EPO and anemia: This may be because the failure to acclimatize with PT2385 treatment results in greater hypoxemia and a higher hypoxic drive on erythropoietin expression; indeed, 10 mg/kg PT2385 treatment over the equivalent time course (8 days) in normoxic male mice does result in a significant reduction in hematocrits (Supplemental Figure 4), in line with the anemia observed in patients treated with PT2385 (15).