Development of an oxygen delivery biotherapeutic for the preservation of myocardial function during pediatric cardiopulmonary bypass

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1. PROJECT SUMMARY/ABSTRACT 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’s lead therapeutic candidate, OMX, is designed to oxygenate hypoxic tissues. Supported by preliminary data from our Phase I/II Fast-Track SBIR and generated with our collaborators, neonatal and pediatric care intensivists Drs. Fineman and Maltepe at the University of California, San Francisco (UCSF), OMX has the potential to address a high unmet need of preserving myocardial function and decreasing morbidity associated with neonatal CPB surgery. The objective of this SBIR Phase IIB proposal is to advance 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 confirm that a more stable variant of OMX preserves myocardial and peripheral organ function after CPB and identify the optimal dose regimen for OMX efficacy (Aims 1 and 2), adapt and optimize a scalable production process suitable for transfer to a GMP (Good Manufacturing Practice) contract development and manufacturing organization (CDMO), including process and analytical development (Aim 3), and prepare and submit an IND for a Phase 1 clinical trial in neonates (Aim 4). 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.