clindamycin phosphate) vaginal gel 2%, or XACIATO (pronounced zah-she-AH-toe).

XACIATO was approved by the FDA in December 2021 as a single-dose prescription medication for the treatment of bacterial vaginosis in females 12 years of age and older.

In March 2022, we entered into an agreement with an affiliate of Organon & Co., Organon International GmbH, or Organon, which became fully effective in June 2022, whereby Organon licensed exclusive worldwide rights to develop, manufacture and commercialize XACIATO.

Accordingly, our potential future revenue from the commercialization of XACIATO will consist of royalties based on net sales and milestone payments from Organon.

Organon commenced U.S.

marketing of XACIATO in the fourth quarter of 2023.

We began assembling our diverse portfolio of clinical-stage product candidates and pre-clinical programs in 2017 through acquisitions, exclusive in-licenses and other collaborations.

Our programs target unmet needs in women's health in the areas of contraception, vaginal health, reproductive health, menopause, sexual health and fertility, and aim to expand treatment options, enhance outcomes and improve ease of use for women.

While we are currently focused on progressing the development of our existing product candidates, we continue to explore opportunities to expand our portfolio in women's health by leveraging assets to which we hold rights or by obtaining rights to new assets.

We are primarily focused on progressing the development of our existing portfolio of product candidates.

However, we also explore opportunities to expand our portfolio by leveraging assets to which we hold rights or obtaining rights to new assets, with continued focus solely on women's health.

We believe the product candidates in our portfolio offer innovative approaches that may provide meaningful benefits over current therapeutic or contraceptive options.

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Our product candidates, if approved for commercial sale, would be physician prescribed products.

The following graphic summarizes our portfolio, including targeted indications, development status and milestones:

The following graphic summarizes the product and product candidates in our portfolio in advanced clinical development (Phase 2-ready to Phase 3), including targeted indications, development status and milestones:

The following graphic summarizes the product candidates in our portfolio in earlier stages of development, including targeted indications, development status and milestones:

Our goal is to bring to market innovative products that address persistent unmet needs in women’s health, primarily in the areas of contraception, vaginal health, reproductive health, menopause, sexual health and fertility - areas in women's health that we believe represent compelling and meaningful market opportunities for products that enhance outcomes and convenience.

We plan to achieve this goal by advancing the drug and drug/device combination product candidates in our portfolio through mid- to late-stage clinical development, and potentially regulatory approval, as well as by establishing and leveraging strategic partnerships and other collaborations to complete product development and commercialize our products, if approved.

We are also exploring opportunities to expand our portfolio through both business development activities that may result in acquiring, or acquiring access to, new product candidates through in-licensing or other collaborative arrangements, and leveraging platform technology assets we previously acquired or in-licensed from third parties that can be modified with different active pharmaceutical ingredients to address multiple indications.

We plan to achieve this goal by advancing the product candidates in our portfolio through mid- to late-stage clinical development, and potentially regulatory approval, as well as by establishing and leveraging strategic partnerships and other collaborations to complete product development and commercialize our products, if approved.

We are primarily focused on progressing the development of our existing portfolio of product candidates.

However, we also explore opportunities to expand our portfolio through both business development activities that may result in acquiring, or acquiring access to, new product candidates through in-licensing or other collaborative arrangements, and leveraging platform technology assets we previously acquired or in-licensed from third parties that can be modified with different active pharmaceutical ingredients to address multiple indications.

As with our current portfolio, we seek innovations in women’s health that have (a) attractive market opportunities with the potential to address an unmet medical need, including through new formulations, manners of application or delivery methods of well-known drug substances that result in novel, product candidates customized for women, (b) human proof-of-concept clinical data previously generated by third parties and/or potential to utilize the FDA's 505(b)(2) pathway, and (c) potential to become a first-in-category or first-line product.

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• Advance clinical development of the product candidates in our portfolio through mid- to late-stage clinical development or regulatory approval .

In 2022, we continued to make important progress in the clinical development of our product candidates, including with (i) the completion of, and positive topline results from, Phase 1/2 studies for DARE-HRT1 and for DARE-VVA1, both of which were conducted by our wholly owned subsidiary in Australia;

(ii) the completion of subject screening for our exploratory Phase 2b RESPOND study of Sildenafil Cream, 3.6%;

and (iii) preparations for a pivotal Phase 3 study of Ovaprene.

In 2023, we plan to build upon that progress, including through the (A) expected announcement of topline results from the exploratory Phase 2b RESPOND study of Sildenafil Cream, 3.6%, (B) commencement of the pivotal Phase 3 study of Ovaprene, (C) preparations for a Phase 3 study of DARE-HRT1, and (D) completion of the Phase 1 study of DARE-PDM1.

In 2023, we continued to make important progress in the clinical development of our product candidates, including with the completion of, and positive topline results from the exploratory Phase 2b RESPOND study of Sildenafil Cream, 3.6%, the Phase 1/2 study of DARE-HRT1 and the Phase 1 study of DARE-PDM1, as well as FDA clearance of our investigational new drug, or IND, application for DARE-VVA1 and the commencement of the pivotal Phase 3 study of Ovaprene.

• Explore opportunities to expand our portfolio, with women’s health as our sole focus .

While simultaneously advancing our current portfolio, we intend to continue to identify other important areas of unmet need in women’s health and to explore opportunities to build our product pipeline by acquiring or in-licensing new programs or leveraging assets we previously acquired or in-licensed to create new programs that meet our selection criteria.

In 2022, we announced three new development programs, DARE-PDM1, DARE-GML and DARE-LBT, which are discussed in more detail below.

For example, in 2023, we entered into a license agreement under which we acquired exclusive rights to develop and commercialize in the U.S.

an investigational anti-viral vaginal insert, which we refer to as DARE-CIN, for the treatment of cervical intraepithelial neoplasia and other human papillomavirus (HPV)-related pathologies.

• Pursue strategic collaborations to fund our business and/or enhance our development and commercialization capabilities .

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We intend to advance development of our programs through a variety of means, including through non-dilutive funding.

To date, we have received non-dilutive funding to support various aspects of development of Ovaprene, DARE-LARC1, DARE-204/214, DARE-PTB1 and DARE-LBT1.

To date, we have received non-dilutive funding to support various aspects of development of seven of our product candidates.

We intend to continue to explore grants and other forms of non-dilutive funding to support development of our product candidates.

XACIATO (clindamycin phosphate) vaginal gel (formerly known as DARE-BV1), a lincosamide antibacterial, received FDA approval in December 2021 for the treatment of bacterial vaginosis in female patients 12 years of age and older.

XACIATO is a clear, colorless, viscous gel, which contains clindamycin at a concentration of 2%, to be administered once intravaginally as a single dose.

XACIATO is our first and only approved product.

XACIATO (clindamycin phosphate) vaginal gel, a lincosamide antibacterial, received FDA approval in December 2021 for the treatment of bacterial vaginosis in female patients 12 years of age and older.

XACIATO is our first and, to date, only approved product.

We achieved FDA approval of XACIATO three years after acquiring rights to the program.

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See "Strategic Agreements for Product Commercialization" below for further discussion of the terms of our agreement with Organon.

Organon has publicly announced that it aims to launch XACIATO in the United States in the first half of 2023 and plans to assess opportunities and potentially seek further marketing authorizations for countries outside the United States.

Under the terms of our agreement with Organon, we will remain the NDA holder of XACIATO for an interim period.

Upon Organon's request, we will assist with the transfer of the NDA by the FDA and the transfer of manufacturing responsibilities to Organon.

As the NDA holder, we will continue to be responsible for regulatory and compliance matters following commercial launch, though Organon is responsible for commercializing, promoting, determining pricing, and negotiating reimbursement matters related to XACIATO.

We remained the NDA holder of XACIATO until December 2023, at which time the NDA was transferred by the FDA to Organon, and Organon assumed all manufacturing responsibilities, regulatory and compliance matters.

Organon is also responsible for commercializing, promoting, determining pricing, and negotiating reimbursement matters related to XACIATO.

See "Sales and Marketing" below for further discussion of manufacturing for XACIATO and "Government Regulation—U.S.

Government Regulation" below for discussion of applicable laws and compliance requirements.

Organon commenced U.S.

marketing of XACIATO in the fourth quarter of 2023.

In December 2023, we entered into a royalty interest financing agreement pursuant to which we sold an interest in the royalty and milestone payments we receive from Organon in respect of the net sales of XACIATO by Organon.

See "Royalty Interest Financing Agreement" below for a discussion of this agreement.

XACIATO previously received both Qualified Infectious Disease Product (QIDP) and Fast Track designations from the FDA for the treatment of bacterial vaginosis in women.

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Ovaprene is composed of both device and drug components and is considered a combination product by the FDA.

Ovaprene previously underwent a request for designation process with the FDA that determined that the Center for Devices and Radiological Health, or CDRH, would lead the review of a premarket approval, or PMA, for potential marketing approval in the U.S.

There is no predicate device for Ovaprene (i.e., there is no existing FDA-approved product that the FDA can use to compare with Ovaprene).

As such, Ovaprene will be reviewed via a premarket approval, or PMA, process and not a 510(k) premarket submission.

While the regulatory process for such a novel product can require more interactions and research to support FDA approval, the benefit is a clearly differentiated product.

Ovaprene previously underwent a request for designation process with the FDA that determined that the Center for Devices and Radiological Health, or CDRH, would lead the review of a PMA application for potential marketing approval in the U.S.

Clinical Data

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No colposcopic abnormalities, no significant changes in vaginal flora and no serious adverse effects were observed.

In November 2019, we announced positive topline results of our PCT clinical trial of Ovaprene.

In November 2019, we announced positive topline results of our PCT clinical trial of Ovaprene (ClinicalTrials.gov ID:

NCT03598088).

We designed the PCT clinical trial to assess general safety and effectiveness in preventing progressively motile sperm from reaching the cervical canal following intercourse and acceptability of the product to the patient.

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Pivotal Phase 3 Clinical Study

In October 2022, we announced that the FDA approved an Investigational Device Exemption, or IDE, application allowing us to conduct a single arm, open-label pivotal contraceptive efficacy study of Ovaprene.

The multi-center, non-comparative pivotal Phase 3 clinical study will evaluate Ovaprene’s effectiveness as a contraceptive device along with its safety and usability over a 12-month (13 menstrual cycles) duration.

We are targeting approximately 200 to 250 subjects to complete the study, and because contraceptive efficacy studies tend to have high drop-out rates, the study will enroll significantly more women in order to achieve the targeted number for completion.

If successful, the study is expected to support a PMA application to the FDA, as well as regulatory filings in Europe and other countries worldwide, to allow for marketing approvals of Ovaprene.

Initiation of recruitment for the study is targeted for mid-2023.

There is no predicate device for Ovaprene (i.e., there is no existing FDA-approved product that the FDA can use to compare with Ovaprene).

As such, Ovaprene will be reviewed via a PMA and not a 510(k) premarket submission.

While the regulatory process for such a novel product can require more interactions and research to support FDA approval, the benefit is a clearly differentiated product.

In order for the planned Phase 3 study to serve as the primary clinical support for a future marketing approval or clearance, the FDA provided additional study design considerations with the IDE approval letter.

We have been working with our collaborators at the National Institutes of Health, or NIH, and at Bayer to review and implement the FDA's study design considerations, which we believe will further position the study to collect safety and effectiveness data to enable the preparation of, and to support the submission of, a PMA application for Ovaprene.

In 2021, we entered into a CRADA, with the U.S.

Department of Health and Human Services, as represented by NICHD, part of the NIH, for the conduct of the Phase 3 study, which will be conducted within NICHD’s

Contraceptive Clinical Trial Network.

In December 2023, we announced commencement of the multi-center, single arm, non-comparative, pivotal Phase 3 clinical study of Ovaprene to evaluate its effectiveness as a contraceptive along with its safety and acceptability (ClinicalTrials.gov ID:

NCT06127199).

The study aims to enroll sufficient participants across approximately 20 study sites in the U.S.

to have approximately 250 participants complete approximately 12 months (13 menstrual cycles) of use.

Based on typical dropout rates for contraceptive efficacy studies, we will seek to enroll more than double the number of subjects we target to complete 13 menstrual cycles of use.

Before commencing the study, we worked with our collaborators at the National Institutes of Health, or NIH, and at Bayer to review and implement study design considerations provided by the FDA with its Investigational Device Exemption, or IDE, approval letter, which we believe will further position the Phase 3 study to collect safety and effectiveness data to enable the preparation of, and to support the submission of, a PMA application for Ovaprene.

The primary objective of the study is to assess the typical use pregnancy rate over 13 menstrual cycles, or the estimated Pearl Index for Ovaprene.

Secondary objectives are to assess Ovaprene's 13-cycle use cumulative pregnancy rate, safety, acceptability, product fit/ease of use, and assessments of vaginal health.

If successful, we expect the study to support a PMA application to the FDA, as well as regulatory filings in Europe and other countries worldwide, to allow for marketing approvals of Ovaprene.

The Phase 3 study is being conducted under our Cooperative Research and Development Agreement, or CRADA, with the U.S.

Department of Health and Human Services, as represented by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, or NICHD, part of the NIH, and within NICHD’s Contraceptive Clinical Trial Network.

We and NICHD will each provide medical oversight and final data review and analysis for the study and will work together to prepare the final report of the results of the study.

We are responsible for providing clinical supplies of Ovaprene, coordinating interactions with the FDA, preparing and submitting supportive regulatory documentation, and providing a total of $5.5 million to NICHD to be applied toward the costs of conducting the Phase 3 study, $5.0 million of which has been paid and the remaining amount is due in the second quarter of 2023.

NICHD will be responsible for the other costs related to the conduct of the Phase 3 study and will manage the payment of expenses to the contract research organization for the study, the clinical sites, and other parties involved with the study.

NICHD is responsible for the other costs related to the conduct of the Phase 3 study and for managing the payment of expenses to the contract research organization for the study, the clinical sites, and other parties involved with the study.

We expect to make the remaining $0.5 million payment to NICHD in the third quarter of 2024.

In the future, depending on the duration of the enrollment period and number of subjects enrolled in the Phase 3 study, there may be costs associated with the study that are not reflected in the current budget under the CRADA, in which case, we and NICHD would discuss the mechanism to potentially provide for additional future payments by us in support of the Phase 3 study.

We do not expect any such potential additional amounts to be payable in 2024.

In addition to the CRADA, we are collaborating with ADVA-Tec, Inc., or ADVA-Tec, and Bayer HealthCare LLC, or Bayer, for the development and commercialization of Ovaprene as part of two strategic collaborations announced in March 2017 and January 2020, respectively.

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While numerous pharmaceutical products have been developed and approved to treat erectile dysfunction in men, women continue to lack effective options for female sexual arousal disorder, or FSAD, the most analogous condition of the various types of female sexual dysfunction disorders.

We are developing Sildenafil Cream, 3.6%, an investigational proprietary cream formulation of sildenafil, a phosphodiesterase-5 inhibitor and the active ingredient in the male erectile dysfunction drug Viagra®, for topical administration to the female genitalia for treatment of FSAD.

Today, there are no FDA-approved products that specifically address the symptoms or underlying pathology of FSAD.

We are developing Sildenafil Cream, 3.6%, or Sildenafil Cream, an investigational proprietary cream formulation of sildenafil, a phosphodiesterase-5 inhibitor and the active ingredient in the male erectile dysfunction drug Viagra®, for topical administration to the female genitalia for treatment of FSAD.

Today, there are no treatments approved by the FDA for FSAD and thus, there are no efficacy endpoints that have been previously validated in a Phase 3 pivotal study for potential treatments for FSAD.

Our Phase 2b RESPOND clinical study of Sildenafil Cream, which is discussed further below, was a first of its kind Phase 2b clinical study that included patient reported outcome (PRO) instruments to screen eligible women and a number of primary, secondary, and exploratory PRO assessments to measure improvement in localized genital sensations of arousal and reduction in the distress that women experience with FSAD.

We are developing the study design for Phase 3 clinical studies of Sildenafil Cream with ongoing feedback from the FDA coming out of our end-of-Phase 2 meeting with the FDA held in late 2023.

We expect the FDA to complete its review of the Phase 2b RESPOND clinical study data and provide comments within the second quarter of 2024 on the proposed primary and secondary PRO endpoints for the planned Phase 3 pivotal trials of Sildenafil Cream to support potential product registration and labeling.

We plan to leverage the existing data and established safety profile of sildenafil and the Viagra® brand to utilize the FDA’s 505(b)(2) pathway to obtain marketing approval of Sildenafil Cream in the U.S.

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If approved, Sildenafil Cream could be the first FDA-approved FSAD treatment option for women.

FSAD is a condition characterized primarily by 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.

This is distinct from hypoactive sexual desire disorder (HSDD) in women, which is characterized primarily by a lack of sexual desire (also commonly referred to as low libido).

FSAD, as described in the Diagnostic and Statistical Manual of Mental Disorders 4th Edition Text Revision ("DSM IV TR"), is a condition characterized primarily by 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.

This is distinct from hypoactive sexual desire disorder (HSDD) in women (also described in DSM IV TR), which is characterized primarily by lack or absence of sexual fantasies and desire for sexual activity (also commonly referred to as low libido).

As with erectile dysfunction in men, FSAD in women is associated with insufficient blood flow to the genitalia.

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Sildenafil Cream demonstrated increases in measurable blood flow to the genital tissue compared to placebo (mean change in vaginal pulse amplitude analysis) using a vaginal photoplethysmograph approximately 30 minutes post-dosing.

A Phase 1, single-dose, double-blind, placebo-controlled, two-way crossover study to evaluate the feasibility of using thermography to assess the pharmacodynamics of Sildenafil Cream, 3.6% in normal healthy women was conducted at a single center.

A Phase 1, single-dose, double-blind, placebo-controlled, two-way crossover study to evaluate the feasibility of using thermography to assess the pharmacodynamics (PD) of Sildenafil Cream in normal healthy women was conducted at a single center.

During the thermography study, genital temperature, a surrogate for genital blood flow, was captured and recorded utilizing an infrared camera capable of detecting heat patterns from blood flow in body tissues.

The study, which was designed to evaluate up to 10 subjects, achieved the study objectives based on a planned interim analysis of the first six completed subjects, and thus additional subjects were not enrolled.

In this study, Sildenafil Cream, 3.6% demonstrated significantly greater increases in genital temperature compared to placebo cream, indicating a positive impact on genital blood flow during the 30-minute post-dosing testing session,

with statistical separation from placebo cream within the first 15 minutes after dosing.

In this study, Sildenafil Cream demonstrated significantly greater increases in genital temperature compared to placebo cream, indicating a positive impact on genital blood flow during the 30-minute post-dosing testing session, with statistical separation from placebo cream within the first 15 minutes after dosing.

Additionally, significantly greater self-reported arousal responses were reported during Sildenafil Cream visits compared to placebo cream visits.

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The findings of that study helped facilitate alignment with the FDA on acceptable efficacy endpoints in our exploratory Phase 2b clinical study and future Phase 3 program, including with respect to the patient reported outcome, or PRO, instruments to be used to screen eligible patients with FSAD and to measure achievement of the primary efficacy endpoint in the Phase 2b study.

Exploratory Phase 2b RESPOND Clinical Study

In 2021, we commenced our exploratory Phase 2b RESPOND clinical study of Sildenafil Cream, 3.6% in premenopausal patients with FSAD.

During the multi-center, double-blind, placebo-controlled study, subjects use Sildenafil Cream, 3.6% and placebo cream in their home setting and document genital arousal symptoms and distress using PRO instruments.

The primary efficacy endpoint of the study is a composite endpoint that includes patient-reported improvement in genital sensations of arousal and reduction in distress associated with FSAD.

The study is designed to evaluate Sildenafil Cream, 3.6% compared to placebo cream over 12 weeks of dosing following both a non-drug and placebo run-in period.

In November 2022, we announced the completion of subject screening.

A total of approximately 160 to 170 subjects (approximately 80 to 85 subjects per arm) are expected to complete the study's 12 week double blind dosing period for inclusion in the topline data assessment, targeted for the second quarter of 2023.

The study was originally expected to randomize a minimum of 400 subjects into the double-blind dosing period from 40 to 50 sites in the U.S.

to achieve 150 subjects per arm completing the 12-week double-blind dosing period.

In August 2022, we announced that, based on the results of an interim analysis to evaluate the relative magnitude of the treatment effect, we expected to complete enrollment in the study with the revised projected number of subjects.

The interim analysis was conducted by an independent third-party statistical resource and we, as well as our collaborator, Strategic Science & Technologies, LLC, continue to remain blinded to results of the study by treatment group.

The reduction in the number of subjects should not be viewed as indicative of the magnitude of the treatment effect and the relative magnitude of the treatment effect seen in the interim analysis should not be viewed as predictive that topline data will show Sildenafil Cream, 3.6% achieved the efficacy endpoints of the exploratory Phase 2b RESPOND study.

Because we have not identified comparable clinical studies for FSAD conducted by third parties to consider when designing our clinical trials of Sildenafil Cream, 3.6%, we designed the exploratory Phase 2b RESPOND study to provide important data for Sildenafil Cream, 3.6% intended to help us assess potential efficacy endpoints for our future Phase 3 clinical studies.

In April 2023, we initiated subject enrollment in a Phase 1, single-dose, double-blind, placebo-controlled, 3-way crossover clinical study of Sildenafil Cream using thermography to assess the PD and pharmacokinetic (PK) characterization of Sildenafil Cream.

The study was closed in March 2024.

Sildenafil Cream was safe and well tolerated in the study.

Data from the study will expand our existing clinical and nonclinical data for Sildenafil Cream and are expected to support the ongoing development of Sildenafil Cream as a potential treatment for FSAD.

In June 2023, we announced topline results from our exploratory Phase 2b RESPOND clinical study of Sildenafil Cream in premenopausal women with FSAD, and in July and November 2023, we announced additional findings based on further analyses of data from the study.

In February 2024, we presented additional findings from the study at the Annual Meeting of the International Society for the Study of Women's Sexual Health.

During the multi-center, double-blind, randomized, placebo-controlled study, subjects used Sildenafil Cream and placebo cream in their home setting over 12 weeks following a 4-week non-drug run-in period and a 4-week, single-blind placebo run-in period.

A total of 252 subjects were enrolled in the 4-week single-blind placebo run-in period and a total of 200 subjects were randomized to the 12-week double-blind dosing period.

A total of seven subjects were randomized but not treated in the double-blind dosing period.

In the intent to treat (ITT) population, 99 subjects were randomized to the Sildenafil Cream group and 94 subjects were randomized to the placebo cream group.

The study did not meet its co-primary or secondary endpoints, which were measured based on the ITT population.

However, subjects in the Sildenafil Cream group showed improvements in multiple pre-specified exploratory endpoints that evaluated various aspects of the sexual experience, and we view the study results as positive and enabling of advancement of Sildenafil Cream into Phase 3 clinical development, which was confirmed by successful completion of our end-of-Phase 2 meeting with the FDA.

The RESPOND study was a first of its kind Phase 2b clinical study that enabled us to identify a subgroup of patients who are most likely to benefit from Sildenafil Cream therapy and achieve meaningful improvement in their FSAD symptoms.

Based on post hoc analyses, in a subgroup of study subjects consisting of healthy premenopausal women with FSAD, including those who suffered from a lack of sexual desire due to their decreased arousal, Sildenafil Cream demonstrated improved arousal sensation, desire, orgasm, as well as reduced stress, guilt, and embarrassment about the sexual dysfunction.

End-of-Phase 2 Meeting and Phase 3 Program

In January 2024, we announced the successful completion of an end-of-Phase 2 meeting with the FDA.

We and the FDA aligned on key elements of the Phase 3 program to support an NDA filing, including confirming that FSAD is acceptable as an indication, the clinical trials can be conducted in a premenopausal FSAD-only population,

and 12-weeks of blinded treatment to assess efficacy may be acceptable, provided that the trials are adequately powered for efficacy assessment.

This is a shorter period of blinded treatment than the 24 weeks recommended in the FDA's 2016 draft guidance for industry on developing drugs for the treatment of low sexual interest, desire and/or arousal in women.

Within the second quarter of 2024, we expect additional feedback from the FDA on our proposed primary and secondary patient reported outcome endpoints for the Phase 3 pivotal trials of Sildenafil Cream, as well as additional information on data that may be needed in an NDA submission to appropriately qualify any ingredient (other than sildenafil) for the vaginal route of administration.

We have also requested clarification on the safety database (size and duration exposure) that the FDA will require for an NDA submission.

We believe FSAD is an area of significant unmet need and that the improvements demonstrated in the Phase 2b RESPOND study in the patient population we plan to study in the Phase 3 program provided an important step towards advancing development of Sildenafil Cream for this challenging condition.

We continue to work toward finalizing the plan for Phase 3 clinical development of Sildenafil Cream.

We are developing Sildenafil Cream with Strategic Science & Technologies-D LLC and Strategic Science & Technologies, LLC (which we refer to collectively as SST) under our license and collaboration agreement announced in February 2018.

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of DARE-HRT1 for the treatment of moderate-to-severe VMS due to menopause in women with intact uteri.

Based on pre-IND communications with the FDA and the topline pharmacokinetic, or PK, data from our Phase 1/2 clinical trial of DARE-HRT1, which is discussed below, we believe 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.

Ongoing activities to support progressing DARE-HRT1 directly into a single Phase 3 clinical study to support registration include manufacturing and non-clinical studies to support an investigational new drug, or IND, submission and the IND-opening Phase 3 study.

Based on pre-IND communications with the FDA and the topline PK data from our Phase 1/2 clinical trial of DARE-HRT1, which is discussed below, we believe 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, with safety evaluations out to 12 months, and a scientifically justified PK “bridge” (via a relative bioavailability trial) between DARE-HRT1 and the selected listed estradiol and progesterone drugs.

We are conducting activities necessary to enable submission of an IND application to the FDA for a pivotal Phase 3 clinical study of DARE-HRT1.

We do not plan to conduct the Phase 3 study until after we secure additional capital.

There are currently no FDA-approved IVRs that deliver bio-identical progesterone in combination with bio-identical estradiol.

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In January 2023, data from our Phase 1 clinical trial of DARE-HRT1 were published in Menopause:

The Journal of The North American Menopause Society in an article entitled, “Evaluation of 28-day estradiol and progesterone vaginal rings in a phase 1 clinical pharmacokinetic study.” We previously announced positive topline results from the study in June 2021.

The Journal of The North American Menopause Society, or the Menopause journal, in an article entitled, “Evaluation of 28-day estradiol and progesterone vaginal rings in a phase 1 clinical pharmacokinetic study.” We previously announced positive topline results from the study in June 2021.

The randomized, open-label, three-arm, parallel group trial evaluated the PK and safety of DARE-HRT1 in approximately 30 healthy, postmenopausal women with intact uteri, and was conducted by our wholly-owned Australian subsidiary at two specialty women's health sites in Australia.

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DARE-HRT1 has also been evaluated in a Phase 1/2 clinical trial conducted by our wholly owned subsidiary in Australia.

We announced topline results from the Phase 1/2 study in January 2023 and October 2022, and we believe topline results from the study support continued clinical development of DARE-HRT1.

The randomized, open-label, two-arm, parallel group Phase 1/2 study of DARE-HRT1 was designed to evaluate the PK of the same two versions of DARE-HRT1 as were evaluated in our earlier Phase 1 clinical study, the 80/4 IVR and the 160/8 IVR, in approximately 20 healthy, postmenopausal women with intact uteri over approximately three consecutive months of use.

In the study, women were randomized (1:1) to either the 80/4 IVR or the 160/8 IVR and used DARE-HRT1 for three 28-day cycles, inserting a new IVR monthly.

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 E2 and P4 over the 12-week evaluation period.

The baseline-corrected steady state release of E2 and P4 from both the 80/4 IVR and the 160/8 IVR demonstrated steady state release levels in month 3 of the 12-week study as shown in the table below:

Steady State C a vg (standard deviation)

DARE-HRT1 80/4 IVR (n=11)

Estradiol (E2)

22.17 (4.47) pg/mL

Progesterone (P4)

1.25 (0.34) ng/mL

DARE-HRT1 160/8 IVR (n=10)

Estradiol (E2)

38.97 (10.79) pg/mL

Progesterone (P4)

1.80 (0.28) ng/mL

The levels of E2 released from both the 80/4 IVR and the 160/8 IVR achieved or exceeded the levels that were targeted for hormone therapy for either the VMS or vaginal symptoms of menopause based on PK levels published for FDA-approved products for both the treatment of VMS as well as the genitourinary symptoms of menopause.

Based on the E2 PK data in the 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 P4 released from both the 80/4 IVR and the 160/8 IVR met the objectives of releasing P4.

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 E2 released from both the 80/4 IVR and the 160/8 IVR 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 the 80/4 IVR and the 160/8 IVR 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 the 80/4 IVR and the 160/8 IVR groups (p<0.01), and this subset also experienced significant decreases in vaginal pain with DARE-HRT1 use (p<0.01).

Both IVRs were well tolerated with the types of most common adverse events consistent with other vaginal products.

There were two early discontinuations due to well known, hormonal related side effects.

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.

Preliminary genitourinary syndrome of menopause (GSM) treatment efficacy was estimated by measuring changes from baseline in vaginal pH, vaginal maturation index (VMI), and changes in the severity of GSM symptoms.

Preliminary systemic VMS efficacy was measured by changes in responses to the Menopause-Specific Quality of Life (MENQOL) questionnaire.

Acceptability was assessed by product experience surveys.

In 2023, data from the Phase 1/2 study of DARE-HRT1 were published in the Menopause journal in articles entitled, “A phase 1/2, open-label, parallel group study to evaluate the safety and pharmacokinetics of DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal rings) over 12 weeks in healthy postmenopausal women” ( Menopause 30(8):p 817-823, August 2023) and “A phase 1/2, open-label, parallel group study to evaluate the preliminary efficacy and usability of DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal rings) over 12 weeks in healthy postmenopausal women” ( Menopause 30(9):p 940-946, September 2023).The first article ( Menopause 30(8):p 817-823, August 2023) found that both versions of DARE-HRT1 evaluated in the Phase 1/2 study were safe and released E2 in systemic concentrations, which were in the low, normal premenopausal range and that systemic P4 concentrations predict endometrial protection.

All treatment emergent adverse events were mild or moderate and were distributed similarly among the 80/4 IVR and the 160/8 IVR users.

The second article ( Menopause 30(9):p 940-946, September 2023) found that (a) preliminary local GSM treatment efficacy was supported by significant decreases in vaginal pH and percentage (%) parabasal cells, and significant increases in the overall VMI and % superficial cells for both DARE-HRT1 groups (all P values <0.01) and (b) preliminary VMS efficacy was supported by significant decreases in all domains of the MENQOL questionnaire from baseline for both dosing groups (all P values <0.01).

Both articles concluded that data from the Phase 1/2 study support further development of DARE-HRT1 for the treatment of menopausal symptoms.

We are developing DARE-HRT1 under our license agreement with Catalent JNP, Inc.

See “Strategic Agreements for Pipeline Development” below for discussion of the terms of that agreement.

DARE-VVA1 is a proprietary formulation of tamoxifen for intravaginal administration.

We are developing DARE-VVA1 as a hormone-free alternative to estrogen-based therapies for the treatment of moderate to severe vulvar and vaginal atrophy, or VVA.

DARE-VVA1 is a proprietary investigational formulation of tamoxifen for intravaginal administration.

We are developing DARE-VVA1 as a hormone-free alternative to estrogen-based therapies for the treatment of moderate-to-severe dyspareunia, or pain during sexual intercourse, a symptom of vulvar and vaginal atrophy, or VVA, associated with menopause.

Tamoxifen is a well-known and well-characterized selective estrogen receptor modulator, or SERM.

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This has the potential to have a favorable effect on vaginal cytology.

VVA is an inflammation of the vaginal epithelium due to the reduction in levels of circulating estrogen, which is characterized by pain during intercourse, vaginal dryness and irritation.

VVA is an inflammation and thinning of the vaginal epithelium due to chronic hypo-estrogenism, which is the reduction in levels of circulating estrogen.

Typical symptoms include vaginal dryness, itching and burning, and dyspareunia.

VVA is a common condition in postmenopausal women and women with, or with a history of, HR+ breast cancer who received anti-cancer therapy.

The prevalence of VVA in postmenopausal breast cancer patients is estimated to be between 42 and 70 percent.

The prevalence of VVA in postmenopausal women is over 50% and survey data indicate only 56% of women experiencing menopausal vaginal changes discuss these symptoms with healthcare professionals, indicating that the syndrome is often underdiagnosed.

Commonly used therapies for VVA are estrogen-based and are often contraindicated in HR+ breast cancer patients, or patients with a genetic predisposition or history of familial disease, because of the concern that estrogen use will promote recurrence or occurrence of disease.

We believe there is a clear unmet medical need for an effective non-hormonal treatment for VVA.

In December 2023, we announced FDA clearance of our IND application for DARE-VVA1, which was supported by results from our Phase 1/2 clinical study of DARE-VVA1 (discussed below), and we are planning for a Phase 2 randomized, double-blinded, placebo-controlled, dose-finding clinical study of DARE-VVA1.

We do not plan to conduct the Phase 2 study until after we secure additional capital.

At the conclusion of our development program, if successful, we intend to leverage the existing safety and efficacy data for tamoxifen to utilize the FDA’s 505(b)(2) pathway to obtain marketing approval of DARE-VVA1 in the U.S.

Clinical Data

An exploratory study of vaginal administration of tamoxifen in four healthy postmenopausal women diagnosed with VVA published in Clinical and Experimental Obstetrics & Gynecology demonstrated that tamoxifen self-administered intravaginally for three months clinically benefited women with symptoms of VVA without significant

systemic absorption of the study drug.

In the open-label prospective cohort study with no placebo arm, participants were instructed to self-administer a vaginal suppository containing tamoxifen (20 mg) daily for one week and twice weekly for three months.

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In comparison, after three months of once daily administration of oral dose of 20-mg tamoxifen, Nolvadex® (tamoxifen citrate) tablets, the average steady state plasma concentration of tamoxifen is 122 ng/ml (range of 71 to 183 ng/ml).

DARE-VVA1 has also been evaluated in a Phase 1/2 clinical study conducted by our wholly-owned subsidiary in Australia.

In November 2022, we announced topline results from of our Phase 1/2 clinical study of DARE-VVA1 conducted by our wholly-owned subsidiary in Australia.

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 PK and pharmacodynamics (PD) of DARE-VVA1.

The randomized, multi-center, double-blind, parallel-arm, placebo-controlled, dose-ranging study enrolled 17 postmenopausal women with moderate-to-severe VVA and evaluated the safety, tolerability, plasma 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.

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Secondary endpoints evaluated preliminary efficacy and PD of DARE-VVA1 in terms of the 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.

We believe 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 studied specifically for the treatment of VVA in hormone adverse patients, such as those with, or at risk of recurrence of, HR+ breast cancer.

In 2023, data from our Phase 1/2 study of DARE-VVA1 were published in Climacteric, the official journal of the International Menopause Society, in an article entitled, “Pharmacokinetics, safety and preliminary pharmacodynamic evaluation of DARE-VVA1:

a soft gelatin capsule containing tamoxifen for the treatment of

vulvovaginal atrophy.” The article concluded that DARE-VVA1 was safe and resulted in minimal systemic exposure to tamoxifen.

Adverse events were mild to moderate in severity and distributed similarly among the DARE-VVA1 and placebo groups.

Plasma tamoxifen concentrations were highest among women using DARE-VVA1 20 mg, but the maximum mean (standard deviation) plasma tamoxifen concentrations on day 1 and day 56 of the treatment period were less than 14% of those measured after one oral tamoxifen dose.

The article also concluded that preliminary efficacy data support further development of DARE-VVA1.

The article found that DARE-VVA1 users had significant decreases from pre-treatment baseline in vaginal pH and proportion of vaginal parabasal cells (p = 0.04 for both endpoints).

Women randomized to use DARE-VVA1 10 mg or DARE-VVA1 20 mg experienced the largest treatment impact.

The severity of vaginal dryness and dyspareunia decreased significantly from baseline with DARE-VVA1 use (p = 0.02 for both endpoints).

We acquired the DARE-VVA1 program through our acquisition of Pear Tree Pharmaceuticals in 2018.

See "Strategic Agreements for Pipeline Development" below for discussion of that merger agreement.

DARE-PDM1 is a hydrogel formulation of diclofenac for vaginal administration, designed to treat primary dysmenorrhea.

DARE-PDM1 utilizes our proprietary hydrogel technology to vaginally deliver the active pharmaceutical ingredient, diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), in a novel way.

DARE-CIN (formerly referred to as R-131-2) is an investigational, proprietary fixed-dose formulation of lopinavir and ritonavir in a soft gel vaginal insert, which we plan to develop for the treatment of cervical intraepithelial neoplasia, or CIN (also known as cervical dysplasia), and other HPV-related pathologies.

CIN is a precancerous condition in women strongly linked to HPV infection, the most common sexually transmitted infection in the U.S.

Disease severity is classified on a scale from one to three based on how much epithelial tissue in the cervix has abnormal cells.

There is no FDA-approved non-surgical pharmaceutical intervention to treat CIN2 or CIN3 (collectively referred to as CIN2+).

Current surgical procedures to treat cervical dysplasia are invasive and can adversely impact future pregnancies.

We believe a non-surgical pharmaceutical approach could provide women with an important alternative to surgical procedures to treat cervical dysplasia.

We are conducting limited activities to support an IND submission to the FDA to enable Phase 2 clinical development of DARE-CIN in the United States.

We do not plan to conduct the Phase 2 study until after we secure additional capital.

Clinical Data

DARE-CIN was previously evaluated in a proof-of-concept clinical study and the results demonstrated its potential as a self-applied therapy for HPV infection and related cervical lesions.

DARE-CIN was also previously evaluated in a Phase 1 clinical study to assess PK.

We are developing DARE-CIN under our license agreement with Douglas Pharmaceuticals, Limited.

See "Strategic Agreements for Pipeline Development" below for discussion of the terms of that agreement.

DARE-PDM1 is an investigational proprietary hydrogel formulation of diclofenac for vaginal administration designed to treat primary dysmenorrhea.

DARE-PDM1 utilizes our proprietary hydrogel technology to vaginally deliver the active pharmaceutical ingredient, diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), in a novel way for the treatment of primary dysmenorrhea.

Primary dysmenorrhea is defined as painful menstruation in girls and women with normal pelvic anatomy, typically described as cramping pain in the low back or lower abdomen before or during the menstrual period.

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Prevalence rates of dysmenorrhea vary but range from 50% to 90%.

Phase 1 Clinical Study

In February 2023 we announced the start of a Phase 1 clinical study of DARE-PDM1, which is being conducted by our wholly owned subsidiary in Australia.

The DARE-PDM1 Phase 1 study, DARE-PDM1-001, is a multi-center, randomized, placebo-controlled, double-blind, three-arm parallel group study expected to enroll approximately 36 healthy, premenopausal women with primary dysmenorrhea.

This study is designed to assess the systemic (plasma) and local mucosal (vaginal fluid) diclofenac PK and safety after a single dose and during three daily doses of vaginally administered DARE-PDM1, given in two different strengths (1% or 3% diclofenac in 2.5 mL of hydrogel) versus placebo.

The study will also assess, as an exploratory endpoint, the preliminary dysmenorrhea treatment efficacy of DARE-PDM1, when dosed in three daily doses at the onset of dysmenorrhea symptoms, compared to a no-treatment, baseline, control cycle.

The study observation period will encompass approximately three menstrual cycles.

We anticipate announcing topline data from the study in 2023.

Clinical Data

DARE-PDM1 has been evaluated in a Phase 1 clinical study, DARE-PDM1-001, conducted by our wholly-owned subsidiary in Australia.

DARE-PDM1-001 was a multi-center, randomized, placebo-controlled, double-blind, three-arm parallel group study that enrolled approximately 42 healthy, premenopausal women with symptomatic primary dysmenorrhea.

This study was designed to assess the systemic (plasma) and local mucosal (vaginal fluid) diclofenac PK and safety after a single dose and during three daily doses of vaginally administered DARE-PDM1, given in two different strengths (1% or 3% diclofenac in 2.5 mL of hydrogel) versus placebo (vaginal hydrogel, no active ingredient).

The study also assessed, as an exploratory endpoint, the preliminary dysmenorrhea treatment efficacy of DARE-PDM1, when dosed in three daily doses at the onset of dysmenorrhea symptoms, compared to a no-treatment, baseline, control cycle.

The study observation period encompassed approximately three menstrual cycles.

In December 2023, we announced topline data from the DARE-PDM1-001 study.

The topline data indicate that the study treatment was well-tolerated, and treatment emergent adverse events profiles were comparable between the DARE-PDM1 treatment groups and the placebo group.

All adverse events were mild or moderate;

most adverse events (85%) were mild.

There were no early discontinuations due to an adverse event, and no serious adverse events were reported.

The vaginal fluid PK results exhibited dose proportionality for the 1% and 3% diclofenac strengths of the DARE-PDM1 study treatment.

Additionally, the vaginal fluid PK results demonstrated that for approximately 75% (21/28) of the women in the DARE-PDM1 treatment groups the product was retained in the vaginal canal through 24 hours.

The plasma PK results similarly exhibited dose proportionality for the 1% and 3% diclofenac strengths of the DARE-PDM1 study treatment.

Plasma levels of diclofenac were at peak plasma concentrations within 3-4 hours for both diclofenac strengths of the DARE-PDM1 study treatment, and diclofenac was no longer detectable in the plasma by 48 hours post study treatment for the majority of subjects in the study.

The plasma PK results for both DARE-PDM1 treatment groups indicate that vaginal dosing could result in systemic exposure which is approximately 1,000 times less than that seen from oral use of diclofenac.

The exploratory endpoint that evaluated the preliminary efficacy of DARE-PDM1 versus placebo in reducing dysmenorrhea-associated pain showed a promising signal, with a statistically significant decrease in pelvic/vaginal and lower back pain scores in the 1% diclofenac DARE-PDM1 treatment group compared to the placebo group, as well as a decrease in pain scores in the 3% diclofenac DARE-PDM1 treatment group.

Additionally, while most participants used at least one non-pharmacologic pain relief method (e.g., heating pad) for dysmenorrhea-associated pain during the no-treatment, baseline, control cycle, the proportion of participants who used at least one non-pharmacologic pain relief method for dysmenorrhea-associated pain decreased significantly in the DARE-PDM1 treatment groups during the dosing period, but not in the placebo group.

There was no difference in the exploratory assessment of frequency of use of rescue medications in the treatment phase between the three groups.

We believe the topline results of the Phase 1 study support continued clinical development of DARE-PDM1 as a treatment for primary dysmenorrhea.

At the conclusion of the development program, if successful, we intend to leverage the existing safety and efficacy data for diclofenac to utilize the FDA's 505(b)(2) pathway to obtain marketing approval of DARE-PDM1 in the U.S.

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These product candidates are being developed as a sub-cutaneous injectable, longer-acting, reversible method of contraception with a more predictable return to fertility.

We are conducting development activities in preparation for Phase 1 clinical studies of these product candidates.

We plan to conduct Phase 1 clinical studies of DARE-204 and DARE-214 in Australia through our wholly-owned subsidiary in Australia.

Additional manufacturing activities are necessary to commence the Phase 1 studies and these activities have not commenced.

If we exercise our option and enter into an exclusive worldwide license agreement for DARE-204 and/or DARE-214, at the conclusion of these development programs, if successful, we intend to leverage the existing safety and efficacy data for etonogestrel to utilize the FDA's 505(b)(2) pathway to obtain marketing approval in the U.S.

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DARE-FRT1 and DARE-PTB1

DARE-FRT1 and DARE-PTB1 are IVRs designed to release bio-identical progesterone over an up to 14-day period.

DARE-FRT1 and DARE-PTB1 are IVRs designed to release bio-identical progesterone continuously for up to 14 days.

DARE-FRT1 is being developed for luteal phase support as part of an in vitro fertilization, or IVF, treatment plan.

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DARE-FRT1 and DARE-PTB1 use the same IVR technology platform as DARE-HRT1.

We are conducting development activities in preparation for Phase 1 clinical studies of these product candidates.

We are conducting development activities to support IND submissions and Phase 1 clinical studies of these product candidates.

We do not plan to conduct the Phase 1 studies until after we secure additional capital.

At the conclusion of these development programs, if successful, we intend to leverage the existing safety and efficacy data for progesterone to utilize the FDA’s 505(b)(2) pathway to obtain marketing approval of DARE-FRT1 and DARE-PTB1 in the U.S.

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• DARE-LARC1 , a contraceptive implant delivering levonorgestrel with a woman-centered design that has the potential to be a long-acting, yet convenient and user-controlled contraceptive option;

• DARE-GML , an intravaginally-delivered potential multi-target antimicrobial agent formulated with glycerol monolaurate (GML), which has shown broad antimicrobial activity, killing bacteria and viruses;

• DARE-LBT , a novel hydrogel formulation for delivery of live biotherapeutics to support vaginal health;

• DARE-RH1 , a novel approach to non-hormonal contraception for both men and women by targeting the CatSper ion channel;

• DARE-PTB2 , a novel approach for the prevention and treatment of idiopathic preterm birth through inhibition of a stress response protein.

DARE-LARC1, our potential user-controlled, long-acting reversible contraceptive, is designed to store and precisely deliver hundreds of therapeutic doses of the contraceptive levonorgestrel over a period of years and to be controlled by the user, without further intervention by a healthcare provider.

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Additional payments are contingent upon the DARE-LARC1 program's achievement of development and reporting milestones specified in the grant agreement.

The DARE-LBT program is being supported by a private foundation grant of approximately $585,000 under a grant agreement that we entered into in November 2022.

The grant funds support activities related to development of a vaginal thermosetting gel formulation for the delivery of live biotherapeutics that can be reconstituted at the point of care.

If successful, the formulation could be carried forward for further development as a delivery vehicle with potential to enhance the availability of novel therapeutics for vaginal health in the United States and worldwide, including in countries with varying climatic conditions and/or where extended storage may be required.

The DARE-LBT program has been supported by a private foundation grant of approximately $585,000 under a grant agreement that we entered into in November 2022.

The grant funds supported activities related to development of a vaginal thermosetting gel formulation for the delivery of live biotherapeutics that can be reconstituted at the point of care.

We believe DARE-LBT merits further development as a delivery vehicle with potential to enhance the availability of novel therapeutics for vaginal health in the United States and worldwide, including in countries with varying climatic conditions and/or where extended storage may be required.

Sales and Marketing

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Manufacturing and Supply

We do not own or operate, nor do we expect to own or operate, facilities for manufacturing, storage and distribution, or testing of our product or product candidates.

We rely on third parties to supply and manufacture our

product candidates and other materials necessary to conduct pre-clinical testing, clinical trials and other activities required for regulatory approval of our product candidates, and expect to continue to do so in the future.

In addition, to the extent our commercialization strategy for a product requires that we undertake commercial supply obligations, we intend to rely on contract manufacturers and suppliers for manufacture, storage, distribution and testing of our finished commercial products and their respective components, including the active pharmaceutical ingredients, or API.

We do not own or operate, nor do we expect to own or operate, facilities for manufacturing, storage and distribution, or testing of our product candidates.

We rely on third parties to supply and manufacture our product candidates and other materials necessary to conduct pre-clinical testing, clinical trials and other activities required for regulatory approval of our product candidates, and expect to continue to do so in the future.

In addition, to the extent our commercialization strategy for any future approved product requires that we undertake commercial supply obligations, we intend to rely on contract manufacturers and suppliers for manufacture, storage, distribution and testing of our finished commercial products and their respective components, including the active pharmaceutical ingredients, or API.

These arrangements require less upfront capital expenditure and allow us to maintain a smaller and more flexible infrastructure.

Under the terms of our license agreement with Organon, we are responsible for providing product supply of XACIATO on an interim basis until Organon assumes such responsibility.

Under the terms of our license agreement with Organon, we were responsible for providing product supply of XACIATO on an interim basis until Organon assumed such responsibility.

In March 2022, we entered into a long-term supply and manufacturing agreement with the contract manufacturing organization, or CMO, that provided clinical supplies of XACIATO for our pivotal Phase 3 DARE-BVFREE clinical study.

This CMO currently is our sole source for commercial supplies of XACIATO.

Under the terms of our agreement, the CMO is responsible for obtaining supplies, at our expense, of all components necessary for the manufacture of XACIATO, including the API, clindamycin.

Our agreement contemplates potential assignment by us to a commercial collaborator.

We expect to have sufficient quantities of XACIATO to support commercial launch in the first half of 2023.

Under the terms of our agreement, the CMO was responsible for obtaining supplies, at our expense, of all components necessary for the manufacture of XACIATO, including the API, clindamycin.

In December 2023, Organon assumed our obligations under the agreement with the CMO and our product supply agreement with Organon was terminated.

Under our agreement with ADVA-Tec, ADVA-Tec is responsible for providing all clinical trial and commercial supplies of Ovaprene, either directly or through a CMO, and except under limited circumstances, we may not obtain supplies of Ovaprene from any source other than ADVA-Tec or its CMO and licensor, Poly-Med, Inc.

Other than our agreement with ADVA-Tec, we have no long-term arrangements for the production or supply of our product candidates or the materials required to produce them.

Under the terms of our license agreement with SST, SST is responsible for providing clinical supplies of Sildenafil Cream, 3.6% for Phase 2 clinical studies in the U.S., and we are responsible for manufacturing or obtaining all other clinical and commercial supplies of Sildenafil Cream, 3.6%.

Under the terms of our license agreement with SST, SST was responsible for providing clinical supplies of Sildenafil Cream for Phase 2 clinical studies in the U.S., and we are responsible for providing supplies of Sildenafil Cream for Phase 3 clinical development and, if approved, for marketing and sale.

Currently, we plan to obtain clinical supplies of Sildenafil Cream from the same CMO that manufactured Sildenafil Cream for the Phase 2b RESPOND clinical study.

We expect that our current arrangements will meet our foreseeable needs for clinical trial materials or, generally, that alternative supply sources will be readily available.

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In addition, some key raw materials or components of our clinical-stage product candidates, including Ovaprene and Sildenafil Cream, have only a single source of supply and alternative supply sources may not be readily available.

Global supply chain disruptions related to the COVID-19 pandemic and recent geopolitical events may contribute to manufacturing and supply delays.

"RISK FACTORS – Risks Related to Product Research & Development and Regulatory Approval – Delays in the manufacture of our clinical and commercial supplies as well as other supply chain disruptions could postpone the initiation of or interrupt clinical studies, extend the timeframe and cost of development of our product candidates, delay potential regulatory approvals and impact the commercialization of any approved products” below.

Global supply chain disruptions, including those related to recent and ongoing geopolitical events, may contribute to manufacturing and supply delays.

"RISK FACTORS – Risks Related to Product Research & Development and Regulatory Approval – Delays in the manufacture of our clinical supplies as well as other supply chain disruptions could postpone the initiation of or interrupt clinical studies, extend the timeframe and cost of development of our product candidates, delay potential regulatory approvals and impact the commercialization of any approved products” below.

Strategic Agreements for Product Commercialization

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In March 2022, we entered into an agreement with Organon, which became fully effective in June 2022, whereby Organon licensed exclusive worldwide rights to develop, manufacture and commercialize XACIATO and other future intravaginal or urological products for human use formulated with clindamycin that rely on intellectual property we control.

Under the agreement, in July 2022, we received a $10.0 million non-refundable and non-creditable payment and are entitled to receive tiered double-digit royalties based on net sales and up to $182.5 million in milestone payments as follows:

$2.5 million following the first commercial sale of a licensed product in the United States, which is expected to occur in the first half of 2023;

and up to $180.0 million in tiered commercial sales milestones and regulatory milestones.

In July 2022, we received a $10.0 million non-refundable and non-creditable payment from Organon, which was recorded as license fee revenue.

In July 2023, received a $1.0 million payment from Organon in connection with the amendment to the license agreement we entered into which was also recorded as license fee revenue.

In connection with the first commercial sale of a licensed product in the United States, we received the $1.8 million milestone payment from Organon in the fourth quarter of 2023.

Under the terms of the license agreement, as amended, we are entitled to receive tiered double-digit royalties based on net sales and potential future milestone payments of up to $180.0 million in tiered commercial sales milestones and regulatory milestones.

Royalty payments will be subject to customary reductions and offsets.

The royalty period for each licensed product will continue on a country-by-country basis from the first commercial sale of the licensed product in the country until the expiration of the later of (i) the date that no valid patent claim would be infringed in the absence of the license granted under the agreement by the sale of the licensed product in the country, (ii) 10 years after the end of the month in which the first commercial sale of the licensed product in the country occurred, and (iii) the expiration of regulatory market exclusivity for the licensed product in that country.

Under our agreement with Organon, we are responsible for regulatory interactions and for providing product supply on an interim basis until Organon assumes such responsibilities.

Until such time, Organon will purchase all of

its product requirements of XACIATO from us at a transfer price equal to our manufacturing costs plus a single-digit percentage markup.

Unless terminated earlier, the agreement will expire on a product-by-product and country-by-country basis upon expiration of the applicable royalty period for each licensed product.

In addition to customary termination rights for both parties, following the first anniversary of the effective date of the agreement, or June 30, 2023, Organon may terminate the agreement in its entirety or on a country-by-country basis at any time in Organon’s sole discretion on 120 days’ advance written notice.

In addition to customary termination rights for both parties, Organon may terminate the agreement in its entirety or on a country-by-country basis at any time in Organon’s sole discretion on 120 days’ advance written notice.

The agreement includes customary representations and warranties, covenants and indemnification obligations of each party.

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and co-exclusive with us with regard to development.

The following is a summary of the other terms of the Bayer license agreement:

Milestone Payments Paid by Bayer.

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Strategic Agreements for Pipeline Development

The following is a summary of certain rights and obligations under our strategic agreements and describes expenses incurred during 2023 and our future payment or potential future payment obligations thereunder.

Douglas License Agreement / The University of Manchester Stand-by Direct License Arrangement

In August 2023, we entered into a license agreement with Douglas Pharmaceuticals Limited, or Douglas, under which we acquired the exclusive rights to develop and commercialize a lopinavir and ritonavir combination soft gel vaginal insert for the treatment of CIN and other HPV-related pathologies, and an agreement with The University of Manchester, pursuant to which The University of Manchester consented to Douglas' sublicense to us of certain rights it previously granted to Douglas and agreed to grant us a direct license to such rights if its license agreement with Douglas is terminated.

As a result of these agreements, we commenced our DARE-CIN program.

Under our agreement with Douglas, we received an exclusive, royalty-bearing license to research, develop and commercialize the licensed intellectual property in the United States for the treatment or prevention of all indications for women in female reproductive health.

We are entitled to sublicense the rights granted to us under the agreement.

Milestone Payments.

We agreed to make potential future milestone payments to Douglas of (1) up to $5.25 million in the aggregate upon achieving certain development and regulatory milestones, which may be paid in shares of our common stock, in our sole discretion subject to specified limitations, and (2) up to $64.0 million in the aggregate upon achieving certain commercial sales milestones for each product covered by the licenses granted under the agreement.

Royalty Payments.

Douglas is eligible to receive tiered royalties in low single-digit to low double-digit percentages based on annual net sales of products and processes covered by the licenses granted under the agreement.

We must use commercially reasonable efforts to develop and introduce to market at least one product or process.

Unless earlier terminated, the agreement expires upon the expiration of the last-to-expire royalty term.

In addition to customary termination rights for both parties, we may elect to terminate the agreement at any time, with or without cause, upon advance written notice to Douglas, and Douglas may terminate the agreement if we materially fail to fulfill diligence requirements with respect to product development.

Hennepin License Agreement

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We are entitled to sublicense the rights granted to us under the agreement.

The following is a summary of other terms of the agreement:

Milestone Payments.

We agreed to make potential future development and sales milestone payments of (1) up to $6.25 million in the aggregate upon achieving certain development and regulatory milestones, and (2) up to $45.0 million in the aggregate upon achieving certain commercial sales milestones for each product covered by the

licenses granted under the agreement, which may be paid, in our sole discretion, in cash or shares of our common stock.

Royalty Payments.

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In July 2021, we entered into a CRADA with the U.S.

Department of Health and Human Services, as represented by NICHD, part of the NIH, for the conduct of a pivotal Phase 3 clinical study of Ovaprene.

Department of Health and Human Services ("HHS"), as represented by NICHD, part of the NIH, for the conduct of a pivotal Phase 3 clinical study of Ovaprene.

See also “Our Pipeline:

Clinical Stage Programs – Ovaprene” above.

Pursuant to the terms of the CRADA, we are responsible for providing clinical supplies of Ovaprene, coordinating interactions with the FDA, preparing and submitting supportive regulatory documentation, and providing a total of $5.5 million in four payments to NICHD to be applied toward the costs of conducting the Phase 3 study, $5.0 million of which has been paid and the remaining $500,000 is due in the second quarter of 2023.

Pursuant to the terms of the CRADA, we are responsible for providing clinical supplies of Ovaprene, coordinating interactions with the FDA, preparing and submitting supportive regulatory documentation, and providing a total of $5.5 million to NICHD to be applied toward the costs of conducting the Phase 3 study, $5.0 million of which has been paid and we expect to make the remaining $0.5 million payment in the third quarter of 2024.

NICHD will be responsible for the other costs related to the conduct of the Phase 3 study and will manage the payment of expenses to other parties involved with the study.

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We agreed to use commercially reasonable efforts to achieve specified development and regulatory objectives relating to DARE-LARC1.

In June 2021, a total of $1.25 million of the contingent consideration became payable upon the achievement of certain of the funding and product development milestone events, $1.0 million of which was recorded as contingent consideration on our consolidated balance sheets upon the completion of the MBI acquisition and $250,000 of which was expensed in 2021.

was expensed in 2021.

In July 2021, our board of directors elected to make these milestone payments in shares of our common stock, to the extent permissible under the terms of the merger agreement with MBI, and, in September 2021, we issued approximately 700,000 shares of our common stock to former stockholders of MBI and paid $75,000 in cash to the stockholders' representative in accordance with the terms of the merger agreement in satisfaction of the $1.25 million in milestone payments associated with milestones achieved in June 2021.

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In March 2022, in connection with entering into our exclusive license agreement with Organon, we entered into a consent, waiver and stand-by license agreement with TriLogic, MilanaPharm and Organon, which further amended the License Agreement.

The following is a summary of other terms of the License Amendment, as amended:

License Fees.

A total of $235,000 in license fees were payable to MilanaPharm, the final installment of which was paid in 2020.

License Amendment, as amended:

Milestone Payments.

We paid MilanaPharm $300,000 in the aggregate upon achievement of certain clinical and regulatory development milestones, the final payment of which was made in 2021.

We may also pay MilanaPharm up to $500,000 upon the first commercial sale in the United States of the first licensed product for each vaginal use and urological use, and up to $250,000 upon the first commercial sale in the United States of successive licensed products for each vaginal or urological use.

We paid MilanaPharm $500,000 in connection with the first commercial sale in the United States of XACIATO in the fourth quarter of 2023.

We may pay up to $250,000 upon the first commercial sale in the United States of successive licensed products for each vaginal or urological use.

In addition, upon achievement of $50.0 million in cumulative worldwide net sales of licensed products, we must pay $1.0 million to MilanaPharm.

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We must use commercially reasonable efforts and resources to (1) develop and commercialize at least one licensed product or process in the United States and at least one licensed product or process in at least one of Canada, the United Kingdom, France, Germany, Italy or Spain, and (2) continue to commercialize that product or process following the first commercial sale of a licensed product or process in the applicable jurisdiction.

Unless earlier terminated, the license term continues until (1) on a licensed product-by-product (or process-by-process basis) and country-by-country basis, the date of expiration of the royalty term with respect to such licensed product in such country, and (2) the expiration of all applicable royalty terms under the MilanaPharm License

Agreement with respect to all licensed products and processes in all countries.

Upon expiration of the term with respect to any licensed product or process in a country (but not upon earlier termination of the MilanaPharm License Agreement), the licenses granted to us under the MilanaPharm License Agreement will convert automatically to an exclusive, fully paid-up, royalty-free, perpetual, non-terminable and irrevocable right and license under the licensed intellectual property.

In addition to customary termination rights for all parties, MilanaPharm may terminate the license granted to us solely with respect to a licensed product or process in a country if, after having launched such product or process in such country, (1) we or our affiliates or sublicensees discontinue the sale of such product or process in such country and MilanaPharm notifies us of such termination within 60 days of having first been notified by us of such discontinuation, or (2) we or our affiliates or sublicensees (A) discontinue all commercially reasonable marketing efforts to sell, and discontinue all sales of, such product or process in such country for nine months or more, (B) fail to resume such commercially reasonable marketing efforts within 120 days of having been notified of such failure by MilanaPharm, (C) fail to reasonably demonstrate a strategic justification for the discontinuation and failure to resume to MilanaPharm, and (D) MilanaPharm gives 90 days’ notice to us.

The following is a summary of other terms of the Assignment Agreement, as amended.

in such country, (1) we or our affiliates or sublicensees discontinue the sale of such product or process in such country and MilanaPharm notifies us of such termination within 60 days of having first been notified by us of such discontinuation, or (2) we or our affiliates or sublicensees (A) discontinue all commercially reasonable marketing efforts to sell, and discontinue all sales of, such product or process in such country for nine months or more, (B) fail to resume such commercially reasonable marketing efforts within 120 days of having been notified of such failure by MilanaPharm, (C) fail to reasonably demonstrate a strategic justification for the discontinuation and failure to resume to MilanaPharm, and (D) MilanaPharm gives 90 days’ notice to us.

Assignment Agreement, as amended

Technology Transfer .

Hammock assigned and transferred to us all of its right, title and interest in and to the MilanaPharm License Agreement and agreed to cooperate to transfer to us all of the data, materials and the licensed technology in its possession pursuant to a technology transfer plan to be agreed upon by the parties, with a goal for us to independently practice the licensed intellectual property as soon as commercially practical in order to develop and commercialize the licensed products and processes.

A total of $512,500 in fees were payable to Hammock, the final installment of which was paid in 2020.

Milestone Payments .

Hammock is eligible to receive up to $1.1 million in the aggregate upon achievement of certain clinical and regulatory development milestones, $100,000 of which we paid in 2020 and $750,000 of which we paid in 2021.

The remaining milestone does not relate to a bacterial vaginosis product.

Hammock is eligible to receive up to $250,000 in the aggregate upon achievement of a regulatory development milestone related to a non-bacterial vaginosis product.

The Assignment Agreement will terminate upon the later of (1) completion of the parties’ technology transfer plan, and (2) payment to Hammock of the last of the milestone payments.

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These payments may be made, in our sole discretion, in cash or in shares of our common stock in accordance with the terms of the merger agreement.

Pear Tree’s licensors are eligible to receive semi-annual royalties based on a single-digit percentage of net sales of licensed products by us or our affiliates, subject to customary reductions and offsets, or a portion of any royalties received by us or our affiliates from sublicensees, and a low double-digit percentage of all sublicensing fees or other lump sum payments or compensation we receive from sublicensees,

subject to customary exclusions.

Portions of certain milestone payments made to Pear Tree’s licensors may be creditable against royalty payments due to Pear Tree’s licensors.

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and (b) a non-exclusive, royalty-bearing worldwide license to use certain technological information owned by Catalent to make, have made, use, have used, sell, have sold, import and have imported products and processes.

As a result of this license agreement, we commenced our DARE-HRT1, DARE-FRT1 and DARE-PTB1 programs.

We are entitled to sublicense the rights granted to us under this agreement.

The following is a summary of other terms of the Catalent license agreement:

We paid a $250,000 non-creditable upfront license fee to Catalent in connection with the execution of the agreement.

Annual Maintenance Fee.

We will pay an annual license maintenance fee of $100,000 to Catalent on each anniversary of the date of the agreement, which will be creditable against royalties and other payments due to Catalent in the same calendar year (including milestone payments and sublicense income), but may not be carried forward to any other year.

We pay an annual license maintenance fee of $100,000 to Catalent on each anniversary of the date of the agreement, which will be creditable against royalties and other payments due to Catalent in the same calendar year (including milestone payments and sublicense income), but may not be carried forward to any other year.

Milestone Payments.

Catalent is eligible to receive (1) up to $13.5 million in the aggregate in payments based on the achievement of specified clinical and regulatory milestones, $1.0 million of which became payable in 2021, and in accordance with the license agreement, the amount was offset by the $100,000 annual maintenance fee, resulting in a net amount of $900,000 paid to Catalent, and (2) up to $30.3 million in the aggregate in payments based on the achievement of specified commercial sales milestones for each product or process covered by the licenses granted under the agreement.

Catalent is eligible to receive (1) up to $12.5 million in the aggregate in payments based on the achievement of specified clinical and regulatory milestones, and (2) up to $30.3 million in the aggregate in payments based on the achievement of specified commercial sales milestones for each product or process covered by the licenses granted under the agreement.

Royalty Payments .

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We may terminate the agreement on a country-by-country basis for any reason by giving 180 days’ notice (or 90 days’ notice if such termination occurs prior to receipt of marketing approval in the United States).

terminates the agreement for the reason described in clause (4) above or if we terminate the agreement, Catalent will have full access including the right to use and reference all product data generated during the term of the agreement that is owned by us.

If Catalent terminates the agreement for the reason described in clause (4) above or if we terminate the agreement, Catalent will have full access including the right to use and reference all product data generated during the term of the agreement that is owned by us.

Adare Development and Option Agreement

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In February 2018, we entered into a license and collaboration agreement with Strategic Science & Technologies-D LLC and Strategic Science & Technologies, LLC, referred to collectively as SST, under which we received an exclusive, royalty-bearing, sublicensable license to develop and commercialize, in all countries and geographic territories of the world, for all indications for women related to female sexual dysfunction and/or female reproductive health, including treatment of female sexual arousal disorder, or the Field of Use, SST's topical formulation of Sildenafil Cream as it existed as of the effective date of this agreement, or any other topically applied pharmaceutical product containing sildenafil or a salt thereof as a pharmaceutically active ingredient, alone or with other active ingredients, but specifically excluding any product containing ibuprofen or any salt derivative of ibuprofen, or the Licensed Products.

The following is a summary of other terms of the SST license agreement:

Invention Ownership.

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(1) prior to receipt of approval by a regulatory authority necessary for commercialization of a Licensed Product in the corresponding jurisdiction, including NDA approval, we may terminate the agreement without cause upon 90 days prior written notice;

(2) following receipt of approval by a regulatory authority necessary for commercialization of a Licensed Product in the corresponding jurisdiction, including NDA approval, we may terminate the agreement without cause upon 180 days prior written

and (3) SST may terminate the agreement with respect to the applicable Licensed Product(s) in the applicable country(ies) upon 30 days’ notice if we fail to use commercially reasonable efforts to perform development activities in substantial accordance with the development plan and do not cure such failure within 60 days of receipt of SST's notice thereof.

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Under the license agreement, in addition to an exclusive, sublicensable license to ADVA-Tec’s and its affiliates’ intellectual property rights for all uses of Ovaprene as a human contraceptive device, we have a right of first refusal to license these patents and patent applications for additional indications.

The following is a summary of other terms of the ADVA-Tec license agreement:

Milestone Payments.

We will pay to ADVA-Tec:

(1) up to $14.6 million in the aggregate based on the achievement of specified development and regulatory milestones, $1.2 million of which has been paid;

and (2) up to $20 million in the aggregate based on the achievement of certain worldwide net sales milestones.

The remaining development and regulatory milestones include:

We may pay to ADVA-Tec:

(1) up to $13.0 million in the aggregate based on the achievement of specified development and regulatory milestones and (2) up to $20 million in the aggregate based on the achievement of certain worldwide net sales milestones.

The future development and regulatory milestones include:

successful completion of a Phase 3/pivotal clinical trial;

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(1) in certain limited circumstances, commercialize Ovaprene in certain designated countries within three years of the first commercial sale of Ovaprene;

(2) satisfy the annual spending obligation described above, (3) use commercially reasonable efforts to complete all necessary pre-clinical and clinical studies required to support and submit a PMA, (4) conduct clinical trials as set forth in the development plan to which we and ADVA-Tec agree, and as may be modified by a joint research committee, unless such failure is caused by events outside of our reasonable control, or (5) enroll a patient in the first non-significant risk medical device study or clinical trial as allowed by an institutional review board within six months of the production and release of Ovaprene, unless such failure is caused by events outside of the our reasonable control.

Royalty Interest Financing Agreement

In December 2023, we entered into a royalty interest financing agreement with United in Endeavour, LLC, or United, pursuant to which we sold to United an interest in the royalty and milestone payments we receive from Organon in respect of net sales of XACIATO.

On the effective date of the agreement, we received a payment of $5.0 million, or the Initial Investment, from United.

Until December 31, 2026, we may, at our sole discretion, elect to receive three additional payments of up to an aggregate of $7.0 million.

We refer to each such payment as a Supplemental Discretionary Investment Amount, and collectively, as the Total Supplemental Discretionary Investment Amount.

We will make payments to United under the agreement until such time when United has received aggregate payments equaling a 12% internal rate of return, or the IRR, on the Initial Investment and the Total Supplemental Discretionary Investment Amount, if any (referred to as the Hard Cap).

Until such time as the IRR has been achieved, we agreed to make payments to United equal to (i) from the date of the agreement through December 31, 2025, 50% of the amount of royalty payments remaining after all amounts that are due and payable and actually paid by us to any licensor or sublicensee on the royalty payments generated and received by us on net sales of XACIATO by Organon have been deducted (such payments referred to as the Net Royalty Payments), (ii) from January 1, 2026 through December 31, 2029, 75% of the Net Royalty Payments, and (iii) from the date of the agreement through December 31, 2029, 10% of the amount of milestone payments remaining after all amounts that are due and payable and actually paid by us to any licensor or sublicensee on the milestone payments generated and received by us on net sales of XACIATO by Organon have been deducted.

After December 31, 2029, we will be required to make certain additional payments to United to the extent United has not received payments equaling the Hard Cap by December 31, 2029, December 31, 2033, and December 31, 2034, respectively.

In addition, if United has not received payments equaling the Hard Cap by December 31, 2035 and we have other sources of assets or income besides XACIATO sufficient to complete such payments, we have agreed to pay United quarterly payments evenly divided over a two-year term, such that United will have obtained the IRR, taking into account all other payments received by United from us under the agreement.

United’s right to receive payments will terminate when United has received the Hard Cap.

We have the right, but not the obligation, at any time, to repurchase all of the interest from United at a repurchase price equal to the Hard Cap, calculated as of the date of we exercise such call option.

The agreement contains representations and warranties, covenants, indemnification obligations, and other provisions customary for transactions of this nature and will terminate on the date that is the earlier of (i) the date upon which the payment of the purchased interest in respect of XACIATO is made in full to United, and (ii) the payment to United of an aggregate amount equal to the Hard Cap.

In connection with the agreement, we issued to United a warrant to purchase up to 5.0 million shares of our common stock.

In addition, for every $1.0 million of Supplemental Discretionary Investment Amount, we agreed to issue an additional warrant to purchase up to 1.0 million shares of our common stock, for an aggregate of additional warrants to purchase up to 7.0 million shares of our common stock.

The warrants are exercisable, in full or in part, at any time on or prior to the fifth anniversary of the date of issuance of the particular warrant at an exercise price of $0.3467 per share, subject to customary anti-dilution adjustments.

The warrants may be exercised for cash, or if at the time of exercise there is no effective registration statement registering for resale the shares underlying the warrants, then in lieu of paying the exercise price in cash, the holder may elect to exercise the warrant on a cashless basis.

Intellectual Property

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and the License Amendment with TriLogic Pharma, LLC and MilanaPharm, LLC, regarding the thermosetting hydrogel platform which includes XACIATO, we are the exclusive licensee of three issued U.S.

patents, two of which are set to expire in December 2028 and one of which is set to expire in September 2036, subject to any extensions or disclaimers, and three foreign patents, including one European Patent Office, or EPO, patent validated in four countries, that expire in December 2028, subject to any extensions or disclaimers, as well as two foreign patents, including one EPO patent validated in 22 countries, that expire in July 2036, subject to any extensions or disclaimers.

One of the three issued U.S.

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Under the terms of the ADVA-Tec license agreement, regarding Ovaprene, we are the exclusive licensee of nine granted U.S.

patents, two pending U.S.

patent application, nine granted foreign patents, including four EPO patents validated in a total of 55 countries, and eighteen pending foreign patent applications.

patents, one pending U.S.

patent application, seven granted foreign patents, including four EPO

patents validated in a total of 55 countries, and four pending foreign patent applications.

Two of the U.S.

patents have terms until August 2028, which includes days added to the term by patent term adjustment, and a third patent has a term that expires in July 2027, including patent term adjustment, each of such terms being subject to any future extensions or disclaimers.

The patent terms for any patents issuing from the pending applications would be expected to expire in 2035 or 2040, subject to any extensions or disclaimers.

Under the terms of the SST license agreement, regarding Sildenafil Cream, 3.6%, we are the exclusive licensee in the Field of Use of 22 issued patents worldwide (nine U.S.

The other U.S.

and foreign patents are expected to expire in 2024, 2025, or 2026.

The patent terms for any patents issuing from the pending applications would be expected to expire in 2035, subject to any extensions or disclaimers.

Under the terms of the SST license agreement, regarding Sildenafil Cream, we are the exclusive licensee in the Field of Use of 23 issued patents worldwide (10 U.S.

patents and 13 foreign patents, including two EPO patents validated in a total of 20 countries).

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The issued U.S.

patents have a patent term that expires in June 2029, including any patent term adjustment, and may be eligible for regulatory exclusivity under the Hatch-Waxman Act, while several foreign patents have a term through that is set to expire in late 2031, each of such terms being subject to any future extensions of disclaimers.

patents have a patent term that expires in June 2029, including any patent term adjustment, and may be eligible for regulatory exclusivity under the Hatch-Waxman Act, while several foreign patents have a term that is set to expire in late 2031, each of such terms being subject to any future extensions or disclaimers.

Under the terms of the Catalent license agreement, regarding our intravaginal ring platform which includes DARE-HRT1, we are the exclusive licensee of four issued U.S.

patents with patent terms set to expire in April 2024, November 2024, February 2025, and September 2027, including patent term adjustment, four issued foreign patents with patent terms until April 2024, including one European patent validated in four countries, as well as one pending U.S.

application and two pending foreign applications that if granted are expected to have patent terms that expire in May 2038, subject to any extensions or disclaimers.

Additionally, relative to the DARE-HRT1 program, we are the sole owner of two pending U.S.

provisional patent applications with an expected term, if granted, until 2044, subject to any extensions or disclaimers.

When we acquired Pear Tree Pharmaceuticals, Inc.

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The Japanese patent has a term that is set to expire in June 2027.

Additionally, relative to the DARE-VVA1 program, we are the sole owner of one pending U.S.

provisional patent application with an expected term, if granted, until 2044, subject to any extensions or disclaimers.

When we acquired MBI in 2019, we obtained the rights to over 100 patents and applications.

The key technology underlying the platform currently is supported by 14 U.S.

patents and 43 foreign patents, including five EPO patents validated in various European countries, and 17 pending patent applications.

patents and 49 foreign patents, including six EPO patents validated in various European countries, and 12 pending patent applications.

We believe that the four most recently filed patent families are directly applicable to our DARE-LARC1 program.

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and other key international markets.

Under the terms of the Hennepin license agreement, we are the exclusive licensee of four issued U.S.

patents and three foreign patents, as well as five pending U.S.

applications and seven pending foreign applications.

Under the terms of the Hennepin license agreement, we are the exclusive licensee of five issued U.S.

patents and four foreign patents, as well as four pending U.S.

applications and twelve pending foreign applications.

patents are set to expire in 2025, 2026, 2028, 2033 and 2034 including any patent term adjustment, extensions or disclaimers, and the foreign patents have patent terms until 2025 or 2033.

and foreign applications, if granted, are expected to have patent terms that expire in 2033, 2037, 2038, and 2042, subject to any extensions or disclaimers.

Under the terms of the Douglas license agreement, we are the exclusive licensee of three granted U.S.

patents and four pending U.S.

patent applications.

The granted patents are expected to expire in 2034 or 2039, including any patent term adjustment, extensions or disclaimers, and the U.S.

applications, if granted, are expected to have patent terms that expire in 2039 and 2040.

We also rely upon trade secret rights to protect our product candidates as well as other technologies that may be used to discover, validate and commercialize our current or any future product candidates.

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• performance of adequate and well-controlled human clinical trials according to good clinical practices, or GCPs, to establish the safety and efficacy of the product candidate for its intended use;

• submission of a NDA to the FDA along with payment of the application user fee and FDA acceptance of that NDA;

• satisfactory completion of an FDA pre-approval inspection of the manufacturing facilities at which the active pharmaceutical ingredient, or API, and finished drug product are produced and tested to assess readiness for commercial manufacturing and conformance to the manufacturing-related elements of the application, to conduct a data integrity audit, and to assess compliance with current good manufacturing practices, or cGMP, in order to assure that the facilities, methods and controls are adequate to preserve the drug candidate’s identity, strength, quality and purity;

• submission of an NDA to the FDA along with payment of the application user fee and FDA acceptance of that NDA;

practices, or cGMP, in order to assure that the facilities, methods and controls are adequate to preserve the drug candidate’s identity, strength, quality and purity;

• possible inspection of selected clinical study sites to confirm compliance with GCP requirements and data integrity;

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Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, detailed information on the product candidate is submitted to the FDA in the form of an NDA requesting approval to market the drug for one or more indications.

An NDA includes all relevant data available from pertinent nonclinical studies and clinical trials, including negative or ambiguous results as well as positive findings, together with detailed information on the product candidate’s chemistry, manufacturing, and controls, or CMC, and proposed labeling, among other things.

labeling, among other things.

To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the product candidate for its intended use to the satisfaction of the FDA.

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A therapeutic candidate designated as a QIDP is eligible for fast track designation, and the first marketing application submitted for a specific drug product and indication for which QIDP designation was granted will be granted priority review.

A subsequent application from the same sponsor for the same product and indication will receive priority review designation only if it otherwise meets the criteria for priority review.

A subsequent application from the same sponsor for the same

product and indication will receive priority review designation only if it otherwise meets the criteria for priority review.

As discussed further below under “New Drug Marketing Exclusivity under the Hatch-Waxman Act Amendments & GAIN Exclusivity Extension - Qualified Infectious Disease Product Exclusivity,” the GAIN Act also provides the possibility of a five-year exclusivity extension that is added to any other marketing exclusivity for which a QIDP-designated drug qualifies upon FDA approval.

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Following approval of a new drug product, the manufacturer and the approved drug are subject to pervasive and continuing regulation by the FDA, including, among other things, monitoring and recordkeeping activities, reporting of adverse experiences with the product, product sampling and distribution restrictions, complying with promotion and advertising requirements, which include restrictions on promoting drugs for unapproved uses or patient populations (i.e., “off-label use”) and limitations on industry-sponsored scientific and educational activities.

physicians may prescribe legally available products for off-label uses, manufacturers may not market or promote such uses.

Although physicians may prescribe legally available products for off-label uses, manufacturers may not market or promote such uses.

The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.

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• mandated modification of promotional materials and labeling and the issuance of corrective information.

In addition, the distribution of prescription pharmaceutical products is subject to a variety of federal and state laws, the most recent of which is still in the process of being phased in to the U.S.

supply chain and regulatory framework.

In addition, the distribution of prescription pharmaceutical products is subject to a variety of federal and state laws.

The Prescription Drug Marketing Act of 1987, or PDMA, was the first federal law to set minimum standards for the registration and regulation of drug distributors by the states and to regulate the distribution of drug samples.

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More recently, the Drug Supply Chain Security Act, or DSCSA, was enacted with the aim of building an electronic system to identify and trace certain prescription drugs distributed in the United States.

The DSCSA mandates phased-in and resource-intensive obligations for pharmaceutical manufacturers, repackagers, wholesale distributors, and dispensers (primarily pharmacies) over a 10-year period that is expected to culminate in November 2023.

It also replaced certain provisions from the PDMA pertaining to wholesale distribution of prescription drugs with a more comprehensive statutory scheme, requiring uniform national standards for wholesale distribution and, for the first time, for third-party logistics providers.

In February 2022, the FDA released proposed regulations to amend the existing national standards for licensing of wholesale drug distributors by the

states (which had been promulgated under the PDMA);

In February 2022, the FDA released proposed regulations to amend the existing national standards for licensing of wholesale drug distributors by the states (which had been promulgated under the PDMA);

to establish new minimum standards for state licensing third-party logistics providers;

and to create a federal system for licensure for use in the absence of a state program, each of which is mandated by the DSCSA.

Most recently, the FDA announced a one-year stabilization period to November 2024, giving entities subject to the DSCSA additional time to finalize interoperable tracking systems and to ensure supply chain continuity.

From time to time, new legislation and regulations may be implemented that could significantly change the statutory provisions governing the approval, manufacturing, and marketing of prescription drug products regulated by the FDA.

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As electronic and digital medical devices have become increasingly connected to the internet, hospital networks, and other medical devices to provide features that improve health care and patient accessibility, FDA and other regulatory authorities have recognized that those same features also increase the risk of potential cybersecurity threats.

These types of medical devices may be vulnerable to security breaches, potentially impacting the safety and effectiveness of the device, and accordingly device manufacturers are responsible for identifying cybersecurity risks and hazards associated with their products.

These types of medical devices may be vulnerable to security breaches, potentially impacting the safety and effectiveness of the device, and accordingly

device manufacturers are responsible for identifying cybersecurity risks and hazards associated with their products.

In recent years, the FDA has increased its scrutiny of this issue as part of the review and marketing authorization process for new medical devices;

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All Class III devices must be reviewed and approved by the FDA through the PMA process.

A PMA must be

supported by extensive data including, but not limited to, technical data, nonclinical studies, clinical trials, manufacturing and labeling to demonstrate to the FDA’s satisfaction the safety and effectiveness of the device for its intended use.

A PMA must be supported by extensive data including, but not limited to, technical data, nonclinical studies, clinical trials, manufacturing and labeling to demonstrate to the FDA’s satisfaction the safety and effectiveness of the device for its intended use.

After a PMA is submitted and the FDA determines the application is sufficiently complete, the agency will accept it for filing and begin an in-depth review of the submitted information.

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Prior to the enactment of FDASIA, a medical device could only be eligible for De Novo classification if the manufacturer first submitted a 510(k) premarket notification and received a determination from the FDA that the device was not substantially equivalent.

FDASIA streamlined the De Novo classification pathway by permitting manufacturers to request De Novo classification directly without first submitting a 510(k) premarket notification to the FDA and receiving a not substantially equivalent determination.

substantially equivalent determination.

The FDA is required under the statute to classify the device within 120 days following receipt of the De Novo application however, the most recent FDA premarket review goals state that in fiscal year 2023, FDA will attempt to issue a decision on 70% of all De Novo classification requests received within 150 days of receipt.

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Under these two options, the manufacturer demonstrates compliance with:

(1) All cGMP regulations applicable to each separate

regulated constituent part included in the combination product;

(1) All cGMP regulations applicable to each separate regulated constituent part included in the combination product;

or (2) either the drug cGMP or the QSR, as well as with specified provisions from the other of these two sets of requirements (also called the “streamlined approach”).

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A certification that the new product will not infringe the already approved product’s listed patents, or that such patents are invalid, is called a Paragraph IV certification.

If the follow-on applicant has provided a Paragraph IV certification to the FDA, the applicant

must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA or 505(b)(2) NDA has been accepted for filing by the FDA.

If the follow-on applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA or 505(b)(2) NDA has been accepted for filing by the FDA.

The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification.

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The length of the patent term extension is related to the length of time the drug or medical device is under regulatory review while the patent is in force.

The restoration period granted on a patent covering a new FDA-regulated medical product is typically one-half the time between the date a clinical investigation on human beings is begun and the submission date of an application for premarket approval of the product, plus the time

between the submission date of an application for approval of the product and the ultimate approval date.

Patent term restoration cannot be used to extend the remaining term of a patent past a total of 14 years from the product’s approval date.

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Failure to timely register a covered clinical study or to submit study results as provided for in the law can give rise to civil monetary penalties and also prevent the non-compliant party from receiving future grant funds from the federal government.

The NIH’s Final Rule on ClinicalTrials.gov registration and reporting requirements became effective in 2017, and the government has recently begun enforcing those requirements against non-compliant clinical trial sponsors.

The NIH’s Final Rule on ClinicalTrials.gov registration and reporting requirements became effective in 2017, and the government has brought enforcement actions against clinical trial sponsors that fail to comply with such requirements.

Health Care Laws and Compliance Requirements

As we are commercializing XACIATO and may commercialize other product candidates, if approved, we are subject to additional health care statutory and regulatory requirements and enforcement by federal government and the states and foreign governments in the jurisdictions in which we conduct our business.

As we plan to commercialize our product candidates, if approved, we are subject to additional health care statutory and regulatory requirements and enforcement by federal government and the states and foreign governments in the jurisdictions in which we conduct our business.

Health care providers, physicians and third-party payors play a primary role in the recommendation and prescription of any product candidates for which we may obtain marketing approval.

Arrangements we may enter into with third-party payors or other customers expose us to broadly applicable fraud and abuse and other health care laws and regulations that constrain the business or financial arrangements and relationships through which we market, sell, and distribute any products for which we obtain marketing approval.

Violations of the fraud and abuse laws, or other health care laws, are punishable by criminal and civil sanctions, including, in some instances, the possibility of exclusion from participation in federal and state health care programs, (including Medicare and Medicaid), and corporate integrity agreements, which impose, among other things, rigorous operational and monitoring requirements on companies.

programs, (including Medicare and Medicaid), and corporate integrity agreements, which impose, among other things, rigorous operational and monitoring requirements on companies.

Similar sanctions and penalties also may be imposed upon executive officers and employees, including criminal sanctions against executive officers under the so-called “responsible corporate officer” doctrine, even in situations where the executive officer did not intend to violate the law and was unaware of any wrongdoing.

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Settlements often include significant civil sanctions, including fines and civil monetary penalties, and corporate integrity agreements.

If the government was to allege or convict us or our executive officers, employees or consultants of violating these laws, our business could be harmed.

If the government were to allege or convict us or our executive officers, employees or consultants of violating these laws, our business could be harmed.

In addition, private individuals have the ability to bring similar actions under some of the fraud and abuse laws described below.

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In the past, the government has enforced the federal Anti-Kickback Statute to reach large settlements with health care companies based on sham consulting and other financial arrangements with physicians.

A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in

order to have committed a violation.

A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act;

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• The Physician Payments Sunshine Act, enacted as part of the ACA (defined below), among other things, imposes reporting requirements on manufacturers of FDA-approved drugs, devices, biologics and medical supplies covered by Medicare or Medicaid to report, on an annual basis, to the Centers for Medicare & Medicaid Services, or CMS, information related to payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), certain advanced non-physician health care practitioners, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members in such manufacturers;

• HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and their respective implementing regulations impose specified requirements relating to the privacy, security and electronic exchange of individually identifiable health information (called "protected health information" under HIPAA) as well as requirements for notification to affected individuals and the government in the event of a breach.

health information" under HIPAA) as well as requirements for notification to affected individuals and the government in the event of a breach.

Among other things, HITECH makes certain of HIPAA’s privacy and all of HIPAA's security standards directly applicable to “business associates,” defined as independent contractors or agents of "covered entities," or organizations subject to HIPAA which include certain health care providers, health plans, and health care clearinghouses.

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In addition, we may be subject to reporting requirements under state transparency laws, as well as state laws that require pharmaceutical companies to comply with the industry’s voluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government that otherwise restricts certain payments that may be made to health care providers and entities.

Under our exclusive license agreement with Organon, Organon is solely responsible for commercializing, promoting, determining pricing, and negotiating reimbursement matters related to XACIATO.

Organon also assumed

responsibility to maintain and enforce a compliance and ethics program containing adequate systems, policies and procedures to facilitate adherence to the rules and health care program requirements with respect to XACIATO.

To the extent we commercialize or co-promote our products, if approved, and because such products could be reimbursed under federal and other governmental health care programs, we are developing an appropriate compliance program, commensurate to the limited commercial activities in which we engage, that establishes internal controls to facilitate adherence to the rules and health care program requirements.

To the extent we commercialize or co-promote our products, if approved, and because such products could be reimbursed under federal and other governmental health care programs, we have developed an appropriate compliance program, commensurate to the limited commercial activities in which we engage, that establishes internal controls to facilitate adherence to the rules and health care program requirements.

Although compliance programs and adherence thereto may mitigate the risk of violation of and subsequent investigation and prosecution for violations of the laws described above, the risks cannot be eliminated entirely.

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If these third-party payors do not consider our products to be cost-effective compared to other therapies, they may not cover our products after approval as a benefit under their plans or, even if they do, the level of payment may not be sufficient to allow us to sell our products on a profitable basis.

Organon has the sole responsibility to negotiate reimbursement approvals from government health care programs and to determine pricing and terms of sale of XACIATO.

Significant uncertainty exists as to the reimbursement status for newly approved prescription products, including coding, coverage and payment.

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Interim payments for new products, if applicable, may also not be sufficient to cover our costs and may not be made permanent.

Payment rates may vary according to the use of the product and the clinical setting in which it is used, may be based on payments allowed for lower cost products that are already reimbursed and may be incorporated into existing payments for other services.

rates may vary according to the use of the product and the clinical setting in which it is used, may be based on payments allowed for lower cost products that are already reimbursed and may be incorporated into existing payments for other services.

Net prices for products may be reduced by mandatory discounts or rebates required by third-party payors and by any future relaxation of laws that presently restrict imports of products from countries where they may be sold at lower prices than in the United States.

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If a drug product is selected by CMS for negotiation, it is expected that the revenue generated from such drug will decrease.

CMS has begun to implement these new authorities but their impact on the pharmaceutical industry in the United States remains uncertain.

CMS has begun to implement these new authorities and entered into the first set of agreements with pharmaceutical manufacturers to conduct price negotiations in October 2023.

However, the IRA's impact on the pharmaceutical industry in the United States remains uncertain, in part because multiple large pharmaceutical companies and other stakeholders (e.g., the U.S.

Chamber of Commerce) have initiated federal lawsuits against CMS arguing the program is unconstitutional for a variety of reasons, among other complaints.

Those lawsuits are ongoing.

We expect that federal, state and local governments in the U.S.

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The ACA also increased the Medicaid rebate rate and the volume of rebated drugs has been expanded to include beneficiaries in Medicaid managed care organizations.

The ACA also expanded the 340B drug discount program (excluding orphan drugs), including a 50% discount on brand name drugs for Medicare Part D participants in the coverage gap, and revised the definition of “average manufacturer price” for reporting purposes, which could increase the amount of the Medicaid drug rebates paid to states.

The ACA also expanded the 340B drug discount program (excluding orphan drugs), including a 50% discount on brand name drugs for Medicare Part D participants in the coverage gap, and revised the

definition of “average manufacturer price” for reporting purposes, which could increase the amount of the Medicaid drug rebates paid to states.

It also contains substantial provisions intended to broaden access to health insurance, reduce or constrain the growth of health care spending, enhance remedies against health care fraud and abuse, add new transparency requirements for the health care industry, impose new taxes and fees on pharmaceutical manufacturers, and impose additional health policy reforms.

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These laws overlap and often conflict and each of these laws is subject to varying interpretations by courts and government agencies, creating complex compliance issues.

If we fail to comply with applicable laws and regulations

we could be subject to penalties or sanctions, including criminal penalties as well as reputational harm.

If we fail to comply with applicable laws and regulations we could be subject to penalties or sanctions, including criminal penalties as well as reputational harm.

Our customers and research partners must comply with laws governing the privacy and security of health information, including HIPAA, HITECH and state health information privacy laws.

If we knowingly obtain protected health information without the authority to do so, our customers or research collaborators may be subject to enforcement and we may have direct liability for the unlawful receipt of protected health information or for aiding and abetting a HIPAA violation.

Even when HIPAA does not apply, according to the Federal Trade Commission, or the FTC, failing to take appropriate steps to keep consumers’ personal information secure, or failing to provide a level of security commensurate to promises made to individual about the security of their personal information (such as in a privacy notice) may constitute unfair or deceptive acts or practices in violation of Section 5(a) of the Federal Trade Commission Act, or the FTC Act.

The FTC expects a company’s data security measures to be reasonable and appropriate in light of the sensitivity and volume of consumer information it holds, the size and complexity of its business, and the cost of available tools to improve security and reduce vulnerabilities.

Individually identifiable health information is considered sensitive data that merits stronger safeguards.

The FTC’s guidance for appropriately securing consumers’ personal information is similar to what is required by the HIPAA Security Rule.

The FTC and states' Attorneys General have brought enforcement actions and prosecuted some data breach cases as unfair and/or deceptive acts or practices under the FTC Act and comparable state laws.

State laws protecting health and personal information are becoming increasingly stringent.

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The CCPA mirrors a number of the key provisions of the European General Data Protection Regulation, or GDPR, described below.

The CCPA establishes a new privacy framework for covered businesses by creating an expanded definition of personal information, establishing new data privacy rights for consumers in the State of California, imposing special rules on the collection of consumer data from minors, and creating a new and potentially severe statutory damages framework for violations of the CCPA and for businesses that fail to implement reasonable security procedures and practices to prevent data breaches.

Additionally, a new privacy law, the California Privacy Rights Act, or CPRA, was approved by California voters in the election on November 3, 2020.

The CPRA went into effect in January of 2023, modifying the CCPA significantly, potentially resulting in further uncertainty, additional costs and expenses in an effort to comply and additional potential for harm and liability for failure to comply.

Among other things, the CPRA established a new regulatory authority, the California Privacy Protection Agency, which will be enacting new regulations and will have expanded enforcement authority.

Other states in the U.S.

are considering privacy laws similar to CCPA.

In Virginia and Colorado enacted similar data protection laws and other U.S.

states have proposals under consideration, increasing the regulatory compliance risk.

The CCPA establishes a new privacy framework for covered businesses by creating an expanded definition of personal information, establishing new data privacy rights for consumers in the State of California, imposing special rules on the collection of consumer data from minors, requiring covered companies to provide new disclosures to consumers about such companies' practices for collection and use of consumer data, and providing customers new ways to opt-out of certain sales or transfers of personal information.

In addition, the CCPA creates a new and potentially severe statutory damages framework for violations of the CCPA and for businesses that fail to implement reasonable security procedures and practices to prevent data breaches.

While there is currently an exception for protected health information that is subject to HIPAA and clinical trial regulations, as currently written, the CCPA may impact our business activities.

More recently, a new privacy law, the California Privacy Rights Act, or CPRA, was approved by California voters in the election on November 3, 2020.

The CPRA went into effect in January of 2023, modifying and strengthening the CCPA significantly, potentially resulting in further uncertainty, additional costs and expenses in an effort to comply and additional potential for harm and liability for failure to comply.

Among other things, the CPRA established a new regulatory authority, the California Privacy Protection Agency, which will be

enacting new regulations and will have expanded enforcement authority.

Various states such as Colorado, Connecticut, Delaware, Florida, Indiana, Iowa, Montana, Oregon, Tennessee, Texas, Utah and Virginia have enacted their own privacy laws similar to the CCPA, and other states are considering proposals for such.

Health Care Reform and Potential Changes to Laws and Regulations

In the United States and some foreign jurisdictions, there have been, and continue to be, several legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of product candidates, restrict or regulate post-approval activities, and affect the ability to profitably sell product candidates that obtain marketing approval.

FDA and other regulatory authority policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates.

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In addition to the IRA's drug price negotiation provisions, discussed above, President Biden's Executive Order 14087, issued October 2022, called for CMS to prepare and submit a report to the White House on potential payment and delivery modes that would complement to IRA, lower drug costs, and promote access to innovative drugs.

As of mid-January 2023 the report had not been released but it is expected to further inform the current Administration's priorities and activities in this area.

In February 2023, CMS published its report which described three potential models focusing on affordability, accessibility and feasibility of implementation for further testing by the CMS Innovation Center.

As of February 2024, the CMS Innovation Center continues to test the proposed models and has started to roll out plans for access model testing of certain product types (e.g., cell and gene therapies) by states and manufacturers.

Other new laws may result in additional reductions in Medicare and other health care funding, which could have an adverse effect on customers for our approved product and, accordingly, our financial operations.

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For countries outside of the EU, such as countries in Eastern Europe, Latin America or Asia, and recently the United Kingdom, the requirements governing the conduct of clinical trials, product approval, pricing and reimbursement vary from country to country.

Regulatory approval in one country or jurisdiction does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country or jurisdiction may negatively impact the regulatory process in others.

Regulatory approval in one country or jurisdiction does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country or jurisdiction may

negatively impact the regulatory process in others.

Moreover, some nations may not accept clinical studies performed for U.S.

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a streamlined application procedure via a single entry point, the “EU portal” called the Clinical Trial Information System, or CTIS;

a single set of documents to be

prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors;

a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors;

and a harmonized procedure for the assessment of applications for clinical trials.

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Devices that comply with the requirements of a relevant directive are entitled to bear the CE conformity marking, indicating that the device conforms to the essential requirements of the applicable directives.

The method of assessing conformity depended on the class of the product, but normally involved a combination of self-assessment by the manufacturer

and a third-party assessment by a “Notified Body.” This third-party assessment may consist of an audit of the manufacturer’s quality system and specific testing of the manufacturer’s product.

In 2017, European Union regulatory bodies finalized a new Medical Device Regulation (“MDR”), which replaced the existing MDD framework and provided three years for transition and compliance, for a final effective date of May 26, 2020.

As a result of the COVID-19 pandemic, however, implementation of the MDR was postponed by one year, giving the medical device industry and Notified Bodies until May 26, 2021 to come into compliance.

The method of assessing conformity depended on the class of the product, but normally involved a combination of self-assessment by the manufacturer and a third-party assessment by a “Notified Body.” This third-party assessment may consist of an audit of the manufacturer’s quality system and specific testing of the manufacturer’s product.

In 2017, European Union regulatory bodies finalized a new Medical Device Regulation (“MDR”), which provided three years for transition and compliance, for a final effective date of May 26, 2020.

As a result of the COVID-19 pandemic, however, the implementation date was postponed by one year to May 26, 2021, and a further transition period until May 26, 2024 gives the medical device industry and Notified Bodies additional time to come into compliance.

The MDR changed several aspects of the existing regulatory framework for medical device marketing in Europe and increased regulatory oversight of all medical devices marketed in the EU, which may, in turn, increase the costs, time and requirements that need to be met in order to place an innovative or high-risk medical device on the European market.

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A CE certificate issued under the MDD before May 26, 2021 may remain valid until May 25, 2024 under certain conditions.

Longer transition periods for various medical device risk classes were proposed by the European Commission in January 2023 in order to mitigate the risk of device shortages in the EU.

Longer transition periods for various medical devices covered by certificates or declarations of conformity issued before May 26, 2021 were implemented by the European Commission in March 2023 in order to mitigate the risk of device shortages in the EU.

The new transition periods permit devices certified in accordance with the MDD to remain on the market under such certifications until May 26, 2026 for class III implantable custom-made devices, December

31, 2027 for Class III and implantable class IIb devices, and December 31, 2028 for all other class IIb and lower risk devices.

As a new market entrant, however, the transition provisions do not apply to our business and we must acquire approvals under the MDR for new products, which could be challenging and costly.

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Rest of the World Regulation

In addition to regulations in the United States and Australia, EU, and Canada, we may become subject to a variety of regulations governing clinical studies and commercial sales and distribution of prescription drug and drug-device combination products in other jurisdictions around the world.

In addition to regulations in the United States, EU, and Canada, we may become subject to a variety of regulations governing clinical studies and commercial sales and distribution of prescription drug and drug-device combination products in other jurisdictions around the world.

These laws and regulations typically require the licensing of manufacturing and contract research facilities, carefully controlled research and testing of product candidates and governmental review and approval of results prior to marketing therapeutic product candidates.

Additionally, they may require adherence to the FDA’s GLPs, GCPs, and GMPs during manufacturing.

The process of new drug approvals by regulators in the United States, Canada and the European Union are generally considered to be among the most rigorous in the world.

Additionally, they may require adherence to the FDA’s GLPs, GCPs, and cGMPs during manufacturing.

The process of new drug approvals

by regulators in the United States, Canada and the European Union are generally considered to be among the most rigorous in the world.

Whether or not FDA, EMA, or Health Canada approval is obtained for a product, we must obtain approval from the comparable regulatory authorities of other countries before we can commence clinical studies or marketing of the product in those countries.

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providing expanded disclosures about how their personal data will be used;

higher standards for organizations to demonstrate that they have obtained valid consent or have another legal basis in place to justify their data processing activities;

limitations on retention of personal data, higher standards for organizations to demonstrate that they have obtained valid consent or have another legal basis in place to justify their data processing activities;

requirements to conduct data protection impact assessments for "high risk" processing;

the obligation to appoint data protection officers in certain circumstances;

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This is because the GDPR allows EU member states to derogate from the requirements of the GDPR mainly in regard to specific processing situations (including special category data and processing for scientific or statistical purposes).

As the EU states continue to reframe their national legislation to harmonize with the GDPR, we will need to monitor compliance with all relevant EU member states’ laws and regulations, including where permitted derogations from the GDPR are introduced.

As the EU member states continue to reframe their national legislation to harmonize with the GDPR, we will need to monitor compliance with all relevant EU member states’ laws and regulations, including where permitted derogations from the GDPR are introduced.

We will also be subject to evolving EU laws on data export, if we transfer data outside the EU to ourselves or third parties outside of the EU.

The GDPR only permits exports of data outside the EU where there is a suitable data transfer solution in place to safeguard personal data (e.g.

The GDPR only permits exports of data outside the EU to countries deemed by the European Commission to have adequate data privacy laws or where there is a suitable data transfer solution in place to safeguard personal data (e.g.

the European Union Commission approved Standard Contractual Clauses).

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This decision a) calls into question certain data transfer mechanisms as between the EU member states and the U.S.

and b) invalidates the EU-

and b) invalidates the EU-U.S.

Privacy Shield on which many companies had relied as an acceptable mechanism for transferring such data from the EU to the U.S.

The CJEU is the highest court in Europe and the Schrems II decision heightens the burden on data importers to assess U.S.

national security laws on their business and future actions of EU data protection authorities are difficult to predict.

Consequently, there is some risk of any data transfers from the European Union being halted.

On July 10, 2023, the European Commission adopted an adequacy decision for a new mechanism for transferring data from the EU to the United States – the EU-US Data Privacy Framework, which provides EU individuals with several new rights, including the right to obtain access to their data, or obtain correction or deletion of incorrect or unlawfully handled data.

The adequacy decision followed the signing of an executive order introducing new binding safeguards to address the points raised in the Schrems II decision.

Notably, the new obligations were geared to ensure that data can be accessed by U.S.

intelligence agencies only to the extent necessary and proportionate and to establish an independent and impartial redress mechanism to handle complaints from Europeans concerning the collection of their data for national security purposes.

The European Commission will continually review developments in the U.S.

along with its adequacy decision.

Adequacy decisions can be adapted or even

withdrawn in the event of developments affecting the level of protection in the applicable jurisdiction.

Future actions of EU data protection authorities are difficult to predict.

Some customers or other service providers may respond to these evolving laws and regulations by asking us to make certain privacy or data-related contractual commitments that we are unable or unwilling to make.

This could lead to the loss of current or prospective customers or other business relationships.

If we have to rely on third parties to carry out services for us, including processing personal data on our behalf, we are required under the GDPR to enter into contractual arrangements to help ensure that these third parties only process such data according to our instructions and have sufficient security measures in place.

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As of March 27, 2024, we had 26 employees.

Twenty five of our employees are full-time and five are part-time, 18 are in research and development and 12 are in general and administrative.

Twenty three of our employees are full-time and three are part-time, 18 are in research and development and eight are in general and administrative.

Given the differing characteristics of our product candidates, our approach is to engage consultants with experience in varying specialties to help us develop such candidates.

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We believe this approach enables us to access the expertise needed in a cost-efficient manner and without the need to rapidly increase the number of full-time employees and their associated costs.

In the future, if we select a commercialization strategy for a product or product candidate that requires us to establish marketing, sales or distribution infrastructure and capabilities, we may need to rapidly increase our employee base.

In the future, if we select a commercialization strategy for a product candidate that requires us to establish marketing, sales or distribution infrastructure and capabilities, we may need to rapidly increase our employee base.

What changed 10-K

Item 1. Business