Ayuvis Research Inc

PHASE-1 Healthy Adult Human Safety and Pharmacokinetic Study of AVR-48, a Small Molecule Macrophage Modulator to Prevent Bronchopulmonary Dysplasia in At-risk Pre-term Infants - Abstract Bronchopulmonary Dysplasia (BPD) Is the Most Common Chronic Respiratory Disease in Infants and Is a Devastating Condition That Disrupts the Developmental Program of the Lung Secondary to Preterm Birth. BPD Affects Neonates Exposed to Mechanical Ventilation and, to Date, There Are No Specific Drugs Available to Prevent or Treat This Life-threatening Condition. the Pathologic Hallmarks of BPD Are Hyperoxia-induced Pulmonary Inflammation, Increased Cell Death, Dysregulated Angiogenic Factors Culminating in Impaired Alveolarization, Dysregulated Vascularization of the Lung and Pulmonary Hypertension. Ayuvis Research, Inc, Is Developing a Novel Class of Low Molecular Weight Natural Oligosaccharide-derived Small Molecules Which Activate Macrophage to a Non-inflammatory Phenotype via TLR4/CD163 Signaling. in Both Mouse and Preterm Lamb BPD Models, the Lead Candidate AVR-48 Binds to Both TLR4 and CD163 Resulting in Selective Activation of the Target Cell to Block Inflammatory Mediators in Lung and Upregulation of Endogenous Vascularization Pathways. the Lead Compound AVR-48 Enhances Production of Certain Host Anti-inflammatory Molecule Such as IL-10 and Growth Factor Vegf With Vascularization Effects Remaining Local to Lungs, Improving Lung Vascularization/alveolization Leading to Improved Lung Function. AVR-48 Also Prevents the Development of BPD Associated Pulmonary Hypertension. Importantly, We Have Assessed the Maximum Tolerated Dose and Determined the Noael Dose of AVR-48 in Adult Rats and Dogs and Efficacy/safety Doses in Lamb BPD Model via Iv Dosing, Which We Will Use to Determine the Dose Ranges of Our Proposed Clinical Studies. We Have Demonstrated All These Above-mentioned Therapeutic Effects in Two BPD Models: Intraperitoneal Injection of AVR-48 Prevents Hyperoxia-induced BPD in a Neonatal Mice Pup Model at 10MG/KG Dose and Intravenous Injection in Invasive Mechanical Ventilator Induced BPD in Pre-term Lambs at 3.0 MG/KG Dose. in Order to Advance the Lead Candidate AVR-48, Ayuvis Is Proposing 1) the Manufacture of GMP Quality AVR-48 in Sufficient Quantities, Stability and Product Packing for Use in Our Clinical Trial, 2) Design the Clinical Protocol and Complete the Crucial Ind and Regulatory Preparation to Support Our Clinical Planning and 3) Perform a Phase 1 Sad/mad Clinical Trial Using Healthy Human Volunteers. the Completion of This Clinical Trial Will Provide the Essential Safety and Pharmacokinetic Data Required to Continue the Product Development of AVR-48. the Data Yielded Through the Completion of the Aims of This Project Will Lead the Way to the Development of Future Clinical Project, Including a Phase Ii Clinical Trial Aimed to Assess the Efficacy and Safety of AVR-48 in Preterm Patients at Risk of Developing BPD. Ultimately, Our Clinical Pipeline Will Bring to Market a Prophylactic Treatment for BPD, Where There Is a Vastly Unmet Clinical Need.