Daré Bioscience(US:DARE)2021-03-29 16:00Product Development and Clinical Trials - Daré Bioscience is focused on advancing innovative products for women's health, particularly in contraception, vaginal health, sexual health, and fertility[13]. - The company has a portfolio that includes three product candidates in advanced stages of clinical development and three candidates that are Phase 1-ready[15]. - DARE-BV1, a treatment for bacterial vaginosis, achieved a clinical cure rate of 70.2% at the primary endpoint visit compared to 35.6% for placebo, with a p-value < 0.001[22]. - The NDA submission for DARE-BV1 is planned for the end of Q2 2021, with potential FDA approval and commercial launch expected in early 2022[23]. - Ovaprene, a hormone-free contraceptive, aims for typical use efficacy comparable to current hormonal methods, which is approximately 91%[24]. - DARE-BV1 received Fast Track designation from the FDA, facilitating more frequent interactions regarding its development plan[20]. - The company plans to utilize the FDA's 505(b)(2) pathway for DARE-BV1, leveraging existing safety and efficacy data on clindamycin[20]. - The DARE-BVFREE Phase 3 trial for DARE-BV1 involved 307 women, demonstrating statistically significant efficacy in all pre-specified secondary assessments[22]. - The clinical cure rate for DARE-BV1 in the per protocol population was 77.2%, significantly higher than the placebo group at 42.6%[23]. - Ovaprene demonstrated 100% effectiveness in preventing more than five progressively motile sperm per high power field in cervical mucus across all evaluated cycles[25]. - In the PCT clinical trial, women using Ovaprene had a mean of 0.48 PMS/HPF compared to a baseline mean of 27.21 PMS/HPF when no contraception was used[25]. - Sildenafil Cream, 3.6% showed significant increases in genital blood flow compared to placebo, with measurable changes observed approximately 30 minutes post-dosing[27]. - The Phase 2b RESPOND clinical study of Sildenafil Cream, 3.6% is expected to randomize 400 to 590 subjects, targeting a topline data readout by year-end 2021[29]. - DARE-HRT1 is designed for sustained drug delivery over weeks to months, with the potential to be the first FDA-approved IVR delivering bio-identical progesterone and estradiol[30]. - The Phase 1 clinical study of DARE-HRT1 completed enrollment in March 2021, with topline data anticipated in the second quarter of 2021[30]. - DARE-FRT1 is being developed for the prevention of preterm birth and broader luteal phase support, with a Phase 1 clinical trial anticipated to start in 2022[32]. - The FDA's 505(b)(2) pathway will be utilized for marketing approval of both DARE-HRT1 and DARE-FRT1, leveraging existing safety and efficacy data[30][32]. - The PCT clinical trial of Ovaprene is designed to support an IDE submission to the FDA for a pivotal clinical study expected to start in Q1 2022[25]. - The company is conducting ongoing communications with the FDA regarding the trial design and product use to ensure alignment prior to the pivotal study commencement[25]. - DARE-VVA1 is being developed as an alternative to estrogen-based therapies for vulvar and vaginal atrophy (VVA) in women with hormone-receptor positive breast cancer, with an estimated prevalence of VVA in post-menopausal breast cancer patients between 42% and 70%[33]. - The company plans to initiate a Phase 1 clinical trial for DARE-VVA1 in the second half of 2021, contingent on the availability of additional funding[33]. Financial and Capital Resources - The company has paid a total of $235,000 in license fees to MilanaPharm for the development and commercialization of products related to bacterial vaginosis[37]. - Milestone payments to MilanaPharm include up to $300,000 for clinical and regulatory milestones and up to $1.75 million for commercial sales milestones[39]. - The company has a license agreement with ADVA-Tec for Ovaprene, with potential milestone payments totaling up to $14.6 million based on development and regulatory achievements[41]. - Bayer has agreed to a $1.0 million upfront payment and potential milestone payments totaling up to $310 million based on the commercialization of Ovaprene in the U.S.[44]. - The company must meet a minimum spending amount of $5 million over the first three years for Ovaprene development activities[41]. - The license agreement with Bayer will continue until the expiration of any valid claim covering Ovaprene or 15 years from the first commercial sale in the U.S.[44]. - The company entered into a license and collaboration agreement with SST for the development and commercialization of Sildenafil Cream, 3.6%, with a royalty structure based on annual net sales ranging from single digits to mid double digits[45]. - SST is eligible for milestone payments totaling between $0.5 million to $18.0 million for clinical and regulatory achievements, and between $10.0 million to $100 million for commercial sales milestones[46]. - The company acquired Microchips Biotech, Inc. in November 2019, issuing approximately 3.0 million shares and agreeing to pay up to $46.5 million contingent on specified milestones[52][53]. - The contingent consideration for Microchips includes tiered royalty payments ranging from low single-digit to low double-digit percentages of annual net sales of products[53]. - The company has rights to over 100 patents and applications from the Microchips acquisition, with key technology supported by 21 U.S. patents and 42 foreign patents[57]. - The company is the exclusive licensee of 19 issued patents worldwide for Sildenafil Cream, with U.S. patents expiring in June 2029[57]. - The Catalent license agreement includes potential milestone payments of up to $13.5 million for clinical and regulatory milestones and up to $30.3 million for commercial sales milestones[49]. - The company is required to pay an annual maintenance fee of $50,000 for the first two years and $100,000 thereafter under the Catalent agreement[49]. - The company actively seeks to protect its proprietary technology through patents, trade secrets, and contracts[54]. - The company holds a domestic registration for the trademark Daré Bioscience and is the exclusive licensee of the Ovaprene registered trademark[57]. - The company has pre-clinical product candidates in women's health, including DARE-LARC1, ORB-204, ORB-214, and DARE-RH1, aimed at expanding contraceptive options and improving outcomes[59]. - The company incurred a net loss of approximately $27.4 million for the year ended December 31, 2020, with an accumulated deficit of approximately $71.4 million[139]. - As of December 31, 2020, the company's cash and cash equivalents were approximately $4.7 million, indicating a need for additional capital to continue operations[139]. - The company expects to continue incurring net losses for the foreseeable future as it develops and seeks to bring its existing product candidates to market[139]. - The company has not obtained any regulatory approvals or generated any product revenue to date, highlighting its clinical-stage status[141]. - The company may need to raise additional capital through various means, including collaborations and strategic alliances, which could lead to dilution for existing shareholders[139]. - The company may face limitations in raising capital due to SEC regulations, particularly the "baby shelf rule," which restricts capital raising when public float is below $75 million[147]. - The company’s financial and technical resources are limited, potentially affecting the development of its product candidates and leading to delays in clinical trials[149]. - The company may need to curtail clinical development programs due to financial constraints, which could result in missed opportunities for product candidates[149]. - The company expects to incur significant legal, accounting, and compliance expenses as a public reporting entity, which may increase if it becomes an "accelerated filer" with a public float of $75 million or more and annual revenues of $100 million or more[161]. Regulatory Environment and Compliance - The FDA approval process for new drug products is extensive and requires significant time and financial resources, including the submission of detailed safety and efficacy data[65]. - The FDA has a ten-month review period for standard NDAs and six months for priority reviews, although these timelines can be extended due to additional information requests[71]. - The company must comply with rigorous regulatory requirements throughout the drug development process, including preclinical studies and clinical trials[68]. - The company is subject to various government regulations that impact all aspects of pharmaceutical development, including manufacturing and marketing[63]. - The company is committed to developing innovative products that meet unmet medical needs, which may include post-approval trials to gather additional data on product safety and efficacy[70]. - The FDA conducts a preliminary review of all NDAs within 60 days to determine if they are sufficiently complete for substantive review[72]. - The FDA may issue a Complete Response Letter (CRL) indicating that the application will not be approved in its present form, which may require minor or major changes[74]. - Fast track designation allows for more frequent interactions with the FDA and may expedite the development and review process for drugs addressing unmet medical needs[75]. - Priority review designation shortens the FDA's goal for taking action on a marketing application from ten months to six months[77]. - Post-approval, manufacturers must comply with ongoing FDA regulations, including monitoring adverse experiences and maintaining cGMP compliance[78]. - The Drug Supply Chain Security Act (DSCSA) mandates phased-in obligations for pharmaceutical manufacturers and distributors to enhance supply chain security, culminating in November 2023[80]. - The FDA may require a Risk Evaluation and Mitigation Strategy (REMS) plan to ensure the benefits of a drug outweigh its risks[72]. - The GAIN Act provides incentives for the development of antibacterial and antifungal drugs, including a five-year exclusivity extension upon FDA approval[75]. - The FDA may impose restrictions on product distribution and labeling based on post-marketing studies or newly discovered safety risks[79]. - Non-compliance with FDA regulations can lead to severe consequences, including product recalls, fines, and withdrawal of product approvals[80]. - Medical devices are classified into three classes by the FDA based on risk, with Class I being low risk, Class II moderate risk, and Class III high risk, requiring different levels of regulatory scrutiny[83]. - Class I devices are mostly exempt from premarket regulation, while Class II devices typically require 510(k) clearance, which aims for a substantial equivalence determination within 90 days[83]. - Class III devices must undergo a premarket approval (PMA) process, which can take between one and three years, and requires extensive data to demonstrate safety and effectiveness[83]. - The FDA has increased scrutiny on cybersecurity risks associated with connected medical devices, impacting the review and marketing authorization process[81]. - The de novo classification procedure allows manufacturers to request down-classification of low to moderate risk devices that are automatically classified as Class III, streamlining the approval process[83]. - Clinical trials are generally required for PMA applications and may also be necessary for 510(k) notifications, with strict regulations governing the conduct of these trials[85]. - Post-marketing requirements for medical devices include compliance with quality system regulations and mandatory reporting of adverse events, similar to prescription drugs[85]. - Manufacturers must report any device malfunctions that could lead to serious injury or death under the FDA's medical device reporting regulations[87]. - The FDA has the authority to require recalls of medical devices if there is a reasonable probability of serious adverse health consequences[87]. - Non-compliance with FDA regulations can result in severe sanctions, including fines, recalls, and delays in product approvals[87]. - Combination products are subject to FDA user fees based on the type of application submitted, such as NDA and PMA fees[90]. - The Hatch-Waxman Act provides a five-year non-patent exclusivity period for the first applicant to gain NDA approval for a new chemical entity (NCE)[94]. - A QIDP designation under the GAIN Act allows for a five-year extension of non-patent marketing exclusivity for approved drugs intended to treat serious infections[96]. - Patent term extensions can restore up to five years for patents lost during product development and FDA review, with a maximum total patent term of 14 years from the product's approval date[97]. - The FDA requires ANDA applicants to certify regarding any patents listed for the reference product in the Orange Book, impacting the approval timeline[93]. - Non-compliance with clinical trial registration and reporting can lead to civil penalties and loss of federal grant eligibility[98]. - The FDA's designation of therapeutic equivalence allows for substitution of generic drugs without physician or patient consent, impacting market dynamics[91]. - The 21st Century Cures Act clarified that Hatch-Waxman Act requirements apply to drug-device combination products, potentially delaying approvals due to patent disputes[90]. - The FDA must determine that a generic drug is bioequivalent to the reference listed drug (RLD) for ANDA approval, affecting market entry[91]. - The FDA's regulations require compliance with cGMP and QSR for combination product manufacturers, ensuring product safety and effectiveness[90]. - The company expects to develop a compliance program to adhere to healthcare laws and regulations, which may involve substantial costs[104]. - The company is subject to state laws governing the privacy and security of health information, complicating compliance efforts[102]. - The company is subject to evolving data privacy laws, including the California Consumer Privacy Act (CCPA) and the California Privacy Rights Act (CPRA), which impose stringent requirements on the handling of personal information[110]. - The FDA Reauthorization Act and other regulatory changes may impact the approval process for product candidates, potentially delaying or preventing market entry[111]. - The 2020 Consolidated Appropriations Act includes the CREATES Act, which allows generic developers to sue brand manufacturers for access to necessary samples, potentially affecting market dynamics[113]. - The company must navigate complex foreign regulatory environments for clinical trials and product approvals, which may differ significantly from U.S. requirements[114]. - The new Clinical Trials Regulation in the EU aims to streamline the approval process, with a maximum evaluation timeframe of 210 days for marketing authorization applications[117]. - The centralized procedure for EU marketing authorization is mandatory for certain products, with a maximum evaluation timeframe of 210 days, and accelerated assessment may be granted in exceptional cases[119]. - The new Medical Device Regulation (MDR) in the EU, effective from May 26, 2021, increases regulatory oversight and may raise costs and requirements for market entry[120]. Market Competition and Commercialization - DARE-BV1, if approved, will compete with existing treatments for bacterial vaginosis, including FDA-approved products like Solosec® and Clindesse®[60]. - The investigational contraceptive product Ovaprene will face competition from a variety of existing contraceptive options, including hormone-free and hormonal products[60]. - The company is developing Sildenafil Cream, 3.6%, which has the potential to be the first FDA-approved treatment for Female Sexual Arousal Disorder (FSAD)[60]. - The company’s ability to successfully market products will depend on factors such as FDA approval, product efficacy, and competition from other organizations[60]. - The commercial success of DARE-BV1 will depend on its effectiveness compared to existing FDA-approved treatments for bacterial vaginosis, which include generic options like clindamycin and metronidazole[181]. - The commercial success of Ovaprene will depend on market acceptance and the effectiveness of Bayer's marketing efforts, as Bayer holds exclusive rights to market and sell the product in the U.S.[184]. - The company faces competition from existing hormone therapies and must demonstrate the efficacy and safety of DARE-HRT1 to gain market acceptance among menopausal women[186]. - The commercial success of Sildenafil Cream, 3.6% will depend on its ability to demonstrate safety and effectiveness in treating female sexual arousal disorder, as well as market acceptance[186]. - The women's health market is increasingly dominated by generic products, making it difficult for the company to introduce new branded products at profitable prices[193]. - The proportion of the U.S. market made up of generic products is rising, which could hinder the company’s ability to achieve acceptable revenue levels from new products[194]. - The company faces uncertainty regarding third-party reimbursement for its products, which could significantly impact market demand and financial prospects[195]. - Changes in health care laws may reduce demand for branded products, leading to a preference for lower-cost generics[194]. - The commercial success of the company’s products will depend on the extent of third-party payor coverage and reimbursement rates[197]. - Legislative efforts to control pharmaceutical pricing may further complicate the company’s ability to market its products profitably[199]. - The Biden Administration's focus on lowering prescription drug prices may impact the company's ability to generate revenue and attain profitability[200]. - The company relies on third-party partners for sales and distribution, which poses risks if these partners fail to effectively market or distribute products[204]. - The commercial success of product candidates is contingent on obtaining FDA approval and favorable product labeling, which is critical for differentiation from competitors[205]. - Many product candidates are in pre-clinical stages, carrying a higher risk of failure and requiring significant safety and efficacy data before advancing to clinical trials[206]. - Macroeconomic factors such as inflation and interest rates could adversely affect the ability of patients and distributors to purchase and distribute products[208]. Operational Challenges and Risks - The company has a limited operating history and has incurred significant losses since inception, expecting to continue incurring losses for the foreseeable future[134]. - The company relies heavily on the success of its lead product candidates, including DARE-BV1, Ovaprene, and Sildenafil Cream, 3.6%, with clinical development being lengthy and expensive[134]. - As of March 29, 2021, the company had 23 employees, with 12 in research and development and 11 in general and administrative roles[130]. - The company must raise additional capital to continue operations, with challenges due to low trading volume, lack of revenue, and limited operating history[134]. - The company is subject to various federal, state, and local environmental, health, and safety laws, which could result in substantial fines if not complied with[129]. - The company may face delays in clinical development programs due to the COVID-19 pandemic, impacting costs and timelines[134]. - The company depends on third parties for significant aspects of product development, and failures by these parties could lead to delays or program failures[134]. - The company must obtain regulatory approvals, particularly from the FDA, for its product candidates, which may require more resources and time than anticipated[134]. - The company has a license agreement with Bayer, but there is a risk of not receiving additional payments, and Bayer may terminate the agreement without cause[134]. - The company is subject to evolving EU laws on data export and must comply with GDPR, which imposes significant penalties for non-compliance[126]. - The company relies on external consultants for product development and operational expertise due to its limited personnel resources[155]. - The company may need to obtain significant additional capital for development or commercialization activities, which may not be available on acceptable terms[154].