Commercialization of ALM-488 for Highlighting Nerves During Image Guided Surgeries

用于在图像引导手术期间突出神经的 ALM-488 的商业化

• 批准号: 10480219
• 负责人: Brett J. Berman
• 金额: $ 167.09万
• 依托单位: ALUME BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10480219
• 关键词: Anatomy; Animals; Award; Binding; Biological Sciences; Canis familiaris; Clinical; Clinical Trials; Color; Companions; Complement; Consult; Contracts; Data; Development; Dose; Dyes; Ensure; Erectile dysfunction; Exhibits; Feedback; Formulation; Funding; Funding Mechanisms; Goals; Grant; Head and Neck Cancer; Head and Neck Surgery; Human; Image; Image-Guided Surgery; Incontinence; Infection; Injury; Interview; Intravenous; Intravenous infusion procedures; Laboratories; Lead; Light; Lighting; Medical Imaging; Methods; Morbidity - disease rate; Motor; National Institute of Neurological Disorders and Stroke; Nerve; Nerve Tissue; Numbness; Operating Rooms; Operative Surgical Procedures; Paralysed; Patient-Focused Outcomes; Patients; Peptides; Perception; Peripheral Nerves; Pharmaceutical Preparations; Pharmacology; Phase; Phase I/II Clinical Trial; Phase I/II Trial; Positioning Attribute; Postoperative Period; Price; Procedures; Process; Production; Rattus; Readiness; Recovery; Resource-limited setting; Risk; Rodent; Safety; Seeds; Series; Site; Small Business Innovation Research Grant; Structure; Surgeon; Surgical Specialties; Surveys; Testing; Texture; Tissues; Toxic effect; Toxicity Tests; Toxicology; Trauma; Tumor Cell Invasion; United States National Institutes of Health; Visual; Visualization; Work; afferent nerve; autonomic nerve; cancer surgery; chronic pain; clinical candidate; clinical efficacy; clinical translation; commercialization; imaging agent; improved; in vivo; instrumentation; manufacturing scale-up; method development; multi-site trial; nerve agent; nerve damage; nerve injury; novel; phase III trial; polypeptide; pre-clinical; preservation; prevent; programs; protein aminoacid sequence

PROJECT SUMMARY Fundamental to the goals of surgery are functional preservation of critical nerves and minimization of post- operative patient morbidity. Unfortunately, inadvertent nerve injury during surgery continues to be a major cause of post-surgical patient morbidity due to the inability of surgeons to visualize nerves during surgery. Nerve injury during surgery can lead to chronic pain, numbness, permanent paralysis, incontinence, and erectile dysfunction. Current nerve identification strategies utilize non-quantifiable criteria such as anatomy, texture, color, and relationship to surrounding structures to distinguish nerves from non-nerve tissues. In instances of trauma, tumor invasion, or infection, nerve identification using the above criteria is especially challenging and often fails to prevent nerve damage. Using white light reflectance, which is the standard mode of illumination in operating rooms, the visual difference between small nerves and adjacent tissue can be imperceptible. There is an unmet need to improve the intraoperative visualization of nerves to preserve nerve function and minimize patient morbidity following surgery. There are currently no clinically approved agents that enhance nerve contrast during surgery. Alume Biosciences has advanced a first-in-class IV-administered agent for nerve visualization. This candidate, ALM-488, is a peptide dye conjugate that binds motor, sensory, and autonomic nerves in vivo and enables nerve visualization with high nerve to non-nerve contrast with no inherent toxicity. ALM-488 is currently being evaluated in a clinical trial in head and neck cancer surgery patients to establish safety and efficacy for clinical use. In this CRP proposal, Alume proposes to accelerate ALM-488 towards a final NDA-enabling Phase 3 trial and commercialization by 1) manufacturing drug substance and drug product stability lots to satisfy NDA requirements; 2) completing Phase 3-enabling toxicology studies; and 3) performing a U.S. market assessment to inform market positioning. Alume anticipates that clinical translation of ALM-488 will be transformative for the surgical field to prevent inadvertent injury during surgery and improve post-operative patient outcomes.

项目概要 手术目标的基础是保留关键神经的功能并最大限度地减少术后并发症 手术患者的发病率。不幸的是，手术期间无意的神经损伤仍然是一个主要原因 由于外科医生在手术过程中无法可视化神经，导致术后患者发病率的增加。神经损伤 手术期间可能导致慢性疼痛、麻木、永久性瘫痪、失禁和勃起功能障碍。 当前的神经识别策略利用不可量化的标准，例如解剖学、纹理、颜色和 与周围结构的关系，以区分神经和非神经组织。在外伤、肿瘤等情况下 使用上述标准进行侵入或感染、神经识别尤其具有挑战性，并且常常无法 防止神经损伤。采用白光反射，这是操作中的标准照明模式 在房间内，小神经和邻近组织之间的视觉差异可能难以察觉。有一个未满足的 需要改善神经的术中可视化，以保留神经功能并最大限度地减少患者 手术后的发病率。目前还没有临床批准的药物可以增强神经对比 外科手术。 Alume Biosciences 开发了一种一流的静脉注射神经可视化药物。这 候选药物 ALM-488 是一种肽染料缀合物，可在体内结合运动神经、感觉神经和自主神经， 使神经可视化具有高神经与非神经对比度，且无固有毒性。 ALM-488 当前为 正在头颈癌手术患者的临床试验中进行评估，以确定安全性和有效性 临床使用。在此 CRP 提案中，Alume 建议加速 ALM-488 进入最终 NDA 启用阶段 3 试验和商业化，1) 生产原料药和药品稳定性批次以满足新药申请 (NDA) 要求; 2) 完成第 3 阶段毒理学研究； 3) 进行美国市场评估 告知市场定位。 Alume 预计 ALM-488 的临床转化将带来变革 手术野，以防止手术期间的意外伤害并改善术后患者的预后。