Ayuvis Research Inc

Phase 1 Safety, Pharmacokinetic Study Followed by Phase 2A Proof-of-concept Study of AVR-48, a Small Molecule Macrophage Modulator to Prevent Bronchopulmonary Dysplasia in Neonates - 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. Preterm Neonates Exposed to Mechanical Ventilation Develop Moderate to Severe BPD That Affects Their Survival (10% Mortality) and Respiratory Function, 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 and the Lead Compound AVR-48 Which Activate Macrophage to an Intermediary Phenotype via TLR4/CD163 Signaling in Human Blood and Mouse Spleen Mononuclear Cells. in Both Mouse and Preterm Lamb BPD Models, the Lead Candidate AVR-48 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 and Survival. 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 Both Juvenile and Adult Rats, in Adult Dogs and Efficacy/safety Doses in Preterm 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 Submitting Ind Application to the Fda and Preparing for PHASE-1 and PHASE-2A Clinical Trials. Here We Propose Two Clinical Trial: 1) Evaluate the Safety and PK Parameters of AVR-48 in a Phase-i Sad and Mad Clinical Trial in Healthy Adult Volunteers and 2) Evaluate the Safety, PK and Efficacy of AVR-48 in an Exploratory PHASE-2A Clinical Trial in Pre-term Infants at Risk of Developing BPD. the Completion of Both Clinical Trials 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 2B/3 Clinical Trial Aimed to Assess the Efficacy of AVR-48 in Preterm Infants at Risk of Developing BPD Using Larger Sample Size. Ultimately, Our Clinical Pipeline Will Bring to Market a Prophylactic Treatment for BPD, Where There Is a Vastly Unmet Clinical Need.