Adrenoleukodystrophy

大会由扬州市人民政府主办，同写意专业策划，以“打造生物医药新质生产力”为主题，邀请众多行业领袖和先锋人物一起取势明道，就如何打造中国医药新质生产力，面向未来创新药如何立项，资本寒冬下的创新药BD与出海，GLP-1&小核酸药物以及抗体药的质量与生产四大主题展开深度研讨，为行业发展提供方向性指引。审核：王永增，合源生物CTO在过去一年中，FDA启动了多项举措以支持细胞和基因疗法的临床开发和监管审查，以应对长期悬而未决的挑战：即大量的细胞和基因疗法临床试验处于临床搁置状态。FDA将此归因于CBER发布的临床搁置数量的整体增加，而这又是因为计划中或已启动的细胞和基因疗法临床试验数量在不断增加。不过，最近的一项分析指出，细胞和基因疗法临床试验在FDA临床搁置总数中占比高达40%，而它们在ClinicalTrials.gov上公示的临床试验中占比仅2%。虽然这种不平衡可能部分反映了细胞和基因疗法领域科学的新颖性，以及许多细胞和基因疗法产品是“first in class”的事实，但搁置率似乎不成比例。如果没有其他原因，我们需要评估一下在产品本身之外，是什么导致了这些临床搁置，以期避免未来的临床搁置。特别需要指出的是，如果长期搁置，可能会延迟患者获得潜在有益的临床试验用药，并不可避免地对公司产生财务影响。更令人担忧的是，在后一种情况下，公司可能会由于缺乏资金而放弃临床试验，而进一步剥夺患者和医生获得有前景的潜在治疗地选择。在细胞和基因治疗开发中，医疗需求很大，技术发展迅速，而其商业模式却如此不确定，因此申办方和FDA应一起努力来减少临床搁置。作为产品开发者的监管顾问，我们经常与大大小小寻求帮助企业合作，帮助解决导致临床搁置的问题。在本文中，我们为申办方提供了一些前瞻性地战略建议，以提高其临床试验能够顺利进行而不被搁置的可能性。我们也给FDA提出了相应地措施建议，以确保仅在必要时和不可避免的情况下才叫停细胞和基因治疗临床试验 - 临床搁置。1细胞和基因疗法的临床搁置：感知与现实细胞和基因治疗临床试验的搁置有多普遍？我们很难确定确切数字。但根据公开披露的信息可以估计，自2020年1月以来，至少有136项细胞和基因治疗临床试验被搁置。大家可能认为这个数字非常大，但根据the Pink Sheet对通过FOIA申请获得的数据进行的分析，每年的搁置数量已经从2018年的峰值——147个，下降到2022年的70个——近年来的最低点。如果想了解眼下临床搁置地格局，那就必须审视被搁置的具体原因。大多数临床搁置是为了应对不良事件或患者死亡而实施的，其中许多不可预测。第二大常见原因是CMC数据缺失或存在问题，包括在检查生产设施期间的发现的问题。生产制造基因和细胞疗法有特殊挑战，因此FDA也尤为关注。细胞和基因治疗领域的申办方通常是学术研究人员或小公司，他们几乎没有FDA法规和程序的操作经验，这使得在做商业生产设施和工艺规模放大时特别具有挑战性，常常导致难以确定临床试验产品和拟议的商业化产品之间的可比性，并最终导致CMC数据包的前后不一致。在一项临床试验被搁置后，项目开发会发生什么？一项研究发现，在2020-2022年间被搁置临床试验项目（n=33）中，约有80%的项目在平均6.2个月后被解除搁置，但有些持续了19个月以上（包括两个30天的时间段，用于CBER发布正式意见，并随后审核申办方的完整回复）。结局差异很大：有几项被搁置的临床试验，在问题得到解决后，随即得以恢复并且取得了显著的积极结果。相比之下，一项临床试验在取消搁置之前因安全问题而终止，另外三项临床试验在取消搁置重启之后不久，很快就终止了。蓝鸟生物的经验为解析这些数据提供了一些见解。该公司的慢病毒基因治疗产品已经获得了三个批准，但每一个都是在临床搁置之后获批的。其中两个产品使用相同的慢病毒载体，即Zynteglo（betibeglogene autotemcel，适用于β地中海贫血）和Skysona （elivaldogene autotemcel，适用于大脑型肾上腺脑白质营养不良），在数名受试者发生骨髓增生异常综合征（MDS）后，于2021年被临床搁置。在细胞、组织和基因疗法办公室（OCTGT）以获益超过风险为基础投票建议批准后，这些搁置被取消，该产品于2022年获得批准。蓝鸟生物最近批准的慢病毒基因疗法Lyfgenia（lovotibeglogene autotemcel，适用于镰状细胞病）也有过2次临床搁置——第一次发生在2021年，也是由于一名受试者被诊断为MDS。第二次是对18岁以下的患者的部分搁置，原因是该年龄组的一名患者出现持续性、非输血依赖型贫血。但最终确定病因是一种潜在的遗传疾病，后续在建立了对患者筛查这一疾病的程序后，取消了搁置。虽然蓝鸟克服临床搁置的经验令人鼓舞，但申办方的目标应该仍然是避免临床搁置。以下部分的建议将进一步实现这一目标，并且为临床项目的整体成功提供支持。2申办方：了解你的监管机构从一开始，申办方应可以预见到与其产品类别和技术相关的不良事件和其他问题，尽管人身体对产品的反应总会出乎所料。但随着该领域的发展，某些产品类别的风险可能会变得更加可预测，但目前这些信息仅限于参与临床试验的研究人员、公司和监管机构。不幸的是，由于数据的商业机密性，监管机构往往无法将这些信息公之于众。但我们建议申办方和研究者多多了解FDA的想法。• 标签和评论。新申办方可以从标签上的语言中很好地了解可能面临的临床试验决策。同样，做出批准决定后发表的综述是申办方获得FDA可接受的非临床和临床试验设计的宝贵资源。• FDA咨询委员会提供了丰富的信息和见解。2021年9月，FDA召开了OCTGT会议，讨论了与基于AAV载体的基因治疗产品相关的各种毒性风险，OCTGT关于个别产品的BLAs还提供关于风险的信息，以及监管机构和专业团体如何将这些风险与潜在益处的证据联系起来。• 尽可能多地了解其他产品被搁置的原因。申办方应寻求有关其技术和产品类别的所有信息，以及其产品特有的风险。FDA在会议上的报告通常会提供大量他们关注的信息，例如，在基因编辑技术方面，FDA对脱靶编辑的可能性表示担忧，至少有一种基因编辑疗法被临床搁置，部分原因是FDA希望看到这一领域的更多分析。• 指南很重要，即使是草稿的形式。FDA已经提供了关于开发利用人类基因组编辑的基因治疗产品的指南草案，以及关于CAR-T细胞产品和用于多个疾病类别的基因治疗产品的指南草案。该机构在撰写指导文件时非常谨慎，以现有的经验为重点，即使有些产品还未被批准。• 在细胞和基因疗法中，临床前数据甚至更重要，要好好利用。在临床前研究中，应全面评估已知的风险和问题，并将其纳入IND申请中提交的风险评估计划，以及如何解决临床试验中出现安全性问题时的方案。• CMC是第一要务。虽然大多数临床搁置是由安全性事件导致的，但也有一部分是由CMC缺陷（过去3年中至少有9种疗法）、临床前数据或项目的其他因素引起。就解决问题所需的时间而言，CMC缺陷引起的问题尤其“昂贵”。上述2023年的研究发现，CMC问题平均需要8.4个月才能解决，而评估不良事件或处理FDA要求修改的方案或提供临床前信息的平均时间为4-6个月。在许多情况下，通过现有指南更好地理解FDA的期望和要求，可以使申办方在提交申请之前就解决可能导致搁置的问题。效价测定就是一个很好的例子。为了避免CMC问题，效价测定必须在临床前和早期临床阶段进行开发和完善。最近的一份指南草案《细胞和基因治疗产品的效力保证》（Potency Assurance for Cellular and Gene Therapy Products）提供了确保产品在已发布的每一批产品中达到预期疗效的效力或特定能力的策略。指南草案还规定了FDA在基于综合风险的效力中对效力试验选择和设计、控制和变更管理以及接受标准的建议。指南草案指出，如果不能保证试验用药的效力，或者说如果IND没有包含足够的信息来保证效力，那么该研究可能被临床搁置。此外，指南解释道，如果用于II期或III期临床试验的IND不能保证产品的效力，说明临床试验设计在支持上市许可产品的有效性上有缺陷，这也会是FDA叫停临床试验的理由。• 与FDA和其他机构合作。在基因疗法生产和控制领域，CBER主任最近指出，企业不仅需要直接与FDA接触，而且需要与整个行业和学术界接触，以便确定有可能固化到标准化生产流程和平台中的最佳实践。为了预防潜在的CMC和临床前并发风险，申办方应在研发前的早期阶段，通过对CBER产品监管建议的初步有目标的沟通（Initial Targeted Engagement for Regulatory Advice on CBER Products，INTERACT）计划召开会议，在pre-IND阶段进行pre-IND会议。虽然会议请求过程可能很长，但是这笔投资是值得的。这些会议为申办方提供了向FDA工作人员询问有关其项目具体问题的机会，并寻求对FDA指南的解释。• 寻求帮助。小型学术中心和新兴公司可能缺乏资源来了解FDA的所有指南，这些指南数量众多且相当细致，更不用说这些指南如何相互衔接，或者在与该机构的互动过程中预期会发生什么。除了直接与FDA会面外，与了解并深刻理解FDA指导和期望的有经验的监管顾问合作通常是最有效的成功途径。就时间和财务资源而言，比起临床搁置，在一开始就获得战略性指导可能是一项明智的投资。顾问还可以向申办方建议其产品可能适合获得哪些认定（例如RMAT、突破性疗法），并指导申办方完成申请特殊认定的过程。如果一个产品满足需求（包括初步的临床证据），申请方将获得与CBER评审人员更早、更密切的互动的优势。鉴于潜在疗效的早期证据，FDA会将额外的资源和注意力用于这些指定的产品。但请注意，组织和先进疗法办公室收到的90%的申请是针对严重或危及生命的疾病，一半是针对罕见疾病，因此该办公室的资源限制仍然适用。此外，认定并不能保证所有可能导致临床搁置的问题都能提前发现。获RMAT或突破疗法认定的临床试验也有被搁置的。• 这不是针对个人。申办方必须接受FDA在IND前和INTERACT会议上提供的反馈，并将建议纳入他们的IND中。FDA可能会根据另一个申办方的经验来给你建议，但细节不会分享。• 关注细节。最后，在最基本的层次上，IND和会议包数据必须完整和详细。不止一项CAR-T细胞疗法临床试验因IND缺乏足够的信息来支持受试者安全性风险评估而被搁置。3FDA：考虑风险CBER主任Peter Marks承认，在某种程度上，临床搁置数量的增加是由于该机构目前审核员的数量难以处理细胞和基因疗法的大量IND申请。我们意识到这个问题的重要性和加强CBER的审查能力需求，不仅仅是因为一个更有能力的审核员就能在最初的30天IND周期中处理好申请需求，还因为更有能力的审核员会有能力与申办方在30天内进行互动并解决问题，而不至于在没有这样的时间和精力的情况下导致默认的临床搁置。此外，正如我们在上面所建议的那样，CBER是否有能力举行INTERACT和pre-IND会议也取决于现有工作人员的数量。我们赞赏FDA最近采取的措施，增加其专门负责细胞和基因疗法的审核人员，并努力为其流程注入更大的灵活性，这些努力主要得益于最近将之前的OTAT重组为治疗产品办公室（Office of Therapeutic Products， OTP）。随着OTP的成立，FDA打算聘用132名专门负责细胞和基因治疗产品审核的新审核人员；然而，由于政府和生物技术行业之间的工资差异，这些职位的招聘是个挑战。同样的现实也影响了高级审评人员的留职。近年来，随着细胞和基因治疗产品数量的增加，FDA有大量专业知识人才流失。最后，为了确保创新和开发继续以相同的速度进行，我们鼓励FDA在不损害IND持有者机密的情况下，继续分享关于特定治疗类别的安全性问题的信息，以便申办方能够提前做好准备（例如通过与公众和申办方会议、咨询委员会、会议述评或出版物评论以及指南），避免临床搁置。参考文献：Reducing The Number Of Clinical Holds On Cell And Gene Therapies: Approaches For Sponsors And The FDA；cell&gene更多优质内容，欢迎关注↓↓↓

Exclusive discussions and finalization of related documentation underway with a leading investor to monetize royalties from TWYMEEG® (Imeglimin) sales in Japan Cash runway estimated to be sufficient until the completion of the transaction expected by the end of April, including tranches already drawn or fully available on the equity-linked financing facility with IRIS LYON, France--(BUSINESS WIRE)-- Regulatory News: POXEL SA (Euronext: POXEL - FR0012432516), a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare metabolic disorders, announces the publication at the end of April 2024 of its 2023 Annual Results, originally scheduled for April 9, 2024, given the expected completion of a transaction by the end of April. The Company, which has made significant progress in securing additional financing, is targeting to close, by the end of April, a transaction relating to the monetization of royalties from TWYMEEG® (Imeglimin) sales in Japan. Poxel expects that its financial resources will be sufficient to maintain its operations until the finalization of this monetization transaction. The Company will communicate its new financial calendar in April 2024 upon completion of this transaction. About Poxel SA Poxel is a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare disorders. For the treatment of NASH, PXL065 (deuterium-stabilized R-pioglitazone) met its primary endpoint in a streamlined Phase 2 trial (DESTINY-1). In rare diseases, development of PXL770, a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator, is focused on the treatment of adrenoleukodystrophy (ALD) and autosomal dominant polycystic kidney disease (ADPKD). TWYMEEG® (Imeglimin), Poxel’s first-in-class product that targets mitochondrial dysfunction, is now marketed for the treatment of type 2 diabetes in Japan by Sumitomo Pharma and Poxel expects to receive royalties and sales-based payments. Poxel has a strategic partnership with Sumitomo Pharma for Imeglimin in Japan, China, and eleven other Asian countries. Listed on Euronext Paris, Poxel is headquartered in Lyon, France, and has subsidiaries in Boston, MA, and Tokyo, Japan. For more information, please visit: All statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the Company’s control. These statements may include, without limitation, any statements preceded by, followed by or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could” and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the Company’s control that could cause the Company’s actual results or performance to be materially different from the expected results or performance expressed or implied by such forward-looking statements. The Company does not endorse or is not otherwise responsible for the content of external hyperlinks referred to in this press release. View source version on businesswire.com: Contacts Contacts - Investor relations / Media NewCap Nicolas Fossiez, Aurélie Manavarere / Arthur Rouillé poxel@newcap.eu +33 1 44 71 94 94 Source: POXEL SA View this news release online at:

- Ongoing Communication with FDA to Align on Next Steps for Larsucosterol in Alcohol-Associated Hepatitis - Webcast of Earnings Call Today, March 27th at 4:30 p.m. ET CUPERTINO, Calif., March 27, 2024 /PRNewswire/ -- DURECT Corporation (Nasdaq: DRRX) today announced financial results for the fourth quarter and year ended December 31, 2023 and provided a business update. "We remain enthusiastic about the improvement in 90-day mortality demonstrated in our Phase 2b AHFIRM clinical trial and are communicating with the U.S. Food and Drug Administration (FDA) about the design of a confirmatory Phase 3 trial to support the potential approval of larsucosterol as a treatment for alcohol-associated hepatitis (AH)," stated James E. Brown, D.V.M., President and CEO of DURECT. "Larsucosterol could be the first FDA-approved treatment to address AH, a highly lethal condition that results in approximately 158,000 hospitalizations in the U.S. annually with a 30% mortality rate at 90 days." Business Update: In November 2023, DURECT announced topline data from the AHFIRM trial that showed a compelling efficacy signal in favor of larsucosterol in the key secondary endpoint of mortality at 90 days. Both the 30 mg and 90 mg larsucosterol doses demonstrated clinically meaningful trends in reduction of mortality at 90 days with mortality reductions of 41% (p=0.068) in the 30 mg arm and 35% (p=0.124) in the 90 mg arm compared with placebo. The reductions in mortality at 90 days were more pronounced in U.S. patients with reductions of 57% (p=0.014) in the 30 mg arm and 58% (p=0.008) in the 90 mg arm compared with placebo. The numerical improvement in the primary endpoint of mortality or liver transplant at 90 days did not achieve statistical significance for either dose of larsucosterol. Larsucosterol appeared safe and well tolerated in the AHFIRM trial with fewer treatment-emergent adverse events (TEAEs) in the larsucosterol arms compared with placebo. DURECT is in ongoing communications with the FDA to align on next steps for the development of larsucosterol, including the design for a pivotal Phase 3 clinical trial in AH. DURECT plans to provide an update in the second quarter of 2024. In March 2024, DURECT announced that it entered into a co-marketing and collaboration agreement with Charles River Laboratories for the ALZET® Osmotic Pumps Portfolio and Associated Product Line in the U.S. and Canada. Charles River Research Models & Services (RMS) sales and marketing teams will collaborate with DURECT to jointly market and commercialize the ALZET product line to existing and new customers in the pharmaceutical industry and academic laboratories over a multi-year period. Financial Highlights for Q4 and Full Year 2023: Total revenues were $2.7 million and net loss was $1.4 million for the three months ended December 31, 2023 compared to total revenues of $3.3 million and net loss of $10.5 million for the three months ended December 31, 2022. Total revenues were $8.5 million and net loss was $27.6 million for the year ended December 31, 2023, compared to total revenues of $19.3 million and net loss of $35.3 million for the year ended December 31, 2022. As of December 31, 2023, cash, cash equivalents and investments were $29.8 million, compared to cash, cash equivalents and investments of $43.6 million at December 31, 2022. Debt as of December 31, 2023 was $16.7 million, compared to $21.2 million as of December 31, 2022. Earnings Conference Call and Webcast We will host a conference call today at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss fourth quarter and 2023 results and provide a corporate update: Wednesday, March 27 @ 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time A live audio webcast of the presentation will be also available by accessing DURECT's homepage at and clicking "Investors." If you are unable to participate during the live webcast, the call will be archived on DURECT's website under "Event Calendar" in the "Investors" section. About the AHFIRM Trial AHFIRM was a Phase 2b randomized, double-blind, placebo-controlled, international, multi-center study conducted in subjects with severe alcohol-associated hepatitis ( AH) to evaluate the sa Fety and eff Icacy of la Rsucosterol treat Ment (AHFIRM). The study was comprised of three arms and enrolled 307 patients, with approximately 100 patients in each arm: (1) SOC, which consists of placebo plus supportive care, with or without methylprednisolone capsules at the investigators' discretion; (2) larsucosterol (30 mg); and (3) larsucosterol (90 mg). Patients in the larsucosterol arms received the same supportive care without steroids. In order to maintain blinding, patients in the two active arms received matching placebo capsules if the investigator prescribed steroids. The primary outcome measure was the 90-Day incidence of mortality or liver transplantation for patients treated with larsucosterol compared to those treated with SOC. The Company enrolled patients at clinical trial sites across the U.S., EU, U.K., and Australia. In November 2023, the Company announced topline data for the AHFIRM Trial, as discussed above. Reflecting the life-threatening nature of AH and the lack of therapeutic options, the U.S. Food and Drug Administration (FDA) has granted larsucosterol Fast Track Designation for the treatment of AH. For more information, refer to ClinicalTrials.gov Identifier: NCT04563026. About Alcohol-associated Hepatitis (AH) AH is an acute form of alcohol-associated liver disease (ALD), associated with long-term heavy intake of alcohol and often occurs after a recent period of increased alcohol consumption (i.e., a binge). AH is typically characterized by severe inflammation and destruction of liver tissue (i.e., necrosis), potentially leading to life-threatening complications including liver failure, acute kidney injury and multi-organ failure. There are no FDA approved therapies for AH and a retrospective analysis of 77 studies published between 1971 and 2016, which included data from a total of 8,184 patients, showed the overall mortality from AH was 26% at 28 days, 29% at 90 days and 44% at 180 days. A subsequent global study published in December 2021, which included 85 tertiary centers in 11 countries across 3 continents, prospectively enrolled 2,581 AH patients with a median Model of End-Stage Liver Disease (MELD) score of 23.5, reported mortality at 28 and 90 days of approximately 20% and 31%, respectively. Stopping alcohol consumption is necessary, but frequently not sufficient for recovery in many moderate (defined as MELD scores of 11-20) and severe (defined as MELD scores >20) patients and therapies that reduce liver inflammation, such as corticosteroids, are limited by contraindications, have not been shown to improve survival at 90 days or one year, and have demonstrated an increased risk of infection. While liver transplantation is becoming more common for ALD patients, including AH patients, the total number of such transplants is still relatively small, and limited by organ availability. Average charges for a liver transplant exceed $875,000, and patients require lifelong immunosuppressive therapy to prevent organ rejection. About Larsucosterol Larsucosterol is an endogenous sulfated oxysterol and an epigenetic modulator. Epigenetic regulators are compounds that regulate patterns of gene expression without modifying the DNA sequence. DNA hypermethylation, an example of epigenetic dysregulation, results in transcriptomic reprogramming and cellular dysfunction, and has been found to be associated with many acute (e.g., AH) or chronic diseases (e.g., MASH). As an inhibitor of DNA methyltransferases (DNMT1, DNMT3a and 3b), larsucosterol inhibits DNA methylation, which subsequently modulates expression of genes that are involved in cell signaling pathways associated with stress responses, cell death and survival, and lipid biosynthesis. This may ultimately lead to improved cell survival, reduced inflammation, and decreased lipotoxicity. As an epigenetic modulator, the proposed mechanism of action provides further scientific rationale for developing larsucosterol for the treatment of acute organ injury and certain chronic diseases. About DURECT Corporation DURECT is a late-stage biopharmaceutical company pioneering the development of epigenetic therapies that target dysregulated DNA methylation to transform the treatment of serious and life-threatening conditions, including acute organ injury and cancer. Larsucosterol, DURECT's lead drug candidate, binds to and inhibits the activity of DNA methyltransferases (DNMTs), epigenetic enzymes that are elevated and associated with hypermethylation found in alcohol-associated hepatitis (AH) patients. Larsucosterol is in clinical development for the potential treatment of AH, for which FDA has granted a Fast Track Designation; metabolic dysfunction-associated steatohepatitis (MASH) is also being explored. In addition, POSIMIR® (bupivacaine solution) for infiltration use, a non-opioid analgesic utilizing the innovative SABER® platform technology, is FDA-approved and is exclusively licensed to Innocoll Pharmaceuticals for sale and distribution in the United States. For more information about DURECT, please visit and follow us on X (formerly Twitter) at . DURECT Forward-Looking Statements This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to: the potential for larsucosterol to demonstrate a reduction in mortality or liver transplant in patients with AH and to save lives, our ability to clarify with the FDA the design of the Phase 3 clinical trial of larsucosterol for AH, the potential FDA or other regulatory approval of larsucosterol for the treatment of AH, the potential to develop larsucosterol for AH, MASH or other indications, and the potential benefits, if any, of our product candidates. Actual results may differ materially from those contained in the forward-looking statements contained in this press release, and reported results should not be considered as an indication of future performance. The potential risks and uncertainties that could cause actual results to differ from those projected include, among other things, the risk that future clinical trials of larsucosterol do not confirm the results from subset analyses of the AHFIRM trial, including geographic or other segmentation, or of earlier clinical or pre-clinical trials, or do not demonstrate the safety or efficacy of larsucosterol in a statistically significant manner, risks that Innocoll may not commercialize POSIMIR successfully, and risks related to the sufficiency of our cash resources, our anticipated capital requirements, our need or desire for additional financing, our ability to meet the minimum bid price for continued listing on Nasdaq, our ability to obtain capital to fund our operations and expenses and our ability to continue to operate as a going concern. Further information regarding these and other risks is included in DURECT's most recent Securities and Exchange Commission (SEC) filings, including its quarterly report on Form 10-Q for the quarter ended September 30, 2023 and annual report on Form 10-K for the year ended December 31, 2023, when filed, under the heading "Risk Factors." These reports are available on our website under the "Investors" tab and on the SEC's website at . All information provided in this press release and in the attachments is based on information available to DURECT as of the date hereof, and DURECT assumes no obligation to update this information as a result of future events or developments, except as required by law. NOTE: POSIMIR® is a trademark of Innocoll Pharmaceuticals, Ltd. in the U.S. and a trademark of DURECT Corporation outside of the U.S. SABER® is a trademark of DURECT Corporation. Other referenced trademarks belong to their respective owners. Larsucosterol is an investigational drug candidate under development and has not been approved for commercialization by the U.S. Food and Drug Administration or other health authorities for any indication. SOURCE DURECT Corporation