Quince discovered a bone-targeting drug platform designed to precisely deliver small molecules, peptides, or large molecules directly to the site of bone disease with the goal of promoting more rapid healing with fewer off-target safety concerns. Our proprietary science enables the connection of bone-specific targeting molecules to approved and novel drugs, biologics, or radionuclides via a small biological linker molecule. The result is delivery of the proven therapeutic payload directly to the site of disease or injury. Quince’s lead compound NOV004 is an anabolic peptide engineered to precisely target and concentrate at a bone fracture site. Preclinical studies demonstrate that this results in rapid increases in bone density, strength, and healing directly at the site of injury.
Science
Precision Skeletal Therapeutics
Publications
Analysis of the Bone Fracture Targeting Properties of Osteotropic Ligands
Although more than 18 million fractures occur each year in the U.S., methods to promote fracture healing still rely primarily on fracture stabilization, with use of bone anabolic agents to accelerate fracture repair limited to rare occasions when the agent can be applied to the fracture surface. Because management of broken bones could be improved if bone anabolic agents could be continuously applied to a fracture over the entire course of the healing process, Quince undertook to identify strategies that would allow selective concentration of bone anabolic agents on a fracture surface following systemic administration.
Biodistribution of Fracture-targeted GSK3β Inhibitor-loaded Micelles for Improved Fracture Healing
Aspartic acid oligopeptides are negatively charged molecules at physiological pH that adsorb to hydroxyapatite, the mineral portion of bone. This general adsorption is the strongest where bone turnover is highest or where hydroxyapatite is freshly exposed. Importantly, both of these conditions are prominent at fracture sites. GSK3β inhibitors are potent anabolic agents that can promote tissue repair when concentrated in a damaged tissue. In this paper, we solve both problems by conjugating the hydrophobic GSK3β inhibitor to a hydrophilic aspartic acid octapeptide using a hydrolyzable bond, thereby generating a bone fracture-targeted water-soluble form of the drug. The resulting amphiphile is shown to assemble into micelles, extending its circulation time while maintaining its fracture-targeting abilities. For measurement of pharmacokinetics, an 125I was introduced at the location of the bromine in the GSK3β inhibitor to minimize any structural differences. Biodistribution studies demonstrate a greater than 4-fold increase in fracture accumulation over healthy bone.
Bone-Fracture-Targeted Dasatinib-Oligoaspartic Acid Conjugate Potently Accelerates Fracture Repair
Approximately 6.3 million bone fractures occur annually in the U.S., resulting in considerable morbidity, deterioration in quality of life, loss of productivity and wages, and sometimes death (e.g., hip fractures). Although anabolic and antiresorptive agents have been introduced for treatment of osteoporosis, no systemically administered drug has been developed to accelerate the fracture-healing process.
Lysine Gingipain Inhibition
Publications
Gingipains Identified in Alzheimer’s Disease Brains Differently Fragment APE Proteins
Alzheimer’s Disease-Like Neurodegeneration in Porphyromonas Gingivalis Infected Neurons with Persistent Expression of Active Gingipains
Treatment of Porphyromonas Gulae Infection and Downstream Pathology in the Aged Dog by Lysine-Gingipain Inhibitor COR388
Porphyromonas Gingivalis in Alzheimer’s Disease Brains: Evidence for Disease Causation and Treatment with Small-Molecule Inhibitors
Presentations
Top-line Results from the GAIN Trial: A Phase 2/3 Study of Atuzaginstat in Mild to Moderate Alzheimer’s Disease
Presented at AD/PD 2022
Top-line Results from the GAIN Trial: A Phase 2/3 Study of Atuzaginstat in Mild to Moderate Alzheimer’s Disease
Presented at CTAD 2021