Sildenaifl Citrate

Daré Bioscience’s DARE-LARC1 Platform Technology has Transformative Potential for Women’s Health as well as in Treating a Broad Range of Diseases Strategic Process Underway to Explore Partnering Opportunities for Additional Indications such as with GLP-1s for Obesity and Metabolic Disorders and Other Conditions Requiring Precise, Prolonged Treatment SAN DIEGO, Dec. 04, 2024 (GLOBE NEWSWIRE) -- Daré Bioscience, Inc. (NASDAQ: DARE), a leader in innovation for the health and wellbeing of women, today announced it received a payment of $2.5 million as the latest installment under a grant agreement to advance the development of Daré’s investigational contraceptive DARE-LARC1 through nonclinical proof of principle studies and other IND-enabling work to allow for the submission of an Investigational New Drug (IND) application with the FDA, approval of which will be required to commence testing in humans. Under the terms of the grant agreement, Daré may receive a total of up to approximately $49 million to support nonclinical development of DARE-LARC1. To date, Daré has received payments totaling approximately $31.8 million. Additional payments are conditioned on the program meeting specified development and reporting milestones. “This latest installment continues to validate our progress and the importance of developing this technology, which can be used to address meaningful unmet needs in reproductive health as well as other therapeutic areas including diabetes, obesity, and other conditions requiring precise and prolonged treatment,” said Sabrina Martucci Johnson, President and CEO of Daré Bioscience. “Like the grant that we announced earlier this month to support development of a novel non-hormonal contraceptive candidate, the DARE-LARC1 product candidate is another one of our novel contraceptive technologies that continues to be supported by non-dilutive funding.” DARE-LARC1 is a potential new category of long-acting, reversible contraceptive (LARC). If successfully developed and approved, DARE-LARC1 could provide women with unparalleled control over the management of their fertility to better meet specific individual family planning goals and objectives. As with other types of LARC products, investigational DARE-LARC1 is intended to provide effective contraception for an extended period without requiring day-to-day effort. Unlike current LARC products, DARE-LARC1’s innovative features include precision dosing, extended device duration and wireless control. DARE-LARC1 utilizes levonorgestrel, which is the active pharmaceutical ingredient in a number of FDA-approved birth control methods. Earlier this year Daré announced that it achieved technological proof of concept for DARE-LARC1 and the underlying innovative drug delivery platform designed to store and precisely deliver therapeutic doses over months or years through a single device. That milestone reflects the drug delivery platform’s potential to address the treatment burden for various conditions where treatment requires frequent dosing or regular injections. The technology behind this drug delivery platform was originally developed at the Massachusetts Institute of Technology by renowned researchers Robert Langer, Ph.D. and Michael J. Cima, Ph.D. and was previously validated in a first-in-human study in osteoporosis patients using an earlier prototype. Daré has since made significant technological enhancements to the design and integration of custom electronics, hardware, and software to achieve drug delivery targets while incorporating user feedback to optimize form and function. Daré’s progress has resulted in a highly versatile platform technology with potential to address meaningful unmet needs in reproductive health as well as other therapeutic areas including diabetes, obesity, and other conditions requiring precise and prolonged treatment. To support development opportunities outside of the reproductive health category, including diabetes, obesity, and other conditions requiring precise and prolonged treatment, Daré is exploring strategic discussions with potential industry partners. Key features of the implant technology include: Precision dosing: Unique design allows for precise dose timing and amount using individually addressable drug micro-reservoirs.Extended duration and dosing interval control: The ability to house up to hundreds of individual doses means a single device can provide dosing over months to years.No external charging or recharging required: A custom implant grade battery is designed to last for up to 20 years, depending on the application.Upgradable platform: Device software can be updated without removal or replacement of the implant.Two-way communication: Smart technology can respond wirelessly to queries from an external communication device to provide status updates, modify dosing, and deliver other application specific information.Smartphone integration: Platform can be paired with custom mobile apps designed for each application to create a personalized experience for the user. About Daré Bioscience Daré Bioscience is a biopharmaceutical company committed to advancing innovative products for women’s health. The company’s mission is to identify, develop and bring to market a diverse portfolio of differentiated therapies that prioritize women's health and well-being, expand treatment options, and improve outcomes, primarily in the areas of contraception, sexual health, pelvic pain, fertility, infectious diseases, and menopause. The first FDA-approved product to emerge from Daré’s portfolio of women’s health product candidates is XACIATO™ (clindamycin phosphate) vaginal gel 2%, a lincosamide antibacterial indicated for the treatment of bacterial vaginosis in female patients 12 years of age and older, which is under a global license agreement with Organon. Visit www.xaciato.com for information about XACIATO. Daré’s portfolio also includes potential first-in-category candidates in clinical development: Ovaprene®, a novel, hormone-free monthly intravaginal contraceptive whose U.S. commercial rights are under a license agreement with Bayer; Sildenafil Cream, 3.6%, a novel cream formulation of sildenafil, the active ingredient in Viagra®, to treat female sexual arousal disorder (FSAD); and DARE-HRT1, a combination bio-identical estradiol and progesterone intravaginal ring for menopausal hormone therapy. To learn more about Daré’s full portfolio of women’s health product candidates and mission to deliver differentiated therapies for women, please visit www.darebioscience.com. Daré Bioscience leadership has been named on the Medicine Maker’s Power List and Endpoints News’ Women in Biopharma 2022. In 2023, Daré's CEO was honored as one of Fierce Pharma’s Most Influential People in Biopharma for Daré’s contributions to innovation and advocacy in the women’s health space. Daré Bioscience placed #1 in the Small Company category of the San Diego Business Journal’s 2023 Best Places to Work Awards. Daré may announce material information about its finances, product and product candidates, clinical trials and other matters using the Investors section of its website (http://ir.darebioscience.com), SEC filings, press releases, public conference calls and webcasts. Daré will use these channels to distribute material information about the company and may also use social media to communicate important information about the company, its finances, product and product candidates, clinical trials and other matters. The information Daré posts on its investor relations website or through social media channels may be deemed to be material information. Daré encourages investors, the media, and others interested in the company to review the information Daré posts in the Investors section of its website and to follow these X (formerly Twitter) accounts: @SabrinaDareCEO and @DareBioscience. Any updates to the list of social media channels the company may use to communicate information will be posted in the Investors section of Daré’s website. Forward-Looking Statements Daré cautions you that all statements, other than statements of historical facts, contained in this press release, are forward-looking statements. Forward-looking statements, in some cases, can be identified by terms such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “design,” “intend,” “expect,” “could,” “can,” “plan,” “potential,” “predict,” “seek,” “should,” “would,” “project,” “target,” “objective,” or the negative version of these words and similar expressions. In this press release, forward-looking statements include, but are not limited to, statements relating to the potential for Daré to receive additional payments under the grant agreement relating to DARE-LARC1, DARE-LARC1’s potential as a safe and effective LARC product, the potential market opportunity for DARE-LARC1, if approved, the potential of the drug delivery technology underlying DARE-LARC1 to be utilized in products for the treatment of a broad range of diseases and conditions, and the potential for Daré to enter into strategic collaborations relating to the drug delivery technology. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Daré’s actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in this press release, including, without limitation, risks and uncertainties related to: Daré’s ability to achieve the DARE-LARC1 pre-clinical development and other milestones required for it to receive additional payments under the grant agreement; the potential that no definitive agreements result from discussions regarding potential strategic collaborations for the drug delivery technology underlying DARE-LARC1; Daré’s ability to raise additional capital when and as needed to advance its product candidates, execute its business strategy and continue as a going concern; Daré’s ability to develop, obtain FDA or foreign regulatory approval for, and commercialize its product candidates and to do so on communicated timelines; failure or delay in starting, conducting and completing clinical trials of a product candidate; Daré’s ability to design and conduct successful clinical trials, to enroll a sufficient number of patients, to meet established clinical endpoints, to avoid undesirable side effects and other safety concerns, and to demonstrate sufficient safety and efficacy of its product candidates; Daré’s dependence on third parties to conduct clinical trials and manufacture and supply clinical trial material and commercial product; the risk that positive findings in early clinical and/or nonclinical studies of a product candidate may not be predictive of success in subsequent clinical and/or nonclinical studies of that candidate; the risk that the FDA, other regulatory authorities, members of the scientific or medical communities or investors may not accept or agree with Daré’s interpretation of or conclusions regarding data from clinical studies of its product candidates; the risk that development of a product candidate requires more clinical or nonclinical studies than Daré anticipates; the loss of, or inability to attract, key personnel; the effects of macroeconomic conditions, geopolitical events, public health emergencies, and major disruptions in government operations on Daré’s operations, financial results and condition, and ability to achieve current plans and objectives; the risk that developments by competitors make Daré’s product or product candidates less competitive or obsolete; difficulties establishing and sustaining relationships with development and/or commercial collaborators; failure of Daré’s product or product candidates, if approved, to gain market acceptance or obtain adequate coverage or reimbursement from third-party payers; Daré’s ability to retain its licensed rights to develop and commercialize a product or product candidate; Daré’s ability to satisfy the monetary obligations and other requirements in connection with its exclusive, in-license agreements covering the critical patents and related intellectual property related to its product and product candidates; Daré’s ability to adequately protect or enforce its, or its licensor’s, intellectual property rights; the lack of patent protection for the active ingredients in certain of Daré’s product candidates which could expose its products to competition from other formulations using the same active ingredients; product liability claims; governmental investigations or actions relating to Daré’s product or product candidates or the business activities of Daré, its commercial collaborators or other third parties on which Daré relies; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; cybersecurity incidents or similar events that compromise Daré’s technology systems or those of third parties on which it relies and/or significantly disrupt Daré’s business; and disputes or other developments concerning Daré’s intellectual property rights. Daré’s forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. For a detailed description of Daré’s risks and uncertainties, you are encouraged to review its documents filed with the SEC including Daré’s recent filings on Form 8-K, Form 10-K and Form 10-Q. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Daré undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. Contacts: Daré Bioscience Investor Relationsinnovations@darebioscience.com Source: Daré Bioscience, Inc.

本文作者：Origami 孔子说，「饮食男女，人之大欲存焉。」 对于性之一字，中国人的态度是复杂的。有人赞美，说金风玉露一相逢，便胜却人间无数；有人痛斥，言色字头上一把刀；也有人顿悟，曰色即是空，空即是色。 书里说，以前车马很慢，书信很远，一生只够爱一个人。2022 年，北京大学和复旦大学联合发布了「中国人私生活调查」报告，其中有一个推论就是中国男人对于性正在变得保守化。[1] 但市场数据给我们的答案有些相悖。 腼腆保守的中国男人，去年至少用了一亿多的小药片，消费了近 80 亿的「伟哥」（指治疗勃起功能障碍的 PED5 抑制剂）。 「伟哥」类药物，一年零售卖爆几十亿 据药企前段时间发布的 2023 年年报，其旗下的 4 大类 9 款药物中，「伟哥」类药物的表现稳定的可怕，依旧是「销售冠军」。销售额达 12.895 亿元，较上一年度增长 22.6%。 据产销量及库存量分析显示，这款药用于治疗男性勃起功能障碍（erectile dysfunction，ED）的药，其一年至少卖出 1 亿多片。[2] 图源：参考资料 2 在网购药物赛道上，伟哥的销量也是一骑绝尘。据米内网发布的「2023 年中国网上药店终端化学药 TOP20 产品」[3]显示，单个药物的销售额超 17 亿元排在冠军，紧随其后的季军就是同赛道的竞品。 以零售药店渠道为例，2017～2022 年，我国抗 ED 药物在零售药店渠道的销售规模逐年递增，由 2017 年的 36.19 亿元增长至 2022 年的 60.81 亿元。[4] 在西北某省地级市医院生殖男科的杨飞医生（化名）有很明显的感觉：通过院内开具相关药物的数量正在逐渐上升，而且新面孔和年轻面孔也丰富了起来。「很多看病的患者都互相认识，有的甚至都是组团来的，有的钓鱼圈子的，也有骑友圈子的，也有健身圈子的。总之聚集效应比较明显。」 连锁药店驻店药师柴霞（化名）同样有这样的感觉，在药店方面，男科药尤其是各种「非」们，都是非常主要的盈利点，但消费群体并不是非常稳定，选择面也很少。但从 2018 年开始，随着各路抗 ED 药（尤其是部分以长效作为特点的抗 ED 药）的上架，柴药师发现在门店消费抗 ED 药物的长期用户们也越来越多了。 图源：图虫创意，与本文提及药物无关 但抗 ED 市场规模像芝麻开花节节高，是否就意味着勃起功能障碍的群体越来越多？ 中国究竟有多少男性患有 ED？这个数字一直都难以明确。在中国男性 ED 患病率上，除了几篇荟萃分析，并没有检索到太新的流行病学数据。 我国《勃起功能障碍诊断与治疗指南》显示，ED 是成年男性的常见病和多发病。但相关的流行病学调查结果差异较大且年代较为久远：一项对我国 30 个省和自治区的 40 岁以上男性调查显示，ED 患病率为 40.6%。对流动人群的调查显示，广东顺德地区和东莞地区流动男性 ED 总患病率分别为 32.2% 和 64.2%。 中山大学某流行病学博士后研究员唐若宇（化名）认为，粗略统计整个中国的 ED 患病率，在价值上可能噱头大于学术，「因为勃起功能障碍是一个病因探索比较清晰的病种，很大程度上和年龄、慢性基础病等因素相关。总体上就是年龄越大，患病率越高。」 但唐若宇也表示，现代中青年男性的生活与劳动生产模式和曾经的男性群体存在差异，比如更长时间的久坐、更紧张的生活节奏以及更高发的代谢疾病等等，「这些因素确实是勃起功能障碍的高风险因素。」 「阳痿率」是否升高，是一个难以论证的问题，但临床相关医生或药师的反馈是：愿意就诊、配合就诊的男患者，确实越来越多了。 走进门诊的患者，超半数在互联网确诊「阳痿」 佛山某医院生殖男科门诊的医生连国强（化名）回忆，以前刚上班的时候，当地卫健委专门组织过男科医生的培训，内容是从门诊患者的语气、暗示甚至一些眼神动作中判断他是不是来治疗「阳痿」的，「以前，大家都戏称我是男科侦探。」 时间轴拉回到现在，连国强发现打直球的患者越来越多了，甚至有些患者的问题也专业起来，「有一次，一个患者直接在我门诊打开他的短视频 APP 收藏夹，里面全是勃起障碍有关的科普视频，想让我一一解答。」 互联网媒体的发展，为「难言之隐」带来了真正的自由地。 广西某地级市三甲医院泌尿外科贺田光（化名）的很多患者，都是他微信公众号和视频号的忠实粉丝。 贺医生说，最开始他做科普的时候只是单纯为了减少患者的骚扰，「男科患者很喜欢问这问那，我又不喜欢加微信，就直接让他们看我的科普，我说你问的问题我都会更新的。」 门诊一台小手机，既说段子也科普。贺医生就是这样成为了当地一个名气还挺大的小网红。 「说实话，做科普之前，我没想到我们这里能有那么多 ED 患者。」贺医生说，自从做了科普以来，鼓起勇气来看 ED 或其他问题的男性朋友越来越多，甚至走进门诊前至少超过半数的人，已经自己在互联网「确诊了」。他现在几万粉丝里，很大一部分是他的患者或者其他同事的患者。 贺医生表示，像男科病这种有病耻感和隐私感的领域，互联网科普带来的增量是很明显的。「有一次我参加个学术峰会，发现整个展厅的同行们都在做男科的科普，有的可能在业界名声不显，一看手机哇一百多万粉丝。」 在短视频平台上搜索相关药物或是「阳痿」等相关字眼，可以看到各路经过专业资质认证的医生们，对着镜头将相关医学科普细细道来，细致到几毫克药量之间有多大的差异。还有皮肤科、普外科医生跨着学科，大讲药物在两性生活中的科普与故事。 互联网平台上海量的抗 ED 药物科普，和男性用户对于男性健康的关注度是分不开的。据巨量算数发布的《抖音用户健康生活方式调研》，男性群体最关注的话题就是男性健康。甚至有 24% 的男性用户，就是在抖音刚刚发现了自己正在被「男题」所困扰。 图源：参考资料 5 热度，是互联网媒体的本质；但盈利，才是商业的基本逻辑。 有病就要吃药，而医生科普了哪些药甚至哪些剂型，都会对这些互联网男性用户们起到一个不小的参考价值。 「男性互联网用户对于阳痿的关注度是非常高的，这也是抗 ED 药物在做患者教育与品类推广中最重要的一个环节。」某药企市场部总监张萍（化名）坦言。 张萍曾经做了很多年传统的学术推广工作，随着合规性的加强，男科药的推广是她最近几年的业务核心。 「其实『伟哥』这个商品名的流传度，就是最好的营销例子，但除了噱头营销以外，细致化的患教科普其实才刚刚起步。」张萍表示，现在抗 ED 药物的品类非常之多，除了药物本身种类不同以外，同类药物也有不同的剂量、不同的剂型甚至不同的包装设计。「推广侧，怎么能让潜在客户知道，你是一个不一样的抗 ED 药并愿意买单，才是核心目的。」 随着社交媒体上男性健康科普的大量铺设，广告饱和攻击、短视频推广背书、事件营销、心智占领的策略，成为了扩容的最佳路径。  患者可以更加便利隐晦地了解到自己的困境，并在医生的指引下完成诊疗。但至于药企是如何引导医生进行详细的精准科普这个问题，张萍表示无可奉告。 节假日会收到的短信推广 图源：同事提供隐秘的角落，和应被正视的需求 除了科普信息的爆炸式增长，互联网医疗的发展也让抗 ED 药物的获取，变得更加「隐晦」也更加便利。 「10 年前，我师父告诉我说药店门口要是有男人带着报纸徘徊，一定要叫他出来，因为这些人都是来买伟哥的，看见我这么年轻的女娃子会害羞，下次就不来了。」柴药师表示，虽然现在部分老年患者可能还保留着曾经的扭捏，但绝大部份的 ED 药物都伴随着一个个快递盒子或者包装袋一起发给各路地址，偶尔封在一起的还有避孕套或其他情趣用品。 但这些地址的信息让柴药师隐隐不安，因八九成是某某酒店、某某民宿：「这些药物，最后都用去哪里了呢？」 这也是一些临床医生看着患者背影消失在门口时的怅然。 上海某男科医生鲁成（化名）回忆，前段时间有个患者找他看病，主要诉求是开一些长效抗 ED 药物，闲聊中患者的一句话让鲁医生思绪万千：「买这么贵的药，回去跟老婆用太亏了。」生性敏感的鲁医生陷入了自责，那一瞬间他觉得自己可能是破坏人家婚姻的元凶。 除此之外，医生更担心的是滥用带来的身体损伤。 贺医生告诉丁香园，现在很多男性朋友不肯看医生，也不愿承认自己的疾病，但对抗 ED 药却有着极高的向往。「我身边就有很多朋友，把长效抗 ED 药当作万能药，认为只要服用就能解决所有性问题，总想让我偷偷安排一下。」 贺医生苦笑不已，尽管他反复强调，这类药物只适用于治疗勃起功能障碍（ED），并不能提高性欲，更不能保证性满意度。但他感觉听进去话的也并没有几个。 在国际上，抗 ED 药物娱乐化使用，已经是一个放在台面上讨论的话题。有研究表示，出于娱乐目的使用勃起功能障碍药物的男性可能会增加心理依赖的风险，这反过来可能导致基于心理的勃起功能障碍症状。相关药物也已成为当今最常见的处方和滥用药物之一。[6] 高校研究员李峰（化名）目前开展的中国抗 ED 药物使用的相关定性研究中，已经观测到有关「滥用」抗 ED 药物的现象，甚至有不少患者依然以「壮阳」为目的，在无处方的情况下擅自服药。 而在具体用途上，李峰初步收集的信息多倾向于在非家庭环境中使用抗 ED 药物。他认为，「男性健康的需求需要被关注，抗 ED 药物在正确使用的教育上才刚刚开始。」 李峰说，传闻在北宋时期，大相国寺中有这样一首阴阳诗： 阳面为「酒是穿肠毒药，色是刮骨钢刀，财是下山猛虎，气是惹祸根苗。」而阴则为「无酒不成礼仪，无色路断人稀，无财世路难行，无气倒被人欺。」 在抗 ED 药物的市场突飞猛进中，性需求与性安全该如何平衡，同样有待观瞻。 监制：carollero 题图来源：图虫创意 参考资料： [1]中国人私生活质量调查：性如何影响家庭、婚姻、95后 https://www.lifeweek.com.cn/article/174237 [2]https://www.sse.com.cn/disclosure/listedinfo/announcement/c/new/2024-03-16/600332_20240316_ISIW.pdf [3]https://3g.menet.com.cn/Article/Detial?aid=148112 [4]观研天下《中国抗 ED 药物行业发展趋势研究与未来前景分析报告（2024-2031）》 [5]巨量算数，抖音用户健康生活方式调研 [6]Frontiers | The Weekend Drug; Recreational Use of Sildenafil Citrate and Concomitant Factors: A Cross-Sectional Study 丁香园是面向医疗从业者的专业平台，以「助力中国医生」为己任。在丁香园，可以和同行讨论病例 ，在线学习公开课，使用用药助手等临床决策工具，在丁香人才找可靠医疗岗位。