Treating sickle cell disease with a pyruvate kinase r activating compound

A method of treating a patient diagnosed with a sickle cell disease (SCD), the method comprising orally administering to the patient in need thereof a total of 25 mg-1,500 mg per day of (S)-1-(5-((2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-7-yl)sulfonyl)-3,4,5,6-tetrahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-hydroxy-2-phenylpropan-1-one in a pharmaceutical composition.

A method of treating a patient diagnosed with a sickle cell disease (SCD), the method comprising orally administering to the patient in need thereof a total of 25 mg-1,500 mg of Compound 1 per day:

• in a pharmaceutical composition comprising Compound 1 and a pharmaceutically acceptable carrier.

A pharmaceutical composition comprising a PKR Activating Compound for use in a method of treating a patient diagnosed with sickle cell disease, comprising administering to the patient the PKR Activating Compound in an amount sufficient to reduce 2,3-DPG levels in the patient's red blood cells by at least 30% after 24 hours, wherein the PKR Activating Compound is a compound of Formula I:

• or a pharmaceutically acceptable salt thereof, having an AC50 value of less than 1 μM using the Luminescence Assay described in Example 2.