Alk4:actriib heteromultimers and uses thereof

A method for treating fibrosis or a disorder or condition associated with fibrosis comprising administering to the patient in need thereof an effective amount of a recombinant ALK4:ActRIIB heteromultimer comprising at least one ALK4-Fc fusion protein and at least one ActRIIB-Fc fusion protein,

• wherein the ALK4-Fc fusion protein comprises one or more amino acid modifications that alter the isoelectric point (pI) of the ALK4-Fc fusion protein, and/or wherein the ActRIIB-Fc fusion protein comprises one or more amino acid modifications that alter the pI of the ActRIIB-Fc fusion protein;
• wherein the ALK4-Fc fusion protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:
• 76, and wherein the ActRIIB-Fc fusion protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:
• 72.

A method for treating kidney disease or a complication of kidney disease, comprising administering to a patient in need thereof an effective amount of a recombinant ALK4:ActRIIB heteromultimer comprising at least one ALK4-Fc fusion protein and at least one ActRIIB-Fc fusion protein,

• wherein the ALK4-Fc fusion protein comprises one or more amino acid modifications that alter the isoelectric point (pI) of the ALK4-Fc fusion protein, and/or wherein the ActRIIB-Fc fusion protein comprises one or more amino acid modifications that alter the pI of the ActRIIB-Fc fusion protein;
• wherein the ALK4-Fc fusion protein comprises an amino acid sequence that is at least 90% to the amino acid sequence of SEQ ID NO:
• 76, and wherein the ActRIIB-Fc fusion protein comprises an amino acid sequence that is at least 90% to the amino acid sequence of SEQ ID NO:
• 72.