Science & Pipeline

Dasatinib, developed by BMS and marketed as Sprycel©, is FDA-approved for some children with CML (November 2017). This on-market tyrosine kinase inhibitor (TKI) demonstrates better toxicological parameters than Rapamycin. Palliative effects on HCM and cardiac function were observed at dosages far below those employed in cancer therapy. This implies that a regiment of low-dose Dasatinib may improve HCM and cardiac function in NS, and reverse HCM in NSML (80% of cases).

IGIA Pharmaceuticals is repurposing dasatinib (IG-100), an orally bioavailable inhibitor of multiple signaling kinases, for the treatment of Noonan Syndrome (NS) and Noonan Syndrome with Multiple Lentigines (NSML) with associated cardiac dysfunction in infants. Infants presenting with hypertrophic cardiomyopathy (HCM) during the first 6 months of life have a 69% risk of dying during the first year of life. Once HCM is established, and particularly after development of Congestive Heart Failure (CHF), it may be too late for effective pharmacological intervention.

This innovative early treatment is thought to effectively treat HCM; stopping and even reversing the thickening of the heart muscle that leads to significant morbidity and mortality. Low dose dasatinib has been shown to block aberrant cell signaling that is responsible for the development of HCM.

Previous clinical experience with dasatinib in pediatric patients with an oncology indication and strong pharmacological evidence for the prevention of cardiac failure in a mouse model of NS and NSML at doses 40 to 100-fold lower than currently used clinically in pediatric oncology patients supports clinical entry.

It is IGIA’s intention to evaluate IG-100 in a Phase 2a study, which will be the first time that low-dose dasatinib is administered to NS and NSML pediatric patients with diagnosed HCM. This study will establish initial safety and pharmacology in infants in order to identify dosing regimens for subsequent studies.