What changed in this filing

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Item 1. Business

2025-03-31 compared with 2024-03-28 · 439 added, 240 removed, 1143 unchanged (37% of the section changed)

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Unless otherwise stated, references to particular years, quarters, months or periods refer to our fiscal years ending December 31 and the associated quarters, months and periods of those fiscal years.

We are a biopharmaceutical company committed to advancing innovative products for women’s health.

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 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.

We are a biopharmaceutical company driven by a mission to challenge the status quo, making women's health a priority.

We exist to accelerate innovation in women’s health and we believe that innovation does not have to start from scratch.

With growing awareness around menopause, sexual health, and vaginal health, the conversation is shifting, but access to real, evidence-based solutions still lags behind.

We continuously hear from healthcare providers, researchers, and women themselves about the urgent need for access to evidence-based treatment options.

Our goal is to fulfill that need by bringing to market as soon as practicable innovative evidence-based treatment solutions that address decades of unmet needs in women’s health and enhance outcomes and convenience, primarily in the areas of contraception, sexual health, pelvic pain, fertility, infectious disease, vaginal health and menopause - areas in women's health that we believe represent compelling and meaningful market opportunities.

The solutions we aim to bring to market will primarily be available only with a physician’s prescription – either as an FDA-approved product or as a compounded drug under Section 503B of the FDCA.

We may also bring to market consumer health products that can be obtained without a physician’s prescription.

We began assembling our diverse portfolio of assets in 2017 through acquisitions, exclusive in-licenses and other collaborations.

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

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

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 2022, we entered into an agreement with an affiliate of Organon & Co., Organon International GmbH, or Organon, whereby Organon licensed exclusive worldwide rights to develop, manufacture and commercialize XACIATO.

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.

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.

We evaluate potential new product candidates based on similar selection criteria as we applied in assembling our existing portfolio.

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

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 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.

marketing of XACIATO in the fourth quarter of 2023 and, in January 2024, Organon announced that XACIATO was available nationwide.

As described below, to provide funding for the development of the product candidates in our pipeline, in April 2024, we entered into an agreement with XOMA (US) LLC, or XOMA, whereby we sold our rights to all royalty and potential milestone payments based on net sales of XACIATO under our agreement with Organon, net of our obligations to certain third parties, until XOMA receives a specified return on its investment, after which we will share equally in the royalty and milestone payments earned on net sales of XACIATO from Organon.

Our product candidates are in various stages of development, from pre-clinical through a pivotal Phase 3 clinical study.

The most advanced product candidates we are developing are:

Ovaprene®, an investigational, hormone-free, monthly intravaginal contraceptive currently being evaluated in a pivotal Phase 3 clinical study, whose U.S.

commercial rights are under a license agreement with Bayer;

Sildenafil Cream, 3.6%, a novel cream formulation of sildenafil, the active ingredient in Viagra®, for the treatment of female sexual arousal disorder (FSAD);

and DARE-HRT1, an intravaginal ring designed to deliver combination menopausal hormone therapy, bio-identical 17β-estradiol and progesterone together, continuously over a 28-day period for the treatment of moderate to severe vasomotor symptoms, also known as hot flashes.

As discussed in more detail below, because we believe women should not have to wait for needed medical treatment solutions, we are expanding our business strategy to include 503B compounding as a dual-path approach to bring some of our proprietary formulations to market as soon as practicable while we continue to pursue FDA approval of our product candidates.

503B compounding refers to the production and supply of compounded drugs by 503B-registered outsourcing facilities without patient-specific prescriptions in accordance with Section 503B of the FDCA.

We are taking action to utilize 503B compounding to bring our proprietary Sildenafil Cream formulation to market, and we are targeting to make it available in the fourth quarter of 2025.

In parallel, we will continue to pursue FDA approval of Sildenafil Cream as a treatment for FSAD.

Bringing our proprietary Sildenafil Cream formulation to market via 503B compounding will not impact the regulatory process or commercial opportunity for an FDA-approved Sildenafil Cream product.

Rather, if successful, 503B compounding will be a source of revenue from existing assets that is non-dilutive to our stockholders.

Our business strategy is to in-license or otherwise acquire the rights to intellectual property and know how that enables us to develop and bring to market differentiated evidence-based solutions that we believe can address unmet needs in women’s health and enhance outcomes and convenience, and that represent compelling and meaningful market opportunities.

Certain assets we have in-licensed have existing clinical proof-of-concept data or an established safety profile for the active pharmaceutical ingredient that we seek to leverage.

We may pursue regulatory approval of a product candidate through clinical development or, if the active pharmaceutical ingredient is on the FDA’s list of bulk drug substances for which there is a clinical need, we may seek to bring it to market under Section 503B of the FDCA.

In certain circumstances, as discussed in more detail below with respect to our proprietary Sildenafil Cream formulation, we may pursue both pathways.

We believe having alternative pathways allows us to bring solutions to market as soon as practicable and optimizes access for women in a fiscally responsible manner.

We are primarily focused on progressing the development and achieving commercialization 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 intellectual property rights and know how 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 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, (c) potential to utilize the FDA's 505(b)(2) pathway, and/or (d) potential to become a first-in-category or first-line product.

We consider a candidate to have potential to become a “first-in-category” product when we believe that, if the candidate were to successfully complete clinical development and receive marketing approval for the use for which it is being developed, or for which we anticipate developing it, the product would address a need in women’s health that is not being met by existing FDA-approved products.

Key elements of our business strategy are as follows:

• Accelerate innovation in women’s health and bring our proprietary formulations and other assets to market as soon as practicable utilizing all available pathways for the asset , including as a compounded drug under Section 503B of the FDCA, as an FDA-approved product, or as a consumer health product that does not require a physician’s prescription.

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

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.

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 .

We intend to develop and maintain strategic relationships with commercial-stage companies that are leaders or emerging leaders in women’s health, as well as with other entities, where we believe such collaborations will help fund our business or accelerate or otherwise improve upon our clinical development and regulatory strengths and/or product manufacturing and commercialization capabilities.

Examples of our efforts to date include our license agreement with Organon to commercialize XACIATO, our license agreement with Bayer to commercialize Ovaprene, if approved and the license becomes effective, and our Cooperative Research and Development Agreement, or CRADA, with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, or NICHD, for the conduct of the Phase 3 clinical study of Ovaprene.

In 2024, we continued to make important progress in the clinical development of our product candidates, including with ongoing enrollment in the pivotal Phase 3 study of Ovaprene.

• Explore opportunities to expand our portfolio, with evidence-based solutions for 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 portfolio 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.

• Pursue strategic collaborations to fund our business, enhance our development and commercialization capabilities, and/or commercial offerings, optimizing for access in a fiscally responsible manner.

With respect to our product candidates, we intend to develop and maintain strategic relationships with commercial-stage companies that are leaders or emerging leaders in women’s health, as well as with other entities, where we believe such collaborations will help fund our business or accelerate or otherwise improve upon our clinical development and regulatory strengths and/or product manufacturing, and commercialization capabilities.

With respect to 503B compounding, we intend to develop and maintain relationships with Section 503B-registered outsourcing facilities to help bring our proprietary formulations to market.

Examples of strategic collaborations to date include our license agreement with Organon to commercialize XACIATO, and our license agreement with Bayer to commercialize Ovaprene, if approved and the license becomes effective.

• Seek non-dilutive sources of funding to support product development.

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 seven of our product candidates.

We intend to advance development of our product candidates through a variety of means, including through non-dilutive funding and potential revenue from 503B compounding.

To date, we have received non-dilutive

funding from federal government agencies and/or a private foundation to support various aspects of our research and development activities, from preclinical discovery to a Phase 3 clinical study, for eight of our programs.

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

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marketing approval, all during the COVID-19 pandemic.

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.

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

In 2022, we licensed to Organon exclusive worldwide rights to develop, manufacture and commercialize XACIATO.

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

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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.

marketing of XACIATO in the fourth quarter of 2023, and, in January 2024, announced that XACIATO was available nationwide.

As described below, to provide funding for the development of the product candidates in our pipeline, in April 2024, we sold to XOMA our rights to all royalty and potential milestone payments based on net sales of XACIATO under our agreement with Organon, net of our obligations to certain third parties, until XOMA receives a specified return on its investment, after which we will share equally in the royalty and milestone payments earned on net sales of XACIATO from Organon.

See below under "Royalty Monetization Transactions" for additional details.

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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an effective, short-acting, hormone-free method of contraception that does not require intervention at the time of intercourse.

Ovaprene is a novel, investigational hormone-free monthly intravaginal contraceptive designed to be worn conveniently over multiple weeks (one menstrual cycle) and with the potential to achieve “typical use” contraceptive efficacy approaching that of current FDA-approved non-implanted hormonal contraceptive methods (pills, patches and vaginal rings), which is approximately 91% typical use efficacy.

Ovaprene is a novel, investigational hormone-free monthly intravaginal contraceptive designed to be worn conveniently over multiple weeks (one menstrual cycle) that currently is being evaluated in a pivotal Phase 3 clinical study.

Based on the results of our pre-pivotal postcoital test, or PCT, clinical trial, as discussed below, we believe Ovaprene has the potential to achieve “typical use” contraceptive efficacy in the range of approximately 86% to 91% at 6-months, which approaches the approximately 93% typical use efficacy at 12-months of current FDA-approved non-implanted, non-injected hormonal contraceptive methods (pills, patches and vaginal rings).

Typical use contraceptive efficacy refers to the expected rate of pregnancy prevention during the first year of actual use of a method, including sometimes using the method in a way that is not correct or not consistent.

Ovaprene features a proprietary knitted polymer barrier to physically block sperm from entering the cervical canal within a silicone-reinforced ring that releases non-hormonal agent ferrous gluconate to impede sperm motility.

Unlike current FDA-approved monthly intravaginal contraceptives, Ovaprene does not contain hormones, but, consistent with those monthly intravaginal contraceptives, including Merck’s NuvaRing®, Ovaprene is designed to be a “one size fits most” monthly, self-administered product.

monthly, self-administered product.

If approved, Ovaprene could be the first hormone-free, monthly contraceptive option for women.

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Clinical Data

In a postcoital test, or PCT, pilot clinical study conducted by the previous sponsor in 20 women and published in The Journal of Reproductive Medicine® in 2009, Ovaprene demonstrated the ability to immobilize sperm and prevent their progression into the cervical mucus.

In a PCT pilot clinical study conducted by the previous sponsor in 20 women and published in The Journal of Reproductive Medicine® in 2009, Ovaprene demonstrated the ability to immobilize sperm and prevent their progression into the cervical mucus.

The study also demonstrated the acceptability of the device to both partners.

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No serious or severe adverse events were reported or observed.

Ovaprene use did not result in cervicovaginal irritation or adverse effects on resident vaginal microbiota, and did not impact transitions from a Lactobacillus-dominated community state type to an anaerobic, diverse vaginal microbiota community state type IV.

Use of Ovaprene resulted in meeting the prespecified criterion for contraceptive effect by all participants during all postcoital test cycles.

The safety and PCT results from this study were published in the peer-reviewed journal Contraception, an international reproductive health journal and the official journal of the Society for Family Planning.

PCT clinical trials have been used as a surrogate marker for contraceptive effectiveness.

Infertility research suggests that higher rates of pregnancy are associated with PMS per HPF of from greater than one to greater than 20 PMS, and less than five PMS per HPF is considered indicative of contraceptive effectiveness.

In a peer-reviewed article published in the journal Biology of Reproduction that analyzed the use of PCT studies in the development of vaginal contraceptives, the authors observed, for instance, that Lea’s Shield and the Ortho and Caya diaphragms had 0 PMS/HPF in their respective PCT studies and six-month typical use failure rates in contraceptive effectiveness trials of 8.7, 7.9, and 12.5%, respectively.

The article concluded that, although ultimate contraceptive efficacy is influenced by the ease and convenience of use of a product, along with patient compliance, a PCT study of a test product can be predictive of contraceptive effectiveness, and PCT results similar to results seen with products such as Lea’s Shield and the Ortho and Caya diaphragms is the best indicator of likely success of the test product in a contraceptive effectiveness study.

Pivotal Phase 3 Clinical Study

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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.

Twenty clinical research sites from within the Eunice Kennedy Shriver National Institute of Child Health and Human Development's (NICHD) Contraceptive Clinical Trials Network (CCTN) were trained on the protocol and were initiated to start screening and enrolling participants in late 2023 and early 2024.

Currently, there are 15 active NICHD CCTN sites following enrolled participants in the study.

Enrollment is currently proceeding at five study sites that were initiated in 2025, funded by a grant we received in 2024 from the Gates Foundation, or the Foundation, to accelerate the overall study timeline.

We anticipate that approximately 125 women, which is half of our target number of participants to complete the study, will complete approximately six months of Ovaprene use by the end of the second quarter of 2025.

This is a designated check point for review of interim data by the study's data safety monitoring board, or DSMB, an independent group of experts which evaluates the safety and integrity of the study.

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.

If successful, we expect the study to support the submission of a premarket approval application for Ovaprene 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, in part, under our Cooperative Research and Development Agreement, or CRADA, with the U.S.

Department of Health and Human Services (HHS), as represented by the NICHD, part of the U.S.

National Institutes of Health (NIH), and within the CCTN.

Under the CRADA, we and NICHD each provide medical oversight and final data review and analysis for the study at these sites and will work together to prepare the final report of the results of the study from these sites.

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.

Executive orders and other actions taken by the new U.S.

presidential administration in the first quarter of 2025 have negatively impacted the Phase 3 study and NICHD’s ability to carry out its responsibilities under the CRADA.

In particular, the NICHD process to enter into contract modifications with the CCTN sites participating in the study in the same manner as it would ordinarily do to provide additional funding to those sites within the current budget under the CRADA has been impacted and remains uncertain.

As a result, to help ensure the CCTN sites remain active for continued follow-up with existing study participants, we and NICHD agreed to pause recruitment of new participants at the CCTN sites.

This pause in recruitment at the CCTN sites does not effect the anticipated timing for reaching the designated check point for DSMB review.

Depending on its duration, it could adversely impact the overall enrollment rate for the study and increase the time and cost to us to complete the study.

In addition, most of the CCTN sites participating in the study are part of colleges or universities, and the federal government recently has terminated or threatened to terminate grants and contracts with colleges and universities, including clinical study contracts with at least one university that is a CCTN site in our study.

To date, these developments have not materially impacted the study, however, if NICHD is unable to enter into new contracts or contract modifications with CCTN sites for a prolonged period, or terminates its contracts with CCTN sites in our study before the study follow-up visits with existing participants are completed or before the study is completed, we may determine to contract directly with those sites to enable them to restart recruitment and enrollment of new participants and/or ensure they remain active sites to continue follow-up with existing participants, which could increase the time and cost to us to complete the study.

There is a high level of uncertainty relating to U.S.

government contracts and funding and regulation of research and development, as well as the functioning and funding of many federal government departments and agencies in general, and future developments may significantly delay or jeopardize the completion of the Phase 3 study and significantly increase the cost of the study to us.

Further, depending on the duration of the enrollment period and number of subjects enrolled in the Phase 3 study, there may be future costs associated with the study that are not reflected in the current budget under the CRADA for the CCTN sites.

We and NICHD have been in discussions regarding the CRADA, which are continuing and which may include discussing a mechanism to potentially provide for additional future payments by us in support of the Phase 3 study for the CCTN sites to complete subjects already enrolled, in the event that the currently budgeted CRADA funds are insufficient.

As discussed above, we have contracted directly with five new study sites, which began recruiting in the

first quarter of 2025, with the support of grant funding we received from the Foundation.

At this time, due to the uncertainty regarding the CCTN sites and because the five new study sites only recently began participant recruitment, we cannot reasonably predict the enrollment rate for the remainder of the study or an estimated time for completion of enrollment.

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.

See "Strategic Agreements for Pipeline Development" and "Strategic Agreements for Product Commercialization" below for discussion of the terms of e ach collaboration.

Sildenafil Cream, 3.6%

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.

While numerous pharmaceutical products have been developed and approved to treat erectile dysfunction (ED) in men, women continue to lack effective options for female sexual arousal disorder, or FSAD, which is clinically analogous to ED in men.

To date, there are no FDA-approved pharmacological treatments for FSAD.

Market research conducted in 2015 suggests that approximately 33% of women in the U.S.

ages 21 to 60 are not satisfied with their sexual arousal, and half of those women, 16% of women in the U.S.

ages 21 to 60, or approximately 10 million women, are distressed from experiencing symptoms associated with FSAD, including lack of or low sexual arousal, and are actively seeking solutions to improve their condition.

In comparison, the prevalence of complete ED in men is estimated to be about 5% of men at age 40, increasing to about 15% at age 70.

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.

Because, today, there are no treatments approved by the FDA for FSAD, 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 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.

The study enabled us to identify a subgroup of patients who are most likely to benefit from Sildenafil Cream therapy and achieve meaningful improvement in their symptoms.

Based on data from the Phase 2b RESPOND study and feedback from the FDA, we are preparing to advance Sildenafil Cream into a Phase 3 clinical study for the treatment of FSAD.

A second confirmatory Phase 3 study will be required to support an NDA submission.

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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Clinical Data

In a Phase 1 clinical study of three escalating doses of topical sildenafil cream (1 g cream with 35 mg sildenafil;

In a Phase 1 clinical study conducted by our licensor Strategic Science and Technologies, LLC, or SST, of three escalating doses of topical sildenafil cream (1 g cream with 35 mg sildenafil;

2 g cream with 71 mg sildenafil;

and 4 g cream with 142 mg sildenafil) in 20 healthy postmenopausal women using a crossover study design, topical sildenafil cream demonstrated significantly lower systemic exposure to sildenafil compared to a 50 mg oral sildenafil dose, and topical sildenafil cream was safe and well tolerated at clinically relevant doses (1-2 g cream).

and 4 g cream with 142 mg sildenafil) in 20 healthy postmenopausal women using a crossover study design, topical sildenafil cream demonstrated significantly lower systemic exposure to sildenafil compared to a 50 mg oral sildenafil dose, and topical sildenafil cream was well tolerated at clinically relevant doses (1-2 g cream).

Study subjects reported favorable product characteristics:

easy to use and readily absorbed.

In a Phase 2a, single center, single-dose, double-blind, placebo-controlled, 2-way crossover study, women with FSAD, ages 21 to 60, received a single 2 g dose of Sildenafil Cream.

In a Phase 2a, single center, single-dose, double-blind, placebo-controlled, 2-way crossover study conducted by SST, women with FSAD, ages 21 to 60, received a single 2 g dose of Sildenafil Cream.

Of the 35 women enrolled, 31 (15 premenopausal and 16 postmenopausal) completed the study.

The primary objective was to evaluate the efficacy of Sildenafil Cream compared to placebo cream assessed by participant-reported levels of subjective cognitive sexual arousal and by physiological genital arousal response.

The primary objective was to evaluate the efficacy of Sildenafil Cream compared to placebo cream assessed by participant-reported levels of subjective

cognitive sexual arousal and by physiological genital arousal response.

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.

Treatment with a single dose of 2 grams of Sildenafil Cream (71 mg sildenafil) applied intravaginally and externally to the labia minora and clitoris in study participants was well tolerated.

No serious adverse events (SAEs) were reported.

A total of 18 treatment emergent adverse events (TEAEs) were reported, with a similar incidence under Sildenafil Cream treatment (8 events in 4 participants [12.1%]) and under placebo treatment (10 events in 4 participants [12.1%]).

The majority of these TEAEs were considered to be related to treatment (14 out of 18).

All TEAEs were all mild or moderate in severity;

in particular, TEAEs reported under Sildenafil Cream treatment were all mild.

Half of the 18 TEAEs reported were in the system organ classification of “Reproductive system and breast disorders”, and events included vaginismus, vulvovaginal burning sensation, vulvovaginal discomfort, and vulvovaginal pain.

There were more of these TEAEs under Sildenafil Cream treatment than under placebo (6 and 3, respectively).

However, these events were typically transient (lasting less than 1 minute) and resolved without medical attention.

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.

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

One postmenopausal subject had a mild vaginal burning sensation following application of both the placebo cream and Sildenafil Cream, which resolved itself and did not require any additional intervention or study withdrawal.

One subject had a small laceration to the perineum post coitus, which was unrelated to study treatment and participation, resolved itself, and did not require additional intervention or withdrawal.

In 2019, as part of our exploratory Phase 2b clinical program for Sildenafil Cream, we completed a non-interventional study, or the content validity study, designed to identify and document the genital arousal symptoms that are most important and relevant to women with FSAD.

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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.

Sildenafil Cream was well tolerated in the study.

Among the 13 enrolled participants, two subjects had a mild vaginal burning sensation following application of Sildenafil Cream and placebo cream.

One subject had a mild vaginal burning sensation following application of Sildenafil Cream and placebo cream, which resolved itself and did not require any additional intervention or study withdrawal.

Three subjects withdrew from the study for asymptomatic orthostatic tachycardia that occurred during the multiple serial blood draws for pharmacokinetics and one subject withdrew due to bacterial vaginosis.

Among the 13 enrolled subjects, ten had adequate paired plasma samples from all three treatments to evaluate.

Plasma PK of sildenafil following a single topical (applied externally to the pre-specified vulvar area and internally intravaginally) administration of Sildenafil Cream was characterized and findings were similar to those reported in a prior Phase 1 PK study conducted by our licensor SST.

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.

In 2024, several peer-reviewed journal articles were published on the study, including efficacy findings in Obstetrics & Gynecology , the official journal of the American College of Obstetricians and Gynecologists (ACOG), and safety findings in The Journal of Sexual Medicine , the official journal of the International Society for the Study of Women’s Sexual Health (ISSWHS).

In February 2024, we presented additional findings from the study at the Annual Meeting of ISSWHS.

In addition, efficacy findings from the study were the featured topic of ACOG Green Room Gynecology Podcast in August 2024.

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.

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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.

A total of 174 participants completed the study (Sildenafil Cream, n=90, placebo cream, n=84).

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

Among the ITT population, which included women with only FSAD as well as those with FSAD and concomitant sexual dysfunction diagnoses or genital pain, though the Sildenafil Cream group demonstrated greater improvement in the Sexual Function Questionnaire (SFQ28) Arousal Sensation (AS) Domain scores, there were no statistically significant differences between Sildenafil Cream and placebo cream users in the co-primary and secondary efficacy endpoints.

An exploratory post-hoc subset of the ITT population with an enrollment diagnosis of FSAD with or without concomitant decreased desire randomized to Sildenafil Cream reported significant increases in their SFQ28 AS Domain score (LS Mean [SE] 2.03 [0.62]) compared to placebo cream (LS Mean [SE] 0.08 [0.71]), p=0.04.

This subset achieved a larger mean improvement in the SFQ28 Desire and Orgasm Domain scores.

This subset population also had significantly reduced sexual distress and interpersonal difficulties with Sildenafil Cream use, as measured by Female Sexual Distress Scale-Desire, Arousal, Orgasm (FSDS-DAO) questions 3, 5, and 10 (all p values≤0.04).

In summary, Sildenafil Cream improved outcomes among women with FSAD, most significantly in those who did not have concomitant orgasmic dysfunction.

In particular, in an exploratory analysis of a subset of women with FSAD with or without concomitant decreased desire, Sildenafil Cream increased sexual arousal sensation, desire, and orgasm and reduced sexual distress.

During the 12-week double-blind dosing period, there were 78 TEAEs reported by 29 of the 99 Sildenafil Cream-assigned participants and 65 TEAEs reported by 28 of the 94 placebo cream-assigned participants (p=0.76).

All TEAEs were mild or moderate in severity.

The most common treatment-related TEAE among these participants was application site discomfort.

There were no differences in the number of treatment-related TEAEs among Sildenafil Cream versus placebo cream users (p>0.99).

Four Sildenafil Cream participants and three placebo cream participants discontinued the study due to TEAEs involving application site discomfort (p>0.99).

There were 9 TEAEs reported by 7 of 91 sexual partners exposed to Sildenafil Cream versus 4 TEAEs reported by 4 of 84 sexual partners exposed to placebo cream (p=0.54).

These data demonstrate that Sildenafil Cream was well tolerated by exposed users and their sexual partners.

Phase 3 Program

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

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

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-only FSAD 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.

In December 2024, we announced plans for a Phase 3 study of Sildenafil Cream reflecting further FDA feedback for safety and efficacy evaluations to support the indication of treatment of FSAD in premenopausal women.

Consistent with the Phase 2b RESPOND study, the planned Phase 3 study will include a 12-week, double-blind treatment period evaluating Sildenafil Cream compared to placebo cream in patients with FSAD with or without concomitant decreased desire.

The currently planned Phase 3 study will have co-primary efficacy endpoints- one assessing arousal sensations and one assessing associated distress, which will be the same co-primary endpoints for arousal sensations and associated distress used in the Phase 2b RESPOND study.

In addition, secondary efficacy endpoints to assess improvement in orgasm, desire, and distress and interpersonal difficulties will be included in the Phase 3 study, as they were in the Phase 2b RESPOND study.

We plan to submit the protocol and statistical analysis plan for an adequate and well-controlled Phase 3 clinical study, reflecting the FDA’s recommendations, to the FDA in the second quarter of 2025, pending review of additional forthcoming recommendations from the FDA that impact our statistical analysis plan.

We are targeting 2025 for commencement of the Phase 3 study pending the forthcoming FDA recommendations.

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

A second confirmatory Phase 3 study will be required to support the NDA submission.

We anticipate that each

Phase 3 study will be approximately $15.0 million in direct R&D costs (as defined below).

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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Unlike other vaginal ring technologies, ours is designed to release drugs via a solid ethylene vinyl acetate polymer matrix without the need for a membrane or reservoir to contain the active drug or control the release, allowing for sustained drug delivery over time periods ranging from weeks to months.

Hormone therapy is considered the most effective treatment for vasomotor symptoms, or VMS, commonly referred to as hot flashes, and the genitourinary syndrome of menopause, and it has been shown to prevent bone loss and fracture.

Hormone therapy is considered the most effective treatment for vasomotor symptoms, or VMS, commonly referred to as hot flashes, and the genitourinary syndrome of menopause, or GSM, and it has been shown to prevent bone loss and fracture.

Following clinical development, we intend to leverage the large body of existing safety and efficacy data on estradiol and progesterone, the active ingredients in DARE-HRT1, to utilize the FDA's 505(b)(2) pathway to obtain marketing approval in the U.S.

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Clinical Data

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

In January 2023, data from our Phase 1 clinical trial of DARE-HRT1 conducted by our wholly owned subsidiary in Australia were published in Menopause:

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.

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The journal article concluded that the 80/4 IVR and the 160/8 IVR gave similar steady-state concentrations of E2 as seen with drug products approved by the FDA for treatment of VMS and genitourinary symptoms of menopause, and that the E2 concentrations of the study support the potential of DARE-HRT1 as a new option for hormone therapy for treatment of VMS and vaginal symptoms associated with menopause.

The IVRs were well tolerated, and no serious adverse events were reported.

The IVRs were well tolerated, and no SAEs were reported.

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

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.

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.

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.

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 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 first article ( Menopause 30(8):p 817-823, August 2023) found that both versions of DARE-HRT1 evaluated in the Phase 1/2 study released E2 in systemic concentrations, which were in the low, normal premenopausal early folicular range and that systemic P4 concentrations were all in the normal post ovulatory range, which predicts endometrial protection.

All TEAEs 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).

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

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.

DARE-VVA1 is a proprietary investigational formulation of tamoxifen in a soft gelatin capsule 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 GSM (formerly called vulvar and vaginal atrophy or vulvovaginal atrophy (VVA)).

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

Tamoxifen has unique properties that produce different effects (estrogen agonist or estrogen antagonist) in different types of tissues.

In breast tissue, tamoxifen acts as an estrogen antagonist, meaning that it can inhibit estrogen's effect and hence why it may be effective in treating hormone-receptor positive (HR+) breast cancer.

In breast tissue, tamoxifen acts as an estrogen antagonist, meaning that it can inhibit estrogen's effect at the tissue level and hence why it may be effective in treating hormone-receptor positive (HR+) breast cancer.

However, in other tissue, including vaginal tissue, tamoxifen has been reported to elicit an estrogen-like response.

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

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

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

GSM 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 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.

GSM 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 GSM 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 GSM 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 moderate-to-severe dyspareunia, a symptom of GSM .

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 conducting activities in preparation for a Phase 2 randomized, double-blinded, placebo-controlled, dose-finding clinical study of DARE-VVA1 for moderate-to-severe dyspareunia.

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.

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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.

The study treatment was effective in reducing vaginal pH and vaginal dryness.

Overall, the study drug was well tolerated.

The primary efficacy endpoints evaluated normalization of vaginal pH and improvement of vaginal dryness.

Vaginal pH and dryness scores using a visual analog scale were recorded at enrollment and subsequent assessments were recorded using self-assessment questionnaires over a three-month period.

Both vaginal pH and vaginal dryness symptoms showed significant improvement after three months compared to baseline, with an approximately 30% improvement in vaginal pH scores and an approximately 63% improvement in vaginal dryness scores.

The secondary endpoint was the measurement of tamoxifen concentrations after eight weeks of vaginal tamoxifen administration.

When measured after eight weeks on the study treatment, serum tamoxifen levels were negligible, 5.8 ng/ml (median), with a range of 1.0 to 10.0 ng/ml.

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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 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.

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.

In November 2022, we announced topline results from the Phase 1/2 study of DARE-VVA1.

In 2023, data from the study 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 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.

Of the 15 participants who reported at least one TEAE, nine reported a TEAE related to the reproductive system, with vulvovaginal discomfort (n=5 participant reports) and vulvovaginal pruritus (n=4 participants reports) being the most common organ system preferred term.

The mean local erythema scores for all visits, for all dosing groups, were in the none\absent (0) to mild (1) range, with a few outliers in the moderate (2) grading, with no discernible pattern or correlation to group.

All endometrial width measurements assessed with transvaginal ultrasound were normal at baseline and at 57 days of treatment, with the maximum measurement not exceeding 4.0 mm.

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.

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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).

Plasma tamoxifen concentrations were significantly and negatively correlated with vaginal pH (Spearman R = -0.51, p<0.01) and % vaginal parabasal cells (Spearman R = -0.53, p<0.01).

Plasma tamoxifen concentrations were significantly and positively correlated with % vaginal superficial cells (Spearman R = 0.45, p<0.01), % vaginal intermediate cells (Spearman R = 0.45, p <0.01) and total vaginal maturation index (VMI) (Spearman R = 0.62, p<0.01).

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

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

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.

DARE-HPV (formerly referred to as R-131-2 and DARE-CIN) 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 genital human papillomavirus (HPV) infection in women as well as 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+).

There is no FDA-approved treatment for HPV infection and no 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.

We are conducting activities necessary to enable submission of an IND application to the FDA for a Phase 2 clinical study of DARE-HPV as a treatment for genital persistent HPV infection with high risk strains.

The IND enabling activities, IND submission, and the Phase 2 study are expected to be supported by non-dilutive funding under awards granted by the federal government in 2024.

"MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS–Recent Events–Non-Dilutive Funding Awards for DARE-HPV," below.

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.

An earlier non-optimized formulation of the same two active pharmaceutical ingredients in DARE-HPV was previously evaluated in 23 non-pregnant, healthy, premenopausal, HIV un-infected Kenyan women with CIN2 or CIN3 in an open-label, proof-of-concept clinical study with all women receiving a 4:1 (133 mg lopinavir and 33 mg ritonavir) oral tablet (Lopimune) which is FDA approved for the treatment of human immunodeficiency virus (HIV), but dosed vaginally twice daily for 14 days in this study.

There were no SAEs.

The most common TEAEs were headache (3/23, 13%) followed by vaginal irritation (2/23, 8.7%);

nausea (2/23, 8.7%);

feeling faint/dizziness (2/23, 8.7%), abnormal vaginal discharge (2/23 8.7%);

and abdominal pains (1/23 4.3%).

In total, 5/23 or 21.7% of study subjects experienced some form of minor complaint within the first month of taking Lopimune as described.

The results demonstrated its potential as a self-applied therapy for HPV infection and related cervical lesions.

The proof-of-concept study is published in the Public Library of Science (PLoS) One.

DARE-HPV was also previously evaluated in 12 healthy, non-pregnant, premenopausal women without high-risk HPV or CIN, in a double-blind, placebo controlled, Phase 1 clinical study to assess PK and safety in New Zealand.

Participants inserted one tablet vaginally daily for 21 days.

Participants reported the amount of vaginal or vulvar irritation they experienced daily using a Likert scale ranging from 0 (none) to 1 (mild, does not require medical attention) to 2 (moderate, requires medical attention) to 3 (severe, requires medical attention and results in study medication being stopped).

The mean daily vaginal irritation score was 1.47 ± 1.29 for active product users (n=8) versus 1.40 ± 0.9 for placebo product users (n=4).

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

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

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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.

Participants received 1% diclofenac (n=14), 3% diclofenac (n=14) or placebo (n=14).

All 42 participants completed the nine study visits.

The topline data indicate that the study treatment was well-tolerated, and TEAE 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.

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

The most common TEAEs were nausea, vomiting and abdominal discomfort, followed by vulvovaginal candidiasis and pelvic discomfort.

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

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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.

We have a grant award from the NIH to support a Phase 1 study of DARE-PTB1, but 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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See "Strategic Agreements for Pipeline Development" below for discussion of the terms of that agreement.

Casea S is an investigational biodegradable contraceptive implant.

Casea S is designed to control release of a well-characterized contraceptive, etonogestrel, for a set period of time (18-24 months) before dissolving.

It is designed to provide women with a long-acting, minimally-invasive contraceptive method that will not require surgical removal by a healthcare provider, which would improve convenience and could eliminate one of the barriers to use associated with existing implanted contraceptives.

Casea S is being tested in a single-center, two-part Phase 1 clinical study to evaluate the PK of etonogestrel, removability, safety, and tolerability of Casea S pellets inserted subdermally in healthy women of reproductive age (ClinicalTrials.gov ID:

NCT05174884).

The ongoing Phase 1 study is being conducted by FHI 360, a nonprofit organization, with support from the Foundation.

There are no development costs to us at this time.

Casea S was recently acquired by Theramex.

In February 2025, we entered into a co-development and licensing agreement with Theramex for the development of Casea S in the U.S.

If we determine that the results from the Phase 1 study are positive and elect to proceed with development, we would be responsible for conducting a Phase 2 study in the U.S., In accordance with our agreement, the costs of such Phase 2 study would be shared by us and Theramex on terms to be agreed upon, taking into account the size of the opportunity for Casea S in our respective markets.

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

503B Compounding

Sildenafil citrate is currently listed as a nominated bulk drug substance that may be used in compounding by 503B-registered outsourcing facilities, and we are taking action to make our proprietary Sildenafil Cream formulation available via prescription under Section 503B of the FDCA.

Under Section 503B of the FDCA, outsourcing facilities, which must be registered with the FDA and are subject to current Good Manufacturing Practice, or cGMP, requirements and FDA inspections, may provide compounded drugs without an individual patient prescription.

See "Government Regulation—U.S.

Government Regulation—Regulation of Compounded Drugs” below for additional

information regarding compounding under Section 503B of the FDCA.

We are targeting to make our proprietary Sildenafil Cream formulation available in the fourth quarter of 2025.

For additional information, see ITEM 7.

“MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS–Recent Events–Sildenafil Cream as a Compounded Drug,” below.

Our Pipeline:

Pre-Clinical Stage Programs

Our pre-clinical stage programs are:

Our pre-clinical stage programs include:

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

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

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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.

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.

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

In 2023, Organon paid us $1.0 million in connection with entering into an amendment to our license agreement, which was also recorded as license fee revenue, and $1.8 million in connection with the first commercial sale of a licensed product in the United States, which was recorded as milestone revenue.

Under the terms of our license agreement, as amended, Organon agreed to pay 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.

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.

As described below, in April 2024, we sold to XOMA our rights to all royalty and potential milestone payments based on net sales of XACIATO under our license agreement with Organon, net of our obligations to certain third parties, until XOMA receives a specified return on its investment, after which we will share equally in the royalty and milestone payments earned on net sales of XACIATO from Organon.

Unless terminated earlier, our license agreement with Organon 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, 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.

In addition, the terms of the agreement provide Organon exclusive worldwide rights of first negotiation for specified potential future products of ours.

Our license agreement with Organon includes customary representations and warranties, covenants and indemnification obligations of each party.

In addition, the agreement provides Organon exclusive worldwide rights of first negotiation for specified potential future products of ours.

Bayer License Agreement

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and co-exclusive with us with regard to development.

Milestone Payments Paid by Bayer.

Royalties and Milestone Payments Payable by Bayer.

We will be entitled to receive (a) a milestone payment in the low double-digit millions upon the first commercial sale of Ovaprene in the U.S.

and escalating milestone payments based on annual net sales of Ovaprene during a calendar year, totaling up to $310.0 million if all such milestones, including the first commercial sale, are achieved, (b) tiered royalties starting in the low double digits based on annual net sales of Ovaprene during a calendar year, subject to customary royalty reductions and offsets, and (c) a percentage of sublicense revenue .

As described below, in April 2024, we sold to XOMA a portion of our rights to the potential $20.0 million payment from Bayer described above and our rights to a portion of future net sales of Ovaprene under our agreement with Bayer.

We will be responsible for the pivotal trial for Ovaprene and for its development and regulatory activities and we have product supply obligations.

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The initial term of the agreement, which is subject to automatic renewal terms, continues until the later of (a) the expiration of any valid claim covering the manufacture, use, sale or import of Ovaprene in the U.S.;

or (b) 15 years from the first commercial sale of Ovaprene in the U.S.

years from the first commercial sale of Ovaprene in the U.S.

In addition to customary termination rights for both parties, Bayer may terminate the agreement at any time on 90 days’ notice and the agreement will automatically terminate if we do not receive the Clinical Trial and Manufacturing Activities Fee if and when due.

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The following is a summary of certain rights and obligations under our strategic agreements and describes expenses incurred during 2024 and our future payment or potential future payment obligations thereunder.

Theramex Co-Development and License Agreement

In February 2025, we entered into a co-development and licensing agreement with Theramex for an investigational biodegradable contraceptive implant called Casea S recently acquired by Theramex.

Under the agreement, we received a royalty-free, exclusive, fully paid up, sublicensable license to the U.S.

patents Theramex recently acquired for Casea S.

We paid a minimal fee to Theramex in connection with entering into the agreement.

There are no development costs to us at this time.

If we determine that the results from the ongoing Phase 1 clinical study are positive and elect to proceed with development, we would be responsible for conducting a Phase 2 study in the U.S.

In accordance with our agreement, the costs of such Phase 2 study, and the costs of a future Phase 3 study in the U.S., would be shared by us and Theramex on terms to be agreed upon, taking into account the size of the opportunity for Casea S in our respective markets.

If we do not elect to proceed with development after reviewing the results from the Phase 1 study, we may terminate the agreement upon notice to Theramex.

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

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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 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.

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, all of which had been paid as of September 30, 2024.

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

However, for recent developments relating to NICHD's performance under the CRADA, see "Our Pipeline:

Clinical Stage Programs–Ovaprene–Pivotal Phase 3 Clinical Study" above.

Either we or NICHD may terminate the CRADA for any reason upon 30 days’ prior written notice to the other party.

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This candidate is now known as DARE-LARC1.

In connection with the MBI acquisition, we issued an aggregate of approximately 3.0 million shares of our common stock to the holders of shares of MBI’s capital stock outstanding immediately prior to the effective time of the merger and agreed to pay the former MBI stockholders:

Under the terms of the merger agreement, the Company agreed to pay former MBI stockholders:

(a) up to $46.5 million contingent upon the achievement of specified funding, product development and regulatory milestones;

(b) up to $55.0 million contingent upon the achievement of specified amounts of aggregate net sales of products incorporating the intellectual property we acquired in the merger;

(c) tiered royalty payments ranging from low single-digit to low double-digit percentages of annual net sales of such products sold by us (but not by sublicensees), subject to customary provisions permitting royalty reductions and offset;

and (d) a percentage of sublicense revenue related to such products.

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.

(b) up to $55.0 million contingent upon the achievement of specified amounts of aggregate net sales of products incorporating the intellectual property the Company acquired in the merger;

and (c) tiered royalty payments ranging from low single-digit to low double-digit percentages based on annual net sales of such products sold by the Company (but not by sublicensee) and a percentage of sublicense revenue related to such products.

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 58,334 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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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 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.

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.

Assignment Agreement, as amended

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(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, or (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.

Royalty Monetization Transactions

Traditional and Synthetic Royalty Purchase Agreements with XOMA

On April 29, 2024, we entered into a traditional royalty purchase agreement and a synthetic royalty purchase agreement with XOMA (which, together, we refer to as the Royalty Purchase Agreements), and XOMA paid $22.0 million to us.

In addition, if XOMA receives total payments under the Royalty Purchase Agreements (as described below) equal to an amount that exceeds $88.0 million (which we refer to as the Revenue Sharing Threshold), XOMA will pay $11.0 million to us for each successive $22.0 million XOMA receives under the Royalty Purchase Agreements (such $11.0 million payments to us we refer to as the Contingent Purchase Price Payments).

Under the Royalty Purchase Agreements, we sold, assigned, transferred and conveyed our right, title and interest in and to the following to XOMA:

(a) 100% of the royalties and potential milestone payments we would otherwise have the right to receive from and after April 1, 2024 under our exclusive license agreement with Organon, based on net sales of XACIATO, net of (i) all royalty and milestone payments due and payable and actually paid by or on behalf of us under our exclusive license agreement with third-party licensors TriLogic and MilanaPharm, and (ii) all payments due and payable and actually paid by or on behalf of us under our royalty interest financing agreement with United in Endeavour, LLC, or UiE, (such net amount we refer to as the Purchased Receivables);

(b) 25% of the potential future $20.0 million payment that we would otherwise have the right to receive under our license agreement with Bayer relating to Ovaprene, if Bayer, in its sole discretion, elects to make the license granted thereunder effective following completion of the pivotal clinical trial of Ovaprene;

(c) a synthetic royalty of 4.0% of our, our affiliates’ and our sublicensees’ future net sales of Ovaprene, and 2.0% of our, our affiliates’ and our sublicensees’ future net sales of Sildenafil Cream;

provided, however , that, if XOMA receives total payments under the Royalty Purchase Agreements, net of any Contingent

Purchase Price Payments made to us, equal to an amount that exceeds $110.0 million, the foregoing percentages will be reduced to 2.5% and 1.25%, respectively (such amounts described in the foregoing clauses (b) and (c) we collectively refer to as the Revenue Participation Right).

Pursuant to the traditional royalty purchase agreement, XOMA, at its sole cost and discretion, may repay in full and retire all of our payment obligations to UiE under our royalty interest financing agreement with UiE.

If XOMA does so, no further amounts in respect of that agreement will be deducted from the net royalties and net milestone payments that XOMA is entitled to receive under the traditional royalty purchase agreement.

As of April 29, 2024, we cannot elect to receive any additional funding from UiE under our royalty interest financing agreement with UiE without XOMA’s prior written consent.

In connection with the synthetic royalty purchase agreement, we granted to XOMA a security interest in certain product assets related to Ovaprene and Sildenafil Cream.

The Royalty Purchase Agreements contain certain representations and warranties regarding our rights and obligations with respect to our license agreement with Organon, our license agreement with Bayer and our in-license agreements relating to XACIATO, Ovaprene and Sildenafil Cream, as well as customary representations and warranties for a transaction of this nature.

The Royalty Purchase Agreements also contain customary covenants for a transaction of this nature, including covenants that limit or restrict our ability to incur indebtedness or liens related to the Purchased Receivables, the Revenue Participation Right, and certain product assets related to Ovaprene and Sildenafil Cream (except pursuant to a suitable intercreditor agreement).

The Royalty Purchase Agreements do not restrict our ability to out-license any of our products or product candidates.

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.

In December 2023, we entered into a royalty interest financing agreement with United in Endeavour, LLC, or UiE, pursuant to which we sold to UiE 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 UiE.

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.

We will make payments to UiE under the agreement until such time when UiE 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 UiE 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 UiE to the extent UiE has not received payments equaling the Hard Cap by December 31, 2029, December 31, 2033, and December 31, 2034, respectively.

In addition, if UiE 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 UiE quarterly payments evenly divided over a two-year term, such that UiE will have obtained the IRR, taking into account all other payments received by UiE from us under the agreement.

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

We have the right, but not the obligation, at any time, to repurchase all of the interest from UiE 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 UiE, and (ii) the payment to UiE of an aggregate amount equal to the Hard Cap.

In connection with the agreement, we issued to UiE a warrant to purchase up to 422,804 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 84,561 shares of our common stock, for an aggregate of additional warrants to purchase up to 591,927 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 $0.410 per share, subject to customary anti-dilution adjustments.

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If issued, the patent term for any patents issuing from these pending applications would be expected to expire in 2036, subject to any extensions or disclaimers.

We own a pending PCT application and one foreign application regarding XACIATO, and a pending PCT application directed to the thermosetting hydrogel platform.

We own a pending U.S.

application and 16 pending foreign applications regarding XACIATO, and a pending U.S.

and five pending foreign applications directed to the thermosetting hydrogel platform.

The patent term for any patents issuing from these pending applications would be expected to expire in 2042, subject to any extensions or disclaimers.

Organon has licensed XACIATO-specific patents and applications from us.

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

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

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.

patent application, seven granted foreign patents, including two EPO patents validated in a total of 36 countries, and two pending foreign patent applications.

Two of the U.S.

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Under the terms of the SST license agreement, regarding Sildenafil Cream, we are the exclusive licensee in the Field of Use of 27 issued patents worldwide (11 U.S.

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

patents and 16 foreign patents, including three EPO patents validated in a total of 20 countries).

Additionally, there is one patent application pending in the US, one in Europe, and two in other international markets.

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 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 three 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.

extensions or disclaimers.

Additionally, relative to the sildenafil program, we are the sole owner of a pending PCT application with an expected term, if granted, until 2044, subject to any 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 two issued U.S.

patents with patent terms set to expire in February 2025 and September 2027, including patent term adjustment.

Additionally, relative to the DARE-HRT1 program, we are the sole owner of one pending PCT application 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.

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

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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.

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

applications and twelve pending foreign applications.

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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.

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

patents and four pending U.S.

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In accordance with the terms of the ADVA-Tec license agreement, we are the exclusive licensee of the Ovaprene registered trademark.

The industries in which we operate (biopharmaceutical, specialty pharmaceutical, biotechnology and medical device) are highly competitive and subject to rapid and significant change.

Our success is highly dependent upon our ability to acquire or in-license, develop and obtain regulatory approval for innovative medical products on a cost-effective basis and to market them successfully, either on our own or together with strategic partners.

We face and will continue to face intense competition from a variety of businesses, including large, fully integrated, well-established pharmaceutical companies that already possess a significant share of the women’s health market.

Many of our potential competitors have greater clinical, regulatory, manufacturing, marketing, distribution, compliance and financial resources and experience than we do.

"RISK FACTORS—Risks Related to Commercialization of XACIATO and Our Product Candidates— Our product candidates, if approved, and XACIATO will face intense competition and our business and operating results will suffer if we, or our commercial collaborators, fail to compete effectively” and “— The women's health market includes many generic products and growth in generics is expected to continue, which could make the successful introduction of our branded products difficult and expensive” below.

XACIATO will compete directly with the multiple generic and branded prescription drug products currently approved in the U.S.

We are solely focused on women’s health.

Women’s health is a broad category that encompasses health conditions that are unique to women, as well as conditions that affect both men and women, but that may affect women differently.

Women’s health products include drug, medical device, cosmetic and dietary supplement products, and generally are products designed for post-pubescent females.

The women’s health sector is very fragmented, highly competitive and subject to rapid and significant change.

We anticipate that our product candidates may compete not only with FDA-approved, prescription and over-the-counter, branded and generic drug products, but also compounded drug products, medical devices, dietary supplements, and cosmetics.

We face and will continue to face intense competition from a variety of businesses, including large, fully integrated, well-established pharmaceutical companies and specialty pharmaceutical companies that already possess a significant share of the women’s health market, as well as generics manufacturers, compounding pharmacies and other drug compounding facilities, and dietary supplements manufacturers.

In addition, academic and other research institutions are and could be engaged in research and development efforts for products in the therapeutic areas targeted by our product candidates.

Our success is highly dependent upon our ability to acquire or in-license, develop and obtain regulatory approval for innovative products on a cost-effective basis and to market them successfully, either on our own or together with strategic partners, or to make our proprietary formulations available as compounded drugs.

Many of our potential competitors have greater clinical, regulatory, manufacturing, marketing, distribution, compliance and financial

resources and experience than we do.

"RISK FACTORS—Risks Related to Commercialization of Products We Develop" and "Risks Related to 503B Compounding" below.

XACIATO competes directly with the multiple generic and branded prescription drug products currently approved in the U.S.

for the treatment of bacterial vaginosis, including oral and vaginal gel formulations of metronidazole and vaginal cream formulations of clindamycin.

Branded, single-dose FDA-approved products for bacterial vaginosis include Solosec® (secnidazole) oral granules manufactured for and distributed by Lupin Pharmaceuticals, Inc., Clindesse® (clindamycin phosphate) vaginal cream, 2% manufactured and distributed by Padagis, and Nuvessa™ (metronidazole vaginal gel 1.3%) distributed by Exeltis USA, Inc.

Based on the XACIATO product profile reflected in the FDA-approved prescribing information, including the consistent cure rates demonstrated among the subsets of patients defined by prior episodes of bacterial vaginosis (≤ 3 and >3 episodes in the previous 12 months), and the labeling for special populations such as pregnant and lactating women, we expect that the product may to be used by health care providers as a first line option for treating bacterial vaginosis.

As a result of our exclusive license agreement with Organon, the commercial success of XACIATO is largely outside of our control.

Our investigational contraceptive products, including Ovaprene, if approved, will compete with a wide range of prescription and over-the-counter contraceptive options, including hormone-free options such as condoms, diaphragms, cervical caps, sponges, copper IUDs, spermicides and vaginal gels, as well as hormonal products such as pills, patches, vaginal rings and injectables.

As a result of our exclusive license agreement with Organon, the commercial success of XACIATO is outside of our control.

Our investigational contraceptive products, including Ovaprene, if approved, will compete with a wide range of prescription and over-the-counter contraceptive options, including hormone-free options such as condoms, diaphragms, cervical caps, sponges, copper intrauterine devices (IUDs), spermicides and vaginal gels, as well as hormonal products such as pills, patches, vaginal rings, IUDs, implantable rods and injectables.

In addition, multiple new methods of pregnancy prevention are in development, including hormone-free options, and some may be marketed in the U.S.

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Sildenafil Cream has the potential to be the first FDA-approved product for the treatment of FSAD.

DARE-HRT1, if approved as a treatment for moderate to severe VMS due to menopause, will compete with the many products on the market targeted or FDA-approved for the treatment of menopausal symptoms, including VMS.

Such products include hormone therapies in the form of pills, patches and creams, some of which are FDA-approved products and others which are prepared in compounding pharmacies.

However, Sildenafil Cream, if approved, may compete directly with compounded drugs available in the market, including those from outsourcing facilities that compound topical cream formulations of sildenafil citrate, the active ingredient in Sildenafil Cream.

In addition, some compounding entities have partnered with telemedicine providers, enabling them to expand the potential market for their compounded drugs.

The availability of other sildenafil products, could potentially make it more challenging for Sildenafil Cream to build and maintain market share.

If we are successful in bringing our proprietary Sildenafil Cream formulation to market under Section 503B of the FDCA, it would compete directly with other topical cream formulations of sildenafil citrate provided by compounding entities described above.

However, our proprietary Sildenafil Cream formulation, as of the filing date of this report, to our knowledge, would be the only compounded form of sildenafil citrate that has completed toxicology studies and Phase 1, and Phase 2 human clinical studies.

DARE-HRT1, if approved as a treatment for moderate to severe VMS due to menopause, will compete with the many products on the market targeted to or FDA-approved for the treatment of menopausal symptoms, including VMS.

Such products include hormone therapies in the form of pills, patches and creams, some of which are FDA-approved products and others which are supplied by compounding entities, as well as non-hormonal products, including an FDA-approved medication (Veozah® (fezolinetant)) and dietary supplements.

Both the supplement and the compounded hormone therapy markets are very significant.

A considerable segment of the compounded hormone therapy market is comprised of compounded hormones in pellet form that are implanted under the skin as a non-daily alternative, which could be directly competitive with DARE-HRT.

In addition, we are aware of non-hormonal drug products in development for the treatment of VMS, including elinzanetant, a dual neurokinin-1 and 3 (NK-1 and NK-3) receptor antagonist, for which Bayer submitted an NDA in August 2024, and is anticipated to launch in the second half of 2025.

We expect the options for hormone therapy to continue to expand with time.

We believe DARE-HRT1 has the potential to address a preference among some women and health care providers for bio-identical hormones delivered in a non-oral route, as well as offer convenience compared to existing FDA-approved hormone therapies in that one IVR is designed to deliver the bio-identical hormones over 28 days without any daily intervention.

Over the longer term, our ability, independently or otherwise, to successfully develop, manufacture, market, distribute and sell any approved products, expand their usage or bring additional new products to the marketplace will depend on many factors, including, but not limited to, FDA and foreign regulatory agency approval of new products and of new indications for existing products, the efficacy and safety of our products (alone and relative to other treatment options), the degree of patent or other protection afforded to particular products, and reimbursement for use of those products.

We intend for DARE-HRT1, if approved by the FDA, to offer advantages to compounded hormone therapy products, including by providing a product with a well characterized safety and efficacy profile that will have been vetted by the FDA.

DARE-VVA1, if approved as a treatment for moderate-to-severe dyspareunia, or pain during sexual intercourse, a symptom of GSM, will compete with other hormonal and non-hormonal products for the treatment of dyspareunia or other GSM symptoms.

Such products include hormone therapies in the form of pills, patches and creams, some of which are FDA-approved products and others which are supplied by compounding entities, as well as non-hormonal products in the form of pills and vaginal inserts, such as FDA-approved Osphena® (ospemifene) oral tablet, which is a SERM, and Intrarosa® (prasterone) vaginal insert, which is a steroid.

We believe that DARE-VVA1 has the potential to address a preference due to personal or medical reasons among some women and healthcare providers to avoid estrogen and/or treatments with active ingredients that are estrogen-like or can metabolize into estrogen.

Currently, there are no FDA-approved therapies for HPV-related cervical disease.

DARE-HPV has the potential to be the first FDA-approved product for the treatment of genital HPV infection in women and/or CIN (also known as cervical dysplasia).

Persistent HPV infections can progress to cervical cancer through a series of cervical

Currently, there are no FDA-approved therapeutic treatments for HPV infections and no non-surgical pharmaceutical intervention to treat CIN2+.

Surgical procedures are performed to remove late-stage cervical lesions to prevent the development of cervical cancer.

We are aware of other product candidates in development to treat HPV-related cervical diseases, including an investigational vaginal insert being developed by Antiva Biosciences as a topical treatment for high-grade cervical intraepithelial neoplasia (HSIL, CIN2+) and for high-risk HPV infection, which currently is being evaluated in two Phase 1/2 clinical trials.

These candidates may complete development, achieve FDA approval and be marketed in the U.S.

before DARE-HPV, potentially creating direct market competition for DARE-HPV, if approved.

Over the longer term, our ability, independently or otherwise, to successfully develop, manufacture, market, distribute and sell any approved products, expand their usage, or bring additional new products or compounded drugs to the marketplace will depend on many factors, including, but not limited to, FDA and foreign regulatory agency approval of new products and of new indications for existing products, changes in 503B compounding regulations, whether the drug substances in our proprietary formulations appear and remain on the FDA’s list of bulk drug substances that may be used in 503B compounding, the actual and perceived efficacy and safety of our products or our proprietary formulations made available via 503B compounding (alone and relative to other treatment options), the degree of patent or other protection afforded to particular products, and coverage and reimbursement by third-party payors.

Many other organizations are developing drug products and other therapies intended to treat the same diseases and conditions for which our product candidates are in development, and the success of others may render potential application of our product candidates obsolete or noncompetitive, even prior to completion of its development.

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• submission of an 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;

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

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The FDA may grant a waiver for some or all of the requirements for a diversity action plan.

It is unknown at this time how the diversity action plan may affect Phase 3 trial planning and timing or what specific information FDA will expect in such plans, but if the FDA objects to a sponsor’s diversity action plan or otherwise requires significant changes to be made, it could delay initiation of the relevant clinical trial.

If the FDA objects to a sponsor’s diversity action plan or otherwise requires significant changes to be made, it could delay initiation of the relevant clinical trial.

Clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with the FDA’s GCP requirements.

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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.

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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Fee waivers or reductions are available in certain circumstances, such as where a waiver is necessary to protect the public health, where the fee would present a significant barrier to innovation, or where the applicant is a small business submitting its first human therapeutic application for review.

Under the goals and policies agreed to by the FDA under PDUFA, the FDA has ten months from receipt in which to complete its initial review of a standard NDA for a drug that is not a new molecular entity, and six months from the receipt date for an application with priority review.

Congress is required to re-authorize the agency's user fee programs every five years, and current legislative provisions supporting the PDUFA program are set to expire on September 30, 2027.

Under the current PDUFA goals and policies agreed to by the FDA, the agency has ten months from receipt in which to complete its initial review of a standard NDA for a drug that is not a new molecular entity, and six months from the receipt date for an application with priority review.

The FDA does not always meet its PDUFA goal dates, and the review process is often significantly extended by FDA requests for additional information or clarification and the sponsor’s process to respond to such inquiries.

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The FDA may also require companies to perform additional studies or measurements, including nonclinical and clinical studies, to support the change from the approved product.

The FDA may then approve the new product candidate for all or some of the labeled indications for which the referenced product has been approved, as well as for any new indication for which the Section 505(b)(2) NDA applicant has submitted data.

The FDA may then approve the new product candidate for all or

some of the labeled indications for which the referenced product has been approved, as well as for any new indication for which the Section 505(b)(2) NDA applicant has submitted data.

The FDA conducts a preliminary review of all NDAs it receives, whether submitted under Section 505(b)(1) or Section 505(b)(2), to ensure that they are sufficiently complete for substantive review before it accepts them for filing.

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In addition, the FDA may require post marketing clinical trials, sometimes referred to as “Phase 4” clinical trials, designed to further assess a product’s safety and effectiveness, and/or testing and surveillance programs to monitor the safety of approved products that have been commercialized.

After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.

After approval, some types of changes to the approved product, such as adding new

indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.

Special FDA Programs to Facilitate and Expedite Development and Review of Certain New Drugs

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To be eligible for a fast track designation, the FDA must determine, based on the request of a sponsor, that a product is intended to treat a serious or life threatening disease or condition and demonstrates the potential to address an unmet medical need by providing a therapy where none exists or a therapy that may be potentially superior to existing therapy based on efficacy or safety factors.

A drug that is designated as a qualified infectious disease product (“QIDP”) is also eligible for fast track status.

A drug that is designated as a qualified infectious disease product, or QIDP, is also eligible for fast track status.

Fast track designation provides opportunities for more frequent interactions with the FDA review team to expedite development and review of the product.

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In addition, fast track designation may be withdrawn by the sponsor or rescinded by the FDA if the designation is no longer supported by data emerging in the clinical trial process.

The Food and Drug Administration Safety and Innovation Act of 2012, or FDASIA, included the Generating Antibiotics Incentives Now Act, or the GAIN Act, which directed FDA to implement QIDP designation program.

The GAIN Act created incentives for the development of antibacterial and antifungal drug products for the treatment of serious or life-threatening infections.

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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Post-Approval Requirements for Prescription Drugs

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.

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.

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

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Today, both the PDMA and state laws limit the distribution of prescription pharmaceutical product samples and impose requirements to ensure accountability in distribution.

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 culminated 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.

The Drug Supply Chain Security Act, or DSCSA, was enacted in 2013 with the aim of building an electronic system to identify and trace certain prescription drugs distributed in the United States.

The DSCSA mandated resource-intensive obligations for pharmaceutical manufacturers, repackagers, wholesale distributors, and dispensers (primarily pharmacies) over a 10-year period that culminated in November 2023.

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);

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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.

Most recently, the FDA announced a one-year stabilization period to November 2024 followed by trading partner-specific exemptions through specified dates in 2025, 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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however, some Class I devices require premarket clearance by the FDA through the 510(k) process.

Notably, the agency has issued a final rule called the Quality Management System Regulation, or QMSR, to harmonize the FDA's medical device current good manufacturing practice regulations with the International Organization for Standardization, or ISO, standard for device quality management systems (ISO 13485:2016).

The effective date for the QMSR final rule is February 2, 2026.

Until then, manufacturers are required to comply with QSR.

Class II devices are moderate risk devices and are subject to the FDA’s general controls, and any other special controls, such as performance standards, post-market surveillance, and FDA guidelines, deemed necessary by the FDA to provide reasonable assurance of the devices’ safety and effectiveness.

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The device to which the sponsor’s device is compared for the purpose of determining substantial equivalence is called a “predicate device.” The FDA’s goal is to make a substantial equivalence determination within 90 days of FDA’s receipt of the 510(k) application, but it often takes longer if the FDA requests additional information.

Most 510(k)s do not require supporting data from clinical trials, but such data is typically required if the predicate device relied in part on clinical trial data to obtain clearance.

Most 510(k)s do not require supporting

data from clinical trials, but such data is typically required if the predicate device relied in part on clinical trial data to obtain clearance.

After a device receives 510(k) clearance, any modification that could significantly affect its safety or effectiveness, or that would constitute a major change in its intended use, will require a new clearance or possibly a pre-market approval.

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This procedure allows a manufacturer whose novel device is automatically classified into Class III to request down-classification of its medical device into Class I or Class II based on a benefit-risk analysis demonstrating the device actually presents low or moderate risk, rather than requiring the submission and approval of a PMA application.

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.

Today, as a result of certain amendments to the FDCA, manufacturers may request De Novo classification from the FDA without first submitting a 510(k) premarket notification and receiving a not 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 2024, FDA will attempt to issue a decision on 80% of all De Novo classification requests received within 150 days of receipt.

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Clinical trials must further comply with the FDA’s regulations for IRB approval and for informed consent and other human subject protections.

Required records and reports are subject to inspection by the FDA.

Required records and reports are subject to inspection by

The results of clinical testing may be unfavorable or, even if the intended safety and efficacy success criteria are achieved, may not be considered sufficient for the FDA to grant approval or clearance of a product.

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Specifically, under regulations issued by the FDA, a combination product may be:

• a product comprised of two or more regulated constituent parts that are physically, chemically, or otherwise combined or mixed and produced as a single entity;

• a product comprising two or more regulated constituent parts that are physically, chemically, or otherwise combined or mixed and produced as a single entity;

• two or more separate products packaged together in a single package or as a unit and comprised of drug and device products;

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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”).

In addition, The 21st Century Cures Act, or the Cures Act, which became law in December 2016 and, among other things, amended provisions of the FDCA, clarified that for drug-device combination products with a device PMOA and an FDA-approved drug constituent part, Hatch-Waxman Act requirements apply.

In addition, The 21st Century Cures Act, or the Cures Act, amended the FDCA to clarify that for drug-device combination products with a device PMOA and an FDA-approved drug constituent part, Hatch-Waxman Act requirements apply.

Accordingly, a potential patent dispute regarding the listed drug that is being referenced by the combination product sponsor may delay the marketing authorization of the combination product.

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Drugs listed in the Orange Book can, in turn, be cited by potential follow-on competitors in support of approval of an ANDA or a 505(b)(2) NDA that relies in full or in part on the reference product.

Patents for drug-device combination products that are listed in the Orange Book have recently come under scrutiny by the Federal Trade Commission, and the controversy regarding the appropriateness of listing such patents has led to numerous lawsuits alleging anticompetitive conduct by biopharmaceutical companies.

When an ANDA applicant submits its application to the FDA, it is required to certify to the FDA concerning any patents listed for the reference product in the FDA’s Orange Book.

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If the follow-on applicant does not challenge the innovator’s listed patents, FDA will not approve the ANDA or 505(b)(2) application until all the listed patents claiming the referenced product have expired.

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.

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.

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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.

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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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.

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

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.

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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The federal Anti-Kickback Statute is subject to evolving interpretations.

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.

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.

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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;

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

• 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.

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

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.

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.

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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Congressional inquiries and proposed bills designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs.

In August 2022, President Biden signed into the law the Inflation Reduction Act of 2022, or the IRA, which includes (among other things) multiple provisions that may impact the prices of drug products that are both sold into the Medicare program and throughout the United States.

In August 2022, President Biden signed into the law the Inflation Reduction

Act of 2022, or the IRA, which includes (among other things) multiple provisions that may impact the prices of drug products that are both sold into the Medicare program and throughout the United States.

Starting in 2023, a manufacturer of drug products covered by Medicare Parts B or D must pay a rebate to the federal government if their drug product’s price increases faster than the rate of inflation.

This calculation is made on a drug product by drug product basis and the amount of the rebate owed to the federal government is directly dependent on the volume of a drug product that is paid for by Medicare Parts B or D.

Additionally, starting for payment year 2026, CMS will negotiate drug prices annually for a select number of single source Part D drugs without generic competition.

Additionally, starting for payment year 2026, CMS is negotiating drug prices annually for a select number of single source Part D drugs without generic competition.

CMS will also negotiate drug prices for a select number of Part B drugs starting for payment year 2028.

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 and entered into the first set of agreements with pharmaceutical manufacturers to conduct price negotiations in October 2023.

CMS has begun to implement these new authorities, entering into the first set of agreements with pharmaceutical manufacturers to conduct price negotiations in October 2023 and ultimately announcing the first round of negotiated prices for the first 10 drugs in August 2024;

those negotiated "maximum fair prices" will be effective as of January 1, 2026 (payment year 2026).

CMS is currently engaged in its second round of negotiations and published the next 15 drugs selected for negotiation in January 2025.

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.

The outcome of such ongoing lawsuits, as well as potential legislative changes enacted by Congress or programmatic changes implemented at CMS by the Trump Administration, may impact the IRA drug price negotiation program in the future.

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

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In December 2020, the U.S.

Supreme Court held unanimously that federal law does not preempt the states’ ability to regulate pharmacy benefit managers, or PBMs, and other members of the health care and pharmaceutical supply chain, an important decision that appears to be leading to further and more aggressive efforts by states in this area.

The Federal Trade Commission in mid-2022 also launched sweeping investigations into the practices of the PBM industry that could lead to additional federal and state legislative or regulatory proposals targeting such entities’ operations, pharmacy networks, or financial arrangements.

Supreme Court held unanimously that federal law does not preempt the states’ ability to regulate pharmacy benefit managers, or PBMs, and other members of the health care and pharmaceutical supply chain, an important decision that has led to further and more aggressive efforts by states in this area.

The Federal Trade Commission in mid-2022 also launched sweeping investigations into the practices of the PBM industry, and published interim reports with its findings in mid-2024 and January 2025, that could lead to additional federal and state legislative or regulatory proposals targeting such entities’ operations, pharmacy networks, or financial arrangements, including in the current 2025-2026 congressional session.

Significant efforts to change the PBM industry as it currently exists 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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Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures reforms may prevent or limit our ability to generate revenue, attain profitability or commercialize our product candidates.

Regulation of Compounded Drugs

Drug compounding is a practice in which a licensed pharmacist, a licensed physician, or in the case of an outsourcing facility, a person under the supervision of a licensed pharmacist, combines, mixes, or alters ingredients of a drug to create a customized medication.

Compounded drugs are regulated at the federal level primarily under Sections 503A and Section 503B of the Federal Food, Drug, and Cosmetic Act, or the FDCA, which we refer to as Section 503A and Section 503B, respectively.

As discussed above, we are seeking to make our proprietary Sildenafil Cream formulation available by prescription as a compounded drug via Section 503B.

The term “outsourcing facility” refers to a facility that produces compounded drugs in accordance with Section 503B and distributes them either pursuant to a patient-specific prescription or in response to an order from a health care provider, such as a hospital, that is not for an identified individual patient (e.g., for office stock).

Outsourcing facilities must be registered with the FDA and are subject to cGMP requirements and FDA inspections.

In addition, an outsourcing facility must meet other conditions described in Section 503B, including reporting adverse events, labeling compounded products with certain information, reporting specific information about the drugs that it compounds, including a list of all of drugs it compounded during the previous six months, and the FDA-registered source of the active ingredients used to compound pursuant to Section 503B(b)(2).

Under Section 503B, outsourcing facilities are prohibited from selling compounded drugs through a wholesale distributor, subject to certain exceptions set forth in FDA guidance.

Under Section 503B, outsourcing facilities are prohibited from compounding a drug that is “essentially a copy” of an FDA-approved drug, unless the drug is on the FDA’s Drug Shortage List at the time of compounding, distribution, and dispensing.

A drug is essentially a copy of an FDA-approved drug if it is identical or nearly identical to the FDA-approved drug, which the FDA has interpreted to mean that it has the same active ingredient(s), route of administration, dosage form, dosage strength and excipients as the approved drug, or if it has the same active ingredient as an approved drug and there is not a change from the approved drug that produces a clinical difference for an individual patient, as determined by the prescribing practitioner.

Outsourcing facilities may only compound using bulk drug substances that either appear on a list established by the FDA of bulk drug substances for which there is a clinical need or drug products on FDA's Drug Shortage List.

Although the FDA has not yet finalized its list of bulk drug substances for which there is a clinical need, the FDA has announced an interim policy pursuant to which bulk drug substances may be nominated for inclusion on such list and, provided certain conditions are met, outsourcing facilities may compound with such bulk drug substances pending evaluation of the substances for inclusion on the FDA’s list of bulk drug substances for which there is a clinical need.

Sildenafil citrate is currently listed in FDA's interim Category 1 List of bulk substances that have been nominated, reviewed by FDA, and may be compounded by outsourcing facilities pending FDA’s final evaluation.

In December 2023, the FDA issued Guidance for Industry addressing the criteria by which the FDA intends to evaluate whether there exists a clinical need for compounding with a bulk drug substance.Under such guidance, the FDA intends to use a two-part analysis if the bulk drug substance is a component of an FDA-approved product, and if the bulk drug substance is not a component of an FDA-approved product, then the FDA intends to use only part 2 of such analysis.

Under part 1 of the analysis, the FDA intends to evaluate whether there is a basis for the FDA to conclude that (a) an attribute of the FDA-approved drug that makes it medically unsuitable to treat certain patients;

and the drug proposed to be compounded is intended to address that attribute;

and (b) the drug proposed to be compounded must be produced from a bulk drug substance rather than from the FDA-approved drug product.

If the answer to either of such questions is "no," then the FDA could determine that there is no clinical need for compounding with the bulk drug substance.

If the answer to both such questions is "yes," then the FDA intends to proceed to part 2 of the analysis.

Under part 2 of the analysis, the FDA intends to conduct a balancing test under which FDA would consider each of the following factors:

(i) the physical and chemical characterization of the bulk drug substance;

(ii) any safety issues raised by the use of the bulk drug substance in compounding;

(iii) the available evidence of effectiveness or lack of effectiveness of a drug product compounded with the bulk drug substance, if any such evidence exists;

and (iv) current and historical use of the bulk drug substance in compounded drug products, including information about medical condition(s) that the substance has been used to treat and any references in peer-reviewed medical literature.

FDA has not announced when it will complete its analysis of nominated bulk substances and make a determination of substances that will be placed, after notice and a comment period, on FDA's final list of bulk substances that may be used in compounding by outsourcing facilities.

The source of any bulk substance active ingredient used in compounding must be a Section 510 registered manufacturer, and the bulk substance must be accompanied by a Certificate of Analysis.

Section 503A of the FDCA exempts licensed pharmacists or licensed physicians who compound drugs for identified, individual patients, based on the receipt of a valid prescription order, from the FDCA’s new drug approval requirements, cGMP requirements, and the requirement to label products with adequate directions for use, provided

certain conditions are met.

These conditions include that the pharmacist or physician does not compound regularly or inordinate amounts any drug that is essentially a copy of an FDA-approved drug.

The framework for assessing if a drug is essentially a copy of an FDA-approved drug under Section 503A is different than the framework under Section 503B described above.

For instance, a Section 503A pharmacy may compound a formulation that is greater than 10% in dosage strength than the commercially available drug product, if that formulation is accompanied by a statement of significant difference.

In addition, the substances that may be used in compounding under Section 503A are much broader than under Section 503B, because Section 503A pharmacies may compound from bulk substances that are components of FDA-approved drug products and substances that are the subject of a USP/NF monograph.

Sections 503A and 503B also prohibit compounding of drugs that present “demonstrable difficulties for compounding.” The FDA must publish a list of such drugs, through notice and comment rulemaking, before implementing the prohibition, and FDA has not yet finalized any such lists for publication.

Data Privacy and the Protection of Personal Information

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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.

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, Kentucky, Maryland, Montana, Nebraska, New Hampshire, New Jersey, Oregon, Rhode Island, 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

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In addition to the sweeping reforms contained in the ACA (summarized above in the section entitled “Coverage, Pricing, and Reimbursement”), other legislative changes have been proposed and adopted in the United States that may affect health care expenditures.

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.

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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We face the risk that the resulting prices would be insufficient to generate an acceptable return to us or any future partner of ours.

If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions, and criminal prosecution.

If we fail to comply with applicable

foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions, and criminal prosecution.

International marketing and distribution of medical devices are also subject to foreign government regulations, which may vary substantially from country to country.

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The decentralized procedure provides for an applicant to apply to one-member state to assess the application (the reference member state) and specifically list other member states in which it wishes to obtain approval (concerned member states).

Under this procedure, an applicant submits an application based on identical dossiers and related materials, including a draft summary of product characteristics, and draft labelling and package leaflet, to the reference member state and each concerned member state.

Under this procedure, an applicant submits an application based on identical dossiers and related materials, including

a draft summary of product characteristics, and draft labelling and package leaflet, to the reference member state and each concerned member state.

The reference member state prepares a draft assessment report and drafts of the related materials within 210 days after receipt of a valid application which is then reviewed and approved commented on by the concerned member states.

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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.

In 2017, European Union regulatory bodies finalized the 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.

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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.

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

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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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.

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.

The approval process varies from country to country and the time may be longer or shorter than that required for the FDA, EMA, or Health Canada approval.

The requirements governing the conduct of clinical studies, product licensing, pricing and reimbursement vary greatly from country to country.

The requirements governing the conduct of

clinical studies, product licensing, pricing and reimbursement vary greatly from country to country.

In some international markets, additional clinical trials may be required prior to the filing or approval of marketing applications within the country.

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the obligation to appoint data protection officers in certain circumstances;

new rights for individuals to be “forgotten” and rights to data portability, as well as enhanced current rights (e.g.

access requests);

new rights for individuals to be “forgotten” and rights to data portability, as well as enhanced current rights (e.g., access requests);

the principal of accountability and demonstrating compliance through policies, procedures, training and audit;

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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 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).

On July 16, 2020, the Court of Justice of the European Union or the CJEU, issued a landmark opinion in the case Maximilian Schrems vs.

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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.

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.

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As of March 28, 2025, we had 23 employees.

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.

Twenty one of our employees are full-time and two are part-time, 17 are in research and development and six 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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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business