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

项目总结 外科手术的基本目标是保留关键神经的功能和最大限度地减少术后并发症 手术病人发病率。不幸的是，手术中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不能观察到神经，手术后病人的发病率。神经损伤 手术中会导致慢性疼痛、麻木、永久性瘫痪、大小便失禁和勃起功能障碍。 目前的神经识别策略使用不可量化的标准，如解剖学、质地、颜色和 与周围结构的关系，以区分神经和非神经组织。在创伤、肿瘤的情况下 使用上述标准进行神经侵袭或感染的鉴定尤其具有挑战性，而且常常失败。 防止神经损伤。使用白光反射率，这是操作中的标准照明模式 在房间里，微小神经和邻近组织之间的视觉差异可能无法察觉。有一个未满足的人 需要提高术中神经的可视化，以保护神经功能，减少患者 手术后的发病率。目前还没有临床批准的药物来增强神经对比剂 做手术。阿鲁姆生物科学公司已经开发出一种用于神经可视化的一流的IV给药制剂。这 候选药物ALM-488是一种多肽染料结合物，可在体内结合运动神经、感觉神经和自主神经 使神经可视化与高神经与非神经对比，没有固有的毒性。ALM-488目前 在头颈部癌症手术患者的临床试验中进行评估，以确定其安全性和有效性 临床应用。在这份CRP提案中，Alume建议将ALM-488加速到最终的NDA启用阶段 3)通过1)生产满足NDA要求的药材和药品稳定性批次进行试验和商业化 要求；2)完成阶段3--支持毒理学研究；3)执行美国市场评估 告知市场定位。Alume预计ALM-488的临床翻译将对 手术领域，以防止手术中的意外伤害，并改善术后患者的预后。

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.