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

项目摘要 手术目标的基础是关键神经的功能保留和最大限度地减少术后并发症。 手术患者发病率。不幸的是，手术过程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期间无法观察神经，导致术后患者发病率增加。神经损伤 在手术过程中可能导致慢性疼痛，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，诸如解剖结构、纹理、颜色和神经元的数目。 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， 入侵或感染，使用上述标准的神经识别是特别具有挑战性的，并且通常不能 防止神经损伤。采用白色光反射，这是标准的照明模式， 在室内，小神经和相邻组织之间的视觉差异可能是不可察觉的。存在未满足的 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 术后并发症。目前还没有临床上批准的药剂，可以增强神经对比度， 手术生物科学公司已经开发出一种用于神经可视化的一流IV给药制剂。这 候选物ALM-488是肽染料缀合物，其在体内结合运动、感觉和自主神经， 使神经可视化具有高神经与非神经对比度，无固有毒性。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 临床应用。在该CRP提案中，Alumme建议加速ALM-488进入最终NDA启用阶段 通过1）生产原料药和制剂稳定性批次以满足NDA要求，进行3次试验和商业化 要求; 2）完成3期毒理学研究; 3）进行美国市场评估 以告知市场定位。Alberme预计，ALM-488的临床转化将是变革性的， 手术区域，以防止手术过程中的意外伤害，并改善术后患者的结果。

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.