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.

项目摘要 手术目标的基础是临界神经的功能保存和最小化。 手术患者发病率。不幸的是，手术期间无意的神经损伤仍然是主要原因 手术后患者的发病率是由于外科医生在手术过程中可视化神经而导致的。神经损伤 手术期间会导致慢性疼痛，麻木，永久性麻痹，尿失禁和勃起功能障碍。 当前的神经识别策略利用了不可量化的标准，例如解剖学，质地，颜色和 与周围结构的关系，将神经与非神经组织区分开。在创伤的情况下 使用上述标准的入侵或感染的神经识别特别具有挑战性，并且通常不会 防止神经损伤。使用白光反射率，这是操作中照明的标准模式 房间，小神经和相邻组织之间的视觉差异是不可察觉的。有一个未满足的 需要改善神经的术中可视化以保持神经功能并最大程度地减少患者 手术后的发病率。目前尚无临床批准的药物可以增强神经对比 外科手术。 Alum Biosciences已推进了一种一流的IV类药物，用于神经可视化。这 候选者ALM-488是一种肽染料结合物，在体内结合运动，感觉和自主神经 使神经可视化具有高神经的可视化，从而没有固有的毒性对形成鲜明对比。 ALM-488目前 在头颈癌手术患者的临床试验中评估，以确立 临床用途。在此CRP提案中，Alume建议将ALM-488加速到最终的NDA阶段 3试验和商业化1）制造药物和药物产品稳定性可满足NDA 要求; 2）完成3阶段的毒理学研究； 3）进行美国市场评估 告知市场定位。 Alum预计ALM-488的临床翻译将对 外科手术领域，可预防手术过程中无意间损伤并改善术后患者的结局。