Pulmonary hypertension is a major cause of morbidity and mortality in neonates in the setting of congenital diaphragmatic hernia, meconium aspiration, respiratory distress syndrome of prematurity, and Group B streptococcal pneumonia. Current treatment regimens to reduce pulmonary blood pressure are cumbersome, expensive and involve potential toxic exposure to health care personnel. Inotek is developing a novel soluble vasodilator, designated C-NO, which is selective for the pulmonary circulation when administered by aerosol. C-NO, which is a modified NO adduct of chitosan, is impermeant to the epithelial tight junction due to steric (MW=160kDa) and electrostatic (high negative change) considerations. NO, being lipophilic, is released from the parent compound and traverses the mucosal epithelium, thus acting as a vasodilator in the vascular smooth muscle of the pulmonary vascular bed. No which crosses further into the circulation is immediately inactivated by hemoglobin; thus, no systemic vasodilation occurs. The half-life of NO release from C-NO is 14 hours; thus, the duration of action after a single administration is suitable for twice daily dosing. Inotek now proposes to establish proof-of- principle utilizing a neonatal porcine model of chronic hypoxia- induced pulmonary hypertension. Upon confirmation that C-NO reverses pulmonary hypertension is this stringent and clinically relevant experimental model, Inotek intends to apply for Phase II SBIR funding to support formal toxicity studies and a Phase I FDA- regulated clinical trial.
The domestic market for a novel, effective therapy for pulmonary hypertension related to neonatal pulmonary hypertension is estimated at $150 million per annum, given an annual incidence of meconium aspiration, PPHN, and congenital diapharmatic herniai in the US population. Global markets are estimated at $450 million. Funding of SBIR Phase I and II will allow for market entry in 3.5 years.
