LystaMab Immunotherapy to Inhibit Pericardial Adhesions

SUMMARY Despite significant advances in the surgical and medical management of congenital heart diseasecongenital cardiac anomalies remain a leading cause of death in the newborn periodMost severe forms of congenital heart disease require multiplestaged surgical interventionsA significant source of the heightened morbidity and mortality associated with these operations is the development of cardiac adhesionsAdhesions are fibrous bands of scar tissue that connect two areas of the body not normally connected and arise due to unavoidable surgical traumaAdhesions are exacerbated by excessive inflammation in the post operative periodDissection of adhesions significantly complicate reoperation by increasing operative and anesthetic time and amplifying the risks of perioperative bleeding and iatrogenic injury to the heart and great vesselswhich are all associated with worse outcomes and increased costCurrently there are no FDA approved products that reduce the incidence of the complications associated with reoperation in congenital heart surgeryWe recently discovered that the LYST protein underlies the development of dense adhesions after cardiothoracic surgery and hypothesize that rational inhibition of LYST will attenuate excessive inflammation following surgerythereby preventing adhesions formationA top priority for Lyst Therapeutics is to de risk the use of anti LYST therapy to inhibit the formation of adhesions after cardiac surgeryIn this proposalwe will investigate the use of celltargeting and local delivery of LystaMaba monoclonal anti LYST antibodyto optimize its safety and efficacy for preventing pericardial adhesionsThe successful development of anti LYST therapy to mitigate the development of cardiac adhesions would represent a novel form of rationally designed immunomodulation that could significantly improve outcomes in the pediatric congenital heart populationDevelopment of safe and effective strategy to prevent the formation of cardiac adhesions would significantly benefit children born with congenital heart defects requiring multiple surgeries and would overcome a major barrier to progress in the field of congenital heart surgery NARRATIVE Congenital cardiac anomalies are the most common birth defect and a leading cause of death in the newborn periodSevere forms of congenital cardiac anomalies require multiple reconstructive surgeriesUnfortunatelycomplications arising from the development of adhesions are a significant cause of postoperative morbidity and mortalityThe development and translation of a safe and effective strategy to prevent the development of cardiac adhesions without adversely effecting wound healing holds great promise for advancing the field of congenital heart surgery and improving outcomes of infants requiring repeat surgical intervention