Omniox is developing a unique oxygen delivery protein, OMX, as a treatment to preserve myocardial and peripheral organ function and significantly reduce morbidity after neonatal cardiopulmonary bypass (CPB) during surgical correction of congenital heart disease (CHD). Of the ~40,000 children born annually with CHD, ~10,000 require urgent surgery to repair heart defects1, 2. Up to 60% of infants who undergo CPB will experience post-operative complications that can result in peripheral organ dysfunction and long-term neurological deficits3-15. A critical driver of the myocardial and peripheral organ tissue damage is oxygen deprivation, or hypoxia3-15. However, there are no current or promising therapeutic approaches that target hypoxia during CPB surgery to stem or alleviate its damaging downstream effects. Omniox' lead therapeutic candidate, OMX, is designed to restore physiologic oxygen levels in hypoxic tissues. Thus, OMX has the potential to address a high unmet need of preserving myocardial function and improving morbidity associated with neonatal CPB surgery. Together with our collaborators, neonatal and pediatric care intensivists Drs. Fineman and Maltepe at the University of California, San Francisco (UCSF), we have demonstrated that OMX attenuates hypoxia- induced myocardial dysfunction in lambs. Furthermore, our preliminary data demonstrate that OMX: 1) restores physiologic oxygen levels specifically in oxygen-deprived tissues; 2) prevents hypoxia-induced cell death after brain ischemia; 3) is stable, safe, and well tolerated in multiple species; and 4) does not increase free radical production or scavenge nitric oxide. The objective of this Fast-Track SBIR Phase I/II proposal is to complete preclinical development of OMX as a novel biologic for the treatment of neonates undergoing CPB by demonstrating its therapeutic utility in oxygenating hypoxic tissue and preserving myocardial and peripheral organ function. We propose to 1) demonstrate OMX preserves myocardial and peripheral organ function during and after CPB in intact newborn lambs (Phase I), then 2) demonstrate OMX' efficacy in a clinically relevant neonatal lamb CHD model undergoing CPB (Phase II). These data will inform an IND application for a neonatal and pediatric clinical trial. Pending good safety and efficacy data in neonatal and pediatric patients undergoing CPB, Omniox plans to expand OMX use to other pediatric indications in which hypoxia drives disease pathology such as persistent pulmonary hypertension in neonates16, 17 and birth asphyxia18-22. Omniox, Inc. ©2016 Confidential Not for Distribution
Public Health Relevance Statement: PROJECT NARRATIVE Omniox is developing a novel oxygen carrier protein, OMX, to preserve heart function during open-heart surgery that requires cardiopulmonary bypass (CPB). Approximately 10,000 children in the US are born every year with congenital heart defects that necessitate urgent open-heart surgery with CPB to correct the defect. However, while the patient is on CPB, the heart and other major organs are exposed to a lack of oxygen (hypoxia). The hypoxic environment drives a vicious cycle in which the heart tissue is damaged, negatively altering blood flow and reducing oxygen levels, and depriving all organ systems even further of oxygen. This cycle can result in a spectrum of post-operative complications, including reduced heart function, long-term neurological deficits, and kidney failure. This Fast-Track SBIR Phase I/II project will focus on testing OMX during bypass surgery in clinically relevant large animal model of congenital heart defect to validate OMX as a therapeutic to preserve heart and peripheral organ function in neonates requiring corrective heart surgery. CONFIDENTIAL ©2016 Omniox, Inc. For review purposes only.
Project Terms: Address; analytical method; Animal Model; Attenuated; Biochemical; Biological Preservation; Biological Response Modifier Therapy; Birth; Blood flow; Blood Vessels; body system; Brain Ischemia; Bypass; California; Cardiac; Cardiac Surgery procedures; Cardioplegic Solutions; Cardiopulmonary; Cardiopulmonary Bypass; Caring; Carrier Proteins; Cell Death; Cerebrum; CHD1 gene; Child; Childhood; Clinical; Clinical Trials; clinically relevant; Closure by clamp; Congenital Heart Defects; congenital heart disorder; Consent Forms; Data; Defect; deprivation; design; Development; Disease; Disease model; Dose; efficacy testing; Endothelin; Environment; experience; Formulation; Free Radicals; Functional disorder; Heart; heart function; hemodynamics; Hepatic; High Pressure Liquid Chromatography; hypoperfusion; Hypoxia; improved; Infant; inhaled nitric oxide; Injury; Kidney; Kidney Failure; Lead; Left; Liver; Lung; manufacturing process; Measures; Medical; method development; Modeling; Morbidity - disease rate; Myocardial; Myocardial dysfunction; Myocardial Ischemia; Neonatal; neonatal patient; neonate; Neurologic; Neurologic Deficit; Newborn Infant; Nitric Oxide; novel; Operative Surgical Procedures; Organ; Oxygen; Pamphlets; Pathology; Patients; pediatric patients; Performance; Peripheral; persistent pulmonary hypertension; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Physiological; Postoperative Period; preclinical development; preclinical study; Preparation; prevent; Process; Production; protective effect; protein degradation; Proteins; repaired; Research Personnel; response; Safety; San Francisco; Shunt Device; Small Business Innovation Research Grant; stem; Surgeon; Techniques; Testing; Therapeutic; therapeutic candidate; time use; Tissues; translational approach; Treatment Efficacy; Universities
