FDA 加快研究性新药（IND）试点项目
正文 · 中文译文
FDA快速研究性新药（IND）试点项目 加速美国早期临床研究 FDA快速研究性新药（IND）试点项目 滚动提交流程与项目结构 快速IND试点项目申请期已结束 感谢各位对FDA快速研究性新药（IND）试点项目的浓厚兴趣。申请期结束后，FDA已收到来自申办方和潜在合格研究机构（QRI）的100多份申请，涵盖多样化的治疗领域、模式和机构类型——均聚焦于在美国启动新研究性产品的首次人体临床试验。这反映了全美范围内创新药物开发的深度与广度，以及我们加速患者获得潜在救命治疗的共同承诺。 FDA目前正在审查申请，预计将于12月18日前通知入选参与者。启动该试点并开始收集这一申办方-QRI合作模式的数据是重要的第一步，将为FDA如何继续现代化并加速首次人体试验路径提供参考。 感谢所有申办方和潜在QRI对推进药物开发的承诺。 项目概述 | 滚动提交流程与结构 FDA快速IND试点项目是HHS“试验闪电战行动”下的一项计划，旨在评估在美国加速首次人体（FIH）临床试验的新方法，同时维持FDA在受试者安全性和科学监管方面的严格标准。 本页内容： 概述、背景与预期成果 参与者特征与利益冲突 选择考虑因素 提交详情与后续步骤 常见问题 资源 项目概述 该试点旨在通过测试一种协作模式，缩短从启动支持IND的活动到FIH试验启动的时间，在该模式中，申办者与潜在合格研究机构（QRI）合作，以支持更高效的药物开发。在该试点下，第三方（可包括学术医学中心、健康网络、合同研究组织、法规顾问或其他研究组织），统称为“QRI”，将与申办者合作，就首次人体IND申报中的药理学与毒理学、临床以及化学、生产和控制（CMC）部分提供专家建议。这些QRI应作为科学专家发挥作用，提供与风险相称的判断，以推动创新、基于科学的、与阶段相适应的监管标准。 由于合格研究人员（QRI）为准备过程带来了专业且大量的科学专业知识，FDA将按滚动方式接受并审查新药临床试验申请（IND）申报中已完成的各个组成部分，而不是等待完整申报包。这种滚动审查模式有可能从根本上改变IND前药物开发的时间线。问题可以被实时识别和解决，过程结束时被临床暂停的风险可能会降低，从科学发现到首次人体（FIH）试验的路径可能变得更快、更可预测、更具协作性。在整个过程中，申办方保留对其IND组成部分申报的所有权和责任。 该试点还寻求鼓励协调可能与IND开发和FDA审查同时进行的活动，例如机构审查委员会（IRB）审查和临床试验 site 启动（在适当情况下）。通过支持更早的规划和更协调的开发活动，该试点旨在减少从申办方开始准备IND申报到首次人体研究开始之间不必要的延迟。 参与试点是自愿的。FDA在整个项目期间保留完整的监管权力，包括负责决定临床研究是否可以推进、是否应实施临床暂停，以及所有其他监管监督活动。参与试点不会改变FDA对IND审评、安全推进判定或临床试验实施的法定或监管标准。 预期结果 快速IND试点项目旨在评估利用QRIs和新的滚动审评流程是否能够在维持FDA对受试者安全和科学监督的严格标准的同时，提高早期临床开发的效率。 通过该试点，FDA力求评估是否能够实现以下结果： 通过跨非临床、临床和CMC学科的结构化、多学科科学投入，提高FIH IND申报中阶段适用数据的质量和提交水平。 更早识别和解决可能延迟1期临床试验启动的科学和监管问题。 通过更高质量的申报和更早的问题识别，减少可能需要进行1期临床暂停或信息请求的情形。 更高效地从非临床开发推进至首次人体研究启动。 在适当情况下，加强临床试验启动活动的协调，包括IRB审评和临床试验现场准备就绪。 除评估这种协作方式是否能提高申报质量、监管效率并缩短早期临床开发周期外，该试点还将生成证据，为未来可能采取的、旨在现代化FDA对早期临床开发支持方式的路径提供参考。例如，该试点可为未来政策举措提供参考，这些举措可对展现出较强科学和监管判断力的QRIs进行认证或认可，目标是建立一个可持续、高质量的机构网络，以支持药物开发并加速首次人体（FIH）试验的时间。 项目背景 美国长期以来一直为制药创新和监管严谨性设定全球标准。但近年来，越来越大部分的早期临床研究转移到海外，威胁到美国作为生物医学创新全球领导者的地位。保护美国的临床研究至关重要，因为这能确保美国患者继续更早获得新疗法，并继续受到世界上最先进监管监督的保护。 早期临床开发在将新疗法带给患者方面发挥着关键作用。能够高效达到首次人体里程碑的申办者，往往更有能力获得额外投资并建立对开发安全有效药物至关重要的合作伙伴关系，同时推动有前景的产品进入后期开发阶段。 为成功提交研究性新药（IND）申请夯实基础，始于pre-IND阶段。随着药物和生物制品领域的药物开发日益复杂多样，申办者必须解决的科学问题的数量与复杂程度正在考验现行pre-IND框架的极限，但同时也存在切实的改进机会。现行框架要求一次不具约束力的pre-IND咨询会议承担大量工作，同时处理非临床、临床、生产、试验设计和患者安全等多方面考量。对于复杂的开发问题，这种活动的高度集中几乎不留空间供申办者开展迭代式、结构化的协作，而这种协作正是构建有力申报所必需的。扩大此类互动机会将使申办者更有能力更高效地为患者带来安全有效的疗法。 申办者随后必须完成试验中心启动活动，例如机构审查委员会审查、中心合同签订和患者入组。目前，这些活动往往按顺序依次完成，而它们本可以并行推进，从而进一步压缩试验启动时间线。 正如HHS“Operation TrialBlazer”所述，FDA致力于通过专门举措主动应对临床开发挑战，以加速临床研究并推动其现代化。首先，FDA正着重完善IND相关要求，使其反映首次人体1期试验在科学上的适当标准，在评估风险的同时优先保障患者安全，以减少过度提交。这不是一次性的修正，而是一项持续承诺，旨在确保与研发阶段相适应的要求能够随着治疗模式和科学认知的演进而同步发展。其次，FDA正在探索新途径，通过“加急IND试点”释放美国创新的力量。 从该试点中汲取的经验教训可能有助于为美国未来支持高效首次人体药物开发的方式提供参考。 参与者特征与利益冲突 申办者研究性新药优先审评 申办者可针对单次IND提交提出参与请求。FDA将对具备以下特征的提交给予优先审评： 候选产品具有新颖性，且将属于CDER新药办公室（OND）、CBER治疗产品办公室（OTP）或肿瘤学卓越中心（OCE）的审评管辖范围。 该IND被归类为商业IND，即申办者意图通过最终提交上市申请将产品商业化。 IND项目针对的是第一阶段首次人体IND申报，且研究用产品尚无现有临床经验。FDA将优先考虑尚无既定临床经验的新分子实体。因此，我们建议申办方不要为利用具有先前临床经验活性成分的研究用产品提交参与该试点的请求。涉及新制剂、递送系统或技术、药物-器械组合、给药途径、剂型或根据505(b)(2)途径开发的产品等，并非该试点的主要关注点。 拟进行的IND申报是针对将在美国开展的第一阶段首次人体（FIH）临床试验 申办方在申请试点项目时拥有足够的初步非临床数据，以支持FDA评估该产品拟议的开发时间表和IND申报时间框架。 该试点将针对申请中所定义的研究用产品。纳入新技术或平台的项目不被排除，但试点支持将仅限于纳入本特定IND的技术，而非该平台或技术的广泛范围。 潜在合格研究机构优先考虑 潜在合格研究机构（QRI）可与申办方合作，提交参与试点的请求，以支持单一IND申报。FDA将优先考虑具有以下特征的QRI： 意向QRI是在美国组织或注册的法律实体，主要营业地在美国，核心咨询人员位于美国。 意向QRI承诺为申办者申请中确定的IND项目提供非临床、CMC和临床领域的IND开发或咨询服务支持。 意向QRI承诺通过自有基础设施或正式签署并有文件记录的合作伙伴安排，支持在美国加速启动1期首次人体（FIH）临床试验。 申办者与QRI利益冲突（COI）要求 FDA将保留完整监管权限，并在快速IND试点期间对所有IND申报进行彻底、独立的审评。申办者与QRI之间的利益冲突由参与机构负责识别和管理。FDA期望QRI实施书面COI程序，并应要求可向FDA提供。 FDA将根据IND申报和QRI建议的质量与客观性评估试点参与方。如发现利益冲突已损害QRI提供客观建议的能力，该QRI-申办者对将被移出试点，FDA在评估QRI模式时可能会考虑这一经验。 书面利益冲突程序可能涵盖的主题示例包括： 识别并披露质量研究机构（QRI）人员与申办方或申办方竞争对手之间的财务、雇佣、合作关系及个人关系； 用于判定已识别的实际或潜在利益冲突属于有问题还是可管理的流程； 对于任何可管理的潜在利益冲突，采取相应管理措施的程序。 QRI咨询团队与机构审查委员会（IRB）利益冲突：若拟设立的QRI同时拥有或运营将审查与试点IND相关临床方案的IRB，则QRI必须制定书面程序，确保IRB成员在QRI试点咨询流程中不兼任双重成员身份或角色。该分离须在整个试点期间持续维持。IRB可自行决定邀请在特定领域具备能力的个人（包括来自QRI的专题专家）协助审查需要超出或补充IRB现有专业知识的复杂问题。这些个人不得与IRB一同投票（依据21 CFR 56.107(f)）。 选择考量 FDA将根据以下参与快速IND试点计划的考量因素，评估申办方开发计划及QRI资质。申请将由双方（申办方与QRI）作为一个整体联合评估。 由于试点旨在纳入多种QRI类型和IND申报，涵盖跨多个治疗领域的新机制项目及更为成熟的方法，申请将相互之间进行比较评估。FDA将力求确保所选队列在治疗领域、产品模式、申办方规模及QRI类型方面体现广度。因此，任何单一因素均不具决定性，将对收到的申请进行整体评估。申办方应注意，未被选入试点不会以任何方式使申办方处于不利地位，不会使申办方失去使用常规pre-IND会议或其他FDA沟通渠道的资格，也不意味着药物开发研究质量较低。 申办方研究性新药选择考量 IND复杂性与试点契合度：试点旨在跨多种模式和项目类型测试滚动提交模式。申请将评估IND的复杂性和模式是否与滚动提交形式良好契合，以及拟议的QRI合作是否在试点时间线内为开发项目增加有意义的价值。 IND开发阶段：FDA将评估IND项目是否处于质量相关互动（QRI）能够在合理时间范围内实质有效推进的阶段。化学、生产和控制（CMC）及非临床开发项目应足够成熟，使IND申报在合理时间范围内可信地可实现，同时又足够早期，以便QRI能够提供有意义的意见，无论是关于研究设计、数据包策略还是申报准备度，而非主要作为接近最终数据包的顾问。申请人将被要求描述其拟议非临床项目的状态，包括CMC，并在试点申请中提供高层次的临床方案概要。 公共卫生影响与未满足的医疗需求：FDA将考虑目标疾病的严重性和负担以及现有治疗的可及性。 申办者概况：该试点旨在吸引小型和新兴生物技术公司以及具有成熟IND经验的大型申办者参与，以检验QRI可能提供的不同形式的价值，无论是作为IND准备过程中的积极开发合作伙伴，还是在滚动审评期间作为IND组成部分的实质性初步审评者。申办者将被要求描述其IND申报经验，并解释他们预期采用哪种QRI互动模式及其原因。 组合考量：由于试点旨在在整个药物开发生态系统中产生学习，上述考量将整体评估，并结合完整申请者池的背景进行。代表未被充分代表的治疗领域、罕见病、儿科适应症或新型模式的申请可能有助于队列多样性，并将被相应考虑。 前瞻性合格研究机构（QRI）选择考量 前瞻性QRI将根据其在以下核心学科中记录的经验进行评估，这些学科对于在IND开发和提交过程中有效支持申办方是必要的。多个专业领域可由单一人选满足。 非临床领导力与专业知识：在设计药理学和毒理学数据包、就起始剂量选择提供建议以及评估非临床数据包是否适用于1期IND提交方面具有经证实的能力。QRI应能够在非临床项目早期识别差距和/或潜在安全性问题，并就如何在确定的时间线内解决这些问题向申办方提供可操作的指导。 化学、制造和控制（CMC）领导力与专业知识：在指导工艺和分析开发与表征策略、识别关键CMC差距以及开发IND的CMC模块以确保安全性和监管充分性方面具有相关背景。QRI应能够评估是否
正文 · 英文原文
FDA Expedited Investigational New Drug (IND) Pilot Program Accelerating Early-Stage Clinical Research in the U.S. FDA Expedited Investigational New Drug (IND) Pilot Program Rolling Submission Process & Program Structure Application Period for the Expedited IND Pilot Program Has Closed Thank you for the overwhelming interest in the FDA's Expedited Investigational New Drug (IND) Pilot Program. Following the close of the application period, FDA has received over 100 applications from sponsors and prospective Qualified Research Institutions (QRIs) spanning a diverse range of therapeutic areas, modalities, and institution types – all focused on initiating first-in-human clinical trials for new investigational products in the United States. This reflects the depth and breadth of innovative drug development happening across the country, and our shared commitment to accelerating patient access to potentially life-saving treatments. FDA is now reviewing applications and anticipates notifying selected participants by December 18. Launching the pilot and beginning to collect data on this model of sponsor-QRI collaboration is an important first step that will inform how FDA continues to modernize and accelerate the path to first-in-human trials. Thank you to all sponsors and prospective QRIs for your commitment to advancing drug development. Program Overview | Rolling Submission Process & Structure The FDA Expedited IND Pilot Program is an initiative under HHS Operation TrialBlazer designed to evaluate new approaches for accelerating first-in-human (FIH) clinical trials in the United States while maintaining FDA's rigorous standards for participant safety and scientific oversight. On this page: Overview, Background & Desired Outcomes Participant Characteristics & Conflict of Interest Selection Considerations Submission Details & Next Steps Frequently Asked Questions Resources Program Overview The pilot seeks to reduce the time from initiation of IND-enabling activities to FIH trial initiation by testing a collaborative model in which sponsors work with prospective qualified research institutions (QRIs) to support more efficient drug development. Under the pilot, third parties (which could include academic medical centers, health networks, contract research organizations, regulatory advisors, or other research organizations), collectively called “QRIs”, would partner with sponsors to provide expert recommendations on pharmacology and toxicology, clinical, and chemistry, manufacturing, and controls (CMC) components of first-in-human IND submissions. These QRIs should function as scientific experts providing risk-proportionate judgement to drive innovative, science-based, phase-appropriate regulatory standards. Because QRIs bring specialized and substantial scientific expertise to the preparation process, the FDA will accept and review individual components of an IND submission on a rolling basis as they are completed, rather than waiting for a complete package. This rolling review model has the potential to fundamentally change the timeline of pre-IND drug development. Issues can be identified and resolved in real time, the risk of a clinical hold at the end of the process may decrease, and the path from scientific discovery to FIH trial will potentially become faster, more predictable, and more collaborative. Sponsors retain ownership of and responsibility for their IND component submissions throughout the process. The pilot also seeks to encourage coordination of activities that may occur alongside IND development and FDA review, such as Institutional Review Board (IRB) review and clinical trial site activation, where appropriate. By supporting earlier planning and more coordinated development activities, the pilot aims to reduce unnecessary delays between the point at which a sponsor begins preparing for an IND submission and the start of first-in-human studies. Participation in the pilot is voluntary. FDA retains full regulatory authority throughout the program, including responsibility for determining whether a clinical investigation may proceed, whether a clinical hold should be imposed, and all other regulatory oversight activities. Participation in the pilot does not modify FDA's statutory or regulatory standards for IND review, safe-to-proceed determinations, or clinical trial conduct. Desired Outcomes The Expedited IND Pilot Program is intended to evaluate whether leveraging QRIs and a new rolling review process can improve the efficiency of early clinical development while maintaining FDA’s rigorous standards for participant safety and scientific oversight. Through this pilot, FDA seeks to assess whether the following outcomes can be achieved: Improved quality and submission of phase-appropriate data for FIH IND submissions through structured, multidisciplinary scientific input across nonclinical, clinical, and CMC disciplines. Earlier identification and resolution of scientific and regulatory issues that may delay initiation of Phase 1 clinical trials. Reduced instances in which Phase 1 clinical holds or information requests may be necessary through higher-quality submissions and earlier issue identification. More efficient progression through nonclinical development to first-in-human study initiation. Greater coordination of clinical trial startup activities, including IRB review and clinical trial site readiness, where appropriate. In addition to evaluating whether this collaborative approach improves submission quality, regulatory efficiency, and early clinical development timelines, the pilot will generate evidence to inform potential future approaches to modernizing FDA’s support of early-stage clinical development. For example, this pilot may inform future policy initiatives that could certify or accredit QRIs demonstrating strong scientific and regulatory judgment with the goal of building a sustainable, high-quality network of institutions to support drug development and accelerate the time to FIH trials. Program Background The United States has long set the global standard for pharmaceutical innovation and regulatory rigor. But in recent years, a growing share of early-stage clinical research has moved overseas, threatening America’s position as the global leader in biomedical innovation. It is critical to protect clinical research in the U.S. because it ensures that American patients will continue to have earlier access to new therapies and remain protected by the world's most advanced regulatory oversight. Early clinical development plays a critical role in bringing new therapies to patients. Sponsors that reach first-in-human milestones efficiently are often better positioned to secure additional investment and establish partnerships critical to the development of safe and effective drugs, as well as advance promising products through later stages of development. Strengthening the foundation for successful Investigational New Drug, or IND, submissions begins at the pre-IND stage. As drug development has grown increasingly complex and diverse across both drugs and biologics, the volume and sophistication of scientific questions sponsors must resolve is testing the limits of the current pre-IND framework, yet there is a meaningful opportunity to evolve. The current framework asks a single nonbinding pre-IND advisory meeting to perform an enormous amount of work, addressing nonclinical, clinical, manufacturing, trial design, and patient safety considerations all at once. For complex development questions, that concentration of activity leaves little room for the iterative, structured collaboration sponsors need to build toward a strong submission. Expanding opportunities for that kind of engagement would better position sponsors to bring safe and effective therapies to patients more efficiently. Sponsors must then complete trial site activation activities, such as institutional review board review, site contracting, and patient enrollment. Currently, these activities are often completed sequentially when they could be pursued in parallel, which could further compress trial activation timelines. As stated in HHS Operation TrialBlazer, FDA is committed to proactively address clinical development challenges through dedicated initiatives to accelerate and modernize clinical research. First, FDA is focusing on refining IND expectations to reflect what is scientifically appropriate for first-in-human Phase 1 trials, prioritizing patient safety while assessing risk to reduce over-submission. This is not a one-time fix, but an ongoing commitment to ensure phase-appropriate expectations keep pace as modalities and scientific understanding evolve. Second, FDA is exploring new ways to unlock the power of American innovation through the Expedited IND Pilot. Lessons learned from the pilot may help inform future approaches to supporting efficient first-in-human drug development in the United States. Participant Characteristics & Conflict of Interest Sponsor Investigational New Drug Prioritization Sponsors may submit a request to participate for a single IND submission. FDA will prioritize submissions with the following characteristics: The product candidate is novel and will fall under the review jurisdiction of CDER Office of New Drugs (OND), CBER Office of Therapeutic Products (OTP), or Oncology Center of Excellence (OCE). The IND is classified as a Commercial IND, i.e., the sponsor intends to commercialize the product by eventually submitting a marketing application. The IND program targets a Phase 1 First-In-Human IND submission, and the investigational product does not have existing clinical experience. FDA will prioritize new molecular entities without established clinical experience. Therefore, we recommend sponsors do not submit a request to participate in this pilot for an investigational product that leverages active ingredients with prior clinical experience. Products such as those involving new formulations, delivery systems or technologies, drug-device combinations, routes of administration, dosage forms, or development under the 505(b)(2) pathway are not the primary focus of the pilot. The intended IND submission is for a FIH Phase 1 clinical trial that will be run in the United States The sponsor has sufficient preliminary nonclinical data at the time of application to the pilot program to support the FDA in evaluating the product’s proposed development timeline and IND submission timeframe. The pilot will address the investigational product as defined in the application. Programs incorporating novel technologies or platforms are not excluded, but pilot support will be limited to the technology as incorporated into this specific IND, not to the platform or technology broadly. Prospective Qualified Research Institution Prioritization Prospective QRIs may submit a request to participate in the pilot in support of a single IND submission in partnership with a sponsor. FDA will prioritize QRIs with the following characteristics: The prospective QRI is a legal entity organized or incorporated in the United States, with a principal place of business in the United States, with core advisory personnel located in the United States. The prospective QRI commits to providing IND development or advisory support across nonclinical, CMC, and clinical disciplines for the IND program identified in the sponsor’s application. The prospective QRI commits to supporting the acceleration of Phase 1 FIH clinical trial initiation in the United States through owned infrastructure or formally executed and documented partnership arrangements. Sponsor & QRI Conflict of Interest (COI) Requirements FDA will maintain full regulatory authority and conduct thorough, independent review of all IND submissions during the Expedited IND Pilot. Conflict of interest between sponsors and QRIs is the responsibility of the participating organizations to identify and manage. FDA expects QRIs to implement written COI procedures that should be available to FDA upon request. FDA will evaluate pilot participants based on the quality and objectivity of IND submissions and QRI recommendations. Should conflict of interest be found to have compromised a QRI's ability to provide objective recommendations, the QRI-sponsor pair will be removed from the pilot, and FDA may consider this experience when evaluating the QRI model . Examples of topics that may be included in the written conflict of interest procedures include: Identification and disclosure of financial, employment, collaborative, and personal relationships between QRI personnel and the sponsor or the sponsor’s competitors; A process for determining whether identified real or potential conflicts are problematic or manageable; For any potential conflicts of interest that can be managed, procedures for doing so. QRI advisory team & IRB Conflict of Interest: In the case of a prospective QRI that also owns or operates an IRB that will review the clinical protocol associated with the pilot IND, the QRI must have written procedures ensuring that IRB members do not hold dual membership or roles within the QRI's pilot advisory process. This separation must be maintained throughout the pilot period. An IRB may, at its discretion, invite individuals with competence in special areas, including subject matter experts from the QRI, to assist in the review of complex issues which require expertise beyond or in addition to that available on the IRB. These individuals may not vote with the IRB (as per 21 CFR 56.107(f)). Selection Considerations FDA will evaluate sponsor development programs and QRI qualifications against the following considerations for participation in the Expedited IND Pilot Program. Applications will be evaluated as a single package across both parties in tandem (the sponsor and QRI). Because the pilot aims to include a variety of QRI types and IND submissions spanning novel mechanism programs and more established approaches across diverse therapeutic areas, applications will be evaluated relative to one another. FDA will seek to ensure the selected cohort reflects breadth across therapeutic areas, product modalities, sponsor sizes, and QRI types. Because of this, no single factor is determinative and will be evaluated holistically across the applications received. Sponsors should note that non-selection for the pilot will not disadvantage sponsors in any way, disqualify sponsors from utilizing typical pre-IND meetings or other FDA interactions, nor does it imply lower-quality drug development research. Sponsor Investigational New Drug Selection Considerations IND Complexity & Pilot Fit: The pilot is designed to test the rolling submission model across a range of modalities and program types. Applications will be assessed on whether the IND's complexity and modality are well-suited to the rolling submission format and whether the proposed QRI partnership adds meaningful value to the development program within the pilot timeline. IND Development Stage: FDA will assess whether the IND program is at a stage where QRI engagement can be substantively productive within a reasonable timeframe. The CMC and nonclinical development program should be sufficiently advanced so that an IND submission is credibly achievable within a reasonable timeframe, while early enough that the QRI can provide meaningful input, whether on study design, data package strategy, or submission readiness, rather than serving primarily as an advisor on a near-final package. Applicants will be asked to describe the status of their proposed nonclinical program, including CMC, and provide a high-level clinical protocol synopsis in the pilot application. Public Health Impact & Unmet Medical Need: FDA will consider the severity and burden of the target condition and the availability of existing treatments. Sponsor Profile: The pilot is designed to engage both small and emerging biotechnology companies and larger sponsors with established IND experience, in order to test the different forms of value a QRI may provide, whether as an active development partner throughout the IND preparation process, or as a substantive preliminary reviewer of IND components during rolling review. Sponsors will be asked to describe their IND submission experience and explain which model of QRI engagement they anticipate, and why. Portfolio Considerations: Because the pilot is designed to generate learning across the drug development ecosystem, the considerations above will be evaluated holistically and in the context of the full applicant pool. Applications representing underrepresented therapeutic areas, rare diseases, pediatric indications, or novel modalities may contribute value to cohort diversity and will be considered accordingly. Prospective Qualified Research Institution (QRI) Selection Considerations Prospective QRIs will be evaluated on their documented experience across the following core disciplines, which are necessary to effectively support the sponsor throughout the IND development and submission process. Multiple areas of expertise may be satisfied by a single person. Nonclinical Leadership & Expertise: Proven capability in designing pharmacology and toxicology data packages, advising on starting dose selection, and assessing whether a nonclinical package will be fit-for-purpose for a Phase 1 IND submission. QRIs should be able to identify gaps and/or potential safety concerns early in the nonclinical program and provide actionable guidance to sponsors on how to address them within a defined timeline. Chemistry, Manufacturing, and Controls (CMC) Leadership & Expertise: Relevant background in guiding process and analytical development and characterization strategies, identifying critical CMC gaps, and developing the CMC module of an IND for safety and regulatory adequacy. QRIs should be able to assess whether