HPPD

HPPD (also known as HPP8668 or HPP-D) is an investigational, oral, first-in-class small molecule modulator of Nrf2 (Nuclear factor erythroid 2-related factor 2) and Bach1 (BTB and CNC homology 1) developed by vTv Therapeutics for the treatment of sickle cell disease (SCD). Mechanistically, HPPD acts as a Bach1 inhibitor, promoting the nuclear export of Bach1 and the translocation of Nrf2 to the nucleus. This dual action activates the expression of heme oxygenase 1 (HMOX1) and induces fetal hemoglobin (HbF) synthesis, which inhibits the polymerization of sickle hemoglobin (HbS). Preclinical studies in the Townes mouse model of sickle cell disease have demonstrated that HPPD is orally active, well tolerated, increases fetal hemoglobin, and reduces oxidative stress and red blood cell sickling. In October 2026, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to HPPD for the treatment of sickle cell disease.