Q4 2022 Dare Bioscience Inc Earnings Call

Speaker 2: results that the year ended December 31st 2022 and to provide a general business update.

Speaker 2: This call is being recorded.

Speaker 2: My name is Abby and I will be your operator today.

Speaker 2: With us today are Sabrina Martucci-Johnson, Dari's President and Chief Executive Officer.

Speaker 2: Marina Martucci-Johnson, Dari's President and Chief Executive Officer. I'm Marina Martucci-Johnson, Dari's President and Chief Executive Officer.

Speaker 2: Daria's Chief Commercial Officer, and Lisa Walters-Hofford, Daria's Chief Financial Officer.

Speaker 2: Ms. Johnson, please proceed.

Speaker 2: Thank you. Good afternoon and welcome to our year-end December 31, 2022 Financial Results and Business Update call for Dari Bioscience.

Speaker 2: Our plan today is to review our four-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.

Speaker 2: 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.

Speaker 2: 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.

Speaker 2: 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.

Speaker 2: 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. Dario undertakes an obligation, deputating any forward-looking statements, to reflect new information or developments after this call, except as required by law.

Speaker 2: By the time 2022 came to a close, we had secured our second commercial collaboration, in this case for our FDA approved product Zaciado 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 OvaPren.

Speaker 2: commercial rights to which you're under a license agreement with Bayer.

Speaker 2: We announced that we completed enrollment in our sebenofil cream female sexual arousal disorder phase 2B study, and we announced two positive phase 1-2 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 and that's a good one.

Speaker 2: milestones include not only objectives related to the programs I just identified, but to other portfolio candidates as well. Those of you who have been following Dara, I know that we are focused solely and squarely on women's health. For those of you who have been following Dara, I know that we are focused solely and squarely on women's health.

Speaker 2: 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.

Speaker 2: It has been reported that a mere 1% of healthcare 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.

Speaker 2: as in those that generate over $500 million in annual sales.

Speaker 2: And those products contribute 35% as a revenue generated by all Blockbuster products.

Speaker 2: 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 of women's health product candidates can potentially represent.

Speaker 2: particularly given that a number of our candidates are in the contraceptive, menopause, and sexual health categories.

Speaker 2: All of which have seen over a billion dollar and even over two billion dollar individual brand

Speaker 2: including the potential of our sexual health program, Sedenafil 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 to be first and more on our Sedenafil program shortly.

Speaker 2: 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 that 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, and in the

Speaker 2: reproductive health, menopause, sexual health, and fertility.

Speaker 2: 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.

Speaker 2: So while we have a broad portfolio, importantly, every single product candidate in our portfolio has to stand on its own merits.

Speaker 2: Third, it should already have demonstrated proof of concept and ideally use well-characterized active pharmaceutical ingredients which commit to 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 as ultimately evidenced by a clearly differentiated product label which is critical for market access and pull-through.

Speaker 2: Our focused efforts to deliver differentiated innovation in women's health have resulted in 12 development stage programs across nine distinct indications. With more than five milestone events anticipated in 2023 that we will discuss shortly, we will discuss shortly.

Speaker 2: 3 candidates in or nearing Phase 3 development

Speaker 2: two potentially transformative, transformational collaborations with leaders in women's health product commercialization, Bayer and Organon, and one FDA-approved product, Zaxiado. I want to share with you now Dari's key 2022 results and milestones and our anticipated 2023 milestones.

Speaker 2: 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 Zaxiado, Oviprene, Selvinafil Cream, DARE VVA1, DARE HRT1, and DARE PDM1.

Speaker 2: So I'm going to focus my comments today primarily on those programs. So let me begin by highlighting our global license agreement with Orgonon that supports the commercialization of Zaxciato, Clindamycin phosphate, vaginal gel 2%.

Speaker 2: As a reminder, Zaxiado is a lincosumide 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. Zaxiado is a lincosumide antibacterial for single dose vaginal administration indicated

Speaker 2: The Zaciata story is a great validation of our portfolio candidate selection and development strategy.

Speaker 2: Bacterial vaginosis is the most common vaginal condition in women of reproductive age.

Speaker 2: estimated to affect approximately 23 million women in the US alone. But yet a number of women with the condition have been underserved by currently available products.

Speaker 2: We hoped that by focusing on improving outcomes and her overall user experience, we could deliver a novel option.

Speaker 2: Understanding the differentiation drives value, we strove to design a Phase 3 study that would generate the data necessary to support the target labeling.

Speaker 2: And by doing so, create the opportunity for a commercialization collaboration that could drive value.

Speaker 2: We are thrilled that Organon, the Women's Health Focus spinout of Merck, is launching Zaxiado and that they will leverage their established Nexplanon sales team to accelerate Zaxiado uptake.

Speaker 2: 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 next plan on sales team will be leveraged for this all shadow.

Speaker 2: 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 Zoshyata commercial activity when John provides his update.

Speaker 2: In terms of our OVIPRINE program, the FDA's acceptance of our OVIPRINE 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.

Speaker 2: Obiprene is our investigational potential first in category, hormone-free, monthly, intervaginal contraceptive whose commercial rights are under a license agreement with Bayer.

Speaker 2: We announced ID 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.

Speaker 2: The study will target having around 200 to 250 subjects complete 13 menstrual cycles of use.

Speaker 2: 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.

Speaker 2: We anticipate initiation of pivotal Phase 3 subject recruitment in the middle of 2023.

Speaker 2: So that's two innovative brands, Zaxiado and Obercream, and two potentially transformational collaborations, one with Organon and one with Bayer.

Speaker 2: So what's next for Dara on our unpartnered program?

Speaker 2: Well, let's begin with Sedenafil Cream, 3.6%, a product candidate with the potential to create a completely novel category in women's health.

Speaker 2: 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 FSAG.

Speaker 2: As I mentioned up front, 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.

Speaker 2: We completed enrollment in our Exploratory Phase 2B study in 2022, and as we approached the Phase 2B Top Line data readout projected for the second quarter of 2023, we wanted to give you a sense of what you can expect.

Speaker 2: First, by way of refresher, previously conducted studies by DARE and our licensor SST demonstrated that this CREAM formulation of sedanofil, which is the same active ingredient as in Viagra, increased blood flow to the female genital tissue.

Speaker 2: both when assessed via an internal vaginal probe and when assessed via an external temperature sensing camera.

Speaker 2: These data provide the proof of concept that the formulation is achieving its target activity in the tissue.

Speaker 2: Obviously vaginal probes and genital temperature sensors are not practical endpoints for a Phase III program.

Speaker 2: Thus, the Exploratory Phase 2B study was designed to evaluate the performance of student NFO cream and to evaluate a number of different potential ways to ask women questions about their genital sensations and improvements, referred to as patient-reported outcomes.

Speaker 2: and the At Home setting in order to identify and select the appropriate patient reported outcomes to take forward into the Phase III program.

Speaker 2: Therefore, as we bring our exploratory phase to be studied 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.

Speaker 2: 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.

Speaker 2: 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.

Speaker 2: Third, I'd like to highlight the positive top line results from the two Phase 1-2 studies completed last year, one for DARE HRT1 and another for DARE VBA1, both of which were conducted through our wholly owned Australian subsidiary.

Speaker 2: So let's start first with the Phase 1, 2 study of DARE-HRT1, 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 Estellas' ad challenging people to answer the question, what is VMS?

Speaker 2: But it may be worth reminding you that VMS stands for vasomotor symptoms and menopause, which are commonly referred to as hot flashes.

Speaker 2: with over 45 million women in the US 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 the subject of a Super Bowl ad.

Speaker 2: 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 of menopause. Specifically, DARE HRT1 is an investigational intervaginal ring.

Speaker 2: designed to release bioidentical estradiol and bioidentical progesterone through the spaginal ring over 28 days.

Speaker 2: SADIR HRT1 has the potential to be the first non-daily, non-oral, monthly format product with both bioidentical hormones.

Speaker 2: hormone therapy remains the most effective treatment for the vasomotor symptoms of menopause and the genital urinary syndrome of menopause and has also been shown to prevent bone loss and fracture.

Speaker 2: The 2022 Hormone Therapy Position Statement of the North American Menopause Society, or NAMS, supports hormone therapy in peri- and post-menopausal women, and NAMS observes that non-oral routes may offer advantages over oral routes administration.

Speaker 2: We previously announced the top-line data from that Phase 1, 2 study of two different dose combinations of DARE-HRT1 over 12 weeks of use in approximately 20 healthy post-menopausal women. And as we reported, the levels of estradiol released from both the lower and the higher dose formulation of DARE-HRT1 achieved a higher level of confidence in women.

Speaker 2: or exceeded the levels that were targeted for hormone therapy.

Speaker 2: 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 VMS as well as the genitourinary symptoms in menopause and vaginal pH and maturation index all at the T less than 0.1 level.

Speaker 2: 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 progesterone specifically, to utilize the FDA's 505b2 pathway.

Speaker 2: to obtain marketing approval of DRH or T1 in the US. That pathway, that 505B2, that's the same pathway we use for Zaxiada.

Speaker 2: 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 uteri. Based on pre-IND communications with the FDA and the top-line pharmacokinetics, or PK, data from the DARE HRT1 Phase 1-2 study, we believe FDA approval of DARE HRT1 for that indication is achievable via that 505b2 pathway.

Speaker 2: study to support registration include manufacturing and nonclinical studies to support the IND admission and the plans for the IND opening phase 3 study.

Speaker 2: as these activities continue to progress this year.

Speaker 2: The second Phase 1-2 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.

Speaker 2: DARE-VVA-1 is an investigational proprietary formulation of tamoxifen for intervaginal administration. Approximately 4 million women in the US 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

Speaker 2: is prevalent in postmenopausal breast cancer survivors with rates estimated at 42 to 70 percent.

Speaker 2: 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 survivors.

Speaker 2: So there is a clear unmet medical need for an effective non-hormonal treatment for VVA. In November of 2022, we announced the positive top-line results from our phase 1-2 study of DARE-VVA1. In that study, DARE-VVA1 demonstrated improvement in vaginal cytology parameters and bothersome symptoms of VVA.

Speaker 2: supporting the ongoing development.

Speaker 2: Following clinical development, we intend to similarly leverage the existing safety and efficacy data on the active ingredients in DRV-V1 tamoxifen and, again, to utilize the FDA's 505b2 pathway to obtain marketing approval of DRV-V1 in the U.S. As we continue to engage with the FDA on the IND process this year, we'll provide additional information on our above.

Speaker 2: our proprietary hydrogel formulation, the same formulation technology that is used in Dashiado.

Speaker 2: We initiated a Phase 1 study of DRPDM1 this year in Australia, and top-line data are also expected this year.

Speaker 2: Primary dysmenorrhea is defined as painful menstruation in women with normal pelvic anatomy, typically described as cramping pain in the lower abdomen before or during menstrual period. Recent market research suggests that the global market for dysmenorrhea treatment is estimated to be valued at $13 billion in 2022.

Speaker 2: and that the size of this market is expected to increase to $28 billion in 2029.

Speaker 2: Primary dysmenorrhea usually begins during adolescence and is a leading cause of recurrent short-term school absence in adolescent girls and a common problem in women of reproductive age. According to the American College of Obstetrics and Gynecologists Committee on Adolescent Health Care,geaismet doug output

Speaker 2: It's the most common menstrual symptom among adolescent girls and young women, and most adolescents experiencing it have primary dysmenorrhea. The prevalence rates range vary, but they range from 15 to 90%. The most common interventions for temporary relief of the painful symptoms include oral NSAIDs or hormonal contraceptives, which often can produce undesirable side effects.

Speaker 2: Oral NSAIDs, which are available over the counter, may cause an increased risk of gastrointestinal adverse events, including nausea, vomiting, bloating, or ulcerations. And hormonal contraceptives can also produce a number of undesirable side effects. So, by leveraging a vaginal and route administration...

Speaker 2: We believe we can provide a localized treatment option that addresses the pain-related symptoms of 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, DRPDM1 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 LBT1, which I have not discussed today, but similarly relies on the hydrogel platform, will benefit from the use of a technology that has already been closely evaluated.

I will now turn it over to John to provide an overview of the two license agreements we have in place for commercialization of Zosteriado and Oviprene respectively.

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 Zaxiado and Novoprene, 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 Dari product to market and the optimum way to provide value to Dari 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 Dari products when we believe its 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 div-

the Zaxiado go-to-market strategy. We continue to remain excited about Zaxiado's launch as we look forward to seeing Zaxiado added to the healthcare providers armamentarium. As Sabrina noted, Organon has been working on launch activities, taking a holistic approach to the product's introduction, which will include direct selling, which is also known as...

personal promotion, as well as non-personal promotion efforts, and utilizing key digital platforms as well as payer and healthcare 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 healthcare 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 Zaxiado 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 maximize Zaxiado uptake at launchgun brought to you by Crystallstruck. This is the Governors represented Doctor?'s.

and they believe there's roughly a 90% overlap of those healthcare providers who are already prescribing Nexplan and have the potential to be Zaxiado prescribers. That strong relationship with the sales team and the provider relationships they have in place is expected to enable access to these HCPs.

Coupled with Organon's payer outreach and plan patient-centered activities, we think that it will allow us to be well-positioned for in-market success, and we look forward to Organon launching the brand by the end of the second quarter.

Under our license agreement with Organon to commercialize Zaxiado, 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 transition now to pre-commercialization activities underway for Overprene, 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 Overprene in the U.S.

Bayer currently supports the Overprene program by providing up to 80 hours per week of an advisory capacity, giving Dari access to Bayer's extensive clinical, regulatory, manufacturing, and commercialization resources while we retain control over Overprene's development and regulatory approval process. Bayer has the right to obtain exclusive rights to commercialize Overprene in the US.

following the completion of a pivotal Phase III study by making a $20 million payment to DARE. 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. DARE 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. Thank you, John , and thanks everyone for joining us today. I'd now like to summarize Dari's financial results for the year end of December 31, 2022, which I will also refer to as the current year or 2022.

Dari's business model is comprised of two parts. The first is to assemble in advance a portfolio of differentiated product candidates that address meaningful and met 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 Zaxiado. And as John just outlined, pursuant to the terms of our global license agreement with Oregon on for Zaxiado, we've already received $10 million up front upon the agreement's 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 Oregon on 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 saledanical cream 3.6% Phase IIB RESPOND clinical trial and manufacturing and regulatory affairs activities related to over-preming.

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 non-dilutive 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 and a federal 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 DARE LARC-1 program under a 2021 grant agreement and for the DARE LBT-1 program under a November 2022 grant agreement. But also, in addition to those sources, our grant funding included an NICHD funding for the DARE 204-214 program.

over-premed 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 Ofroprene 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.

five 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 outstanding. 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, Dari had a

to review the more detailed discussion of our financials, our financial conditions, liquidity, capital, resources, and risk factors on our Form 10-K for the year-end of December 31, 2022, which we filed this afternoon. I would now like to turn the call over to the operator.

Thank you for attending the conference call. We will now begin our question and answer session. If you would like to ask a question during this time, please press star and the number one on your telephone keypad. We'll pause for just a moment to compile the question and answer roster.

Your first question comes from the line of Catherine Novak from Jones Research. Your line is open.

Hi. Good afternoon. Congrats on all the progress. Thanks for taking my question. So, 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 endpoints, both the SFQ-28 and the FQ-28?

SDSDAO, 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 are enrolling into the Phase IIB? Great, great question. So, thank you. And thank you for the kind words about our...

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. Your question specifically about what happens...

in the general 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 to what Sedenafil does. And the distress questionnaire that we use, the arousal condition definition includes the fact that this lack of inability to attain or maintain a sufficient general arousal response can lead to distress.

And so there is, therefore, as part of the co-primary, a 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 questions that we had.

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 happens 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 necessary.

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 so that as we do exactly what you've outlined is then we take all that information, we take the exit interviews that were 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 three and why. And that's a great tie into the second part of your question, which is how does our population, patient population, how does the endpoints we're looking at, how does that all relate to different definitions and different populations within the arousal disorder community? Because the nomenclature and how the condition is defined, like in the DSM, which is where this condition is defined.

a physical arousal response, a portion of the population will...

not be interested over time, right? Because they're no longer, you know, it's all related in some ways. And so there is a population, some studies have estimated around 50% who have both.

arousal disorder, and lack of interest. So similarly, we have attempted to conduct our phase 2B study and our selection of the patient populations, and this is part of why we took time in enrolling subjects and characterizing them and screening them so that we will actually be able to, with our dataset, look at data a lot of different ways. Women who only have arousal disorder, women who have a combination of arousal and lack of interest.

as well as others, right? There's women who have a rousal disorder and anagasmia. 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, you know, it's a big step for the field to be getting these data, and I think there's going to be a lot that we're going to be able to dig into and then hopefully, you know, get ready for those interactions with the FDA on the next step.

That was a long answer to your question, but hopefully that covered it.

That's helpful. Looking forward to the data readout next quarter. Thanks again for taking my questions. Have a great afternoon. Thank you. Thanks.

Thanks, Kim. Your next question comes from the line of Douglas Sow from H.C. Wainwright. Your line is open.

Hi, good afternoon. Thanks for taking the questions. So, just maybe first on the Sidenafil CREAM program, how are you thinking about the commercialization strategy? And what I mean specifically is obviously with Zashado and Overpreem, you've pursued partners. I know in the past you've contemplated or said that you're thinking...

before a phase three program. And then also as a final follow up, just in terms of enrollment or thinking about the phase three.

You know, I understand your point about sort of looking at the data in terms of cuts in terms of patients with arousal as well as lack of interest. But you know, 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. Thank you.

I'm actually going to take them in the opposite. I'm going to start with the second one and then I'll talk about our go-forward strategy. They're kind of tied together. So first of all, as you highlighted, that's why we really refer to this as a Phase IIB exploratory study. There's a lot we're going to learn from this study. You know, being …

to define it at the best we can for our cream, our sedentaphil cream and where this product is going to do well and do well in a way that you know whoever follows is going to have a hard time meeting. And so you know as we're thinking about the patient population to study and this is why purposefully

in the phase 2b, 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, you know, what direction we want to go for the phase 3. You know, we do think that actually we are going to need two phase 3 trials.

is adequate. This is one where two phase 3s 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 first part of your question, which I'm taking the second part. So first of all, as we said before and John highlighted just today, right, we look at each of our products on an individual basis.

products on market at the same time potentially, 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 Overprint as a great example. You know, we in Bayer aligned together 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 DARE to take the lead on that development program through the people who study with Bayer behind us, supporting us, lifting us up, giving us advice.

you know, giving us insights, but that we would lead that program. And whereas with Zosciato in bacterial vaginosis, that's a very straightforward regulatory approval pathway, and, you know, we knew what we needed to do to get a very differentiated label there. And we knew also that we didn't need a commercial partner's insight.

along the journey and that we could get it there. So as we think about this identical program, there are always pros and cons. And this is a long way of me saying, you know, in the end we will always evaluate the opportunities and we evaluate what the program needs and we evaluate what Dari 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 Sudena Phil 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 a lot of opportunities

all different go-to-market strategies because we're not, you know, we're not relying on a single product. Great, thank you so much.

because we are not relying on a single product. Great, thank you so much.

Your next question comes from the line of Kumar Raja from Roth Capital. Your line is open. Thanks for taking my question. So I had a question on PDM1. So in terms of the doses that are being tested, how do they compare with the...

systemically dosed versions and is the expectation that a single dose would be sufficient for most of the patients where pain is typically seen in the first 24 hours? Both great questions. Thanks for asking about that program. I you know

to answer exactly what you're asking. So, first of all, you know, we, of course, did take into consideration what's delivered with the oral doses of diclofenac and what you see, you know, 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.

systemically. That's why we were able to get some of the safety labeling we were able to get in Zosciado is because of that. But 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 were...

And so the way the study is designed, first of all, the women in the study will have the condition. So it's like, it's healthy normals, but they're healthy normals with dysponeuria. So they will have the conditions. That's why we're also able to look at.

not powered for efficacy, but also be able to look at what effects 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 insights. Again, we know from our Zaxiado 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 Zaxiado how the product and how that formulation technology performs.

So we took that into consideration as we designed DARE PDM1 and then the phase one is really designed to answer those exact questions. Like how long does the product stay resident? How long of effect does she have after one time of dosing? How long does it stay resident? And then what happens if we allow her actually to dose multiple times? Great. I just had a question on that. I think you can come back to the moment on your presentation of the unhappiness of this content. There is something other than this. There is some really interesting things around that's really how it's gonna be altered. You know? It's videos of Ceylon Williams. So the one thing we can point to to the audience more specifically as we go forward

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 where you guys stand there right now.

Yeah, absolutely. So let me say a couple words and then I'll turn it over to John in the event he has anything to add. So first of all, I want to clarify one thing because I think it sometimes does get confusing sometimes because we talk about launch and then we talk about first commercial sale. So as John alluded to, activities that you do, right, that are part of that launch.

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 are an organizer of publicly traded companies, we are not in a position to share the specifics around all the activities we are 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 where step editing, even if it was required, is not as big of an impediment as it might be in another category because of how recurrent spectro-vegenesis is and the fact that many of these women will have already been through that. If you can maybe just talk a little bit about...

know, the recurrence rate of bacterial vaginosis and how common it is for women to have already been on a treatment in a prior period and you know what that means for having already stepped through. Yes, will do. Thank you, Sabrina. Yeah, and I think just taking a step back, so bacterial vaginosis, you know, it's not a very heavily managed category. It's not a big budget hit for a lot of health plans, so there's not

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 step through a previous therapy. So that step, if there's a step edit, which we're 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 have already quote unquote stepped through and should have access to the brand. All right, thanks for coming.

Thank you John . Yeah, that's very helpful. Thanks so much. Sure. Absolutely.

Your next question comes from the line of Jason McCarthy from Naxum Group. Your line is open. Hi. Good afternoon. This is Joanne Lee on the call for Jason McCarthy. Congratulations on all the progress and thanks for taking my questions. So lots of questions were asked around the identical program, but I wanted to ask about the HRT1 program as well.

for which we saw the positive efficacy data on Q4, and this was followed by the safety and PK outcomes earlier this year. And now the company, you know, you guys are positioned to file the Phase 3 IND. Can you briefly, just as a reminder, walk us through some of the key data that has emerged from the Phase 1, Phase 1, Phase 2, 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 timelines around the IND submission and the study initiation? Thank you. Great. Thank you for asking. First of all, thank you again for the kind words. And thank you for asking about that product.

you know, 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 care, right, as something that's important to them and they've really studied menopause and studied, you know, 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, I think it's important to educate them.

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 woman's quality of life and her ability to function. We joke about hot flashes but the distrust...

So hormone therapy, as the North American and the pasta side, you 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 two hormones together, and clinicians have been a little bit limited because they haven't had, and ideally because these hormones are not efficiently metabolized through the oral route, you, and therefore you have to give really high, higher doses, right, when you're dosing orally. A non-oral route can have benefits, but you really want both hormones together. So...

We're excited about HRC1 because there's not been a product yet that does that in this convenient once a month, both homelands together, vaginal form, you're delivering them in that red administration. So very much in 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

products that are RDFT approved and have demonstrated benefits. So you can go through one exercise and just look at our levels and compare them to RDFT approved products to say, okay, check. Yep, we're delivering enough 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 her to...

a certain part of her cycle in the premenopausal phase, right, when she had certain levels of hormones, not the high levels that she has when she's ovulating, but the low levels that she has at certain phases of her cycle. So the PK data basically allow us to see that. They allow us to make that comparison to see, yep, we're at low doses, but look, we're at effective levels.

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…

you know, having the reason you have three IND discussions is to clarify what is expected in the IND and there's some non-clinical 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 timeline, like so what does that mean in terms of when exactly we expect to

to be in that phase three study, what I can say is that is one of our very important milestones for this year, right? Are the IND-related activities for GARE HRT1 and the phase three 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 are very, very excited about this program. Got it. I appreciate all the additional color. And for the company's earlier stage program, which there are several assets you guys are planning to advance, specifically regarding DARAPM 1, which as you've mentioned is being developed using this program, I'm Heart free. Thank you very much!

the same validated platform technology user develops, so denocle cream. I wanted to ask if you could talk a bit about the importance of bringing a safer drug to this population of women with primary dysmenorrhea. And given the 505D2 drug pathway, as Diclofenac is a well-established NSAID, what could we interpret a positive phase one 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 works, which...

I think I've heavily dis-risked the program already. Thank you. Yeah, thank you for the question. And for clarity, it's the same gel that's in Zosciato. Yeah, so we are definitely to one. Like the 505E2 pathway, obviously, we've talked about so much today. We love that pathway, right? Because you're getting to rely 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 safety. What we have, and so first I'm going to talk about the regulatory part, and then I'm going to tell you, talk about the other part of your question, which is like the unmet need and the why. But from a regulatory perspective, we know that the risk of diclofenac is not the case.

What I will say, what we have, you know, we, the beauty of working in one therapeutic category and being so broadened as we are is we have a lot of interactions at the FDA all the time with, you know, 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, of the way we work. So the trend we have seen is that, and Sudenna Phil is a great example where we've had very mature discussions at the FDA.

both hormones together vaginally, you know, their support for a single phase three 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 syndication 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 1 data robustly to the benefit of a more efficient, you know, streamlined registration program, but you know a little early to project on that one. What I will say about the unmet need though is that...

You know, I alluded to a lot of the women that are very bothered by this are reproductive age women, thus younger women. It doesn't get better. It's not, you know, it's not like they just grow out of it, you know, in a year. You know, this is a problem that can be very persistent for them, very disruptive for them, and there are a lot of data, right, around.

the potential risk of long-term use of oral NSAIDs in terms of other, you know, just risk factors and complications, apart from just the disturbance in the side-effect profile that they can have from a GI perspective. So, you know, so there's therefore interest, right, in thinking about how great it would be for these women.

to have an option that can deliver effectiveness in a non-oral route, in a vaginal route administration that again 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 is more in mind and delivering something more resident to where she's having the problem.

Thank you, that was really helpful. And yes, I did meet Nashiara, so thank you for that as well. Yes, I know you did. Congratulations again on all the accomplishments and we're looking forward to all the additional updates this year.

Great, thank you so much. Your final question comes from the line of Kemp Golliver from Brookline Capital Markets. Your line is open. Alright, thank you. I'm going to ask two, hopefully, brief questions. First, how are you thinking about

2023 spending levels relative to 2022? Yeah, 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, GMA is around, last year it was around $11 million. What we spend is primarily associated with the development programs. 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, right, our research and development expenses are going to be primarily associated with the completion of the sedentaphil study and manufacturing activities around the Oviprene study, right, to prepare for Oviprene.

So we are always closely monitoring our cash and our resources, and thinking about the timing of incurring expenses versus our opportunities to bring in capital. We are a development stage company. We are always bringing in capital in different ways and means.

So, you know, so as we think about this year, we obviously we have some important activities around selvenafil and oviprin primarily that we're very focused on in the first half of this year. But we obviously have expansions, right, that yes, we can control but that we're going to occur 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 GNA has been very fixed over time, pretty consistent. It's really around where we spend on development.

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 long, how many questions or answers are in this questionnaire 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 3 design?

Yeah, that's a fantastic question. So, first of all, in terms of just the primary and secondary, you know, it's a very reasonable number, right? It's less than 10, you know, 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...

can, you know, to pull all these data together and get, you know, get it to the FDA this year. You know, that is a clear, you know, priority for us. And so, you know, we'll have top-line data in the second quarter as we talked about.

And then we're looking to very shortly thereafter have the full data set and we've already lined up our advisors to be working with us as we kind of mine through that and prepare and request that. We're going to walk straight over so somebody will send us their financial advice on that

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

That's very helpful, thank you. That concludes our question and answer session. Ms. Johnson, I turn the call back over to you. 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 DARI stakeholders, the women, the healthcare providers, our shareholders.

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 nine distinct indications. The more than five milestones anticipated for this year, 2023, the three candidates stand our nearing phase three development.

our two potentially transformational collaborations with the Leaders in Women's Health Product Commercialization, Baren, Organon, and our first FDA approved product, Zaxiado. 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 at NFL CREAM, discreet

The U.S. launch of Zosciata by Organon, the initiation of our pivotal study of Oviprene, the IND-related activities that we were talking about for DARE HRT1 and DARE VBA1, and importantly the Phase III and Phase II, respectively, clinical study initiation plans, and those are 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.

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