CLT-1081

CLT-1081 is a small molecule fetal hemoglobin (HbF) inducer developed by Cellarity for the treatment of sickle cell disease (SCD) and beta-thalassemia. Identified using Cellarity's proprietary machine learning and single-cell RNA sequencing platform, the compound promotes the expression of HBG1 and HBG2 (gamma-globin) while concomitantly decreasing HBB (beta-globin) transcripts. Mechanistically, CLT-1081 has been shown to reduce the expression of BCL11A, a key transcriptional repressor of HbF, thereby mimicking the effects of genetic BCL11A knockdown. In preclinical in vitro assays using human CD34+ hematopoietic stem and progenitor cells, CLT-1081 demonstrated superior HbF induction compared to hydroxyurea and BCL11A CRISPR knockdown.