Use of the pyruvate kinase activator tebapivat in the treatment of renal fibrosis and other renal diseases

Abstract

Provided herein is the use of pyruvate kinase (PK) activators or pharmaceutically acceptable salts or compositions thereof, for treating renal fibrosis and other renal diseases.

Description

Attorney Docket No.: AGS-132WOUSE OF A PYRUVATE KINASE ACTIVATOR IN THE TREATMENT OF RENAE FIBROSIS AND OTHER RENAL DISEASESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of, and priority to, U.S. Provisional Application No. 63 / 712,869, filed on October 28, 2024, the contents of which are hereby incorporated by reference herein in their entirety for all purposes.FIELD OF THE DISCLOSURE

[0002] The disclosure relates generally to use of a pyruvate kinase (PK) activator in the treatment of renal fibrosis and other renal diseases.BACKGROUND

[0003] Kidney disease is common in patients with sickle cell disease (SCD) and portends a poor prognosis, accounting for approximately 10% of mortality. Sickle cell nephropathy (SCN) manifests in various renal syndromes and diseases, mainly due to an underlying vasculopathy. The mechanisms underlying SCD contribute to kidney problems, often leading to albuminuria, deteriorating glomerular filtration rate (GFR), fibrosis, and progressing to chronic kidney disease (CKD) and end-stage renal disease (ESRD), which are significant predictors of mortality in this population. In patients with SCN, improving anemia and reducing sickling and hemolysis through the activation of pyruvate kinase R (PKR) may help lessen kidney damage by improving perfusion, reducing sickling-related ischemia, and minimizing the direct toxicity of free heme to the kidneys. Additionally, pyruvate kinase muscle isoenzyme 2 (PKM2) activation has been reported to provide renal protective effects in diabetic kidney disease and acute kidney injury. Accordingly, PK activators have the potential to improve and / or help maintain kidney health in patients suffering from a disease that adversely affects kidney health and function. The present disclosure investigates the effect of PK activators for the treatment and / or improvement of renal fibrosis and associated diseases.SUMMARY OF THE DISCLOSURE

[0004] The disclosure is based, in part, on the use of a pyruvate kinase (PK) activator or a pharmaceutically acceptable salt or composition thereof in the treatment of renal fibrosis and other renal diseases. Among other things, the present disclosure sets forth the surprising discovery that small molecule allosteric-activators of PKR and PKM2 (such as mitapivat andAttorney Docket No.: AGS-132WO tebapivat) have promise as a treatment (or intervention) for various kidney diseases that are characterized by inflammation and / or fibrosis.

[0005] In some embodiments, the present disclosure provides a method of treating chronic kidney disease (CKD) in a subject with sickle cell disease, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0006] In some embodiments, the present disclosure provides a method of treating chronic kidney disease (CKD) in a subject with sickle cell disease, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0007] In some embodiments, the present disclosure provides a method of treating renal fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0008] In some embodiments, the present disclosure provides a method of treating renal fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0009] In some embodiments, the present disclosure provides a method of preserving renal function in a subject with sickle cell disease, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0010] In some embodiments, the present disclosure provides a method of preserving renal function in a subject with sickle cell disease, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0011] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0012] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0013] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a dose of aboutAttorney Docket No.: AGS-132WO1 mg to about 30 mg of tebapivat, once daily (QD) and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure.

[0014] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD) and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure.

[0015] In some embodiments, the present disclosure provides a method of treating kidney fibrosis in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0016] In some embodiments, the present disclosure provides a method of treating kidney fibrosis in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0017] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD) and wherein the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

[0018] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD) and wherein the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

[0019] In some embodiments, the present disclosure provides a method of treating kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, or hypertension in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0020] In some embodiments, the present disclosure provides a method of treating kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, or hypertension in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).Attorney Docket No.: AGS-132WO

[0021] In some embodiments, the present disclosure provides a method of treating diabetic kidney disease in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0022] In some embodiments, the present disclosure provides a method of treating diabetic kidney disease in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0023] In some embodiments, the present disclosure provides a method of treating acute kidney injury in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0024] In some embodiments, the present disclosure provides a method of treating acute kidney injury in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0025] In some embodiments, the present disclosure provides a method for improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0026] In some embodiments, the present disclosure provides a method for improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0027] In some embodiments, the present disclosure provides a method of treating chronic kidney disease (CKD) in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0028] In some embodiments, the present disclosure provides a method of treating chronic kidney disease (CKD) in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0029] In some embodiments, the present disclosure provides a method of reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).Attorney Docket No.: AGS-132WO

[0030] In some embodiments, the present disclosure provides a method of reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD) .

[0031] In some embodiments, the present disclosure provides a method of reducing kidney fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0032] In some embodiments, the present disclosure provides a method of reducing kidney fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0033] In some embodiments, the present disclosure provides a method of treating kidney damage in a subject, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia.

[0034] In some embodiments, the present disclosure provides a method of treating kidney damage in a subject, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension, or thalassemia.

[0035] In some embodiments, the present disclosure provides a method of reducing collagen formation in the kidneys of a subject, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension, or thalassemia.

[0036] In some embodiments, the present disclosure provides a method of reducing collagen formation in the kidneys of a subject, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension, or thalassemia.

[0037] In some embodiments, the present disclosure provides a method of reducing inflammation in the kidneys of a subject, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension, or thalassemia.Attorney Docket No.: AGS-132WO

[0038] In some embodiments, the present disclosure provides a method of reducing inflammation in the kidneys of a subject, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension, or thalassemia.

[0039] In some embodiments, the present disclosure provides a method of treating sickle cell nephropathy in a subject, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0040] In some embodiments, the present disclosure provides a method of treating sickle cell nephropathy in a subject, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0041] In some embodiments, the present disclosure provides a method of treating diabetic nephropathy in a subject, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0042] In some embodiments, the present disclosure provides a method of treating diabetic nephropathy in a subject, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0043] In some embodiments, the present disclosure provides a method of treating nephropathy in a subject with sickle cell disease, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0044] In some embodiments, the present disclosure provides a method of treating nephropathy in a subject with sickle cell disease, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0045] In one aspect, the present disclosure provides a method of treating chronic kidney disease (CKD) in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. InAttorney Docket No.: AGS-132WO some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0046] In some embodiments, the present disclosure provides a method of treating chronic kidney disease (CKD) in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments tebapivat is administered as a free base or a composition thereof. In some embodiments tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0047] In some embodiments, the present disclosure provides a method of treating chronic kidney disease (CKD) in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or aAttorney Docket No.: AGS-132WO composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0048] In another aspect, the present disclosure provides a method of treating renal fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0049] In some embodiments, the present disclosure provides a method of treating renal fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered asAttorney Docket No.: AGS-132WO tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0050] In some embodiments, the present disclosure provides a method of treating renal fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0051] In yet another aspect, the present disclosure provides a method of preserving renal function in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a compositionAttorney Docket No.: AGS-132WO thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0052] In some embodiments, the present disclosure provides a method of preserving renal function in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0053] In some embodiments, the present disclosure provides a method of preserving renal function in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0054] In yet another aspect, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivatAttorney Docket No.: AGS-132WO administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof. In some embodiments, the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

[0055] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator isAttorney Docket No.: AGS-132WO tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0056] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof and wherein the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0057] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat isAttorney Docket No.: AGS-132WO administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally. In some embodiments, the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

[0058] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0059] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof and wherein the nephritis isAttorney Docket No.: AGS-132WO selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0060] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally. In some embodiments, the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

[0061] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered mitapivat sulfate or a compositionAttorney Docket No.: AGS-132WO thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0062] In some embodiments, the present disclosure provides a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof and wherein the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0063] In yet another aspect, the present disclosure provides a method of treating kidney fibrosis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a compositionAttorney Docket No.: AGS-132WO thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0064] In some embodiments, the present disclosure provides a method of treating kidney fibrosis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0065] In some embodiments, the present disclosure provides a method of treating kidney fibrosis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0066] In yet another aspect, the present disclosure provides a method of treating kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, or hypertension in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as aAttorney Docket No.: AGS-132WO free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0067] In some embodiments, the present disclosure provides a method of treating kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, or hypertension in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0068] In some embodiments, the present disclosure provides a method of treating kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, orAttorney Docket No.: AGS-132WO hypertension in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0069] In yet another aspect, the present disclosure provides a method of treating diabetic kidney disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0070] In some embodiments, the present disclosure provides a method of treating diabetic kidney disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivatAttorney Docket No.: AGS-132WO is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0071] In some embodiments, the present disclosure provides a method of treating diabetic kidney disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0072] In yet another aspect, the present disclosure provides a method of treating acute kidney injury in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or aAttorney Docket No.: AGS-132WO composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0073] In some embodiments, the present disclosure provides a method of treating acute kidney injury in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0074] In some embodiments, the present disclosure provides a method of treating acute kidney injury in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.Attorney Docket No.: AGS-132WO

[0075] In yet another aspect, the present disclosure provides a method for improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0076] In some embodiments, the present disclosure provides a method for improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administeredAttorney Docket No.: AGS-132WO as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0077] In some embodiments, the present disclosure provides a method for improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0078] In yet another aspect, the present disclosure provides a method of treating chronic kidney disease (CKD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a compositionAttorney Docket No.: AGS-132WO thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0079] In some embodiments, the present disclosure provides a method of treating chronic kidney disease (CKD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0080] In some embodiments, the present disclosure provides a method of treating chronic kidney disease (CKD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0081] In yet another aspect, the present disclosure provides a method of reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceuticallyAttorney Docket No.: AGS-132WO acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0082] In some embodiments, the present disclosure provides a method of reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0083] In some embodiments, the present disclosure provides a method of reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceuticallyAttorney Docket No.: AGS-132WO acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0084] In yet another aspect, the present disclosure provides a method of reducing kidney fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0085] In some embodiments, the present disclosure provides a method of reducing kidney fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered asAttorney Docket No.: AGS-132WO tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0086] In some embodiments, the present disclosure provides a method of reducing kidney fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0087] In yet another aspect, the present disclosure provides a method of treating kidney damage in a subject, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides a method of treating kidney damage in a subject, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered asAttorney Docket No.: AGS-132WO tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0088] In some embodiments, the present disclosure provides a method of treating kidney damage in a subject, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides a method of treating kidney damage in a subject, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0089] In some embodiments, the present disclosure provides a method of treating kidney damage in a subject, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides a method of treating kidney damage in a subject, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable saltAttorney Docket No.: AGS-132WO or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0090] In yet another aspect, the present disclosure provides a method of reducing collagen formation in the kidneys of a subject, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides a method of reducing collagen formation in the kidneys of a subject, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0091] In some embodiments, the present disclosure provides a method of reducing collagen formation in the kidneys of a subject, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides a method of reducing collagen formation in the kidneys of a subject, the method comprising administering to the subject a therapeutically effective amountAttorney Docket No.: AGS-132WO of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0092] In some embodiments, the present disclosure provides a method of reducing collagen formation in the kidneys of a subject, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides a method of reducing collagen formation in the kidneys of a subject, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0093] In yet another aspect, the present disclosure provides a method of reducing inflammation in the kidneys of a subject, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides a method of reducing inflammation in the kidneys of a subject, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administeredAttorney Docket No.: AGS-132WO as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0094] In some embodiments, the present disclosure provides a method of reducing inflammation in the kidneys of a subject, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides a method of reducing inflammation in the kidneys of a subject, the method comprising administering to the subj ect a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a compositionAttorney Docket No.: AGS-132WO thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0095] In some embodiments, the present disclosure provides a method of reducing inflammation in the kidneys of a subject, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides a method of reducing inflammation in the kidneys of a subject, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0096] In some embodiments, the present disclosure provides a method of treating sickle cell nephropathy in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In someAttorney Docket No.: AGS-132WO embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0097] In some embodiments, the present disclosure provides a method of treating sickle cell nephropathy in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0098] In some embodiments, the present disclosure provides a method of treating sickle cell nephropathy in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0099] In some embodiments, the present disclosure provides a method of treating diabetic nephropathy in a subject with diabetes, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In someAttorney Docket No.: AGS-132WO embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0100] In some embodiments, the present disclosure provides a method of treating diabetic nephropathy in a subject with diabetes, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0101] In some embodiments, the present disclosure provides a method of treating diabetic nephropathy in a subject with diabetes, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.Attorney Docket No.: AGS-132WO

[0102] In some embodiments, the present disclosure provides a method of treating nephropathy in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of a pyruvate kinase (PK) activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0103] In some embodiments, the present disclosure provides a method of treating nephropathy in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of tebapivat, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.Attorney Docket No.: AGS-132WO

[0104] In some embodiments, the present disclosure provides a method of treating nephropathy in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of mitapivat, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0105] In some embodiments, the present disclosure provides tebapivat for use in the treatment of chronic kidney disease (CKD) in a subject with sickle cell disease, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0106] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of chronic kidney disease (CKD) in a subject with sickle cell disease, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0107] In some embodiments, the present disclosure provides tebapivat for use in the treatment of renal fibrosis in a subject with sickle cell disease, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0108] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of renal fibrosis in a subject with sickle cell disease, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0109] In some embodiments, the present disclosure provides tebapivat for use in preserving renal function in a subject with sickle cell disease, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0110] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in preserving renal function in a subject with sickle cell disease, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).Attorney Docket No.: AGS-132WO

[0111] In some embodiments, the present disclosure provides tebapivat for use in the treatment of nephritis in a subject in need thereof, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0112] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of nephritis in a subject in need thereof, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0113] In some embodiments, the present disclosure provides tebapivat for use in the treatment of nephritis in a subject in need thereof, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD), and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure.

[0114] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of nephritis in a subject in need thereof, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure.

[0115] In some embodiments, the present disclosure provides tebapivat for use in the treatment of kidney fibrosis in a subject in need thereof, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0116] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of kidney fibrosis in a subject in need thereof, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0117] In some embodiments, the present disclosure provides tebapivat for use in the treatment of nephritis in a subject in need thereof, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD), and wherein the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

[0118] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of nephritis in a subject in need thereof, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that isAttorney Docket No.: AGS-132WO equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

[0119] In some embodiments, the present disclosure provides tebapivat for use in the treatment of kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, or hypertension in a subject in need thereof, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0120] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, or hypertension in a subject in need thereof, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0121] In some embodiments, the present disclosure provides tebapivat for use in the treatment of diabetic kidney disease in a subject in need thereof, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0122] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of diabetic kidney disease in a subject in need thereof, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD) .

[0123] In some embodiments, the present disclosure provides tebapivat for use in the treatment of acute kidney injury in a subject in need thereof, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0124] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of acute kidney injury in a subject in need thereof, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0125] In some embodiments, the present disclosure provides tebapivat for use in improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).Attorney Docket No.: AGS-132WO

[0126] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0127] In some embodiments, the present disclosure provides tebapivat for use in the treatment of chronic kidney disease (CKD) in a subject in need thereof, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0128] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of chronic kidney disease (CKD) in a subject in need thereof, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0129] In some embodiments, the present disclosure provides tebapivat for use in reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0130] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0131] In some embodiments, the present disclosure provides tebapivat for use in reducing kidney fibrosis in a subject with sickle cell disease, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0132] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in reducing kidney fibrosis in a subject with sickle cell disease, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0133] In some embodiments, the present disclosure provides tebapivat for use in the treatment of kidney damage in a subject, wherein tebapivat is administered to the subject in aAttorney Docket No.: AGS-132WO dose of about 1 mg to about 30 mg, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia.

[0134] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of kidney damage in a subject, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia.

[0135] In some embodiments, the present disclosure provides tebapivat for use in reducing collagen formation in the kidneys of a subject, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia.

[0136] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in reducing collagen formation in the kidneys of a subject, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia.

[0137] In some embodiments, the present disclosure provides tebapivat for use in reducing inflammation in the kidneys of a subject, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia.

[0138] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in reducing inflammation in the kidneys of a subject, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia.

[0139] In some embodiments, the present disclosure provides tebapivat for use in the treatment of sickle cell nephropathy in a subject, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0140] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of sickle cell nephropathy in a subject, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).Attorney Docket No.: AGS-132WO

[0141] In some embodiments, the present disclosure provides tebapivat for use in the treatment of diabetic nephropathy in a subject, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0142] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of diabetic nephropathy in a subject, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0143] In some embodiments, the present disclosure provides tebapivat for use in the treatment of nephropathy in a subject with sickle cell disease, wherein tebapivat is administered to the subject in a dose of about 1 mg to about 30 mg, once daily (QD).

[0144] In some embodiments, the present disclosure provides a pharmaceutically acceptable salt of tebapivat for use in the treatment of nephropathy in a subject with sickle cell disease, wherein the pharmaceutically acceptable salt of tebapivat is administered in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

[0145] In one aspect, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of chronic kidney disease (CKD) in a subject with sickle cell disease, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as aAttorney Docket No.: AGS-132WO pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0146] In some embodiments, the present disclosure provides tebapivat for use in the treatment of chronic kidney disease (CKD) in a subject with sickle cell disease, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments tebapivat is administered as a free base or a composition thereof. In some embodiments tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0147] In some embodiments, the present disclosure provides mitapivat for use in the treatment of chronic kidney disease (CKD) in a subject with sickle cell disease, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0148] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of renal fibrosis in a subject with sickle cell disease, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, theAttorney Docket No.: AGS-132WOPK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0149] In some embodiments, the present disclosure provides tebapivat for use in the treatment of renal fibrosis in a subject with sickle cell disease, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0150] In some embodiments, the present disclosure provides mitapivat for use in the treatment of renal fibrosis in a subject with sickle cell disease, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0151] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in preserving renal function in a subject with sickle cell disease, wherein theAttorney Docket No.: AGS-132WOPK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0152] In some embodiments, the present disclosure provides tebapivat for use in preserving renal function in a subject with sickle cell disease, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0153] In some embodiments, the present disclosure provides mitapivat for use in preserving renal function in a subject with sickle cell disease, wherein mitapivat is administeredAttorney Docket No.: AGS-132WO as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0154] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of nephritis in a subject in need thereof, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof. In some embodiments, the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

[0155] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of nephritis in a subject in need thereof, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, the PK activator is administeredAttorney Docket No.: AGS-132WO orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0156] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of nephritis in a subject in need thereof, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof and wherein the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator isAttorney Docket No.: AGS-132WO mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0157] In some embodiments, the present disclosure provides tebapivat for use in the treatment of nephritis in a subject in need thereof, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally. In some embodiments, the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

[0158] In some embodiments, the present disclosure provides tebapivat for use in the treatment of nephritis in a subject in need thereof, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments,Attorney Docket No.: AGS-132WO tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0159] In some embodiments, the present disclosure provides tebapivat for use in the treatment of nephritis in a subject in need thereof, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof and wherein the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0160] In some embodiments, the present disclosure provides mitapivat for use in the treatment of nephritis in a subject in need thereof, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally. In some embodiments, the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

[0161] In some embodiments, the present disclosure provides mitapivat for use in the treatment of nephritis in a subject in need thereof, wherein mitapivat is administered as a freeAttorney Docket No.: AGS-132WO base or a pharmaceutically acceptable salt or a composition thereof and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0162] In some embodiments, the present disclosure provides mitapivat for use in the treatment of nephritis in a subject in need thereof, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof and wherein the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0163] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of kidney fibrosis in a subject in need thereof, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator isAttorney Docket No.: AGS-132WO mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0164] In some embodiments, the present disclosure provides tebapivat for use in the treatment of kidney fibrosis in a subject in need thereof, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0165] In some embodiments, the present disclosure provides mitapivat for use in the treatment of kidney fibrosis in a subject in need thereof, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0166] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, or hypertension in a subject in need thereof, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activatorAttorney Docket No.: AGS-132WO is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0167] In some embodiments, the present disclosure provides tebapivat for use in the treatment of kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, or hypertension in a subject in need thereof, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0168] In some embodiments, the present disclosure provides mitapivat for use in the treatment of kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, or hypertension in a subject in need thereof, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments,Attorney Docket No.: AGS-132WO mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0169] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of diabetic kidney disease in a subject in need thereof, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0170] In some embodiments, the present disclosure provides tebapivat for use in the treatment of diabetic kidney disease in a subject in need thereof, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administeredAttorney Docket No.: AGS-132WO as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0171] In some embodiments, the present disclosure provides mitapivat for use in the treatment of diabetic kidney disease in a subject in need thereof, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0172] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of acute kidney injury in a subject in need thereof, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a compositionAttorney Docket No.: AGS-132WO thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0173] In some embodiments, the present disclosure provides tebapivat for use in the treatment of acute kidney injury in a subject in need thereof, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0174] In some embodiments, the present disclosure provides mitapivat for use in the treatment of acute kidney injury in a subject in need thereof, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0175] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, orAttorney Docket No.: AGS-132WO hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0176] In some embodiments, the present disclosure provides tebapivat for use in improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0177] In some embodiments, the present disclosure provides mitapivat for use in improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. InAttorney Docket No.: AGS-132WO some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0178] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of chronic kidney disease (CKD) in a subject in need thereof, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0179] In some embodiments, the present disclosure provides tebapivat for use in the treatment of chronic kidney disease (CKD) in a subject in need thereof, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments,Attorney Docket No.: AGS-132WO tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0180] In some embodiments, the present disclosure provides mitapivat for use in the treatment of chronic kidney disease (CKD) in a subject in need thereof, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0181] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.Attorney Docket No.: AGS-132WO

[0182] In some embodiments, the present disclosure provides tebapivat for use in reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0183] In some embodiments, the present disclosure provides mitapivat for use in reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0184] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in reducing kidney fibrosis in a subject with sickle cell disease, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In someAttorney Docket No.: AGS-132WO embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0185] In some embodiments, the present disclosure provides tebapivat for use in reducing kidney fibrosis in a subject with sickle cell disease, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0186] In some embodiments, the present disclosure provides mitapivat for use in reducing kidney fibrosis in a subject with sickle cell disease, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0187] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of kidney damage in a subject, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. InAttorney Docket No.: AGS-132WO some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of kidney damage in a subject, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0188] In some embodiments, the present disclosure provides tebapivat for use in the treatment of kidney damage in a subject, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides tebapivat for use in the treatment of kidney damage in a subject, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof.Attorney Docket No.: AGS-132WOIn some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0189] In some embodiments, the present disclosure provides mitapivat for use in the treatment of kidney damage in a subject, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides mitapivat for use in the treatment of kidney damage in a subject, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0190] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in reducing collagen formation in the kidneys of a subject, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in reducing collagen formation in the kidneys of a subject, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator isAttorney Docket No.: AGS-132WO mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0191] In some embodiments, the present disclosure provides tebapivat for use in reducing collagen formation in the kidneys of a subject, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides tebapivat for use in reducing collagen formation in the kidneys of a subject, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0192] In some embodiments, the present disclosure provides mitapivat for use in reducing collagen formation in the kidneys of a subject, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides mitapivat for use in reducing collagen formation in the kidneys of a subject, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.Attorney Docket No.: AGS-132WO

[0193] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in reducing inflammation in the kidneys of a subject, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in reducing inflammation in the kidneys of a subject, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, the PK activator is mitapivat. In some embodiments, the PK activator is mitapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is mitapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is mitapivat administered as mitapivat sulfate or a composition thereof.

[0194] In some embodiments, the present disclosure provides tebapivat for use in reducing inflammation in the kidneys of a subject, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides tebapivat for use in reducing inflammation in the kidneys of a subject, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In someAttorney Docket No.: AGS-132WO embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0195] In some embodiments, the present disclosure provides mitapivat for use in reducing inflammation in the kidneys of a subject, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the present disclosure provides mitapivat for use in reducing inflammation in the kidneys of a subject, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof, and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension or thalassemia. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0196] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of sickle cell nephropathy in a subject with sickle cell disease, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.Attorney Docket No.: AGS-132WO

[0197] In some embodiments, the present disclosure provides tebapivat for use in the treatment of sickle cell nephropathy in a subject with sickle cell disease, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0198] In some embodiments, the present disclosure provides mitapivat for use in the treatment of sickle cell nephropathy in a subject with sickle cell disease, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0199] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of diabetic nephropathy in a subject with diabetes, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or aAttorney Docket No.: AGS-132WO composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0200] In some embodiments, the present disclosure provides tebapivat for use in the treatment of diabetic nephropathy in a subject with diabetes, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0201] In some embodiments, the present disclosure provides mitapivat for use in the treatment of diabetic nephropathy in a subject with diabetes, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0202] In some embodiments, the present disclosure provides a pyruvate kinase (PK) activator for use in the treatment of nephropathy in a subject with sickle cell disease, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the PK activator is administered orally. In some embodiments, the PK activator is tebapivat. In some embodiments, the PK activator is tebapivat administered as a free base or a composition thereof. In some embodiments, the PK activator is tebapivat administered as a pharmaceutically acceptable salt or a composition thereof. InAttorney Docket No.: AGS-132WO some embodiments, the PK activator is tebapivat administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat sulfate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat phosphate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat L-tartrate or a composition thereof. In some embodiments, the PK activator is tebapivat administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0203] In some embodiments, the present disclosure provides tebapivat for use in the treatment of nephropathy in a subject with sickle cell disease, wherein tebapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a free base or a composition thereof. In some embodiments, tebapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, tebapivat is administered as a sulfate, phosphate, tartrate, or hydrochloride salt or a composition thereof. In some embodiments, tebapivat is administered as tebapivat sulfate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat phosphate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat DL-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat L-tartrate or a composition thereof. In some embodiments, tebapivat is administered as tebapivat hydrochloride or a composition thereof. In some embodiments, tebapivat or the pharmaceutically acceptable salt of tebapivat and compositions thereof are administered orally.

[0204] In some embodiments, the present disclosure provides mitapivat for use in the treatment of nephropathy in a subject with sickle cell disease, wherein mitapivat is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as a free base or a composition thereof. In some embodiments, mitapivat is administered as a pharmaceutically acceptable salt or a composition thereof. In some embodiments, mitapivat is administered as mitapivat sulfate or a composition thereof. In some embodiments, mitapivat or the pharmaceutically acceptable salt of mitapivat and compositions thereof are administered orally.

[0205] In some embodiments, in a method described in the present disclosure (e.g., any method described herein) and / or for a provided use described in the present disclosure (e.g.,Attorney Docket No.: AGS-132WO any use described herein), a subject is administered a dose of tebapivat that is about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 2.5 mg, about 5 mg, or about 7.5 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 1 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 1.5 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 2 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 2.5 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 3 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 3.5 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 4 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 4.5 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 5 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 5.5 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 6 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 6.5 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 7 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 7.5 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 8 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 8.5 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 9 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 9.5 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 10 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 12 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 14 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 15 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 16 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 18 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 20 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 22 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 24 mg, once daily (QD). In some embodiments, a subject isAttorney Docket No.: AGS-132WO administered a dose of tebapivat that is about 25 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 26 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 28 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 30 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 1 mg to about 10 mg, about 1 mg to about 4 mg, about 2 mg to about 5 mg, about 3 mg to about 6 mg, about 4 mg to about 7 mg, about 5 mg to about 8 mg, about 6 mg to about 9 mg, about 7 mg to about 10 mg, about 9 mg to about 15 mg, about 12 mg to about 18 mg, about 15 mg to about 22 mg, about 18 mg to about 26 mg, about 22 mg to about 28 mg, or about 25 mg to about 30 mg, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat that is about 1 mg to about 10 mg, once daily (QD).

[0206] In some embodiments, in a method described in the present disclosure (e.g., any method described herein) and / or for a provided use described in the present disclosure (e.g., any use described herein), a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, or about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg of tebapivat, once daily. In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 2 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 2.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 3 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 3.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 4 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose ofAttorney Docket No.: AGS-132WO about 4.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 5.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 6 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 6.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 7 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 8 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 8.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 9 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 9.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 10 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 12 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about14 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about15 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about16 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 18 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered aAttorney Docket No.: AGS-132WO pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 20 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 22 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about24 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about25 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about26 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 28 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 10 mg, about 1 mg to about 4 mg, about 2 mg to about 5 mg, about 3 mg to about 6 mg, about 4 mg to about 7 mg, about 5 mg to about 8 mg, about 6 mg to about 9 mg, about 7 mg to about 10 mg, about 9 mg to about 15 mg, about 12 mg to about 18 mg, about 15 mg to about 22 mg, about 18 mg to about 26 mg, about 22 mg to about 28 mg, or about 25 mg to about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 10 mg of tebapivat, once daily (QD).

[0207] In some embodiments, in a method described in the present disclosure (e.g., any method described herein) and / or for a provided use in the present disclosure (e.g., any use described herein), a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, or about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 1 mg of tebapivat, once daily. In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt ofAttorney Docket No.: AGS-132WO tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 1.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 2 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 2.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 3 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 3.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 4 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 4.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 5.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 6 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 6.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 7 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate,Attorney Docket No.: AGS-132WO tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 8 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 8.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 9 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 9.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 10 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 12 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 14 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 15 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 16 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 18 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 20 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 22 mg of tebapivat, once daily (QD). In someAttorney Docket No.: AGS-132WO embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 24 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 25 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 26 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 28 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 1 mg to about 10 mg, about 1 mg to about 4 mg, about 2 mg to about 5 mg, about 3 mg to about 6 mg, about 4 mg to about 7 mg, about 5 mg to about 8 mg, about 6 mg to about 9 mg, about 7 mg to about 10 mg, about 9 mg to about 15 mg, about 12 mg to about 18 mg, about 15 mg to about 22 mg, about 18 mg to about 26 mg, about 22 mg to about 28 mg, or about 25 mg to about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of a pharmaceutically acceptable salt of tebapivat selected from a sulfate, phosphate, tartrate, or hydrochloride salt in an amount that is equivalent to a dose of about 1 mg to about 10 mg of tebapivat, once daily (QD).

[0208] In some embodiments, in a method described in the present disclosure (e.g., any method described herein) and / or for a provided use in the present disclosure (e.g., any use described herein), a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, or about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 1 mg of tebapivat, once daily. In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 1.5 mg of tebapivat, once daily (QD). In some embodiments, aAttorney Docket No.: AGS-132WO subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 2 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 2.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 3 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 3.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 4 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 4.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 5.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 6 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 6.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 7 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 8 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 8.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 9 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 9.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 10 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 12 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 14 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that isAttorney Docket No.: AGS-132WO equivalent to a dose of about 15 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 16 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 18 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 20 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 22 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 24 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 25 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 26 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 28 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 1 mg to about 10 mg, about 1 mg to about 4 mg, about 2 mg to about 5 mg, about 3 mg to about 6 mg, about 4 mg to about 7 mg, about 5 mg to about 8 mg, about 6 mg to about 9 mg, about 7 mg to about 10 mg, about 9 mg to about 15 mg, about 12 mg to about 18 mg, about 15 mg to about 22 mg, about 18 mg to about 26 mg, about 22 mg to about 28 mg, or about 25 mg to about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat sulfate in an amount that is equivalent to a dose of about 1 mg to about 10 mg of tebapivat, once daily (QD).

[0209] In some embodiments, in a method described in the present disclosure (e.g., any method described herein) and / or for a provided use in the present disclosure (e.g., any use described herein), a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, or about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 1 mg of tebapivat, once daily. In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount thatAttorney Docket No.: AGS-132WO is equivalent to a dose of about 1.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 2 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 2.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 3 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 3.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 4 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 4.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 5.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 6 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 6.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 7 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 8 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 8.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 9 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 9.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 10 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 12 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in anAttorney Docket No.: AGS-132WO amount that is equivalent to a dose of about 14 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 15 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 16 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 18 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 20 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 22 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 24 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 25 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 26 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 28 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 1 mg to about 10 mg, about 1 mg to about 4 mg, about 2 mg to about 5 mg, about 3 mg to about 6 mg, about 4 mg to about 7 mg, about 5 mg to about 8 mg, about 6 mg to about 9 mg, about 7 mg to about 10 mg, about 9 mg to about 15 mg, about 12 mg to about 18 mg, about 15 mg to about 22 mg, about 18 mg to about 26 mg, about 22 mg to about 28 mg, or about 25 mg to about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat phosphate in an amount that is equivalent to a dose of about 1 mg to about 10 mg of tebapivat, once daily (QD).

[0210] In some embodiments, in a method described in the present disclosure (e.g., any method described herein) and / or for a provided use in the present disclosure (e.g., any use described herein), a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, or about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivatAttorney Docket No.: AGS-132WO tartrate in an amount that is equivalent to a dose of about 1 mg of tebapivat, once daily. In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 1.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 2 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 2.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 3 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 3.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 4 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 4.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 5.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 6 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 6.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 7 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 8 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 8.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 9 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 9.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 10 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 12 mg of tebapivat,Attorney Docket No.: AGS-132WO once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 14 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 15 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 16 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 18 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 20 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 22 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 24 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 25 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 26 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 28 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 1 mg to about 10 mg, about 1 mg to about 4 mg, about 2 mg to about 5 mg, about 3 mg to about 6 mg, about 4 mg to about 7 mg, about 5 mg to about 8 mg, about 6 mg to about 9 mg, about 7 mg to about 10 mg, about 9 mg to about 15 mg, about 12 mg to about 18 mg, about 15 mg to about 22 mg, about 18 mg to about 26 mg, about 22 mg to about 28 mg, or about 25 mg to about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat tartrate in an amount that is equivalent to a dose of about 1 mg to about 10 mg of tebapivat, once daily (QD). In some embodiments, the dose of tebapivat tartrate salt administered to a subject is a dose of tebapivat DL-tartrate. In some embodiments, the dose of tebapivat tartrate administered to a subject is a dose of tebapivat L-tartrate.

[0211] In some embodiments, in a method described in the present disclosure (e.g., any method described herein) and / or for a provided use in the present disclosure (e.g., any use described herein), a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg of tebapivat,Attorney Docket No.: AGS-132WO once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, or about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 1 mg of tebapivat, once daily. In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 1.5 mg of tebapivat, once daily (QD) . In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 2 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 2.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 3 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 3.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 4 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 4.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 5.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 6 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 6.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 7 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 7.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 8 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 8.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 9 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered aAttorney Docket No.: AGS-132WO dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 9.5 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 10 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 12 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 14 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 15 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 16 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 18 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 20 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 22 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 24 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 25 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 26 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 28 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 1 mg to about 10 mg, about 1 mg to about 4 mg, about 2 mg to about 5 mg, about 3 mg to about 6 mg, about 4 mg to about 7 mg, about 5 mg to about 8 mg, about 6 mg to about 9 mg, about 7 mg to about 10 mg, about 9 mg to about 15 mg, about 12 mg to about 18 mg, about 15 mg to about 22 mg, about 18 mg to about 26 mg, about 22 mg to about 28 mg, or about 25 mg to about 30 mg of tebapivat, once daily (QD). In some embodiments, a subject is administered a dose of tebapivat hydrochloride in an amount that is equivalent to a dose of about 1 mg to about 10 mg of tebapivat, once daily (QD).Attorney Docket No.: AGS-132WO

[0212] In some embodiments, in accordance with any of the methods or uses described in the present disclosure, tebapivat or the pharmaceutically acceptable salt of tebapivat is administered orally.

[0213] In some embodiments, in accordance with any of the methods or uses described in the present disclosure, the albumin-to-creatinine ratio (ACR) of the subject is reduced by about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, or greater, as compared to the subject’s baseline ACR, during treatment. In some embodiments, the ACR of the subject is reduced by about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, or greater, as compared to the subject’s baseline ACR, after being administered the treatment for about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, or longer.

[0214] In some embodiments, in accordance with any of the methods or uses described in the present disclosure, the ACR of the subject is reduced by about 30% or greater during treatment, as compared to the subject’s baseline ACR. In some embodiments, the ACR of the subject is reduced by about 30% or greater, as compared to the subject’s baseline ACR, after being administered the treatment for about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, or longer. In some embodiments, the ACR of the subject is reduced by about 30% or greater, as compared to the subject’s baseline ACR, after being administered the treatment for about 6 months.

[0215] In some embodiments, in accordance with any of the methods or uses described in the present disclosure, the ACR of the subject is stably maintained at about ±20%, as compared to the subject’s baseline ACR, during treatment. In some embodiments, the ACR of the subject is at about ±20%, as compared to the subject’s baseline ACR, after being administered the treatment for about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, or longer. In some embodiments, the ACR of the subject is at about ±20%, as compared to the subject’s baseline ACR, after being administered the treatment for about 6 months.Attorney Docket No.: AGS-132WOBRIEF DESCRIPTION OF THE DRAWINGS

[0216] The disclosure can be more completely understood with reference to the following drawings, in which:

[0217] FIG. 1 is a study design to test the effects of AG-348 on hemin-induced sickle cell nephropathy in the Berkeley sickle cell (“BSC”) mouse model. Abbreviations used in the figure: ACR=albumin-creatinine ratio; CBC=complete blood count; GFR=glomerular filtration rate; MTS=Masson’s trichrome staining; PB=Prussian blue; PD=pharmacodynamic; q2d=every other day.

[0218] FIGs. 2A-2C are graphs of the mean (±SEM) blood ATP / 2,3-DPG ratio (FIG. 2A), ATP (FIG 2B), and 2,3-DPG concentrations (FIG. 2C), in wild-type (WT) and BSC mice after treatment with AG-348 for 25 weeks. Abbreviations: 2,3-DPG= 2,3-diphosphoglycerate; ATP=adenosine triphosphate; WT+V= group of WT mice administered vehicle (PBS) with normal chow; WT+H= group of WT mice administered hemin with normal chow; SC+V=a group of BSC mice administered vehicle (PBS) with normal chow; SC+H=a group of BSC mice administered hemin with normal chow; SC+H+ AG-348=a group of BSC mice administered hemin with AG-348 chow. Statistical analysis: One-way analysis of variance followed by Tukey’s multiple comparison test, *p<0.05, **p<0.01, ****p<0.0001.

[0219] FIGs. 3A-3D are graphs of the mean (±SEM) peripheral hematological parameters, hematocrit (HCT) (FIG. 3A), hemoglobin (Hb) (FIG. 3B), red blood cells (RBC) (FIG. 3C), and reticulocytes (RET) (FIG. 3D) in WT and Berkeley SC mice after treatment with AG-348 for 25 weeks. Abbreviations: WT+V= group of WT mice administered vehicle (PBS) with normal chow; WT+H= group of WT mice administered hemin with normal chow; SC+V=a group of BSC mice administered vehicle (PBS) with normal chow; SC+H=a group of BSC mice administered hemin with normal chow; SC+H+ AG-348=a group of BSC mice administered hemin with AG-348 chow; Statistical analysis: One-way analysis of variance followed by Tukey’s multiple comparison test, *p<0.05, ****p<0.0001.

[0220] FIGs. 4A-4B are graphs of the mean (±SEM) glomerular filtration rate (GFR) (FIG. 4A) and urinary albumin-creatinine ratio (ACR) (FIG. 4B) in WT and Berkeley SC mice after treatment with AG-348. Abbreviations: WT+V= group of WT mice administered vehicle (PBS) with normal chow; WT+H= group of WT mice administered hemin with normal chow; SC+V=a group of BSC mice administered vehicle (PBS) with normal chow; SC+H=a group of BSC mice administered hemin with normal chow; SC+H+ AG-348=a group of BSC miceAttorney Docket No.: AGS-132WO administered hemin with AG-348 chow. Statistical analysis: One-way analysis of variance followed by Tukey’s multiple comparison test, *p<0.05.

[0221] FIGs. 5A-5I are graphs of the mean (±SEM) microscopic morphologic findings in the kidneys (pigment deposition in cortical tubule epithelium (FIG. 5A), interstitial mononuclear inflammation (FIG. 5B), vasculitis mononuclear (FIG. 5C), chronic progressive nephropathy (FIG. 5D), congestion of medulla (FIG. 5E), mineralization of medullary tubule (FIG. 5F), membranous glomerulopathy (FIG. 5G), hyaline degeneration of vascular (FIG. 5H), and protein cast (FIG. 51)) ofWT and Berkeley SC mice after treatment with AG-348 for 25 weeks. Abbreviations: WT+V= group of WT mice administered vehicle (PBC) with normal chow; WT+H= group of WT mice administered hemin with normal chow; SC+V=a group of BSC mice administered vehicle (PBS) with normal chow; SC+H=a group of BSC mice administered hemin with normal chow; SC+H+ AG-348=a group of BSC mice administered hemin with AG-348 chow. Note: The absence of a bar indicates the scores were 0. Statistical analysis: **p<0.01, as determined by Mann-Whitney unpaired T-test.

[0222] FIGs. 6A-6H are graphs of the mean (±SEM) Prussian Blue (PB) staining of iron deposition in total (FIG. 6A), cortex (all animals) (FIG. 6B), inner medulla (all animals) (FIG. 6C), outer medulla (all animals) (FIG. 6D), inner medulla (male) (FIG. 6E), inner medulla (female) (FIG. 6F), cortex (male) (FIG. 6G), cortex (female) (FIG. 6H), in the WT and Berkeley SC mice after treatment with AG-348 for 25 weeks. Abbreviations: WT+V= group of WT mice administered vehicle (PBS) with normal chow; WT+H= group of WT mice administered hemin with normal chow; SC+V=a group of BSC mice administered vehicle (PBS) with normal chow; SC+H=a group of BSC mice administered hemin with normal chow; SC+H+AG-348=a group of BSC mice administered hemin with AG-348 chow. Statistical analysis: *p<0.05, as determined by the Mann- Whitney unpaired T-test.

[0223] FIGs. 7A-7D are representative images of PB staining of iron deposition in kidneys ofWT and Berkeley SC mice after treatment with AG-348 for 25 weeks. FIG. 7A is an image from group ofWT mice administered vehicle (PBS) with normal chow and shows no signs of lesions. FIG. 7B is an image of a stained kidney section from a group of BSC mice administered vehicle with normal chow, showing moderate iron deposition in the cortex, mild iron deposition in the inner medulla, and minimal iron deposition in the outer medulla. FIG. 7C is an image from a stained kidney section from a group of BSC mice administered hemin with normal chow, showing moderate iron deposition in the cortex, mild iron deposition in the inner medulla, and minimal iron deposition in the outer medulla. FIG. 7D is an image from a kidney section from a group of BSC mice administered hemin with AG-348 chow showingAttorney Docket No.: AGS-132WO mild iron deposition in the cortex, minimal iron deposition in the inner medulla, and minimal iron deposition in the outer medulla.

[0224] FIGs. 8A-8C are graphs of the mean (±SEM) Masson’s trichrome staining of renal interstitial fibrosis, Masson’s trichrome (all) (FIG. 8A), Masson’s trichrome (female) (FIG. 8B), Masson’s trichrome (male) (FIG. 8C), in the WT and Berkeley SC mice after treatment with AG-348 for 25 weeks. Abbreviations: WT+V= group of WT mice administered vehicle (PBS) with normal chow; WT+H= group of WT mice administered hemin with normal chow; SC+V=a group of BSC mice administered vehicle (PBS) with normal chow; SC+H=a group of BSC mice administered hemin with normal chow; SC+H+ AG-348=a group of BSC mice administered hemin with AG-348 chow. Statistical analysis: **p<0.01, as determined by the Mann-Whitney unpaired T-test.

[0225] FIGs. 9A-9D are representative images of Masson’s trichrome staining of renal interstitial fibrosis in the WT and Berkeley SC mice after treatment with AG-348 for 25 weeks. FIG.9A is an image from group of WT mice administered vehicle (PBS) with normal chow, showing no signs of lesions. FIG. 9B is an image of a stained kidney section from a group of BSC mice administered vehicle with normal chow, showing mild interstitial fibrosis (blue staining). Arrow identifies areas of increased fibrosis. FIG. 9C is an image of a stained kidney section from a group of BSC mice administered hemin with normal chow, showing marked interstitial fibrosis. FIG. 9D is an image from a kidney section from a group of BSC mice administered hemin with AG-348 chow, showing mild interstitial fibrosis.

[0226] FIG. 10 is a study design to test the effects of AG-946 (tebapivat) in anti -glomerular basement membrane (GBM) serum-induced nephritis in SvJ mice. Abbreviations: CFA=Complete Freund’s Adjuvant; IP=intraperitoneally; IV=intravenous; PO= oral gavage; DPBS=distilled phosphate buffered saline; DEX=dexamethasone.

[0227] FIG. 11A is an image of a Western blot showing expression levels of PKM1, PKM2, and PKM1 / 2 in liver, kidney, heart, and skeletal muscles of C57 mice. FIG.11B is an image of Immunohistochemistry (IHC) showing IHC stained positive for PKM2 isoform in the nephron tubule epithelium along the kidney cortex of C57 mice.

[0228] FIG. 12 is a graph of mean (-SEM) percentage of body weight change in different study groups across study days. Abbreviations: BW=body weight, Gl: NS V is a SvJ mouse injected with normal serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G2: Anti-GBM-V is a SvJ mouse injected with anti-GBM serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G3: Anti-GBM AG-946 is a SvJ mouse injected with anti-GBM serum and treated with AG-946; G4: Anti-GBM-DEX isAttorney Docket No.: AGS-132WO a SvJ mouse injected with anti-GBM serum and treated with dexamethasone. Note: The grey- shaded region represents the treatment days. Statistical analysis: Two-way analysis of variance followed by Tukey’s multiple comparison test, *p<0.05; **p<0.01; ***p<0.001 when compared to G2: Anti-GBM V.

[0229] FIG. 13 is a graph of mean (-SEM) urinary protein content in different study groups across study days. Abbreviations: Gl: NS V is a SvJ mouse injected with normal serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G2: Anti-GBM-V is a SvJ mouse injected with anti-GBM serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G3: Anti-GBM AG-946 is a SvJ mouse injected with anti- GBM serum and treated with AG-946; G4: Anti-GBM-DEX is a SvJ mouse injected with anti- GBM serum and treated with dexamethasone. Note: The grey-shaded region represents the treatment days. Statistical analysis: Two-way analysis of variance followed by Tukey’s multiple comparison test, *p<0.05; ***p<0.001 when compared to G2 Anti-GBM V.

[0230] FIG. 14 is a graph of mean (+SEM) kidney weights at terminal collection on day 10. Abbreviations: Gl: NS V is a SvJ mouse injected with normal serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G2: Anti-GBM-V is a SvJ mouse injected with anti-GBM serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G3: Anti-GBM AG-946 is a SvJ mouse injected with anti-GBM serum and treated with AG-946; G4: Anti-GBM-DEX is a SvJ mouse injected with anti-GBM serum and treated with dexamethasone. Statistical analysis: One-way analysis of variance followed by Tukey’s multiple comparison test, p>0.05.

[0231] FIG. 15 is a graph of mean (+SEM) blood urea nitrogen levels at terminal collection on day 10. Abbreviations: Gl: NS V is a SvJ mouse injected with normal serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G2: Anti-GBM-V is a SvJ mouse injected with anti-GBM serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G3: Anti-GBM AG-946 is a SvJ mouse injected with anti-GBM serum and treated with AG-946; G4: Anti-GBM-DEX is a SvJ mouse injected with anti-GBM serum and treated with dexamethasone. Statistical analysis: One-way analysis of variance followed by Tukey’s multiple comparison test, p>0.05 when compared to G2 Anti-GBM V.

[0232] FIGs. 16A-16B are graphs showing mean pyruvate kinase (PK) activity (FIG. 16A) and the fold change (FIG. 16B) in mice at terminal collection on day 10. Circles denote individual PK activity readings. Abbreviations: Gl: NS V is a SvJ mouse injected with normal serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G2: Anti- GBM-V is a SvJ mouse injected with anti-GBM serum and treated with vehicle (0.2% v / vAttorney Docket No.: AGS-132WOTween-80 and 99.8% v / v methylcellulose); G3: Anti-GBM AG-946 is a SvJ mouse injected with anti-GBM serum and treated with AG-946; G4: Anti-GBM-DEX is a SvJ mouse injected with anti-GBM serum and treated with dexamethasone. Statistical analysis: One-way analysis of variance followed by Tukey’s multiple comparison test, p<0.001 when compared to G2 Anti-GBM V.

[0233] FIGs. 17A-17D are graphs of mean (+SEM) histopathological assessment of kidneys, glomerular diameter (FIG. 17A), interstitial inflammation score (FIG. 17B), protein casts score (FIG. 17C), and vasculitis score (FIG. 17D). Abbreviations: Gl: NS V is a SvJ mouse injected with normal serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G2: Anti-GBM-V is a SvJ mouse injected with anti-GBM serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G3: Anti-GBM AG- 946 is a SvJ mouse injected with anti-GBM serum and treated with AG-946; G4: Anti-GBM- DEX is a SvJ mouse injected with anti-GBM serum and treated with dexamethasone. Statistical analysis: Unpaired t-test, *p=0.01; ** p=0.001, 0.002, 0.003, 0.008; *** p<0.001.

[0234] FIGs. 18A-18B are graphs of mean (+SEM) glomeruli with crescents score (FIG. 18A), and percent of glomeruli with crescents (FIG. 18B). Abbreviations: Gl: NS V is a SvJ mouse injected with normal serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G2: Anti-GBM-V is a SvJ mouse injected with anti-GBM serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose); G3: Anti-GBM AG- 946 is a SvJ mouse injected with anti-GBM serum and treated with AG-946; G4: Anti-GBM- DEX is a SvJ mouse injected with anti-GBM serum and treated with dexamethasone. Statistical analysis: Unpaired t-test, *p=0.017; **p=0.004, 0.002; ***p<0.001.

[0235] FIG. 19 is a graph of a volcano-plot proteomic analysis of anti-GBM V (SvJ mouse injected with anti-GBM serum and treated with vehicle (0.2% v / v Tween-80 and 99.8% v / v methylcellulose)) versus anti-GBM AG-946 (tebapivat) (SvJ mouse injected with anti-GBM serum and treated with AG-946). Note: Cutoff for change ±0.6; Cutoff for p-value<0.05.

[0236] FIG. 20 is a study design to test the effects of AG-348 on diabetic nephropathy in female hypertensive unilateral nephrectomized DB / DB mice. Abbreviations: AAV= adeno- associated virus; AI=artificial intelligence; BG=blood glucose; BW=body weight; F4 / 80=epidermal growth factor-like module -containing mucin-like hormone receptor-like 1; G=Group; HbAlC=hemoglobin A1C; IHC=immunohistochemistry; IV=intravenous; KIM- l=kidney injury molecule 1; PAS=periodic acid Schiff; PO=orally; QD=once daily; UNx=unliteral nephrectomization; WB=whole blood.Attorney Docket No.: AGS-132WO

[0237] FIGs. 21A-21B are graphs of mean (±SEM) kidney PKM2 activity (FIG. 21A) and PKM2 activity fold-change normalized to G2 (FIG. 21B) in healthy control (HC) and DN / HT Mice after 17 weeks of treatment with AG-348. Abbreviations: DN / HT=diabetic nephropathy / hypertension; PKM2=pyruvate kinase muscle isoenzyme 2. Statistical analysis: One-way analysis of variance followed by Dunnett’s multiple comparison test against the healthy control group, ***p<0.001.

[0238] FIG. 22 is a graph of mean (±SEM) blood ATP and 2,3-DPG concentrations, shown as ATP / 2,3-DPG Ratio, in healthy control (HC) and DN / HT mice after 17 weeks of treatment with AG-348. Abbreviations: 2,3-DPG= 2,3-diphosphoglycerate; ATP=adenosine triphosphate; DN / HT=diabetic nephropathy / hypertension. Statistical analysis: One-way analysis of variance followed by Dunnett’s multiple comparison test against healthy control group, ***p<0.001.

[0239] FIGs. 23A-23B are graphs of mean (±SEM) absolute body weight (FIG. 23A) and kidney weight (FIG. 23B) in healthy control (HC) and DN / HT mice after 17 weeks of treatment with AG-348. Abbreviations: DN / HT=diabetic nephropathy / hypertension. Statistical analysis: One-way analysis of variance followed by Dunnett’s multiple comparison test against the DN / HT control group, ***p<0.001.

[0240] FIGs. 24A-24C are graphs of mean (±SEM) blood glucose (FIG. 24A), blood HbAlc (FIG. 24B), and plasma urea (FIG. 24C) in healthy control (HC) and DN / HT mice after 17 weeks of treatment with AG-348. Abbreviations: DN / HT=diabetic nephropathy / hypertension; HbAlc=hemoglobin Ale. Statistical analysis: One-way analysis of variance followed by Dunnett’s multiple comparison test against the DN / HT control group, *p<0.05, **p<0.01, ***p<0.001.

[0241] FIG. 25 is a graph of mean (±SEM) urine ACR in healthy control (HC) and DN / HT mice after 17 weeks of treatment with AG-348. Abbreviations: ACR=albumin-to-creatinine ratio; DN / HT=diabetic nephropathy / hypertension. Statistical analysis: Two-way analysis of variance followed by Dunnett’s multiple comparison test against the DN / HT control group, **p<0.01, ***p<0.001.

[0242] FIGs. 26A-26D are graphs of mean (±SEM) percent of glomerulosclerosis scores (FIG. 26A), glomerulosclerosis index (FIG. 26B), and percent of glomerulosclerosis scores of 3 and 4 (FIG. 26C) in healthy control (HC) and DN / HT mice after 17 weeks of treatment with AG-348, and representative PAS images (FIG. 26D). Representative of PAS staining (20x, scale bar=100 pm), as shown in images A-D in FIG. 26D, highlight the basement membrane in the kidney. Image A represents the healthy control group with no signs of lesions. Image BAttorney Docket No.: AGS-132WO represents a stained kidney section from the DN / HT vehicle group, showing a glomerulosclerosis index with a mean GS of 2.22 (slightly more than 50% are affected). Image C represents a stained kidney section from the DN / HT + AG-348 group, showing a 21% improvement in severity compared to the DN / HT vehicle group. Image D represents the DN / HT + lisinopril group kidney section, showing a 70% improvement in severity compared to the DN / HT vehicle group. Abbreviations: AI=artificial intelligence; DN / HT=diabetic nephropathy / hypertension; GS=glomerulosclerosis score; ns=not significant; PAS=periodic acid Schiff. Statistical analysis: One-way analysis of variance followed by Dunnett’s multiple comparison test against the DN / HT control group, *p<0.05, ***p<0.001.

[0243] FIGs. 27A-27C are graphs of mean (±SEM) Masson’s trichrome staining of renal interstitial fibrosis, total content (FIG. 27A) and percent fractional area (FIG. 27B), in healthy control (HC) and DN / HT mice after 17 weeks of treatment with AG-348, and representative Masson’s trichrome images (FIG. 27C). Representative images of Masson’s trichrome staining (20x, scale bar=100 pm) of renal interstitial fibrosis are shown in images A-D of FIG. 27C. Image A represents the healthy control group with no signs of lesions. Image B represents a stained kidney section from the DN / HT group, showing greater than 3% stained positive for interstitial fibrosis (blue staining) compared to healthy controls. Image C represents a stained kidney section from the DN / HT + AG-348 group, showing a 40% reduction in positive staining for interstitial fibrosis compared to the DN / HT vehicle group. Image D represents a kidney section from the DN / HT + lisinopril group, showing a lesion level similar to that of the healthy control group. Abbreviations: DN / HT=diabetic nephropathy / hypertension. Statistical analysis: One-way analysis of variance followed by Dunnett’s multiple comparison tests against the DN / HT control group, *p<0.05, **p<0.01, ***p<0.001.

[0244] FIGs. 28A-28C are graphs of mean (±SEM) Col lai staining of type I collagen, total content (FIG. 28A) and percent of fractional area (FIG. 28B), in healthy control (HC) and DN / HT mice after 17 weeks of treatment with AG-348 and representative images (FIG. 28C). Representative images of Collal staining of Type I collagen (20x, scale bar=100 pm) are shown in images A-D of FIG. 28C. Image A represents the healthy control group with a positive Collal expression level of 12%. Image B represents a stained kidney section from the DN / HT vehicle group, showing a marked expression level of type I collagen staining of 18%. Image C represents a stained kidney section from the DN / HT + AG-348 group, showing only 8% less Collal positive staining than the DN / HT vehicle group. Image D represents a kidney section from the DN / HT + lisinopril group, showing fewer Collal positive staining than the healthy group. Abbreviations: Collal=collagen, type 1, al; DN / HT=diabeticAttorney Docket No.: AGS-132WO nephropathy / hypertension. Statistical analysis: One-way analysis of variance followed by Dunnett’s multiple comparison tests against the DN / HT control group, **p<0.01, ***p<0.001.

[0245] FIGs. 29A-29C are graphs of mean (±SEM) KIM-1 staining of renal proximal tubule injury, total content (FIG. 29A) and percent fractional area (FIG. 29B), in healthy control (HC) and DN / HT mice after 17 weeks of treatment with AG-348 and representative images (FIG. 29C). Representative images of KIM-1 proximal tubule injury staining (20 x, scale bar=100 pm) are shown in images A-D of FIG. 29C. Image A represents the healthy control group with no signs of KIM- 1 expression. Image B represents a stained kidney section from the DN / HT vehicle group, showing 4% stained positive for KIM-1 expression. Image C represents a stained kidney section from the DN / HT + AG-348 group, showing 25% less positive staining for KIM-1 expression than the DN / HT vehicle group. Image D represents a kidney section from the DN / HT + lisinopril group, showing an 85% reduction in KIM-1 expression compared to the DN / HT vehicle group. Abbreviations: DN / HT=diabetic nephropathy / hypertension; KIM-1= kidney injury molecule-1; ns=not significant. Statistical analysis: One-way analysis of variance followed by Dunnett’s multiple comparison tests against the DN / HT control group, ***p<0.00I.

[0246] FIGs. 30A-30C are graphs of mean (±SEM) F4 / 80 staining of inflammation, total content (FIG. 30A) and percent fractional area (FIG. 30B), in healthy control and DN / HT mice after 17 weeks of treatment with AG-348 and representative images (FIG. 30C). Representative images of F4 / 80 staining of inflammation (20 x, scale bar=100 pm) are shown in images A-D of FIG. 30C. Image A represents the healthy group with 1% positive F4 / 80 expression. Image B represents a stained kidney section from the DN / HT vehicle group, showing marked F4 / 80 expression of 3%. Image C represents a stained kidney section from the DN / HT + AG-348 group, showing 8% fewer positive F4 / 80 signals than the DN / HT vehicle group. Image D represents a kidney section from the DN / HT + lisinopril group, showing F4 / 80 expression levels similar to the healthy group. Abbreviations: DN / HT=diabetic nephropathy / hypertension. Statistical analysis: One-way analysis of variance followed by Dunnett’s multiple comparison tests against the DN / HT control group, ***p<0.00I.

[0247] FIGs. 31A-31C are graphical representations of the quantified signal densitometry of the intracellular proteins Fibronectin (FN1) and Type 1 Collagen (COL1A1) (FIG. 31A and FIG. 31B, respectively) measured via western blot analysis following TGF-J31 (5ng / ml) mediated differentiation for 48-hours of NRK-49F rat renal tubulointerstitial cells into myofibroblasts under varying concentrations of glucose, glycine and with or without lOpM Mitapivat. FIG. 31 C is an image of the western blot membrane following immunoblotting forAttorney Docket No.: AGS-132WOFN1, C0L1A1 and a-Tubulin. FIG. 31 A shows a reduction in intracellular COL1A1 protein with Mitapivat treatment under 2.5mM and 3.5mM glucose conditions for both the 40pM and 290pM groups. FIG. 31B shows a reduction in intracellular FN1 protein with Mitapivat treatment under 2.5mM, 3.5mM and 7.5mM glucose conditions for both the 40pM and 290pM groups.DETAILED DESCRIPTION

[0248] The disclosure is based, in part, on the use of PK activators such as mitapivat and tebapivat for treatment of diseases that may have damaging effects on kidneys (e.g. , sickle cell disease, nephritis, sickle cell nephropathy, diabetes, diabetic nephropathy, fibrosis / excessive deposition of extracellular matrix (ECM) or collagen leading to renal fibrosis or scarring). To facilitate an understanding of the present disclosure, a number of terms and phrases are defined below.

[0249] The terms “a” and “an” as used herein mean “one or more” and include the plural unless the context is inappropriate.

[0250] The terms “subject” and “patient” are used interchangeably herein and refer to a mammal in need of treatment, e.g., companion animals (e.g., dogs, cats, and the like), farm animals (e.g., cows, pigs, horses, sheep, goats, and the like) and laboratory animals (e.g., rats, mice, guinea pigs, and the like). Unless stated to the contrary, the subject is a human in need of treatment. In some embodiments, the subject is an adult human (e.g., > 18 years of age). In other embodiments, the subject is a human child (e.g., < 18 years of age). In still other embodiments, the subject is a human female (adult or child). In yet other embodiments, the subject is a human male (adult or child). It should also be understood that the terms subject or patient includes both singular and plural forms of the terms. It should further be understood that the terms subject and patient (which may further include the term “in need thereof’) as used herein refer to individuals that have or are suffering from a disease or disorder. In some embodiments, the subject is suffering from sickle cell disease. In some embodiments, the subject is suffering from a kidney disease. In some embodiments, the subject is suffering from nephritis. In some embodiments, the subject is suffering from lupus. In some embodiments, the subject is suffering from diabetes. In some embodiments, the subject is suffering from obesity. In some embodiments, the subject is suffering from heart disease. In some embodiments, the subject is suffering from high blood pressure. In some embodiments, the subject is suffering from thalassemia. In some embodiments, the subject is suffering from a kidney disease that isAttorney Docket No.: AGS-132WO associated with one or more other conditions, such as sickle cell disease, lupus, diabetes, obesity, heart disease, high blood pressure or hypertension, and / or thalassemia. In some embodiments, the subject is suffering from acute kidney injury (AKI) that is associated with persistent inflammation and / or chronic health conditions such as diabetes, high blood pressure (hypertension), and obesity. In some embodiments, the acute kidney injury is associated with renal fibrosis, which may progress to chronic kidney disease. In other embodiments the subject is suffering from sickle cell nephropathy. In other embodiments, the subject is suffering from diabetic nephropathy. In some embodiments, the subject is suffering from renal fibrosis. In some embodiments, a kidney disease to be treated with a provided composition or method can be any kidney disease that is associated with kidney fibrosis.

[0251] The terms “administer,” “administering,” or “administration” refer to providing, implanting, absorbing, ingesting, injecting, inhaling, or otherwise introducing a compound described herein, or a pharmaceutically acceptable salt or composition thereof, to, in or on a subject.

[0252] The terms “treatment,” “treat,” and “treating” refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of a disease or one or more symptoms of a disease described herein. In some embodiments, treatment may be administered after one or more signs or symptoms of the disease have developed or have been observed (i.e., therapeutic treatment). In other embodiments, treatment may be administered in the absence of signs or symptoms of the disease. For example, treatment may be administered to a susceptible subject prior to the onset of symptoms (i.e., prophylactic treatment) (e.g., in light of a history of symptoms and / or in light of exposure to a pathogen). Treatment may also be continued after symptoms have resolved, for example, to delay or prevent recurrence. In certain embodiments, treatment includes delaying the onset of at least one symptom of the disorder for a period of time.

[0253] As used herein, the term “baseline” refers to a level or concentration of a particular analyte that is measured or established prior to treatment or at a point during treatment with a compound (e.g., a PK activator) disclosed herein or a pharmaceutically acceptable salt or composition thereof. For example, as used herein, the term “baseline albumin-creatinine ratio” refers to a subject’s baseline albumin-creatinine ratio that is measured or established prior to treatment or at a point during treatment with a compound disclosed herein or a pharmaceutically acceptable salt or composition thereof. In another example, as used herein, the term “baseline cystatin C level” refers to a subject’s cystatin C level that is measured orAttorney Docket No.: AGS-132WO established prior to treatment or at a point during treatment with a compound disclosed herein or a pharmaceutically acceptable salt or composition thereof. In another example, as used herein, the term “baseline creatinine level” refers to a subject’s creatinine level that is measured or established prior to treatment or at a point during treatment with a compound disclosed herein or a pharmaceutically acceptable salt or composition thereof. In another example, as used herein, the term “baseline renal iron accumulation level” refers to a subject’s renal iron accumulation level that is measured or established (e.g. , by serum iron levels) prior to treatment or at a point during treatment with a compound disclosed herein or a pharmaceutically acceptable salt or composition thereof.

[0254] As used herein, the recitation of a range of values is intended to serve as a shorthand method of referring individually to each separate value falling within the range as well as the highest and lowest values that define the range and each value is incorporated into the specification as if it were individually recited herein, unless expressly stated to the contrary. For example, a range of values from X to Y includes both X and Y and all the values in between X and Y.

[0255] The use of any and all examples, or exemplary language (e.g., “such as” or “for example”) provided herein, is intended to better illustrate the disclosure and is not a limitation on the scope of the disclosure unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the disclosure.

[0256] The term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art, for example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19.

[0257] Pharmaceutically acceptable salts of mitapivat and tebapivat include those derived from suitable inorganic and organic acids. Examples of pharmaceutically acceptable acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate,Attorney Docket No.: AGS-132WO benzenesulfonate, benzoate, besylate bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, gentisate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2- naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, tosylate p-toluenesulfonate, undecanoate, valerate salts, and the like.

[0258] Mitapivat or tebapivat or a pharmaceutically acceptable salt of mitapivat or tebapivat may be formulated and administered as a pharmaceutical composition. Pharmaceutical compositions can be prepared by methods known in the art of pharmacology. In one aspect, the pharmaceutical compositions are orally administered in an orally acceptable dosage form including, but not limited to, granules or minitablets, capsules, tablets, emulsions and aqueous suspensions, dispersions, and solutions. Unless expressly stated otherwise, the terms “composition” and “pharmaceutical composition” are used interchangeably herein and should be understood to refer to compositions comprising mitapivat or tebapivat or a pharmaceutically acceptable salt of mitapivat or tebapivat. Similarly, unless expressly stated otherwise, the terms “composition thereof’ and “pharmaceutical composition thereof’ are used interchangeably herein and should be understood to refer to compositions comprising mitapivat or tebapivat or a pharmaceutically acceptable salt of mitapivat or tebapivat.

[0259] Unless expressly stated to the contrary, the terms “a pharmaceutically acceptable salt” and “a pharmaceutically acceptable salt thereof’ are used interchangeably herein and should be understood to refer to a pharmaceutically acceptable salt of mitapivat or tebapivat.

[0260] In the application, where an element or component is said to be included in and / or selected from a list of recited elements or components, it should be understood that the element or component can be any one of the recited elements or components, or the element or component can be selected from a group consisting of two or more of the recited elements or components.

[0261] Further, it should be understood that elements and / or features of a composition or a method described herein can be combined in a variety of ways without departing from the spirit and scope of the present disclosure, whether explicit or implicit herein. For example, whereAttorney Docket No.: AGS-132WO reference is made to a particular compound, that compound can be used in various embodiments of compositions of the present disclosure and / or in methods of the present disclosure, unless otherwise understood from the context. In other words, within this application, embodiments have been described and depicted in a way that enables a clear and concise application to be written and drawn, but it is intended and will be appreciated that embodiments may be variously combined or separated without departing from the present teachings and aspects and embodiments of the present disclosure. For example, it will be appreciated that all features described and depicted herein can be applicable to all aspects of the disclosure described and depicted herein.

[0262] It should be understood that the expression “at least one of’ includes individually each of the recited objects or elements after the expression and the various combinations of two or more of the recited objects or elements unless otherwise understood from the context and use. The expression “and / or” in connection with two or more recited objects or elements should be understood as including each of the recited objects or elements individually or the various combinations of two or more of the recited objects or elements, unless otherwise understood from the context. For example, the expression “A and / or B” should be understood as meaning “A and B” or “A or B”.

[0263] The use of the terms “include,” “includes,” “including,” “have,” “has,” “having,” “contain,” “contains,” or “containing,” including grammatical equivalents thereof, should be understood generally as open-ended and non-limiting, for example, not excluding additional unrecited elements or steps, unless otherwise specifically stated or understood from the context.

[0264] Where the use of the term “about” is before a quantitative value, the present disclosure also includes the specific quantitative value itself, unless specifically stated otherwise. As used herein, the term “about” refers to a ± 10% variation from the nominal value unless otherwise indicated or inferred.

[0265] It should be understood that the order of steps or order for performing certain actions is immaterial so long as the various aspects and embodiments of the present disclosure remain operable. Moreover, two or more steps or actions may be conducted simultaneously.

[0266] The use of any and all examples, or exemplary language herein, for example, “such as” or “including,” is intended merely to better illustrate the present disclosure and does not pose a limitation on the scope of the disclosure unless claimed. No language in the specificationAttorney Docket No.: AGS-132WO should be construed as indicating any non-claimed element as essential to the practice of the various aspects and embodiments of the present disclosure.I. Pyruvate Kinase Activators

[0267] Glycolysis is a vital metabolic process that converts glucose into pyruvate, producing ATP and nicotinamide adenine dinucleotide. Pyruvate kinase, a key enzyme in glycolysis, catalyzes the conversion of PEP to pyruvate which is further converted to lactic acid or acetyl coenzyme A for use in the tricarboxylic acid cycle in the mitochondria, which generates energy precursors for oxidative phosphorylation. There are four subtypes: pyruvate kinase isoform L, PKR, pyruvate kinase muscle isoenzyme 1, and pyruvate kinase muscle isoenzyme 2 (PKM2), each found in different tissues. Pyruvate kinase muscle isoenzyme 2 is the dominant form of PK in kidney tissue (Alquraishi et al., “Pyruvate kinase M2: A simple molecule with complex functions,” Free Radic Biol Med. 2019;143: 176-192) and plays a crucial role in kidney disease.

[0268] The kidney maintains physiological homeostasis in the body through various metabolic processes, which differ significantly between the regions of the kidney. The renal cortex relies on fatty acid oxidation and the proximal tubules of the cortex are highly aerobic and responsible for fluid reabsorption. In contrast, the medulla relies on glycolysis for energy and has lower oxygen tension. Significant glycolysis occurs in the medulla papilla and distal convoluted tubules under normal conditions (Tang and Wei, 2023), and podocytes primarily utilize glycolysis for energy (Brinkkoetter et al., 2019). Glycolysis is also crucial for maintaining phosphate homeostasis which is disrupted in kidney disease (Nakagawa et al., 2020; Ito et al., 2022).

[0269] The present disclosure is based in part on the discovery that the activation of PKR and / or PKM2 may help reduce kidney damage and / or preserve renal function, in part, by improving perfusion, reducing sickling-related ischemia and minimizing the direct toxicity of free heme. Additionally, activation of PKM2 may render a renal protective effect by increasing glucose metabolic flux, inhibiting the production of toxic glucose metabolites and reducing fibrosis.

[0270] Activation of PKR can reduce 2,3-diphosphoglycerate (2,3-DPG), as well as can increase ATP, which promotes membrane health and reduces hemolysis. One aspect of the present disclosure is the recognition that renal complications resulting from the pathogenesis of sickle cell disease (SCD) can be improved by administration of PK activating compounds. Accordingly, in one embodiment, PKR activation (e.g., by administration of a therapeuticallyAttorney Docket No.: AGS-132WO effective amount of a PK activator to a subject with SCD) reduces kidney damage by improving perfusion. In certain embodiments, PKR activation (e.g. , by administration of a therapeutically effective amount of a PK activator to a subject with SCD) reduces sickling-related ischemia. In certain embodiments, PKR activation (e.g., by administration of a therapeutically effective amount of a PK activator to a subject with SCD) minimizes the direct toxicity of free heme. As used herein, “PK activator” is a compound that activates PKR and / or PKM2 and is selected from the group consisting of mitapivat and tebapivat, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.(i) Mitapivat (AG-348)

[0271] Provided herein are methods of treatment using a compound having the structural formula:A / -(4-(4-(cyclopropylmethyl)piperazine-1-carbonyl)phenyl)quinoline-8- sulfonamide(Mitapivat) wherein the compound is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0272] Mitapivat is also known by its chemical name N-(4-(4- (cyclopropylmethyl)piperazine-l-carbonyl)phenyl)quinoline-8-sulfonamide as well as the sulfate form of mitapivat, mitapivat sulfate. The chemical name of mitapivat sulfate is 8- quinolinesulfonamide, N-[4-[[4 (cyclopropylmethyl)- l-piperazinyl]carbonyl]phenyl]-, sulfate, hydrate (2: 1:3).Attorney Docket No.: AGS-132WO

[0273] The chemical structure of mitapivat sulfate is represented by the following structural formula and noted as AG-348:(AG-348)

[0274] Throughout the embodiments and claims provided herein, AG-348 or mitapivat may refer to the sulfate salt of mitapivat depicted above. It will be understood by a skilled artisan that in some embodiments, AG-348 or mitapivat may also refer to the free base, N-(4- (4-(cyclopropylmethyl)piperazine- 1 -carbonyl)phenyl)quinoline-8-sulfonamide, unless expressly stated to the contrary, and reference to a “pharmaceutically acceptable salt thereof’ refers to and includes all pharmaceutically acceptable salts of N-(4-(4- (cyclopropylmethyl)piperazine- l-carbonyl)phenyl)quinoline-8-sulfonamide, unless expressly stated to the contrary.

[0275] AG-348 / mitapivat is an orally bioavailable allosteric activator of PKR and PKM2 that has been approved in the US for the treatment of adults with pyruvate kinase deficiency. It is currently in clinical development for the treatment of additional forms of hemolytic anemia such as alpha and beta thalassemia and sickle cell disease. The present disclosure exhibits the protective effect of PK activators, such as, for example, AG-348 or mitapivat, in the treatment of sickle cell nephropathy (SCN).(ii) Tebapivat (AG-946)

[0276] Provided herein are various methods of treatment using a PK activator compound having the structural formula:-946 or tebapivat); wherein the compound is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0277] AG-946 or tebapivat is also known by the following chemical names: 2-((lH- pyrazol-3-yl)methyl)-6-((6-aminopyridin-2-yl)methyl)-4-methyl-4H- thiazolo [5 ',4' : 4,5]pyrrolo [2,3 -d]pyridazin-5 (6H)-one ; 2-(( lH-pyrazol-3 -yl)methyl)-6-((6-Attorney Docket No.: AGS-132WO aminopyridin-2-yl)methyl)-4-methyl-4,6-dihydro-5H-thiazolo[5',4':4,5]pyrrolo[2,3- d]pyridazin-5-one; 6-[(6-aminopyridin-2-yl)methyl]-4-methyl-2-[(lH-pyrazol-3-yl)methyl]- 4,6-dihydro-5H-[ l,3]thiazolo[5',4':4,5]pyrrolo[2,3-r / ]pyridazin-5-one; and 5H- thiazolo[5',4':4,5]pyrrolo[2,3-d]pyridazin-5-one, 6-[(6-amino-2-pyridinyl)methyl]-4,6- dihydro-4-methyl-2-(lH-pyrazol-3-ylmethyl).

[0278] Throughout the embodiments and claims provided herein, the pharmaceutically acceptable salt of tebapivat may refer to a sulfate salt, a phosphate salt, a tartrate salt, or a hydrochloride salt of tebapivat. In some embodiments, the tartrate salt is the DL-tartrate salt. In some embodiments, the tartrate salt is the L-tartrate salt.

[0279] The chemical structure of tebapivat sulfate is represented by the following structural formula:The chemical name of tebapivat sulfate is 6-[(6-aminopyridin-2-yl)methyl]-4-methyl-2-[(lH- pyrazol-3-yl)mcthyl |-4.6-dihydro-5 / / -| l .3 |thiazolo|5'.4':4.5 |pyrrolo|2.3- |pyridazin-5-onc hemi-sulfate, hemi -hydrate.

[0280] The chemical structure of tebapivat phosphate is represented by the following structural formula:

[0281] The chemical structure of tebapivat DL-tartrate is represented by the following structural formulas:Attorney Docket No.: AGS-132WO

[0282] The chemical structure of tebapivat L-tartrate is represented by the following structural formula:

[0283] The chemical structure of tebapivat hydrochloride is represented by the following structural formula:

[0284] It will be understood by a skilled artisan that in some embodiments, AG-946 or tebapivat may also refer to the free base, 6-[(6-aminopyridin-2-yl)methyl]-4-methyl-2-[(lH- pyrazol-3-yl)methyl]-4,6-dihydro-5H-[ l,3]thiazolo[5',4':4,5]pyrrolo[2,3-aQpyridazin-5-one, unless expressly stated to the contrary, and reference to a “pharmaceutically acceptable salt thereof’ refers to and includes all pharmaceutically acceptable salts of 6-[(6-aminopyridin-2- yl)methyl]-4-methyl-2-[(lH-pyrazol-3-yl)methyl]-4,6-dihydro-5H- [l,3]thiazolo[5',4':4,5]pyrrolo[2,3-< / |pyridazin-5-one, unless expressly stated to the contrary.

[0285] AG-946 is an orally bioavailable small molecule that activates various PK isoforms, including PKR and PKM2. The present disclosure, among other things, demonstrates the effect of AG-946 in improving glomerulonephritis by enhancing the activity of PKM2 and thereforeAttorney Docket No.: AGS-132WO increasing glycolysis in the regions of the kidney that are heavily reliant on this process. PKM2 activation in the kidney by AG-946 could also potentially decrease toxic glucose metabolites and reduce podocyte apoptosis. Furthermore, PKM2 activation could slow or prevent further fibrosis development in the kidney by reducing the glycolytic flux of 3 -phosphoglycerate to glycine, which accounts for one third amino acid sequence of collagen (see Qi etal., “Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction,” Nat Med. 2017;23(6):753-762).II. Methods of Treatment

[0286] The present disclosure provides methods of treatment comprising administering to a subject in need thereof a therapeutically effective amount of a PK activator, wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0287] Sickle cell nephropathy (SCN) is common in SCD patients and indicates poor prognosis. Renal complications resulting from the pathogenesis of SCD, including albuminuria, deteriorating glomerular fdtration rate, fibrosis, and progression to chronic kidney disease and kidney failure, are responsible for 16-18% of mortality in patients with SCD (Nath KA et al., “Sickle cell disease: renal manifestations and mechanisms,” Nat Rev Nephrol. 2015; 11(3): 161-171). In patients with SCN, improving anemia and reducing sickling and hemolysis through the activation PKR may help reduce kidney damage by improving perfusion, reducing sickling -related ischemia and minimizing the direct toxicity of free heme. Furthermore, nonclinical research has demonstrated that activating PKM2 plays a significant role in providing renal protection in diabetic kidney disease and acute kidney injury. This occurs through increased glucose metabolic flux, inhibition of damaging glucose metabolite production, and reduction of fibrosis, potentially due to the activity of PKM2 (Chen et al., “Targeting pyruvate kinase M2 for the treatment of kidney disease,” Front Pharmacol. 2024;15: 1376252; Liu H et al., “The PKM2 activator TEPP-46 suppresses kidney fibrosis via inhibition of the EMT program and aberrant glycolysis associated with suppression of HIF- lalpha accumulation, ” J Diabetes Investig. 2021;12(5):697-709; Qi etal., “Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction,” Nat Me d. 2017;23(6):753-762).

[0288] Additionally, preclinical studies have shown that PKM2 activation renders renal protective effects in diabetic kidney disease and acute kidney injury. This occurs through increased glucose metabolic flux, inhibition of damaging glucose metabolite production, andAttorney Docket No.: AGS-132WO reduction of fibrosis, potentially due to the activity of PKM2. (Chen et al., 2024; Liu et al., 2021; Qi et al., 2017).

[0289] In certain embodiments, provided herein is a method of treating a kidney disease (e.g., any kidney disease described herein) in a subject with sickle cell disease comprising administering to the subject a therapeutically effective amount of a PK activator (e.g. , mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, a provided composition or method is used in accordance with the present disclosure to treat fibrosis in a subject, wherein the fibrosis is associated with a kidney disease or disorder, or a disease or disorder that affects healthy kidney function.

[0290] Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue. Excess deposition of fibrous tissue is associated with pathological conditions that can lead to impairment of organ or tissue function. Affected organs can include the lungs (lung or pulmonary fibrosis), liver (liver or hepatic fibrosis), kidney (kidney or renal fibrosis), and heart (cardiac fibrosis). In certain embodiments, provided herein is a method of treating renal fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0291] In certain embodiments, provided herein is a method of preserving renal function in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0292] In certain embodiments, provided herein is a method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In certain embodiments, the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure. In certain embodiments, nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, Alport syndrome, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.Attorney Docket No.: AGS-132WO

[0293] In certain embodiments, provided herein is a method of treating kidney fibrosis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0294] In certain embodiments, provided herein is a method of treating kidney inflammation associated with hemolysis, sickle cell disease, diabetes, or hypertension in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0295] In certain embodiments, provided herein is a method of treating diabetic kidney disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0296] In certain embodiments, provided herein is a method of treating acute kidney injury in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0297] In certain embodiments, provided herein is a method for improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0298] In certain embodiments, provided herein is a method of treating chronic kidney disease (CKD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0299] In certain embodiments, provided herein is a method of reducing iron accumulation in the kidneys of a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.Attorney Docket No.: AGS-132WO

[0300] In certain embodiments, provided herein is a method of reducing kidney fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0301] In certain embodiments, provided herein is a method of treating diabetic nephropathy in a subject with diabetes, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0302] In certain embodiments, provided herein is a method of treating sickle cell nephropathy in a subject with sickle cell disease, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0303] In certain embodiments, provided herein is a method of treating acute kidney injury in a subject, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof.

[0304] In some embodiments, the present disclosure provides a method of treating a kidney disease in a subject, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the kidney disease is a kidney disease that is associated with renal fibrosis. In some embodiments, the kidney disease is nephritis (e.g., glomerulonephritis or interstitial nephritis). In some embodiments, the kidney disease is ischemic nephropathy. In some embodiments, the kidney disease is obstructive nephropathy. In some embodiments, the kidney disease is Mesoamerican / agricultural nephropathy. In some embodiments, the kidney disease is diabetic nephropathy. In some embodiments, the kidney disease is thalassemia associated nephropathy. In some embodiments, the kidney disease is sickle cell nephropathy. In some embodiments, the kidney disease is caused by nephrotoxicity (e.g., by exposure to one or more nephrotoxins). In some embodiments, the kidney disease is chronic kidney disease (CKD). In some embodiments, the kidney disease is acute kidney injury (AKI) (e.g., AKI that is associated with or causes renal fibrosis). In some embodiments, the PK activator is mitapivatAttorney Docket No.: AGS-132WO(e.g., mitapivat sulfate, or any other form of mitapivat described herein). In some embodiments, the PK activator is tebapivat (e.g., any form of tebapivat described herein).

[0305] In some embodiments, the present disclosure provides a method of treating chronic kidney disease (CKD) in a subject, the method comprising administering to the subject a therapeutically effective amount of a PK activator (e.g., mitapivat or tebapivat), wherein the PK activator is administered as a free base or a pharmaceutically acceptable salt or a composition thereof. In some embodiments, the CKD is associated with nephritis (e.g., glomerulonephritis or interstitial nephritis). In some embodiments, the CKD is associated with ischemic nephropathy. In some embodiments, the CKD is associated with obstructive nephropathy. In some embodiments, the CKD is associated with Mesoamerican / agricultural nephropathy. In some embodiments, the CKD is associated with diabetic nephropathy. In some embodiments, the CKD is associated with thalassemia related nephropathy. In some embodiments, the CKD is associated with sickle cell disease (SCD) or sickle cell nephropathy (SCN). In some embodiments, the CKD is associated with nephrotoxicity or exposure to one or more nephrotoxins. In some embodimen...

Claims

1. Attorney Docket No: AGS-132WOCLAIMSWHAT IS CLAIMED IS:

1. A method of treating chronic kidney disease (CKD) in a subject with sickle cell disease, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

2. A method of treating chronic kidney disease (CKD) in a subject with sickle cell disease, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

3. A method of treating renal fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

4. A method of treating renal fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

5. A method of preserving renal function in a subject with sickle cell disease, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

6. A method of preserving renal function in a subject with sickle cell disease, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

7. A method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

8. A method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

9. A method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, onceAttorney Docket No: AGS-132WO daily (QD) and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure.

10. A method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD) and wherein the subject has a disease selected from lupus, diabetes, obesity, heart disease, and high blood pressure.

11. A method of treating kidney fibrosis in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

12. A method of treating kidney fibrosis in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

13. A method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD) and wherein the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

14. A method of treating nephritis in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD) and wherein the nephritis is selected from acute glomerulonephritis, lupus nephritis, hereditary nephritis, chronic glomerulonephritis, IgA nephropathy, and interstitial nephritis.

15. A method of treating kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, or hypertension in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

16. A method of treating kidney inflammation associated with hemolysis, thalassemia, sickle cell disease, diabetes, or hypertension in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivatAttorney Docket No: AGS-132WO in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

17. A method of treating diabetic kidney disease in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

18. A method of treating diabetic kidney disease in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

19. A method of treating acute kidney injury in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

20. A method of treating acute kidney injury in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

21. A method for improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

22. A method for improving kidney health in a subject with sickle cell disease, thalassemia, lupus, diabetes, obesity, heart disease, or high blood pressure, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

23. A method of treating chronic kidney disease (CKD) in a subject in need thereof, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

24. A method of treating chronic kidney disease (CKD) in a subject in need thereof, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).Attorney Docket No: AGS-132WO25. A method of reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

26. A method of reducing iron accumulation in the kidneys of a subject with sickle cell disease or thalassemia, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

27. A method of reducing kidney fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

28. A method of reducing kidney fibrosis in a subject with sickle cell disease, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

29. A method of treating kidney damage in a subject, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension, or thalassemia.

30. A method of treating kidney damage in a subject, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension, or thalassemia.

31. A method of reducing collagen formation in the kidneys of a subject, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension, or thalassemia.

32. A method of reducing collagen formation in the kidneys of a subject, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension, or thalassemia.

33. A method of reducing inflammation in the kidneys of a subject, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, onceAttorney Docket No: AGS-132WO daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension, or thalassemia.

34. A method of reducing inflammation in the kidneys of a subject, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD), and wherein the subject is diagnosed with diabetes, sickle cell disease, hypertension, or thalassemia.

35. A method of treating sickle cell nephropathy in a subject, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

36. A method of treating sickle cell nephropathy in a subject, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

37. A method of treating diabetic nephropathy in a subject, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

38. A method of treating diabetic nephropathy in a subject, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

39. A method of treating nephropathy in a subject with sickle cell disease, the method comprising administering to the subject a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

40. A method of treating nephropathy in a subject with sickle cell disease, the method comprising administering to the subject a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 30 mg of tebapivat, once daily (QD).

41. The method according to any one of claims 1-40, wherein tebapivat or the pharmaceutically acceptable salt of tebapivat is administered orally.

42. The method according to any one of claims 1-41, wherein the albumin-to-creatinine ratio (ACR) of the subject is reduced by about 30% or greater, as compared to the subject’s baseline ACR, during treatment.Attorney Docket No: AGS-132WO43. The method according to any one of claims 1-41, wherein the ACR of the subject is maintained at about ±20%, as compared to the subject’s baseline ACR, during treatment.

44. The method according to any one of claims 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25,27, 29, 31, 33, 35, 37, 39, and 41-43, wherein the subject is administered a dose of tebapivat that is about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg, once daily (QD).

45. The method according to any one of claims 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26,28, 30, 32, 34, 36, 38, 40, and 41-43, wherein the subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, about 7.5 mg or about 10 mg of tebapivat, once daily (QD).

46. The method of claim 44, wherein the subject is administered a dose of tebapivat that is about 2.5 mg, about 5 mg, or about 7.5 mg, once daily (QD).

47. The method of claim 45, wherein the subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 2.5 mg, about 5 mg, or about 7.5 mg of tebapivat, once daily (QD).

48. The method according to any one of claims 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25,27, 29, 31, 33, 35, 37, 39, and 41-43, wherein the subject is administered a dose of tebapivat that is about 1 mg to about 10 mg, once daily (QD).

49. The method according to any one of claims 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26,28, 30, 32, 34, 36, 38, 40, and 41-43, wherein the subject is administered a dose of a pharmaceutically acceptable salt of tebapivat in an amount that is equivalent to a dose of about 1 mg to about 10 mg, once daily (QD).

50. The method according to any one of claims 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 41-43, 45, 47, and 49, wherein the pharmaceutically acceptable salt of tebapivat is selected from a sulfate, phosphate, tartrate, or hydrochloride salt.

51. The method according to claim 50, wherein the pharmaceutically acceptable salt of tebapivat is a sulfate salt.

52. The method according to claim 50, wherein the pharmaceutically acceptable salt of tebapivat is a phosphate salt.

53. The method according to claim 50, wherein the pharmaceutically acceptable salt of tebapivat is a tartrate salt.Attorney Docket No: AGS-132WO54. The method according to claim 53, wherein the tartrate salt is DL-tartrate.

55. The method according to claim 53, wherein the tartrate salt is L-tartrate.

56. The method according to claim 50, wherein the pharmaceutically acceptable salt of tebapivat is a hydrochloride salt.

Images