Phase I Amount
$1,670,941
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.
Public Health Relevance Statement: NARRATIVE There is an unmet need to improve the intraoperative visualization of nerves to preserve nerve function and minimize patient morbidity following surgery. Alume Biosciences has developed a novel peptide dye conjugate (ALM-488) that can be delivered intravenously before surgery as an agent to aid visualization of nerves during surgery. In this proposal, Alume proposes to complete critical studies that will accelerate ALM-488 towards a final NDA-enabling Phase 3 trial and commercialization.
Project Terms: Recovery; Erectile dysfunction; Toxicity Testing; Toxicity Tests; Funding; Malignant Head and Neck Neoplasm; head/neck cancer; malignant head and neck tumor; Head and Neck Cancer; Contracting Opportunities; Contracts; Companions; Intravenous; programs; Texture; sensory nerve; afferent nerve; Palsy; Plegia; paralysis; paralytic; Paralysed; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; Consult; Surgeon; Toxicities; Toxic effect; Structure; novel; Position; Positioning Attribute; cancer surgery; protein aminoacid sequence; peptide aminoacid sequence; peptide sequence; Image-Guided Surgery; intra-operative imaging; intraoperative imaging; surgical imaging; nerve agent; Molecular Interaction; Binding; Tumor Invasion; Tumor Cell Invasion; preventing; prevent; polypeptide; Preparedness; Readiness; Dose; Data; Head and Neck Surgery; Motor; in vivo; Funding Mechanisms; Patient-Focused Outcomes; Patient outcome; Patient-Centered Outcomes; Phase I/II Trial; Phase 1/2 trial; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Process; Development; developmental; Image; imaging; pre-clinical; preclinical; National Institute of Neurological Disorders and Stroke; NINDS; National Institute of Neurological Diseases and Stroke; clinical efficacy; Trauma; commercialization; multi-site trial; multisite trial; manufacturing scale-up; phase III trial; phase 3 trial; imaging agent; Formulation; clinical candidate; clinical translation; preservation; Visualization; Phase I/II Clinical Trial; Phase 1/2 Clinical Trial; nerve damage; Resource-limited setting; Low-resource area; Low-resource community; Low-resource environment; Low-resource region; Low-resource setting; Resource-constrained area; Resource-constrained community; Resource-constrained environment; Resource-constrained region; Resource-constrained setting; Resource-limited area; Resource-limited community; Resource-limited environment; Resource-limited region; Resource-poor area; Resource-poor community; Resource-poor environment; Resource-poor region; Resource-poor setting; Anatomy; Anatomic; Anatomic Sites; Anatomic structures; Anatomical Sciences; Animals; Award; Biological Sciences; Biologic Sciences; Bioscience; Life Sciences; Clinical Trials; Color; Complement; Complement Proteins; Canis familiaris; Canine Species; Dogs; Dogs Mammals; canine; domestic dog; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Dyes; Coloring Agents; Exhibits; Feedback; Goals; Grant; Human; Modern Man; Incontinence; Infection; Intravenous infusion procedures; IV Infusion; intravenous infusion; instrumentation; Interview; Laboratories; Lead; Pb element; heavy metal Pb; heavy metal lead; Light; Photoradiation; Lighting; Illumination; Medical Imaging; Methods; Morbidity - disease rate; Morbidity; NIH; National Institutes of Health; United States National Institutes of Health; Nerve; Nervous Tissue; Nerve Tissue; Loss of Sensation; Numbness; Operating Rooms; Patients; Peptides; Perception; Peripheral Nerves; Pharmacology; Post-Operative; Postoperative; Postoperative Period; Production; Common Rat Strains; Rat; Rats Mammals; Rattus; Risk; Rodentia; Rodents Mammals; Rodent; Safety; Plant Embryos; Plant Zygotes; seed; Seeds; Surgical Profession; surgery specialty; Surgical Specialties; Survey Instrument; Surveys; Testing; Tissues; Body Tissues; Toxicology; Work; Price; pricing; chronic pain; nerve injury; neural injury; Injury; injuries; method development; improved; Procedures; Site; Clinical; Phase; Series; autonomic nerve; Ensure; Visual
