DARE - Dare Bioscience Inc. (DARE) Q4 2022 Earnings Call Transcript

2023-03-30 23:16:05 ET

Dare Bioscience, Inc. (DARE)

Q4 2022 Earnings Conference Call

March 30, 2023 16:30 ET

Company Participants

Sabrina Johnson - President & Chief Executive Officer

Lisa Walters-Hoffert - Chief Financial Officer

John Fair - Chief Strategy Officer

Conference Call Participants

Catherine Novack - Jones Research

Douglas Tsao - H.C. Wainwright

Kumaraguru Raja - ROTH Capital

Joanne Lee - Maxim Group

Kemp Dolliver - Brookline Capital Markets

Presentation

Operator

Welcome to the conference call hosted by Daré Bioscience to review the company's Financial Results for the Year Ended December 31, 2022 and to provide a general business update. This call is being recorded. My name is Abby and I will be your operator today.

With us today are Sabrina Martucci Johnson, Daré's President and Chief Executive Officer; John Fair, Daré's Chief Commercial Officer; and Lisa Walters-Hoffert, Daré's Chief Financial Officer.

Ms. Johnson, please proceed.

Sabrina Johnson

Thank you. Good afternoon and welcome to our year-end December 31, 2022 financial results and business update call for Daré Bioscience. Our plan today is to review our full year results, discuss development since our last call in November and use the time to review our business strategy, including why we believe investment in women's health is efficient and disproportionately impactful and to highlight some important objectives and milestones anticipated in 2023.

Before we begin, I'd like to remind you that today's discussion will include forward-looking statements within the meaning of federal securities laws which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Any statements made during this call that are not statements of historical facts should be considered forward-looking statements. Actual results or events could differ materially from those anticipated or implied by these statements due to known and unknown risks and uncertainties. You should not place undue reliance on forward-looking statements. Forward-looking statements are qualified in their entirety by the cautionary statements in the company's SEC filings, including our annual report on Form 10-K for the year ended December 31, 2022 which was filed today.

I'd also like to point out that the content of this call includes time-sensitive information that is current only as of today, March 30, 2023. Daré undertakes no obligation to update any forward-looking statements to reflect new information or developments after this call, except as required by law.

By the time 2022 came to a close, we had secured our second commercial collaboration in this case, for our FDA-approved product, XACIATO with Organon. We received FDA acceptance to commence what we believe will be the single pivotal study required for our monthly hormone-free contraceptive candidate, Ovaprene, commercial rights to which our under license agreement with Bayer. We announced that we completed enrollment in our Sildenafil Cream female sexual arousal disorder Phase IIb study and we announced 2 positive Phase I/II study top line readouts, one for our hormone-free vaginal atrophy treatment candidate, DARE-VVA1; and one for our 28-day vaginal ring hormone therapy candidate for the vasomotor symptoms in menopause, DARE-HRT1.

These accomplishments in 2022 position us well to potentially achieve additional commercialization, clinical and regulatory milestones in 2023, that I look forward to sharing shortly. And our 2023 milestones include not only objectives related to the programs I just identified but to other portfolio candidates as well.

Those who have been following Daré know that we are focused solely and squarely on women's health. With 12 independent stand-alone development stage candidates in our portfolio, we have, to our knowledge, the deepest pipeline of women's health product candidates of any other company, including global pharmaceutical companies.

It has been reported that a mere 1% of health care research is invested in female-specific conditions beyond oncology. And yet, based on IQVIA data for 2013 to 2022, women's health products make up 27% of the blockbuster products as in those that generate over $500 million in annual sales. And those products contribute 35% as a revenue generated by all blockbuster products.

Thus, given those statistics, with 12 development stage candidates in our portfolio, we like our odds of generating value for our shareholders and the disproportionately impactful investment, a women's health product candidate can potentially represent particularly given that a number of our candidates are in the contraceptive, menopause and sexual health categories, all of which have seen over $1 billion and even over $2 billion individual brand, including the potential of our sexual health program, Sildenafil Cream, since there is yet to be an FDA-approved product for arousal disorder in women, the most analogous condition in women to erectile dysfunction in men. We would love the first and more on our cinemas program shortly.

So as such, it is our belief that prioritizing women's health is not only good for the many women lacking effective or convenient therapeutic options. And for the broad set of stakeholders, they care about women's health, including family members and partners but importantly, also for those investing in the category.

Our current innovation efforts are focused in contraception, vaginal health, reproductive health, menopause, sexual health and fertility. We chose these areas because we saw opportunities to bring new innovation to women in indications where we could be first to market, have a first-in-category product or develop the first-line product in a given therapeutic category.

So while we have a broad portfolio, importantly, every single product candidate in our portfolio has to stand on its own merits to justify our investment in that individual product candidate. Specifically, before we select a new candidate for development, we make a determination that it meets the strict criteria.

First, the product candidate has to address a meaningful market opportunity in the form of a persistent unmet need. Second, it has to have the potential to be first line or first in category or both. Third, it should already have demonstrated proof of concept and ideally use well-characterized active pharmaceutical ingredients which committed gate development time, cost and even risk. And finally, it should represent an opportunity to deliver a clear improvement over the standard of care as measured by clinical outcomes and patient acceptability and is ultimately evidenced by a clearly differentiated product label which is critical for market access and pull-through.

Our focused efforts to deliver differentiated innovation in women's health have resulted in 12 development-stage programs across 9 distinct indications. With more than 5 milestone events anticipated in 2023 that we will discuss shortly, 3 candidates in or nearing Phase III development, 2 potentially transformative transformational collaborations with leaders in women's health product commercialization, Bayer and Organon and 1 FDA-approved product XACIATO.

I want to share with you now Daré's key 2022 results and milestones and our anticipated 2023 milestones. In addition to my remarks, I encourage you to read our press release issued this morning since it provides a more comprehensive review of our 2022 accomplishments. We have important upcoming milestones for XACIATO, Ovaprene, Sildenafil Cream, DARE-VVA1, DARE-HRT1 and DARE-DPM1. So I'm going to focus my comments today primarily on those programs.

So let me begin by highlighting our global license agreement with Organon that supports the commercialization of XACIATO, clindamycin phosphate vaginal gel 2%. As a reminder, XACIATO is a lencostamide antibacterial for single-dose vaginal administration indicated for the treatment of bacterial vaginosis in female patients 12 years of age and older in the United States.

The XACIATO story is a great validation of our portfolio candidate selection and development strategy. Bacterial vaginosis is most common vaginal condition in women of reproductive age, estimated to affect approximately 23 million women in the U.S. alone. But yet a number of women with the condition have been underserved by currently available products. We hoped that by focusing on improving outcomes and her overall user experience, we could deliver a novel option.

Understanding the differentiation drives value, we stroke to design a Phase III study to generate the data necessary to support the target labeling. And by doing so, create the opportunity for a commercialization collaboration that could drive value. We are thrilled that Organon, the women's health focused spin out of Merck is launching XACIATO and that they will leverage their established Nexpenon sales team to accelerate XACIATO uptake.

Specifically, with the manufacturing validation activities required to support the commercial launch now nearly completed, we are excited about the commercial launch activities underway at Organon, in preparation for what will be Organon's first pharmaceutical product launch into the women's health category since spinning out of Merck.

Given that the Nexplanon sales team will be leveraged for the XACIATO to launch, we expect to benefit from the track record of commercial success that team has demonstrated. Organon believes that there is roughly a 90% overlap of those health care providers who prescribe Nexplanon and our viable XACIATO targets based on treatment patterns. The strong relationships the sales team has with these providers are expected to enable immediate access. We anticipate the first commercial sale before the end of the second quarter, more on the XACIATO commercial activity when John provides his update.

In terms of our Ovaprene program, the FDA's acceptance of our Ovaprene IDE last year was an important milestone for the program, as it allows us to commence what we believe will be the single pivotal clinical study required to support the PMA submission for registration. Ovaprene is our investigational potential first-in-category hormone-free, monthly intravaginal contraceptive, whose commercial rights around a license agreement with Bayer.

We announced IDE approval for our planned pivotal study by the FDA in October 2022 and confirmed our belief that a single pivotal study of approximately 12 months duration will be sufficient to support a PMA submission to the FDA. The study will target having around 200 to 250 subjects complete, 13 mental cycles of use. The pivotal study is being conducted under a collaborative research and development agreement, or CRADA, with the NIH's NICHD division and with NICHD's contraceptive clinical trial network. And in December, NICHD brought the investigators from those sites together for an investigator meeting.

We anticipate initiation of pivotal Phase III subject recruitment in the middle of 2023. So that's 2 innovative brands, XACIATO and Ovaprene and 2 potentially transformational collaborations, one with Organon and one with Bayer. So what's next for Daré on our unpartnered programs. Well, let's begin listen premium 3.6% to a product candidate with the potential to create a completely novel category in women's health. We are looking to address the lack of physical general arousal response and sensations and the associated distress that are the hallmark of female sexual arousal disorder, or FSAD.

As I mentioned upfront, FSAD is analogous to erectile dysfunction or ED in men, both in terms of pathophysiology as well as target pharmacology and the addressable markets are also quite comparable in size. We completed enrollment in our exploratory Phase IIb study in 2022. And as we approach the Phase IIb top line data readout projected for the second quarter of 2023, we wanted to give you a sense of what you can expect.

First, by way of refresher, previously conducted studies by Daré and our licensor, SST, demonstrated that this cream formulation of Sildenafil which is the same active ingredient as in Viagra, increased blood flow to the female genital tissue, both when assessed to be an internal vaginal probe and when assessed via an external temperature sensing camera. These data provide the proof of concept that the formulation is achieving its target activity in the tissue.

Obviously, vaginal probes and genital temperature sensors are not practical endpoints for a Phase III program. Thus, the exploratory Phase IIb study was designed to evaluate the performance of Sildenafil Cream and to evaluate a number of different potential ways to ask women questions about their general sensations and improvements referred to as patient reported outcomes in the at-home setting, in order to identify and select the appropriate patient-reported outcomes to take forward into Phase III program.

Therefore, as we bring our exploratory Phase IIb study to a conclusion, we will, as a first step, report top line data for a number of the assessment tools we utilized in the study and subsequent to reporting the top line results, when we have the full data set from the study, we will formalize our proposals to the FDA regarding the patient population to study and the endpoints to evaluate in the Phase III program.

Our goal is to bring a much-needed solution to the women estimated to be 10 million in the United States alone who are distressed and seek treatment for low or no sexual arousal and no FDA-approved product option to address their condition today.

Third, I'd like to highlight the positive top line results from the 2 Phase I/II studies completed last year, one for DARE-HRT1 and another for DARE-VVA1, both of which were conducted through our wholly owned Australian subsidiary. So let's start first with the Phase I/II study of DARE-HRT1, a menopausal hormone therapy for the treatment of the vasomotor symptoms of menopause, or VMS. Fortunately, many of you probably watched the Super Bowl and saw Astellas's ad challenging people to answer the question, what is VMS. But it may be worth reminding you that VMS stands for vasomotor symptoms in menopause which are commonly referred to as hot flashes.

With over 45 million in women in the U.S. estimated to be in or approaching menopause each year and with the legacy brand in the category, having generated $2 billion in annual revenue, it's not surprising that the condition was a subject of a Super Bowl ad. So what are we developing for the condition? Well, DARE=HRT1 has the potential to be a first-in-category convenient combination hormone delivering monthly vaginal product for the treatment of the vasomotor symptoms in menopause. Specifically, DARHRT1 is an investigational intervaginal ring designed to release bioidentical estradiol and bioidentical progesterone through this vaginal ring over 28 days.

So DARE-HRT1 has the potential to be the first nondaily, nonoral monthly format product with both bioidentical hormones. There are no FDA-approved options with both hormones and 1 monthly IBR. Hormone therapy remains the most effective treatment for the vasomotor symptoms of menopause and the genitourinary syndrome of menopause and has also been shown to prevent bone loss and fracture. The 2022 hormone therapy position statement of the North American Menopause Society, or NAMS, supports hormone therapy in peri and postmenopausal women and NAMS observes that nonoral routes may offer advantages over oral routes administration.

We previously announced the top line data from that Phase I/II study of 2 different dose combinations of DARE-HRT1 over 12 weeks of use in approximately 20 healthy postmenopausal women. And as we reported, the levels of estradiol released from both the lower and the higher dose formulation of DARE-HRT1 achieved or exceeded the levels that were targeted for hormone therapy.

In addition, despite the small sample size, the levels of estradiol released from both the lower and higher dose formulation evaluated in the study achieved statistically significant improvement compared to baseline in BMS as well as the genitourinary symptoms of menopause and vaginal PH and maturation index, all at the P less than 0.1 level. These data support the potential of DARE-HRT1 to deliver effective hormone therapy in a convenient 28-day vaginal ring. Following clinical development, we intend to leverage the existing safety and efficacy data on the active ingredients in DARE-HRT1, estradiol and pedestrone specifically to utilize the FDA's 505(b)(2) pathway to obtain marketing approval of DAIR-A2T1 in the U.S., that pathway that 505(b)(2), that's the same pathway we use for XACIATO.

We intend to seek FDA approval of DARE-HRT1 for the treatment of moderate-to-severe vasomotor symptoms due to menopause in women with intact uterine. Based on pre-IND communications with the FDA and the top line pharmacokinetic or PK data from the DARE-HRT1 Phase I/II study, we believe FDA approval of DAER-HRT1 for that indication is achievable via that 505(b) pathway supported by a single placebo-controlled Phase III clinical trial of DARE-HRT1 and a scientifically justified PK bridge basically via relative bioavailability trial between DARE-HRT1 and the selected listed estradiol and progesterone drugs.

Ongoing activities to support the pressing directly into that single Phase III study to support registration, include manufacturing and nonclinical studies to support the IND submission and the planned therefore IND opening Phase III study. We look forward to providing further updates on the time lines to Phase III as these activities continue to progress this year.

The second Phase I/II study conducted in Australia was for DARE-VVA1, our hormone-free vaginal atrophy treatment candidate. There are currently no FDA-approved products labeled as safe for use in hormone receptor positive breast cancer. DARE-VVA1 has the potential to be the first in category hormone-free vaginal treatment for vulvar and vaginal atrophy, or VVA. DARE-VVA1 is an investigational proprietary formulation of tamoxifen for intravaginal administration. Approximately 4 million women in the U.S. have a history of invasive breast cancer. It's estimated that more than 66% are hormone receptor positive cases.

VVA which can lead to painful intercourse and associated interpersonal distress is prevalent in postmenopausal breast cancer survivors with rates estimated at 42% to 70%. These women are generally not candidates for hormone-containing therapies despite their vaginal atrophy symptoms, as the use of estrogen in any form is often contraindicated for hormone receptor positive breast cancer patients and survivor. So there is a clear unmet medical need for an effective nonhormonal treatment for VVA. And in November of 2022, we announced the positive top line results from our Phase I/II study of DARE-VVA1. In that study, DARE-VVA1 demonstrated improvement in vaginal cytology parameters and bothersome symptoms of VVA supporting the ongoing development.

Following clinical development, we intend to similarly leverage the existing safety and efficacy data on the active ingredient in DARE-VVA1 tamoxifen and again, to utilize the FDA's 505(b)(2) pathway to obtain marketing approval of DARE-VVA1 in the U.S. As we continue to engage with the FDA on the IND process this year, we'll provide additional updates on the time line to Phase II.

Last development candidate I'd like to highlight is DARE-PDM1, our investigational product to treat primary dysmenorrhea, or menstrual cramps by delivering the NSAD diclofenac vaginally, utilizing our proprietary hydrogel formulation, the same formulation technology that is used in XACIATO. We initiated a Phase I study of DARE-PDM1 this year in Australia and top line data are also expected this year.

Primary dysmenorrhea is defined as painful menstruation in women with normal pelvic anatomy typically described as cramping pain in the lower abdomen before, during the menstrual period. Recent market research suggested the global market for dysmenorrhea treatment is estimated to be valued at $13 billion in 2022 and that the size of this market is expected to increase to $28 billion in 2029.

Primary dysmenorrhea usually begins during adolescence and is a leading cause of recurrent short-term school absence and adolescent girls and a common reproductive age. According to the American College of Obstetrics and Gynecologists Committee on adolescent Healthcare, it's the most common menstrual symptom of adolescent girls and young women and most adolescents experiencing it have primary dysmenorrhea. The preference rates range vary but they range from 15% to 19% [ph].

The most common interventions for temporary relief for the painful symptoms, include oral NSAIDs or hormonal contraceptives which often can produce undesirable side effects, oral NSAIDs which are available over the counter may cause an increased risk of gastrointestinal adverse events, including nausea, vomiting, bloating alterations and hormonal contraceptives can also produce a number of undesirable side effects.

So by leveraging a vaginal administration, we believe we can provide a localized treatment option that addresses the pain-related symptoms at the condition while minimizing side effects commonly seen with the oral medications. Because there are currently no FDA-approved vaginal diclofenac treatment options for primary dysmenorrhea, DARE-PDM1 has the potential to be a first-in-category product, delivering diclofenac in a convenient vaginal format that may extend the duration of pain relief and reduce side effects commonly associated with the oral delivery of NSAIDs.

Now in my opening comments, I noted that part of our strategy is to identify promising candidates that can be developed efficiently in terms of time and cost. The ability to leverage our hydrogel platform technology that has recently undergone successful preclinical and clinical testing and regulatory review could offer both time and cost savings and advantages in the development of new candidates to address meaningful unmet needs in women's health.

It is our hope that the development of DARE-PDM1 and DARE-LDT1 which I've not discussed today but similarly relies on the hydrogel platform, will benefit from the use of that technology that has already been closely evaluated.

I will now turn it over to John to provide an overview of the 2 license agreements we have in place for commercialization of XACIATO and Ovaprene, respectively.

John Fair

Thank you, Sabrina. As Sabrina outlined, we strive to develop differentiated first-line or first-in-category products. We believe this creates optionality for our commercialization strategy by allowing us to enter into commercialization agreements as we have with XACIATO and Ovaprene on a product-by-product basis and in those circumstances where we believe a collaborator with an established commercial capability in women's health is the most effective and efficient way to bring a Daré product to market and the optimum way to provide value to Daré stakeholders.

Our model gives us the flexibility to work with top commercial companies in women's health for certain products but also directly engage in commercial activities for other Daré products when we believe it's most appropriate strategy given the target product profile and the stage of development within our portfolio.

As Sabrina outlined, we retain this level of optionality with the remaining 11 development stage product candidates in our portfolio. To date, we have entered into commercialization license agreements with what we believe to be our 2 of the best commercial companies in women's health. The value of having the breadth and experience of a women's health commercial market leader behind the brand is clear when we consider the XACIATO go-to-market strategy. We continue to remain excited about XACIATO's launch as we look forward to seeing XACIATO added to the health care providers armamentaria.

As Sabrina noted, Organon has been working on launch activities, taking a holistic approach to the products introduction which will include direct selling which is also known as personal promotion as well as nonpersonal promotion efforts and utilizing key digital platforms as well as payer and health care provider channels. Organon has what we believe to be a truly integrated go-to-market plan targeting all of the key stakeholders which are the health care providers, the payers and the patients in order to quickly drive interest and awareness in the brand.

And importantly, we have reported previously Organon's market access team has been meeting with health plans and PBMs to review XACIATO and obtain competitive coverage in the bacterial vaginosis category which is critical to support patient access and product pull-through, as Sabrina mentioned earlier.

Organon will leverage its established Nexplanon sales team to optimize XACIATO uptake at launch. And they believe there's roughly a 90% overlap of those health care providers who are already prescribing Nexplanon and have the potential to be XACIATO prescribers. That strong relationship with the sales team and the provider relationships they have in place is expected to enable access to these HCPs and coupled with Organon's payer outreach and planned patient-centered activities, we think that allow us to be well positioned for in-market success and we look forward to launching the brand by the end of the second quarter.

Under our license agreement with Organon to commercialize XACIATO, we received a $10 million cash payment from Organon after the license became effective in June and we are entitled to receive $2.5 million following the first commercial sale. We are also eligible to receive potential additional milestone payments of up to $180 million as well as tiered double-digit royalties based on net sales.

Let me transit announce on pre-commercialization activities underway for Ovaprene, our novel hormone-free monthly intravaginal contraceptive candidate whose U.S. commercial rights are under a license agreement with Bayer. As a reminder, as part of our license agreement with Bayer to commercialize Ovaprene in the U.S., Bayer currently supports the Ovaprene program by providing up to 80 hours per week of an advisory capacity giving Daré access to Bayer's extensive clinical, regulatory, manufacturing and commercialization resources while we retain control over Ovaprene's development and regulatory approval process.

Bayer has the right to obtain exclusive rights to commercialize Ovaprene in the U.S., following the completion of a pivotal Phase III study by making a $20 million payment to Daré. Thereafter, we will be entitled to receive commercial milestone payments potentially totaling $310 million in addition to double-digit tiered royalties based on net sales. Bayer has initiated activities to gain meaningful market and key stakeholder insights. Bayer continues to be a great collaborator, including recently sharing important commercial input that we were able to leverage for the Phase III study design.

And with that, I'll turn it over to Lisa for a financial update.

Lisa Walters-Hoffert

Thank you, John and thanks, everyone, for joining us today. I'd now like to summarize Daré's financial results for the year ended December 31, 2022 which I will also refer to as the current year or 2022. Daré's business model is comprised of 2 parts. The first is to assemble and advance a portfolio of differentiated product candidates that address meaningful unmet needs we've identified in women's health. The investment required to do so includes corporate overhead, portfolio acquisition and maintenance costs and ongoing research and development or R&D expenses.

The second part of our model involves monetizing the value of the portfolio's clinical and regulatory advances over the near and long term. There are many ways to generate value from a portfolio and one approach includes securing payments upfront and over time in the form of license fees, commercial milestones and royalties on net sales. This is the arrangement we put in place for XACIATO.

And as John just outlined, pursuant to the terms of our global license agreement with Organon for XACIATO, we've already received $10 million upfront upon the agreements effectiveness and we will be entitled to receive a milestone of $2.5 million following the first commercial sale. And thereafter, we will be eligible to receive potential additional milestones of up to $180 million and tiered double-digit royalties on net sales.

But back to our current year. During 2022, we recognized our first revenue from the $10 million license fee from Organon that I just mentioned. Our general and administrative, or G&A, expenses were approximately $11.2 million. Our R&D expenses across our entire portfolio which vary from period to period based on our clinical, preclinical manufacturing, regulatory and other activities, they were approximately $30 million and primarily reflected the costs of our late-stage programs, such as the ongoing Sildenafil Cream, 3.6% Phase IIb RESPOND clinical trial and manufacturing and regulatory affairs activities related to Ovaprene.

Our comprehensive loss for 2022 was approximately $31.1 million. We ended 2022 with approximately $34.7 million in cash and cash equivalents. During the year, we received approximately $24.1 million in nondilutive funding. This included the $10 million license fee from Organon, approximately $13.3 million in grant funding and approximately $800,000 from an Australian government -- from the Australian government as a research and development cash rebate from clinical studies that we have performed in 2021.

Grant funding consisted primarily of funding for the Daré-LAT1 program under a 2021 brand agreement and for the DARE-LVT1 program under a November 2022 grant agreement. But also, in addition to those sources, our brand funding included an NICHD funding for the Daré 204 214 and DARE-PTB1 program.

As we've said before, nondilutive sources have and will continue to play a very important role in our funding strategy. Our with the NICHD will allow Daré to share cost of the upcoming Ovaprene pivotal study and to tap into the NICHD's extensive experience in conducting contraceptive studies. Under our existing crater, we are responsible for providing clinical surprise of Ovaprene for the study, coordinating interactions with the FDA, preparing and submitting supporting regulatory documentation and providing a total of $5.5 million to the NICHD to be applied towards the cost of conducting the pivotal study, $5 million of which has already been paid. NICHD is responsible for other costs related to the conduct of the study.

As of December 31, 2022, we had outstanding warrants issued in February of 2018 that were exercisable for up to approximately 1.4 million shares of our common stock. Subsequent to the end of the year, all of those warrants were either exercised or have expired. And today, none of those warrants are expanding. We received approximately $1.3 million in cash and issued approximately 1.4 million shares as a result of such warrant exercises. As of March 28, 2023, Daré had approximately 86.2 million shares of common stock outstanding.

In closing, we will endeavor to be creative, collaborative and opportunistic in seeking the capital necessary to advance our candidates and to build shareholder value. We also encourage investors to review the more detailed discussion of our financials, our financial condition, liquidity, capital, resources and risk factors on our Form 10-K for the year ended December 31, 2022 which we filed this afternoon.

I would now like to turn the call over to the operator.

Question-and-Answer Session

Operator

[Operator Instructions] Your first question comes from the line of Catherine Novack from Jones Research.

Catherine Novack

Congrats on all the progress. Just thinking about the upcoming RESPOND data, can you talk about the different components that are going into the arousal sensation domains in both of the primary composite endpoint for both the SFQ 28 and the SBSBAO, what would be considered a clinically meaningful improvement on some of these endpoints? And then again, thinking about this patient population, what proportion of women with FSIID would fall under the category that you're enrolling into the Phase IIb?

Sabrina Johnson

Great question. And thank you for the kind words about our accomplishments. So let's start first with the questionnaires and the nature of the question specifically in those primary endpoints. And that's a great and what's clinically meaningful, right? That's a great place to kind of take a step back. And again, explain what the use of this study is, right? And what we're trying to do here. And you just highlighted one of them. So in any clinical trial, you can only use as your primary endpoint, something that has already been validated. And in the place of sexual health, there are not a lot of validated questionnaires for women, not surprisingly, given that there haven't been a lot of sponsor programs, right, to take products through the FDA. But the endpoints you highlighted, those questionnaires have been and those questionnaires on the sexual functioning questionnaire, it does have a subset of questions. It has questions about pretty much everything you can imagine that happens in a sexual experience all across the journey. And some of those questions are very specific to what you would experience as part of a genital arousal response, right? Those -- their questions specifically about what happens in the genital region, specifically actually when you get blood flow to the region because that's what elicits that those sensations that you -- that she could experience.

So it does have some questions that are very relevant, right, to what Sildenafil does. And the distressed questionnaire that we use, the definition, right, the arousal condition definition includes the fact that this lack of an inability to attain or maintain sufficient general arousal response can lead to distress. And so there is -- therefore, as part of the co-primary and specific question about distress. Because these questionnaires have not been used before, in the context of arousal disorder, there is an opportunity for us on the primaries as well as actually on all of our exploratory endpoints. So we included a number of exploratory endpoints in this study that specifically came out of what's called content validity work we did with women with the condition to understand the words they use specifically to talk about it and the symptoms they care about and what they might feel is a clinically meaningful improvement.

So all of that was included in the Phase IIb as well as a whole component that has to do with exit interviews as well as psychometric work that had after we have all the study data that is important to do exactly what you just asked about, to demonstrate what amount of improvement is considered clinically meaningful and to validate any of the endpoints that we have included here so that any of the endpoints we have included here are candidates for the Phase III. And that is why I say. So this is a super exciting study. It's a very rich study in terms of the data that we are going to be generating which is why I say we will make a top line data announcement, obviously, as soon as we have this data in the second quarter but there will definitely be a deeper dive assessment as we do exactly what you've outlined. Then we take all that information, we take the exit interviews that we're done, we take what we have demonstrated to be a clinically meaningful improvement and we pick what do we want to take forward in Phase III and why.

And that's a great tie-in to the second part of your question which is how does our population, patient population, how does the endpoints you're looking at, right? How does that all relate to different definitions and different populations within the arousal disorder community because the nomenclature and how that condition is defined like in the DSM which is where this condition is defined have continues to evolve. And that's because there is an interplay. This should not be surprising for anyone. Again, no different than erectile dysfunction. There is a physical component to an arousal response. And then there's an emotional, right, component, an interest level component.

If you are not able to have a physical arousal response, a portion of the population will not be interested over time, right, because they're no longer -- it's all related in some ways. And so there is a population, some studies have estimated at around 50% who have both arousal disorder and lack of interest. So similarly, we have attempted to conduct our Phase IIb study and our selection of the patient population and this is part of why we took time in rolling subjects and characterizing them and screening them so that we will actually be able to, with our data set, look at data a lot of different ways, women who only have arousal disorder, women who have a combination of arousal or lack of interest as well as other, right?

There's women who have arousal disorder like so there's lots of different permutations that we're going to be able to look at and we're super excited to be getting -- it's a big step for the field to be getting these data and there's going to be a lot that we're going to be able to dig into and then hopefully get ready for those interactions with the FDA on the next step. That was a long answer to your question and hopefully that covered it.

Operator

Your next question comes from the line of Douglas Tsao from H.C. Wainwright.

Douglas Tsao

Just maybe first on the Sildenafil Cream program. How are you thinking about the commercialization strategy? And what I mean specifically is, obviously with XACIATO and Ovaprene you've pursued partners. I know in the past, you've contemplated or said that you're thinking about the right time to potentially become a commercial organization. When do you think you need to make that decision? Is that something that would be done like XACIATO after we have Phase III data and maybe not necessarily after approval but -- or would this be something that potentially could happen before a Phase III program?

And then also, as a final follow-up, just in terms of enrollment, you're thinking about the Phase III. I understand your point about sort of looking at the data in terms of and cuts in terms of patients with arousal as well as lack of interest. But is there -- is one study enough to potentially sort of validate or give you confidence that you could enroll patients with sort of multiple manifestations of sexual dysfunction?

Sabrina Johnson

Great. Both of those great questions. I'm actually going to take them in the -- I'm going to start with the second one and then I'll talk about our go-forward strategy. They're kind of tie together. So first of all, as you highlighted, -- and that's why we really refer to this as a Phase II exploratory study. There's a lot we're going to learn from this study being -- it's fantastic to be groundbreaking as we are in this way. It really affords you a lot of opportunities to pave the path that others will have to follow who come behind you. And so that's definitely something that we're going to be looking at closely here as we look at these data is how do we want to define the patient population. We want to define it at the best we can for our cream, our Sildenafil Cream and where this product is going to do well and do well in a way that whoever follows is going to have a hard time meeting.

And so as we're thinking about the patient population to study and this is why purposefully in the Phase IIb, we worked hard to make sure that we had some different patient profiles to be able to analyze. It's really going to allow us to figure out and to determine what direction we want to go for the Phase II. We do think that actually we are going to need 2 Phase III trials for registration because this is such a novel indication and novel formulation of Sildenafil. So even though it is the 505(b)(2) pathway that I talked a lot about today, this would be a circumstance unlike XACIATO, unlike HRT1, where one Phase III is adequate. This is one where 2 Phase IIIs would be required. And that does also give us some opportunity to potentially have some differences in those studies, all of which would need to be discussed with the FDA.

And that kind of goes to the second, the first part of your question which I'm taking the second part. So first of all, as we've said before and John highlighted just today, right, we look at each of our products on an individual basis and further with 12 development stage candidates in our portfolio, we certainly have a lot of flexibility in terms of how we think about go-to-market strategy because we have such a broad portfolio in women's health, all the same call point that there comes a time where it's not a single product going to market, it's multiple products on market at the same time, potentially, right, as you think about the portfolio as it advances.

So we take into consideration a couple of different factors as we think about how and when to partner. First of all, it comes down to how and who is going to be running the development program and how that can be done in a way that is most advantageous for the brand. I'm going to take Ovaprene is a great example. We and Bayer align together that for that program and the nature of that kind of very novel product, novel education, needing to be nimble, needing to be flexible and creative that it made a lot of sense for Daré to take the lead on that development program through the PIVOT study with Bayer behind us, supporting us, lifting us up, giving us advice, giving us insights but that we would lead that program.

And whereas with XACIATO in bacterial vaginosis, that's a very straightforward regulatory approval pathway and we knew what we needed to do to get a very differentiated label there. And we knew also that we did meet, right, our commercial partners insight along the journey and that we could get it there.

So as we think about the Sildenafil program, there are always pros and cons. And this is a long way of me saying, in the end, we always evaluate the opportunities and we evaluate what the program needs and we evaluate what Daré needs. And ultimately, we evaluate what is going to be best in building the value, the biggest value we can create and the fastest way to get to that value. And that's exactly the analysis that's going to come on the Sildenafil program. Clearly, there aren't a lot of opportunities to have such a groundbreaking product. It's truly creating a new category and that obviously generates interest.

And so we will just have to be -- as we do, we evaluate everything and we evaluate the possibilities and we'll make the determination on what makes sense. And the beauty for Daré is that we have that optionality. We have a portfolio that supports us being able to contemplate all different go-to-market strategies because we're not relying on a single product.

Operator

Your next question comes from the line of Kumar Raja from Roth Capital.

Kumaraguru Raja

I had a question on PDMI. So in terms of doses that are being tested, how do they compare with systemically dosed versions? And is the expectation that a single dose would be sufficient for most of the patients that the pain is typically seen in the 24 hours?

Sabrina Johnson

Both great questions. Thanks for asking about that program. Since we've initiated the study, we've just been so excited about the level of interest in that program that we're running in Australia. So we're very much looking forward to the results. And the trial is very much in the dosage forms that we're studying is very much designed to answer exactly what you're asking. So first of all, we, of course, did take into consideration what's delivered with the oral doses of diclofenac and what you see systemically and diclofenac, in particular, has demonstrated benefits in dysmenorrhea, actually not just for the pain but also even sometimes in the heavy bleeding that women can have. So we did look at that.

But as you can appreciate, when you're going from systemic oral delivery to delivering localized, it's not one to one. Again, XACIATO is a wonderful example here. We have very low levels of clindamycin systemically. That's why we were able to get some of the safety labeling we were able to get in XACIATO because of that. that we have very good concentrations of clindamycin locally, right, where you need it. So we're trying to do the same thing with PDM1. So we selected doses, again, taking into consideration the amount of diclofenac you have systemically but not trying to match those dose levels but trying to think about, therefore, the amounts that we would want to be achieved localized in the localized tissue environment. So that's how we selected the doses.

And to your question on how fast we see effect and duration of effect, similarly, that's what we're looking to understand better in this study. And so the way the study is designed, the women -- first of all, women in the study will have the condition. So it's like it's healthy normals but they're healthy normals with dysmenorrhea. So they will have the conditions. So that's why we're also able to look at and not powered for efficacy but also be able to look at what effect they may experience with the product and it's designed to look at both single administration and multiple administration. So it's going to give us a lot of insight.

Again, we know from our XACIATO experience that this formulation stays resident in the vaginal environment. So it's not just at the time of dosing but beyond that, when you look at both vaginal and systemic PK levels, so we're expecting to see the same thing. So I wish I had answers to you today. But what we're hoping, we know from XACIATO, how the product and how that formulation technology performs. So we took that into consideration as we designed DARE-PDM1. And then the Phase 1 is really designed to answer those exact questions. Like how long does the product stay resident, how long of effective she have after one time of dosing, how long does it say resident and then what happens if we allow her actually to dose multiple times.

Kumaraguru Raja

Great. I just tied to a question on XACIATO. John alluded to this a little bit. So in terms of payer negotiation, what can you guys share with us? And is the expectation that there is going to be some step edits there? Maybe just a little bit of clarity on like where you guys stand there right now.

Sabrina Johnson

Yes, absolutely. So let me say a couple of words and then I'll turn it over to John in even thing could add. So first of all, I want to clarify one thing because I think it sometimes does get confusing sometimes because you talk about launch, then we talk about first commercial sale. So as John alluded to, activities that you do, right, to that are part of that launch strategy, such as payer interactions those started. Those actually started last year, right? Those activities have been underway. And as you noted, right, very, very important activities. It's the actual first commercial sale that is being targeted for the second quarter. But those kind of launch activities and launch preparation activities have obviously already been underway.

And while we are not in a position, given that we organized our publicly traded companies, right? We're not in a position to share the specifics around all the activities they're doing and all the details on what the objectives are. What we can do is give you a little more perspective on just your question specifically around step edits because that's something really important to understand that is very unique about this category compared to other categories. We're step-editing even if it was required is not as big of an impediment as it might be another category because of how recurrent bacterial vaginosis is and the fact that many of these women will have already been through that.

So John, if you can maybe just talk a little bit about the recurrence rate of bacterial vaginosis and how common it is for women who have already been on a treatment in the prior period? And what that means having already stepped through products.

John Fair

Yes, we'll do. Thank you, Sabrina. Yes. And I think just taking a step back, so bacterial vaginosis, it's not a very heavily managed category. It's not a big budget hit for a lot of health plan. So there's not a lot of utilization management happening in there already. But in terms of your direct question, in about 50% of all cases women are going to recur. And recurrent bacterial vaginosis is essentially 3 or more episodes in a given year. When a step edit is applied, it's generally when she needs to graduate through something to get to something. And in our situation and again, we believe this to be the case, we're not speaking for anybody else, there are going to be a number of women who will automatically sort of stepped through a previous therapy. So that step -- if there's a step edit which not clear that there will be because, again, the category is not managed that tightly. But if there is, it's very likely that a big portion of the population will already "step through" and should have access to the brand.

Operator

Your next question comes from the line of Jason McCarthy from Maxim Group.

Joanne Lee

This is Joanne Lee, on the call for Jason McCarthy. Congratulations on all the progress. So a lot of questions were asked around the Sildenafil program but I wanted to ask about the HRT1 program as well, for which we saw the positive efficacy data in Q4 and this was followed by the safety and PK outcomes earlier this year. And now the company you guys are positioned to file the Phase III IND. Can you briefly, just as a reminder, walk us through some of the key data that has emerged from the Phase I/II as well as other factors, including maybe the unmet need in the space that may have attributed to the decision to progress that drug straight into the Phase III program? And as a follow-up, what are the expectations in terms of the time lines around the IND submission and the study initiation?

Sabrina Johnson

Great. Thank you for -- first of all, thank you again for the kind words and thank you for asking about that product. It is definitely one that we're quite passionate about at the company for some of the reasons that you cited. So first of all, taking a step back and I mentioned this briefly into my comments but the North American Menopause Society, by the way, a little commercial for anyone looking for information about menopause, they are a great reputable source of information. These are the clinicians that have very much taken on menopause share, right, as something that's important to them and they've really studied menopause and studied what happens during menopause and what are the needs that women have during menopause. And what are the appropriate approaches to address that.

And as a medical group, I think as a group, they've been, it's frustrating that there are not as many options as one would hope to address these conditions. And these symptoms that are very debilitating in terms of a women quality of life and her ability to function, right? We joke about hot flashes but the disruption to the sleep and the downstream consequences that are a big deal. But there's other factors that happen in women when the hormones deplete, right? So there are factors related to bone health. There are factors related to cardiovascular health. So hormone therapy as a North American menopause study say, can play a very important role. But the objective is you really want to deliver hormones, particularly the estradiol at the lowest possible dose that you can to still see beneficial effects and you want to counterbalance it for safety with progesterone.

So you really want the 2 hormones together. And clinicians have been a little bit limited as they haven't had. And ideally, because these hormones are not efficiently metabolized through the oral route to -- and therefore, you have to give really higher doses, right, when you're dosing orally and non-oral route can have benefits but you really want both hormones So we're excited about HRT1 because there's not been a product yet that does that in this convenient once a month, both hormones together, vaginal form, you're delivering them in that route administration. So very much an unmet need. And very excited about a product that can address that unmet need and excited to have the opportunity, hopefully, to deliver something that is aligned with what the North American Menopause Society position paper on menopause indicates may have a lot of value.

Now having said that, to your question on what do we see? Why are we excited? Well, we're excited. Obviously, that's a form factor for all the reasons I said. But with hormone therapy, we know, right, with hormone therapy, we know the levels that you want to see. We know them for 2 reasons. We know them because of the products that are already FDA approved and have demonstrated benefits. So you can go through 1 exercise and just look at our levels and compare them at FDA-approved products to say, okay, check, yes, we're delivering it out like that product. But also importantly, what you're doing with hormone therapy is you're replacing the hormones that she no longer has. And we know what targets we want to replace. We want to get it to a certain part of her cycle in the premenopausal phase, right? We set certain levels of format, not the high levels that she has when she's ovulating but the low levels that she has at certain phases of recycle. So the PK data basically allow us to see that. They allow us to make that comparison to see yes, we're at low doses but look, we're at effective levels because we know what it's been achieved with some other products and their form factors, what they've seen systemically. And then we also know our target is to what you want to achieve in the premenopausal women.

So for all those -- that's why we are so thrilled and obviously thrilled with the significance we saw, even though it was a small study, the fact that we were able to exhibit that level of improvement.

In terms of what we need to do, though and so therefore, we were thrilled in the pre-IND discussions with the FDA that this path of going to a single Phase III is an option for us. What that means now is we have to execute against that. So from a manufacturing perspective, obviously, we've got to manufacture the GMP product for the Phase III trial. And so there are, obviously, activities underway to support that to be able to support those supplies being ready for the Phase III. And then similarly, having -- the reason you have pre-IND discussions is to clarify what is expected in the IND. And there's some nonclinical work that we will need to do as well to support that for the IND. So all of that work is underway. What I wish I could do for you today but I can't yet but we look forward to giving that update when we can is tell you the exact time line. Like so what does that mean in terms of when exactly we expect to be in that Phase III study. What I can say is that is one of our very important milestones for this year, right? Are the IND-related activities for DARE-HRT1 and the Phase III clinical study initiation plans and work that needs to happen. So please stay tuned for more on that one. We definitely look forward to giving more updates because we -- we're very, very excited about this program.

Joanne Lee

Got it. I appreciate all the additional color. And for the company's earlier stage program which there are several assets that you guys are planning to advance. Specifically regarding DARA-PM1 which, as you've mentioned, is being developed using the same validated platform technology you to develop Sildenafil Cream. I wanted to ask if you could talk a bit about the importance of bringing a safe drug to this population of women with primary dysmenorrhea. And given the 505(b)(2) drug pathway as diclofenac is well NSAID. What could we interpret a positive Phase I study to mean? And although it's not powered for efficacy, would PK be almost sufficient to imply efficacy because we already know the drug sort of worked which heavily derisks the program already?

Sabrina Johnson

Yes. Thank you for the question. And for clarity, it's the same gel that's in XACIATO. Yes, so we are definitely got one, like the 505(b)(2) pathway, obviously, we've talked about so much today. We love that pathway, right, because you're getting to on drugs that have already demonstrated safety and have already demonstrated efficacy. So in the case of PDM1, we absolutely can look at -- we know the levels of diclofenac systemically for effectiveness. We don't know the local levels of diclofenac for effectiveness but we know the systemic levels. And we know the systemic levels for sure, for safety.

What we have -- and so first, I'm going to talk about the regulatory part and then I'm going to tell you to talk about the other part of your question which is like the unmet need and the why. But from a regulatory perspective, what I will say, what we have -- the beauty of working in one therapeutic category and being so broaden as we are is we have a lot of interactions with the FDA all the time with a lot of the same people at the FDA and you start to see trends. That's part of also the value of the way we work and the efficiency, right and the way we work. So the trend we have seen is that -- and Sildenafil is a great example where we've had very mature discussions with the FDA that because in the case of Sildenafil, it's a brand-new indication and it's a brand-new route of delivery they want 2 trials, right, 2 Phase III trials. So -- and we saw with HRT1 that because we know about hormone therapy and even though it's novel for us to have both hormones together, vaginally, their support for a single Phase III trial.

PDM1, hard to know today where it's going to land because to your point, diclofenac is already well known, very well established, labeled for this indication already. We're just delivering it in a different form. So we are hopeful, obviously, that we will be able to get to leverage the Phase I data robustly to the benefit of a more efficient, streamlined registration program but a little early to project on that one.

What I will say about the unmet need, though, is that I alluded to, a lot of the women that are very bothered by this, a reproductive age women, that's younger women, it doesn't get better. It's not like they grow out of it in a year. This is a problem that can be very persistent for them, very disruptive for them. And there is -- there are a lot of data, right, around the potential risk of long-term use of oral NSAIDs in terms of other just risk factors and complications apart from just the disturbance in the side effect profile that they can have from a GI perspective.

So there is, therefore, interest, right and thinking about how great it would be for these women to have an option that can deliver effectiveness in a nonoral route, in a vaginal route administration that, again, is -- has that potential benefit. So that's why we're looking forward to and excited about it and excited to have a possibility of giving women an option that's very different from anything that is available to them today. And again, it's more in mind in delivering something more resident to where she's having the problem.

Operator

Your final question comes from the line of Kemp Dolliver from Brookline Capital Markets.

Kemp Dolliver

I'm going to ask 2, hopefully, brief questions. First, how are you thinking about 2023 spending levels relative to 2022?

Sabrina Johnson

Yes, great question. As you know, we typically don't give a lot of like forward-looking guidance around our spend. And we have been fairly consistent historically with how we spend. But the important thing to keep in mind is that the spending, you heard G&A is around last year is $11 million, right? What we spend is primarily associated with the development programs, right? That's the bulk of where we use our capital. And the majority of the expenses, again, not surprising, is with our later-stage programs, right? And so as we think about the first half of this year, you're right, our research and development expenses are going to be primarily associated with the completion of the Sildenafil study and manufacturing activities around the Ovaprene study, right, to prepare for Ovaprene.

So we're always closely monitoring our cash and our resources and thinking about the timing of incurring expenses versus our opportunities to bring in capital, right? We also always we're a development stage company. We're always bringing in capital in different ways and means. So as we think about this year, we obviously -- we have some important activities around Sildenafil and Ovaprene primarily that we're very focused on in the first half of this year but we obviously have expenses, right, that yes, we can control but that we're going to incur as we think about progressing the other programs in the later part of the year that we talked about. But that's where the variability is, the G&A has been very fixed over time, pretty consistent. It's really around where we spend on development.

Kemp Dolliver

Super. And my second question relates to the Sildenafil study. And the question -- so the questionnaire and the amount of data you need to analyze. And so how many question answer -- questions or answers or in this question depending on what's the better way to think about it? And then how long do you think you'll need to analyze the data to put together the Phase III design?

Sabrina Johnson

Yes, that's a fantastic question. So first of all, in terms of just the primary and secondary, it's a very reasonable number, right? It's less than 10, kind of individual questions and domains. The bigger piece is related to the exploratory. This study was designed to ask even sometimes the same question in different ways. So we have electronic diary data that is post sexual event over the course of the week, over the course of the month, we have other data that's collected only on a monthly basis, right? So there is absolutely a lot of information.

Having said that, we are very motivated to go as quickly as we possibly can to pull all these data together and get it to the FDA this year. That is a clear priority for us. And so we'll have top line data in the second quarter, as you talked about and then we're looking to very shortly thereafter, have the full data set. And we've already lined up our advisers to be working with us as we kind of mine through that and prepare and request that end of Phase II meetings with the FDA.

And as we always do, I alluded to already a lot of interactions with the FDA and we try to be super communicative. So we have already given the FDA know where we are on the program and that we look forward to speaking with them about the Phase III results. So our hope is that we will be able to move very quickly this year towards those conversations.

Operator

That concludes our question-and-answer session. Ms. Johnson, I turn the call back over to you.

Sabrina Johnson

Thank you. And I'm looking at the time and thank everyone for your time this afternoon to hear about our recent updates and our ongoing commitment to driving value for all of our stakeholders, the women, the health care providers, our shareholders, with our diversed portfolio, we really seek to bring to market differentiated prescription therapies that prioritize women's health and wellbeing, expand those treatment options were not exist enhance the outcomes where current standard of care has meaningful sure comings and improve ease of use for women where a more compelling form factor can drive adoption. And as we talked about today, primarily in the areas of contraception, vaginal health, reproductive health, menopause, sexual health and fertility. -- and our focused efforts to deliver differentiated innovation in women's health, as we talked about, it resulted in our 12 development stage programs across 9 distinct indications, the more than 5 milestones anticipated for this year 2023, the 3 candidates and are nearing Phase III development, our 2 potentially transformational collaborations with the leaders in women's health product commercialization Organon and our first FDA-approved product, XACIATO.

So as I mentioned at the onset of the call, it's our belief that prioritizing women's health is good for the many women lacking effective or convenient therapeutic choices and good for a broad set of stakeholders, including their families and partners and, of course, our shareholders. So we very much look forward to keeping you updated on our progress, on the milestones that I outlined earlier that we have anticipated for this year. So we're talking a lot about this Sildenafil Cream, Phase III RESPONSE study top line results, the U.S. launch is XACIATO by Organon, the initiation of our pivotal study of Ovaprene, the IND-related activities that we were talking about for DARE-HRT1 and DARE-VVA1 and importantly, the Phase III and Phase II, respectively, clinical study initiation plans and DARE-PDM1 Phase I study top line data that we're looking forward to this year as well.

So thank you for your time today. Thank you for following and thank you for those who asked all the great questions.

Operator

This concludes today's conference call. You may now disconnect.

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Dare Bioscience, Inc. (DARE) Q4 2022 Earnings Call Transcript