Dare Bioscience Inc (DARE) 2023 Q4 法說會逐字稿

Welcome to the conference call hosted by Daré Bioscience to review the company's fourth quarter financial results and to provide a general business update. This call is being recorded. My name is Lisa and I will be your operator today. With us today from Daré are Sabrina Martucci Johnson, President and Chief Executive Officer; and MarDee Haring-Layton, Chief Accounting Officer. Ms. Johnson, please proceed.

歡迎參加由 Daré Bioscience 主辦的電話會議，回顧該公司第四季度的財務業績並提供一般業務更新。此通話正在錄音。我叫麗莎，今天我將成為您的接線生。今天與我們一起來自 Daré 的是總裁兼首席執行官 Sabrina Martucci Johnson；和首席會計官 MarDee Haring-Layton。約翰遜女士，請繼續。

Thank you. Good afternoon, and welcome to the Daré Bioscience financial results and business update call for the year ended December 31, 2023. Today, we'll review our financial results for 2023 and discuss developments and expectations for our pipeline and portfolio. Before we began, 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.

謝謝。下午好，歡迎參加 Daré Bioscience 截至 2023 年 12 月 31 日止年度的財務業績和業務更新電話會議。今天，我們將回顧 2023 年的財務業績，並討論我們的產品線和產品組合的發展和預期。在開始之前，我想提醒您，今天的討論將包括聯邦證券法含義內的前瞻性陳述，這些陳述是根據 1995 年《私人證券訴訟改革法案》的安全港條款制定的。

Any statements made during this call that are not statements of historical fact 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 Form 10-K for the year ended December 3, 2023, which was filed today.

本次電話會議期間所做的任何非歷史事實陳述的陳述均應被視為前瞻性陳述。由於已知和未知的風險和不確定性，實際結果或事件可能與這些陳述中預期或暗示的結果或事件有重大差異。您不應過度依賴前瞻性陳述。前瞻性陳述完全符合公司向 SEC 提交的文件中的警示性聲明，包括今天提交的截至 2023 年 12 月 3 日的年度 10-K 表格。

I would also like to point out that the content of this call includes time-sensitive information that is current only as of today, March 28, 2024. Daré undertakes no obligation to update any forward-looking statements to reflect new information or developments after this call, except as required by law. As you know, women's health is our sole focus at Daré. Women's health products make up 27% of total blockbuster products, while contributing to 35% of total blockbuster sales, and there continue to be many unmet needs in the market.

我還想指出，本次電話會議的內容包含時效性訊息，這些訊息僅截至今天（2024 年 3 月 28 日）。除非法律要求，否則 Daré 不承擔在本次電話會議後更新任何前瞻性陳述以反映新資訊或發展的義務。如你所知，女性健康是 Daré 唯一關注的焦點。女性保健品佔重磅產品總量的27%，同時貢獻了重磅產品總銷售額的35%，市場上仍存在許多未滿足的需求。

To our knowledge, Daré is the only publicly traded company focused solely on women's health pharmaceutical product development broadly, and we remain committed to advancing through clinical development, regulatory review, and ultimately to market disruptive products for women. Our commitment and focus is to make a difference for women in a relatively efficient timeline, by leveraging the basic science and pharmacology that is understood about certain active pharmaceutical ingredient and marketed products to accelerate innovative treatments that women want and need. We seek to optimize these treatments for our target indications to enhance outcomes, convenience, and side effect profile, or to address a novel indication where the pharmacology is well seeded, but has not previously been applied to the indication in question for women.

據我們所知，Daré 是唯一一家廣泛專注於女性健康藥品開發的上市公司，我們仍致力於推動臨床開發、監管審查，並最終向女性推出顛覆性產品。我們的承諾和重點是在相對有效的時間內為女性帶來改變，利用對某些活性藥物成分和上市產品的基礎科學和藥理學的了解，加速女性想要和需要的創新治療。我們尋求針對我們的目標適應症優化這些治療方法，以提高結果、便利性和副作用，或解決藥理學基礎良好但先前尚未應用於女性相關適應症的新適應症。

We believe we have built a premier company in women's health, with the broadest portfolio of potential high impact, first and category product candidates; many of which have already demonstrated proof of concept. And that our robust pipeline of product candidates positions us well for the short, medium and long-term. I'm excited to share today, the strides we made in 2023 to advance innovative therapies for women, updates on our most promising near-term opportunities, and the milestones we look forward to in 2024. In 2023 alone, Daré had 15 interactions with the FDA across six product candidates, indication. Completed the Phase 2b study of our investigational Sildenafil Cream product for female sexual arousal disorder and the Phase 1 study of our investigational vaginal diclofenac product for menstrual pain.

我們相信，我們已經建立了一家女性健康領域的一流公司，擁有最廣泛的潛在高影響力、一流和類別候選產品組合；其中許多已經展示了概念驗證。我們強大的候選產品管道使我們在短期、中期和長期都處於有利地位。今天，我很高興與大家分享我們在 2023 年為推進女性創新療法所取得的進展、我們最有前途的近期機會的最新情況，以及我們期待在 2024 年實現的里程碑。光是 2023 年，Daré 就六種候選產品與 FDA 進行了 15 次互動。完成了針對女性性喚起障礙的研究性西地那非乳膏產品的 2b 期研究，以及針對月經疼痛的研究性陰道雙氯芬酸產品的 1 期研究。

We received IND clearance for DARE-VVA1, our hormone-free candidate for sexual pain, and we commenced the Phase 3 study for our investigational hormone-free monthly contraceptive candidate Ovaprene. Before we continue, I also want to acknowledge a few recent industry developments that underscore what a fantastic time it is to be working in women's health and the significant opportunity in this space. As you may know, in November of 2023, the White House announced the first ever White House initiative on women's health research, an effort led by first lady, Dr. Jill Biden, and the White House agenda Policy Council to bring together congressional leaders, the private sector, research institutions, and philanthropy to quote, fundamentally changed how we approach and fund Women's Health Research.

我們獲得了 DARE-VVA1 的 IND 批准，DARE-VVA1 是我們治療性疼痛的無激素候選藥物，並且我們開始了我們的研究性無激素每月避孕候選藥物 Ovaprene 的 3 期研究。在我們繼續之前，我還想感謝最近的一些行業發展，這些發展強調了從事女性健康工作的美好時光以及該領域的重大機會。如你所知，2023 年 11 月，白宮宣布了有史以來第一項關於女性健康研究的白宮倡議，該倡議由第一夫人吉爾·拜登博士和白宮議程政策委員會牽頭，匯集了國會領導人、私營部門、研究機構和慈善事業從根本上改變了我們處理和資助婦女健康研究的方式。

In February 2024, Daré was invited to participate in an ARPA-H ideation event, where Dr. Jill Biden announced, along with ARPA-H leadership, the $100 million deployment of capital for women's health. Earlier this month, the president called on Congress to make bold transformative investment of $12 billion in new funding for women's health research. And just last week, I had the honor and privilege of attending a reception at the White House in honor of Women's History Month, where President Biden signed an executive order dedicated to advancing women's health research. It's encouraging to see further comprehensive executive action aimed at increasing investments in women's health and making it a priority in various ways, because initiatives like these brings focus, bring financial support for the entire ecosystem to boldly innovate for women.

2024 年 2 月，Daré 受邀參加 ARPA-H 的構思活動，吉爾·拜登博士在會上宣布與 ARPA-H 領導層一起部署 1 億美元的資金用於婦女健康。本月早些時候，總統呼籲國會為女性健康研究提供 120 億美元的大膽變革性投資。就在上週，我有幸參加了在白宮舉行的婦女歷史月招待會，拜登總統在會上簽署了一項致力於推進婦女健康研究的行政命令。令人鼓舞的是，看到進一步全面的行政行動，旨在增加對婦女健康的投資，並以各種方式將其作為優先事項，因為此類舉措帶來了焦點，為整個生態系統帶來了財政支持，從而為婦女大膽創新。

Even more, these positive tailwinds can be expected to boo in investors' interest and funding in this sector long term. Most importantly, we believe our achievements in 2023 demonstrate that our approach to accelerating clinical development works and that our leading programs have disruptive potential in the conditions and populations they aim to treat along with significant revenue potential, if approved. I'm going to put those 2023 accomplishments and our anticipated 2024 milestones into further perspective shortly, particularly in the context of metrics that are important to any current or future shareholder, specifically, the addressable market, their probability of success, and what it would take to advance the programs, with a focus on our on-market asset, XACIATO, and our Phase 3, Ovaprene and Sildenafil Cream. Before I do so, I'm going to first turn it over to our Chief Accounting Officer, MarDee, to review the 2023 financial results.

更重要的是，從長遠來看，這些積極的推動因素預計會提振投資者對該行業的興趣和資金。最重要的是，我們相信我們在2023 年取得的成就表明，我們加速臨床開發的方法是有效的，而且我們的領先計畫在其目標治療的疾病和人群中具有顛覆性潛力，如果獲得批准，還具有巨大的收入潛力。我很快就會進一步審視這些2023 年的成就和我們預期的2024 年里程碑，特別是在對任何當前或未來股東都很重要的指標背景下，特別是潛在市場、成功的可能性以及它將帶來什麼採取措施來推進這些計劃，重點關注我們的市場資產 XACIATO 以及我們的第 3 階段 Ovaprene 和西地那非乳膏。在此之前，我將首先將其交給我們的首席會計官 MarDee，以審查 2023 年的財務表現。

Thanks, Sabrina, and thanks, everyone, for joining us today. By way of introduction, my name is MarDee Haring-Layton, and I've been at Daré for more than six years, previously serving as the Vice President of Accounting and Finance since October 2018. I'm excited to be here with you all. I will summarize Daré's financial results for the full year 2023. But before I do, I would like to put them in context for those of you who are newer to the story.

謝謝薩布麗娜，也謝謝大家今天加入我們。順便介紹一下，我叫 MarDee Haring-Layton，在 Daré 工作了六年多，自 2018 年 10 月起擔任會計和財務副總裁。我很高興能和大家在一起。我將總結 Daré 2023 年全年的財務表現。但在此之前，我想為那些剛接觸這個故事的人介紹它們的背景。

Daré's business strategy is to assemble and advance a portfolio of differentiated product candidates that address meaningful unmet needs we've identified in women's health, and then monetize the value of our portfolio's clinical and regulatory advances over the near and long-term. The investment required to build in advance of portfolio includes corporate overhead, portfolio acquisition and maintenance costs, and ongoing research and development or R&D expenses. During 2023, we recognized total revenue of approximately $2.8 million, which included a $1 million payment in July 2023, and an additional $1.8 million milestone payment in October 2023 from our commercial collaborator, Organon, relating to XACIATO, the first FDA-approved product to emerge from our portfolio, as well as a nominal amount of royalty revenues based on net sales of XACIATO during the fourth quarter.

Daré 的業務策略是整合和推進差異化候選產品組合，以滿足我們在女性健康領域發現的有意義的未滿足需求，然後將我們組合的近期和長期臨床和監管進步的價值貨幣化。預先建立投資組合所需的投資包括公司管理費用、投資組合收購和維護成本以及持續的研究和開發或研發費用。2023 年期間，我們確認總收入約為280 萬美元，其中包括2023 年7 月支付的100 萬美元，以及我們的商業合作夥伴Organon 於2023 年10 月額外支付的180 萬美元里程碑付款，該付款與XACIATO 相關，XACIATO 是第一個FDA 批准的產品來自我們的投資組合，以及基於 XACIATO 第四季度淨銷售額的名義特許權使用費收入。

XACIATO became more widely available by prescription to treat bacterial vaginosis in January of this year. Our general and administrative or G&A expenses were approximately $12.1 million, which was up slightly compared to the prior year. Our R&D expenses across our entire portfolio were approximately $21.5 million, and primarily reflected the costs of our Phase 1 and Phase 2b study of Sildenafil Cream, our Phase 1 study of DARE-PDM1, vaginal diclofenac for menstrual cramping and manufacturing activities, as well as preparing for and beginning enrollment in our Phase 3 study of our intervaginal, hormone-free monthly contraceptive candidate, Ovaprene. As a reminder, R&D expenses vary from period to period based on our clinical, preclinical, manufacturing, regulatory, and other development activities. We reported a net loss for 2023 of $30.1 million and ended the year with approximately $10.5 million in cash and cash equivalents.

今年 1 月，XACIATO 透過處方得到更廣泛的應用，用於治療細菌性陰道炎。我們的一般和行政或 G&A 費用約為 1210 萬美元，與前一年相比略有增加。我們整個產品組合的研發費用約為2150 萬美元，主要反映了西地那非霜的1 期和2b 期研究、DARE-PDM1、用於月經痙攣和製造活動的陰道雙氯芬酸的1 期研究的成本，以及準備並開始參加我們的陰道間無激素每月避孕藥 Ovaprene 的第 3 期研究。需要提醒的是，研發費用會根據我們的臨床、臨床前、製造、監管和其他開發活動的不同而有所不同。我們報告 2023 年淨虧損為 3,010 萬美元，年底現金和現金等價物約為 1,050 萬美元。

During the year, we received approximately $4.7 million in non-dilutive grant funding. We also completed a $7 million registered direct offering in September, and a $12 million royalty backed investments in December; of which, we took down $5 million in December. The remaining $7 million is available to us to take down through three tranches over time at Daré's options. The financing structure entitles investor to a percentage of the royalty and milestone payments to be received by Daré, under its global license agreement for XACIATO with Organon, only until the investor achieves a targeted return on investment.

這一年，我們收到了約 470 萬美元的非稀釋性補助金。我們也在 9 月完成了 700 萬美元的註冊直接發行，並在 12 月完成了 1,200 萬美元的特許權使用費支持投資；其中，我們在 12 月減少了 500 萬美元。剩下的 700 萬美元可供我們根據 Daré 的選擇分三期支付。根據與 Organon 簽訂的 XACIATO 全球授權協議，融資結構使投資者有權獲得 Daré 收到的一定比例的特許權使用費和里程碑付款，直至投資者實現目標投資回報。

As of March 27, 2024, Daré had approximately 100 million shares of common stock outstanding. Since our inception, we have made fiscal responsibility a top priority, maintaining a lean and focused team, and managing our overhead costs closely. To that end, we expect a reduction in our 2024 G&A expenses to approximately $10 million, which to be clear, does not reflect $10 million in capital required to fund G&A expenses, since approximately $3 million of that estimate is estimated accrual based non-cash expenses. In addition, as previously noted, our R&D expenditure is predicated on ongoing development programs.

截至 2024 年 3 月 27 日，Daré 擁有約 1 億股已發行普通股。自成立以來，我們一直將財務責任視為重中之重，維持一支精幹且專注的團隊，並密切管理我們的管理費用。為此，我們預計2024 年的一般管理費用將減少至約1000 萬美元，需要明確的是，這並不反映為一般管理費用提供資金所需的1000 萬美元資本，因為該估計中約300 萬美元是基於權責發生製的非現金估計花費。此外，如前所述，我們的研發支出取決於正在進行的開發計劃。

In 2023, we had four active clinical studies that contributed to our $21.5 million of R&D expenditures. In 2024, our only active clinical study at this time is our Phase 3 pivotal Ovaprene study, for which, we have already remitted in prior years, all but $0.5 million of funds due to the NIH under our cooperative research and development agreement. And therefore, planned Ovaprene expenses in the 2024 year will be primarily associated with certain manufacturing activities. Apart from Ovaprene related expenses, our currently projected 2024 R&D expenses are primarily carryover/close-out expenses from the studies completed in 2023.

2023 年，我們進行了四項活躍的臨床研究，為我們的研發支出貢獻了 2,150 萬美元。到 2024 年，我們目前唯一活躍的臨床研究是我們的 3 期關鍵 Ovaprene 研究，為此，我們在前幾年已經根據我們的合作研發協議向 NIH 匯出了除 50 萬美元以外的所有資金。因此，2024 年計劃的 Ovaprene 支出將主要與某些製造活動相關。除了 Ovaprene 相關費用外，我們目前預計的 2024 年研發費用主要是 2023 年完成的研究結轉/結清費用。

Therefore, until such time, as we commence an additional late-stage clinical study, we anticipate 2024 R&D expenses to be considerably less than the 2023 R&D expenses. Looking ahead, we will continue to evaluate a wide range of financing opportunities, including more creative and innovative alternatives to fund our broad portfolio of differentiated product candidates, which we believe, opens the door to financing opportunities that other companies may not have access to. These opportunities may include, but are not limited to non-dilutive grants, as we have for many of our preclinical programs, and these earlier-stage programs with grant funding enhance our pipeline: equity sales, license agreements, structured financing, and strategic collaborations or alliances. We will continue to explore a variety of options to fund our operations, advance our candidates, monetize the value of our assets, and build shareholder value.

因此，在我們開始額外的後期臨床研究之前，我們預計 2024 年的研發費用將大大低於 2023 年的研發費用。展望未來，我們將繼續評估廣泛的融資機會，包括更具創意和創新的替代方案，為我們廣泛的差異化產品組合提供資金，我們相信，這為其他公司可能無法獲得的融資機會打開了大門。這些機會可能包括但不限於非稀釋性贈款，就像我們的許多臨床前專案一樣，這些具有贈款資金的早期專案增強了我們的管道：股權銷售、許可協議、結構性融資和策略合作或聯盟。我們將繼續探索各種選擇來為我們的營運提供資金、提升我們的候選人、將我們的資產價值貨幣化並建立股東價值。

As we've said previously, we look to be creative, collaborative, and opportunistic in seeking the capital needed to meet our objectives and to build shareholder value. We believe our December financing met that goal, and we'll work to identify similar opportunities moving forward. We also encourage investors to review the more detailed discussion of our financial condition, liquidity, capital resources, and risk factors on our Form 10-K for the year ended December 31, 2023, which we filed this afternoon. I would now like to turn the call back over to Sabrina.

正如我們之前所說，我們希望以創造性、協作性和機會主義的方式尋求實現我們的目標和建立股東價值所需的資本。我們相信我們 12 月的融資已經實現了這一目標，我們將努力尋找類似的機會繼續前進。我們也鼓勵投資者查看我們今天下午提交的截至 2023 年 12 月 31 日止年度的 10-K 表格中有關我們的財務狀況、流動性、資本資源和風險因素的更詳細討論。我現在想將電話轉回給 Sabrina。

Thank you. As I mentioned earlier, I'm now going to put our 2023 accomplishments and our anticipated 2024 milestones into the context of their potential, including the addressable markets for our product candidates, their probability of success, and what it will take to advance them, with the focus on our on-market asset XACIATO and Phase 3 asset, Ovaprene and Sildenafil Cream. But first, a high-level statement on R&D spend that MarDee just discussed. So over the last few years, our R&D spend has averaged around $26 million per year, despite the fact that we have typically had multiple ongoing clinical studies in any one-year. For context, late-stage development studies for the women's health indications we are pursuing are generally in the tens of millions, compared to hundreds of millions can be the case in other indications and therapeutic categories.

謝謝。正如我之前提到的，我現在將把我們2023 年的成就和我們預期的2024 年里程碑放在其潛力的背景下，包括我們候選產品的潛在市場、它們成功的可能性以及推進它們需要採取什麼措施，重點關注我們的市場資產 XACIATO 和 3 期資產 Ovaprene 和 Sildenafil Cream。但首先是 MarDee 剛剛討論過的關於研發支出的高層聲明。因此，在過去幾年中，我們的研發支出平均每年約為 2,600 萬美元，儘管事實上我們通常在任何一年都會進行多項正在進行的臨床研究。就背景而言，我們正在追求的女性健康適應症的後期開發研究通常為數千萬個，相比之下，其他適應症和治療類別的情況為數億個。

This is in part what has contributed to our capital efficient model. Historically, industry-wide, we see this trend. Only 1% of healthcare investment has gone into women's health and that 1% investment though has generated 27% of the blockbuster brands. That is reflective of what we believe is the efficiency of the women's health investment thesis and that we're leveraging in our programs.

這在某種程度上促成了我們的資本效率模式。從歷史上看，在全行業範圍內，我們看到了這種趨勢。只有 1% 的醫療保健投資投入女性健康領域，但這 1% 的投資卻創造了 27% 的熱門品牌。這反映了我們認為婦女健康投資論文的效率以及我們在我們的計劃中所利用的效率。

So now, to transition to our programs, in the fourth quarter of 2023, we achieved our first commercial milestone for XACIATO. And now, in the first quarter of 2024, XACIATO is available by prescription across the United States. As reminder, XACIATO, which is clindamycin phosphate vaginal gel, is a colorless, single-dose vaginal gel that can be applied at any time of day and is formulated with the goal of limiting leakage and increasing vaginal retention time, which is time spent in place. XACIATO is indicated for the treatment of bacterial vaginosis in females, 12 years of age and older in the United States.

因此，現在，為了過渡到我們的項目，我們在 2023 年第四季實現了 XACIATO 的第一個商業里程碑。現在，2024 年第一季度，XACIATO 可在美國各地透過處方購買。提醒一下，XACIATO 是克林黴素磷酸酯陰道凝膠，是一種無色、單劑量陰道凝膠，可在一天中的任何時間使用，其配製目的是限制滲漏並增加陰道保留時間，即在陰道內停留的時間。地方。XACIATO 適用於在美國治療 12 歲及以上女性的細菌性陰道炎。

And since this product is already on market, I'll focus on the what's it worth. In the context of the potential patient population and our commercialization agreement with Organon, the prevalence of bacterial vaginosis in the United States is estimated to be 23 million women. And as an on-market product, XACIATO, represents a non-dilutive source of revenue for Daré. We are eligible to receive double digit royalties and up to $180 million in milestone payments from Organon.

由於該產品已經上市，我將重點放在它的價值。根據潛在的患者群體以及我們與 Organon 的商業化協議，美國細菌性陰道炎的盛行率估計為 2,300 萬名女性。作為一款上市產品，XACIATO 代表了 Daré 的非稀釋性收入來源。我們有資格從 Organon 獲得兩位數的特許權使用費和高達 1.8 億美元的里程碑付款。

We look forward to providing that quarterly revenue updates that we booked, as we receive them from Organon. And we are impressed with Organon to go to market strategy that leverages the knowledge and experience of their established NEXPLANON commercial team. In 2023, we also shared positive data from our exploratory Phase 2b RESPOND study of Sildenafil Cream, as a treatment for female sexual arousal disorder. In terms of market and revenue potential, there are no FDA approved treatments for any form of sexual arousal disorder in women; and therefore, Sildenafil Cream has the potential to be the first.

我們期待提供我們預訂的季度收入更新，因為我們從 Organon 收到了這些更新。我們對 Organon 的市場策略印象深刻，該策略利用了其現有的 NEXPLANON 商業團隊的知識和經驗。2023 年，我們也分享了西地那非乳膏作為治療女性性喚起障礙的探索性 2b 期 RESPOND 研究的正面數據。就市場和收入潛力而言，目前尚無 FDA 批准的針對任何形式的女性性喚起障礙的治療方法；因此，西地那非乳膏有潛力成為第一。

Sildenafil is the active ingredient in tablet form for oral administration, currently marketed under the brand name Viagra for the treatment of erectile dysfunction in men, which was undoubtedly one of the most successful prescription products ever launched. Market research suggests that approximately 20 million women in the US experience symptoms of low or no sexual arousal. We believe this is a promising untapped market, given the numerous equivalent products approved for men, not only Viagra but also Cialis, [Lee tried], to name a few, and Viagra alone generated $2 billion annually at its peak. In terms of probability of success, we've already demonstrated that Sildenafil Cream increased genital tissue blood flow in quantitative studies.

西地那非是口服片劑形式的活性成分，目前以威而鋼為品牌銷售，用於治療男性勃起功能障礙，這無疑是有史以來推出的最成功的處方產品之一。市場研究表明，美國約有 2000 萬名女性存在性喚起低下或無性喚起的症狀。我們相信，這是一個充滿希望的、尚未開發的市場，因為有許多同類產品被批准用於男性，不僅有偉哥，還有希愛力（李嘗試過）等等，僅偉哥在巔峰時期每年就創造了20 億美元的收入。就成功的可能性而言，我們已經在定量研究中證明西地那非乳膏可以增加生殖器組織的血流量。

And in the Phase 2b at-home study, that was specifically designed to identify the patient population that experienced the most meaningful improvement from Sildenafil Cream and the questions to ask them that best reflect that improvement so that we could take those forward into the Phase 3 clinical development. The patient population and the endpoints we have proposed to the FDA are the ones where our post-hoc analyses of the Phase 2b study data showed that Sildenafil Cream demonstrated a statistically significant and meaningful patient improvement. In terms of next steps and what it will take to bring Sildenafil Cream through Phase 3 and to a potential approval? Well, we had a positive end of Phase 2 meeting with the FDA in December of 2023, and we are continuing to interact with them as they review, in particular, the data we generated on the proposed endpoints to take forward into Phase 3.

在2b 階段在家研究中，專門設計用於確定從西地那非乳膏中獲得最有意義改善的患者群體，並向他們提出最能反映這種改善的問題，以便我們可以將這些問題推進到3 階段臨床開發。我們向 FDA 提出的患者群體和終點是我們對 2b 期研究數據的事後分析表明西地那非乳膏顯示出統計上顯著且有意義的患者改善的終點。就後續步驟而言，以及如何使西地那非乳膏通過第三階段並獲得潛在批准？嗯，我們在 2023 年 12 月與 FDA 的第 2 階段會議取得了積極的成果，我們將在他們審查時繼續與他們互動，特別是我們產生的關於擬議終點的數據，以推進第 3 階段。

The Phase 2b study was importantly the first study of its kind, and the FDA has indicated they anticipate giving us additional feedback on the Phase 3 design in the second quarter of 2024. We've already aligned that female sexual arousal disorder, FSAD, is an approvable indication, as well as the opportunity to perform the efficacy assessments after just 12 weeks of use. Based on the feedback received to date and the effect size that we saw on multiple measures of sexual function in the patient population, we've identified to take forward into Phase 3. We would anticipate the cost of the Phase 3 efficacy trial to be comparable to the cost in the Phase 2b study, so, specifically, in the $15 million range for each efficacy study.

重要的是，2b 期研究是同類研究中的第一個，FDA 表示他們預計在 2024 年第二季度向我們提供有關 3 期設計的更多回饋。我們已經確定女性性喚起障礙 (FSAD) 是一個可批准的適應症，並且有機會在使用 12 週後進行功效評估。根據迄今為止收到的回饋以及我們在患者群體中多項性功能測量中看到的效果大小，我們已確定進入第三階段。我們預期 3 期功效試驗的成本與 2b 期研究的成本相當，因此，具體而言，每項功效研究的成本在 1500 萬美元範圍內。

We look forward to providing further updates on the FDA discussions, the Phase 3 designs and plans and any relevant updates on our collaboration strategy. In 202, we also commenced our pivotal Phase 3 study of Ovaprene are potentially first in category, hormone-free, monthly inter-vaginal contraceptive candidate. In terms of market and revenue potential, we believe Ovaprene has the potential to be a disruptive product in the contraceptive category, and potentially life-changing for women who cannot take hormone-based birth control products or those who would prefer not to do so. In addition to providing innovation as a hormone-free contraceptive, the clear differentiation and disruptive potential of Ovaprene is in its convenience and potential efficacy.

我們期待提供有關 FDA 討論、第三階段設計和計劃以及我們合作策略的任何相關更新的進一步更新。202 年，我們也開始了關鍵的 3 期研究，Ovaprene 可能是無激素每月陰道避孕候選藥物中的第一個。就市場和收入潛力而言，我們相信 Ovaprene 有潛力成為避孕類別中的顛覆性產品，並可能改變無法服用荷爾蒙避孕產品或不願服用荷爾蒙避孕產品的女性的生活。除了作為無激素避孕藥提供創新之外，Ovaprene 的明顯差異化和顛覆性潛力還在於其便利性和潛在功效。

Its convenience includes easy, monthly use, and self-administration, without requiring action at the time of intercourse. And we believe Ovaprene has the potential to demonstrate efficacy approaching hormonal birth control methods. There are currently no FDA-approved monthly hormone-free contraceptive. And based on market research, approximately 35 million women in the US are potential candidates for Ovaprene.

它的便利性包括簡單、每月使用和自我管理，無需在性交時採取行動。我們相信 Ovaprene 有潛力證明其功效接近荷爾蒙避孕方法。目前還沒有 FDA 批准的每月一次的無激素避孕藥。根據市場研究，美國約有 3500 萬名女性是 Ovaprene 的潛在候選人。

We see parallels to NuvaRing when it entered the market as the first monthly inter-vaginal (technical difficulty) contraceptive. And at peak, it generated $900 million in annual revenue. Bayer is a leader in commercializing contraceptive products in the United States, and they hold the right to obtain US commercial rights to Ovaprene under their license agreement with us. Under that agreement, we're eligible to receive a $20 million milestone payment at Bayer sole discretion, following the completion of the ongoing Phase three study, as well as up to $310 million in commercial milestones and double-digit tiered royalties.

我們看到 NuvaRing 作為第一個每月陰道內（技術難度）避孕藥進入市場時的相似之處。在巔峰時期，它的年收入達到了 9 億美元。拜耳是美國避孕產品商業化的領導者，根據與我們的許可協議，他們有權獲得 Ovaprene 在美國的商業權利。根據該協議，在完成正在進行的第三階段研究後，我們有資格獲得拜耳自行決定的 2000 萬美元里程碑付款，以及高達 3.1 億美元的商業里程碑和兩位數的分級特許權使用費。

And in terms of probability of success, the pre-pivotal study that we completed before we entered into our commercialization collaboration with Bayer, indicated that Ovaprene had the potential to demonstrate typical use contraceptive effectiveness, approaching user-controlled hormonal contraceptive, but without the use of hormones. And in terms of next steps in bringing Ovaprene toward potential approval, the pivotal study is a multicenter, single-arm non-comparative Phase 3 contraceptive study of Ovaprene, to evaluate its effectiveness as a contraceptive, along with its safety and usability over the course of approximately 12 months of use. Based on communications to date with the FDA, if successful, we believe that just the single registration study will be required to support a premarket approval application submission with the FDA.

就成功機率而言，我們在與拜耳進行商業化合作之前完成的關鍵前研究表明，Ovaprene 有潛力展示典型使用避孕藥的有效性，接近用戶控制的激素避孕藥，但無需使用荷爾蒙。就使 Ovaprene 獲得潛在批准的後續步驟而言，關鍵研究是 Ovaprene 的多中心、單臂非比較第 3 期避孕研究，以評估其作為避孕藥的有效性以及整個過程中的安全性和可用性大約可使用12 個月。根據迄今為止與 FDA 的溝通，如果成功，我們認為僅需要一項註冊研究即可支持向 FDA 提交上市前批准申請。

As mentioned by MarDee, in previous periods, we remitted funds, specifically $5 million, to the NIH to support study activities. In addition to that, we are responsible for manufacturing activities and certain external activities, such as the advertising campaign for the study. And as of this month, the central advertising campaign for the study is live and enrollment is well underway at 17 sites across the United States. Since the Phase 3 is a 12-month study that commenced late last year, we will not have final data this year, but it is an open label study, and therefore, we will look forward to providing recruitment and any relevant data updates in the coming quarters.

正如 MarDee 所提到的，在先前的時期，我們向 NIH 匯出了資金，具體來說是 500 萬美元，以支持研究活動。除此之外，我們也負責製造活動和某些外部活動，例如研究的廣告活動。截至本月，該研究的中央廣告活動已經開始，美國 17 個地點的註冊工作正在順利進行中。由於第 3 階段是一項為期 12 個月的研究，於去年年底開始，我們今年不會獲得最終數據，但這是一項開放標籤研究，因此，我們將期待在未來幾季。

So in summary, I'm very excited about the incredible progress we made last year and the promise that 2024 holds for Daré. Our investigational products to some of the most potentially disruptive candidates for women in decades, and we collaborate with leading companies, including Organon for XACIATO and Bayer for Ovaprene, to commercialize and deliver these treatments to as many women as possible. And we do all of this, the thoughtful and efficient capital deployment and by leveraging nondilutive sources of capital wherever feasible. I'd now like to turn the call over to the operator for Q&A.

總而言之，我對我們去年取得的令人難以置信的進步以及 2024 年對 Daré 的承諾感到非常興奮。我們的研究產品面向數十年來對女性最具潛在顛覆性的一些候選人，我們與領先公司合作，包括 XACIATO 的 Organon 和 Ovaprene 的拜耳，將這些治療方法商業化並向盡可能多的女性提供。我們做到了這一切，深思熟慮且有效率的資本部署，並在可行的情況下利用非稀釋性資本來源。我現在想將電話轉給接線員進行問答。

(Operator Instructions) Douglas Tsao, H.C. Wainwright.

（操作說明）Douglas Tsao, H.C.溫賴特。

Hi, good afternoon, thanks for taking the questions. Sabrina, I know you're not responsible for commercialization, but it would maybe be helpful just to provide a little perspective on the exact status of the XACIATO launch, just given -- the scripts aren't really necessarily taking off and are scripts fully reflective of what's going on in the market? I know, with some products going through specialty pharmacies, on [IQVIA] isn't necessarily capturing everything. Thank you.

你好，下午好，感謝您提出問題。Sabrina，我知道你不負責商業化，但僅僅提供一些關於 XACIATO 發布的確切狀態的觀點可能會有所幫助，只是給出 - 腳本並不一定會成功，並且腳本完全反映了市場上正在發生的事情？我知道，對於一些經過專業藥局銷售的產品，[IQVIA] 不一定能捕捉所有資訊。謝謝。

Yeah, no, thank you. That's a great question. So first of all, yeah, absolutely, I think as we're all aware, with different product brands and different types of launches. And so the advent of specialty pharmacies and the time, some of our historic data sources on Folsom, as maybe we've gotten accustomed with other products. So what I can say, specifically, about the XACIATO are a few things that obviously have already been said by our commercialization, collaborator, Organon.

是的，不，謝謝。這是一個很好的問題。首先，是的，絕對的，我想我們都知道，有不同的產品品牌和不同類型的發布。因此，專業藥房的出現和時間，我們在福爾瑟姆的一些歷史資料來源，也許我們已經習慣了其他產品。因此，關於 XACIATO，我可以具體說的是我們的商業化合作夥伴 Organon 顯然已經說過的一些事情。

So first of all, while launch activities in terms of us meeting our commercial sales milestone commenced in 2023, as Organon put out the press release in January of this year, the product became available nationwide in January. So that's really when certain activities, obviously, commenced in terms of the product availability. Obviously, we're in early days of launch, just given that we're literally just months in at that, in terms of the timing of the products really becoming available. And so, that's why we're looking forward to the year and the activities that are projected for this year.

首先，雖然我們在 2023 年開始了實現商業銷售里程碑的啟動活動，但正如 Organon 在今年 1 月發布的新聞稿一樣，該產品於 1 月在全國範圍內上市。因此，顯然，這確實是在產品可用性方面某些活動開始的時候。顯然，我們正處於發布的早期階段，考慮到我們實際上只有幾個月的時間，就產品真正上市的時間而言。因此，這就是為什麼我們期待今年以及預計今年的活動。

The product, as I mentioned, is in the hands of their NEXPLANON sales force. We've previously talked about the reason that we selected Organon and their NEXPLANON commercial team, quite frankly, for this product, in terms of the overlap, in terms of the provider base that prescribes contraceptives, as well as those that prescribe and treat bacterial vaginosis, which is primarily a condition of women of reproductive age. Any opportunity for those sales reps to ensure that clinicians and the right providers get an experience with the product and that the product is available through all of the appropriate channels. And so beyond that, we are I can say, very enthusiastically, we are very happy with the work that Organon is doing and the progress that they're making with the brand, and what they have planned and what they're executing on with the brands this year.

正如我所提到的，該產品由他們的 NEXPLANON 銷售人員負責。我們之前已經討論過我們選擇 Organon 及其 NEXPLANON 商業團隊的原因，坦白說，對於該產品，就重疊而言，就處方避孕藥以及處方和治療細菌的提供者基礎而言陰道病，主要是育齡婦女的一種病症。這些銷售代表有任何機會確保臨床醫生和合適的供應商獲得產品的體驗，並且產品可以透過所有適當的管道獲得。除此之外，我可以非常熱情地說，我們對 Organon 正在做的工作、他們在品牌方面取得的進展、他們的計劃和執行情況感到非常滿意今年的品牌。

And we're very much looking forward to giving you updates as the year continues and particularly as those royalty revenue dollars show up in our income in our financial statements.

我們非常期待在今年繼續為您提供最新信息，特別是當這些特許權使用費收入出現在我們的財務報表中的收入中時。

And Sabrina, maybe as a follow up, so Organon made the product fully available nationally in January. I mean, do you know when it's had the full attention of the NEXPLANON sales force? And do you know the relative position in the rep's bag between NEXPLANON and XACIATO?

而 Sabrina，也許是作為後續行動，所以 Organon 於一月份在全國範圍內全面提供了該產品。我的意思是，您知道 NEXPLANON 銷售人員什麼時候會全力關注它嗎？您知道 NEXPLANON 和 XACIATO 在代表包中的相對位置嗎？

Yeah, so obviously we can't on any of the information, as you can appreciate might be proprietary obviously to Organon. But what we can say is that again, we selected them because of the NEXPLANON sales force. And part of the beauty of that is that sales force only had NEXPLANON in their bag prior to XACIATO. And so, anyone who's been in sales situation or selling situation understands how important it is to have more than one product in the bag, how value that's the value that can be how important it is to have something novel to talk with the healthcare provider about, especially when it's a condition like bacterial vaginosis which can be very frustrating historically for providers when treatment options were didn't suit their patients maybe as well as they hope and didn't have some of the features that XACIATO has.

是的，很明顯我們無法獲取任何信息，正如您所知，這些信息顯然可能屬於 Organon 專有。但我們可以說的是，我們選擇他們是因為 NEXPLANON 的銷售團隊。其美妙之處之一在於，在 XACIATO 之前，銷售人員的包包裡只有 NEXPLANON。因此，任何經歷過銷售情況或銷售情況的人都明白，袋子裡有不止一種產品是多麼重要，它的價值是多麼重要，與醫療保健提供者談論一些新穎的東西是多麼重要。 ，特別是當像細菌性陰道炎這樣的病症時，歷史上對提供者來說可能非常令人沮喪，因為治療方案可能不適合患者，並且不具備XACIATO 所具有的一些功能。

And so we really selected Organon because of the attention in the commercial organization that this product would guide, and particularly, that it would be in the hands of a commercial organization that really would only have these two products to be promoting. And obviously, NEXPLANON is a very important brand, obviously, for Organon, as you've seen in their own numbers. But this gives that sales organization something novel right to talk about in terms of XACIATO. Beyond that, in terms of the specifics, I mean, I can't add.

因此，我們真正選擇 Organon 是因為該產品將引起商業組織的關注，特別是它將掌握在真正只推廣這兩種產品的商業組織手中。顯然，NEXPLANON 對於 Organon 來說是一個非常重要的品牌，正如您在他們自己的數據中看到的那樣。但這為銷售組織提供了一些新穎的權利來談論 XACIATO。除此之外，就具體細節而言，我的意思是，我無法補充。

Okay, thank you so much.

好的，非常感謝。

Absolutely.

絕對地。

(Operator Instructions) Will Hidell, Brookline.

（操作員指示）Will Hidell，布魯克林。

Hi, thank you for taking the questions. I just have one quick question, regarding the other trials, the VVA1, PDM1, HRT1, what is your plan going forward with these trials? Do you have a priority or an emphasis on any of them?

您好，感謝您提出問題。我只有一個簡單的問題，關於其他試驗，VVA1、PDM1、HRT1，您對這些試驗有何計劃？您有優先考慮或重點關注其中任何一個嗎？

Absolutely. Great questions, and thanks for highlighting some of the other disruptive products in the portfolio. And so, with all of the other programs, we're really at a stage with the various programs, whether certain preparatory, I would describe them activities that are under way. And so for instance, with HRT1, we have had interactions with the FDA that we have, obviously, be published a number of the outcomes of the two different studies that we've run with that product in humans. And we have had interactions with the FDA in order to prepare for an IND submission, as well as get clarity that just the one pivotal study would be required to support registration.

絕對地。很好的問題，感謝您強調了產品組合中的其他一些顛覆性產品。因此，對於所有其他計劃，我們確實處於各種計劃的階段，無論是某些準備工作，我都會描述它們正在進行的活動。例如，對於 HRT1，我們與 FDA 進行了互動，顯然，我們已經發布了我們在人體中對該產品進行的兩項不同研究的一些結果。我們與 FDA 進行了互動，以便準備 IND 提交，並明確指出僅需要一項關鍵研究即可支持註冊。

We are currently conducting the activities necessary to enable the submission of the IND application, so that we can then start that pivotal Phase 3 clinical trial. So we are still undergoing the activities that the FDA has communicated to us that are needed to support that IND. And so, that's ongoing. As soon as we have an update on that, we will definitely provide that update. And then that timing will obviously be important in determining next steps.

我們目前正在進行必要的活動以提交 IND 申請，以便我們可以開始關鍵的 3 期臨床試驗。因此，我們仍在進行 FDA 告知我們的支持該 IND 所需的活動。所以，這一切仍在繼續。一旦我們有更新，我們一定會提供該更新。那麼這個時機顯然對於確定下一步很重要。

But the next steps with that program with the FDA and the submission, its next phase, would be to go into a single Phase 3 registration study. And then in terms of VVA1, and as I mentioned, and as you noted that we have the IND application that is cleared and was supported by our Phase 1/2 results that we had generated last year. So at this stage, I mean, we're definitely doing activities that would support preparations to moving into a Phase 2 study in terms of identifying clinical sites, protocol preparation, things like that. We don't plan to conduct the Phase 2 study until after we secure additional capital that was supported, but the next phase for that program would be the Phase 2.

但該計劃的下一步是向 FDA 提交申請，即下一階段，將進入單一的第 3 階段註冊研究。然後就 VVA1 而言，正如我所提到的，正如您所指出的，我們已經批准了 IND 申請，並得到了我們去年產生的 1/2 期結果的支持。所以在這個階段，我的意思是，我們肯定會進行一些活動，以支持進入第二階段研究的準備工作，包括確定臨床地點、方案準備等。在獲得支持的額外資金之前，我們不打算進行第二階段研究，但該計劃的下一階段將是第二階段。

And as part of our IND process, we got really great feedback from the FDA on the Phase 2 design, so that we can ensure that that would put the product where it needs to be to advance after that and really leverage dispersed and category opportunity as a non-hormonal product for sexual pain. (multiple speakers)

作為我們 IND 流程的一部分，我們從 FDA 獲得了關於第 2 階段設計的非常好的反饋，這樣我們就可以確保這將使產品達到其需要的位置，並真正利用分散和類別的機會一種治療性交疼痛的非荷爾蒙產品。（多個發言者）

Okay, thank you.

好的謝謝。

Yes, absolutely. Yes, we are doing all we can to get them ready to move forward.

是的，一點沒錯。是的，我們正在盡一切努力讓他們做好繼續前進的準備。

Yeah, thank you.

是的，謝謝。

Absolutely.

絕對地。

And with that, that concludes the question-and-answer session. I would like to turn the call back over to Sabrina Martucci Johnson for any additional or closing remarks.

問答環節到此結束。我想將電話轉回薩布麗娜·馬圖奇·約翰遜 (Sabrina Martucci Johnson)，以徵求任何補充或結束語。

Well, thank you, guys, for taking the time this afternoon and the afternoon before the holiday weekend for some. Thank you for taking the time to hear about our recent updates and our ongoing commitment to drive value for all Daré stakeholders by transforming women's health. As you heard today, we made important progress in 2023 with our novel investigational treatment options that have the potential to expand choices and improve health outcomes. And we continue to work towards the goal of bringing innovative new treatments to market every day.

好吧，謝謝你們今天下午和假日週末前的下午抽出時間來幫助一些人。感謝您抽出寶貴時間了解我們的最新動態以及我們透過改變女性健康為所有 Daré 利害關係人創造價值的持續承諾。正如您今天所聽到的，我們在 2023 年透過新穎的研究性治療方案取得了重要進展，這些方案有可能擴大選擇並改善健康結果。我們繼續努力實現每天將創新療法推向市場的目標。

We expect to have numerous 2024 milestones, including the quarterly revenue updates on XACIATO, as that launch progresses this year, Ovaprene pivotal study updates as we work to complete what we expect will be a single registration study, and updates on our discussions with the FDA and activities to commence Phase 3 for our potential first in category, treatment option for women with female sexual arousal disorder, our Sildenafil Cream program. And while not the focus of today's call, our grant funded product candidates enhanced the portfolio, and we look forward to providing relevant updates on those ongoing programs as well this year. With our unique model support of our commercial collaborators and focus on fiscal responsibility, we believe are well positioned to accelerate innovation for women, in a manner that also drive shareholder value.

我們預計 2024 年將有許多里程碑，包括 XACIATO 的季度收入更新（隨著今年的上市研究）、Ovaprene 關鍵研究更新（我們努力完成我們預期的單一註冊研究），以及我們與 FDA 討論的更新以及為患有女性性喚起障礙的女性治療選擇西地那非霜計劃啟動第三階段的活動。雖然不是今天電話會議的重點，但我們的贈款資助的候選產品增強了產品組合，我們期待今年也提供這些正在進行的項目的相關更新。憑藉我們對商業合作者的獨特模式支持以及對財務責任的關注，我們相信我們能夠以同時推動股東價值的方式加速女性創新。

We look forward to keeping you updated on our progress towards the milestones we discussed today. Thank you again for your time and your questions.

我們期待向您通報我們今天討論的里程碑的最新進展。再次感謝您的寶貴時間和您的問題。

Thank you. And that does conclude today's presentation. Thank you for your participation today, and you may now disconnect.

謝謝。今天的演講到此結束。感謝您今天的參與，您現在可以斷開連接。