PanK activator for pantothenate kinase-associated neurodegeneration (PKAN) & organic acidemias

estimated prevalence



PKAN, organic acidemias and CASTOR

Genetic Source

PANK2 (pantothenate kinase)

Clinical Phase

Phase 1


small molecule

Coenzyme A (CoA) plays a crucial role in energy metabolism and is implicated in a large number of disorders, including ultra-rare diseases like pantothenate-kinase associated neurodegeneration, or PKAN, and organic acidemias (OAs), such as propionic acidemia (PA) and methylmalonic acidemia (MMA). BBP-671 is a novel small-molecule approach designed to modulate Coenzyme A (CoA) levels by leveraging recent research about the CoA synthetic pathway. While PanK2 is inactivated in PKAN patients, other isoforms known as PanK1 and PanK3 are still active. This leads to decreased PanK activity and impaired CoA synthesis. Conversely, in organic acidemias, build-up of metabolic intermediates can inhibit the activity of all three isoforms of PanK and impair CoA synthesis. Early experiments have shown that our small molecules can bind to all three PanK isoforms, prevent feedback inhibition, and thereby increase PanK activity and increase CoA synthesis. BridgeBio believes initial findings from its Phase 1 study of healthy volunteers demonstrate target engagement and proof of mechanism of BBP-671 provided by evidence that BBP-671 can cross the blood brain barrier. Based on these data, BridgeBio intends to move forward with the second part of the Phase 1 clinical study in patients with propionic acidemia and methylmalonic acidemia in the second half of 2022, and plans to initiate a pivotal Phase 2/3 study in PKAN in 2023.

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