Abstract: In some aspects, the invention teaches pharmaceutical compositions that include a TGF-? ligand trap, and methods of using a TGF-? ligand trap to treat, prevent, or reduce the progression rate of pulmonary hypertension (PH). The invention also provides methods of using a TGF-? ligand trap to treat, prevent, or reduce the progression rate of a variety of conditions including, but not limited to, pulmonary vascular remodeling, pulmonary fibrosis, right ventricular hypertrophy, diseases associated with excessive TGF-? signaling, diseases associated with excessive GDF15 signaling, and diseases associated with excessive PAI-1 signaling. The invention further provides methods of using a TGF-? ligand trap to reduce right ventricular systolic pressure in a subject.

Abstract: In certain aspects, the disclosure provides soluble heteromeric polypeptide complexes comprising an extracellular domain of a type I serine/threonine kinase receptor of the TGF-beta family and an extracellular domain of a type II serine/threonine kinase receptor of the TGF-beta family. In some embodiments, the disclosure provides soluble polypeptide complexes comprising an extracellular domain of a type II receptor selected from: ActRIIA, ActRIIB, TGFBRII, BMPRII, and MISRII. In some embodiments, the disclosure provides soluble polypeptide complexes comprising an extracellular domain of a type I receptor selected from: ALK1, ALK2, ALK3, ALK4, ALK5, ALK6, and ALK7. Optionally the soluble complex is a heterodimer. In certain aspects, such soluble polypeptide complexes may be used to regulate (promote or inhibit) growth of tissues or cells including, for example, muscle, bone, cartilage, fat, neural tissue, tumors, cancerous cells, and/or cells of hematopoietic lineages, including red blood cells.

Abstract: In certain aspects, the disclosure provides multispecific binders (e.g., ActRIIA:T?RII heteromultimers comprising an ActRIIA polypeptide and a TfiRU polypeptide). The disclosure further provides that such multispecific binders (e.g., ActRIIA:T?RII heteromultimer) may be used to treat various disorders or conditions.

Abstract: In certain aspects, the disclosure provides ALK7 antagonists. In certain aspects, these ALK7 antagonists are can be used to improve metabolic parameters in a patient in need thereof. In certain aspects, these ALK7 antagonists can be used to treat or prevent one or more kidney-associated disease or condition in a patient in need thereof. In certain aspects, these ALK7 antagonists can be used to treat or prevent cancer.

Abstract: In certain aspects, the disclosure provides soluble heteromeric polypeptide complexes comprising an extracellular domain of a type I serine/threonine kinase receptor of the TGF-beta family and an extracellular domain of a type II serine/threonine kinase receptor of the TGF-beta family. In some embodiments, the disclosure provides soluble polypeptide complexes comprising an extracellular domain of a type II receptor selected from: ActRIIA, ActRIIB, TGFBRII, BMPRII, and MISRII. In some embodiments, the disclosure provides soluble polypeptide complexes comprising an extracellular domain of a type I receptor selected from: ALK1, ALK2, ALK3, ALK4, ALK5, ALK.6, and ALK7. Optionally the soluble complex is a heterodimer. In certain aspects, such soluble polypeptide complexes may be used to regulate (promote or inhibit) growth of tissues or cells including, for example, muscle, bone, cartilage, fat, neural tissue, tumors, cancerous cells, and/or cells of hematopoietic lineages, including red blood cells.

Abstract: In certain aspects, the disclosure provides multispecific binders (e.g., ActRIIB:T?RII heteromultimers comprising an ActRIIB polypeptide and a T?MII polypeptide). In some embodiments, the disclosure provides for novel binders comprising a T?RII polypeptide and a heterologous portion. The disclosure further provides that such multispecific binders (e.g., ActRII:T?RII heteromultimer) may be used to treat various disorders or conditions.

Abstract: In certain aspects, the disclosure provides soluble heteromeric polypeptide complexes comprising an extracellular domain of an ALK4 receptor and an extracellular domain of ActRIIB. In certain aspects, such soluble ALK4:ActRIIB complexes may be used to regulate (promote or inhibit) growth of tissues or cells including, for example, muscle, bone, cartilage, fat, neural tissue, tumors, and/or cancerous cells. In certain aspects, such ALK4:ActRIIB complexes are can be used to improve muscle formation, bone formation, metabolic parameters, and disorders associated with these tissues, cellular networks, kidney, and endocrine systems.

Abstract: In certain aspects, the present disclosure relates to T?RII fusion polypeptides comprising a heterologous portion and a truncated, ligand-binding portion of the extracellular domain of T?RII polypeptide useful to selectively antagonize a T?RII ligand. The disclosure further provides compositions and methods for use in treating or preventing TGF? associated disorders.

Abstract: In certain aspects, the present disclosure relates to polypeptides comprising a truncated, ligand-binding portion of the extracellular domain of T?RII polypeptide useful to selectively antagonize a T?RII ligand. The disclosure further provides compositions and methods for use in treating or preventing TGF? associated disorders.

Abstract: In certain aspects, the present disclosure relates to T?RII fusion polypeptides comprising a heterologous portion and a truncated, ligand-binding portion of the extracellular domain of T?RII polypeptide useful to selectively antagonize a T?RII ligand. The disclosure further provides compositions and methods for use in treating or preventing TGF? associated disorders.

Abstract: In certain aspects, the disclosure provides soluble heteromeric polypeptide complexes comprising an extracellular domain of a type I serine/threonine kinase receptor of the TGF-beta family and an extracellular domain of a type II serine/threonine kinase receptor of the TGF-beta family. In some embodiments, the disclosure provides soluble polypeptide complexes comprising an extracellular domain of a type II receptor selected from: ActRIIA, ActRIIB, TGFBRII, and MISRII. In some embodiments, the disclosure provides soluble polypeptide complexes comprising an extracellular domain of a type I receptor selected from: ALK1, ALK2, ALK3, ALK4, ALK5, ALK.6, and ALK7. Optionally the soluble complex is a heterodimer. In certain aspects, such soluble polypeptide complexes may be used to regulate (promote or inhibit) growth of tissues or cells including, for example, muscle, bone, cartilage, fat, neural tissue, tumors, cancerous cells, and/or cells of hematopoietic lineages, including red blood cells.

Abstract: In certain aspects, the present disclosure relates to polypeptides comprising a truncated, ligand-binding portion of the extracellular domain of T?RII polypeptide useful to selectively antagonize a T?RII ligand. The disclosure further provides compositions and methods for use in treating or preventing TGF? associated disorders.

Abstract: In certain aspects, the present disclosure provides compositions and methods for inhibiting activity of TGF? superfamily ligands, particularly ligands such as GDF8, GDF11, activin A, activin B, activin C and activin E, in vertebrates, including rodents and primates, and particularly in humans. In some embodiments, the compositions of the disclosure may be used to treat or prevent diseases or disorders that are associated with abnormal activity of a follistatin-related polypeptide and/or a follistatin ligand.

Abstract: In certain aspects, the present disclosure relates to polypeptides comprising a truncated, ligand-binding portion of the extracellular domain of T?RII polypeptide useful to selectively antagonize a T?RII ligand. The disclosure further provides compositions and methods for use in treating or preventing TGF? associated disorders.

Abstract: In certain aspects, the disclosure provides single-arm heteromeric polypeptide complexes comprising an extracellular domain of a co-receptor of the TGF-beta superfamily. In some embodiments, the disclosure provides single-arm polypeptide complexes comprising an extracellular domain of a co-receptor selected from: endoglin, betaglycan, Cripto-1, Cryptic, Cryptic family protein 1B, Crim 1, Crim2, BAMBI, BMPER, RGM-A, RGM-B, MuSK, and hemojuvelin. Optionally the complex is a heterodimer. In certain aspects, such polypeptide complexes may be used for the treatment or prevention of various TGF-beta associated conditions, including without limitation diseases and disorders associated with, for example, cancer, muscle, bone, fat, red blood cells, metabolism, fibrosis and other tissues that are affected by one or more ligands of the TGF-beta superfamily.

Abstract: In certain aspects, the disclosure provides soluble heteromeric polypeptide complexes comprising an extracellular domain of an ALK4 receptor and an extracellular domain of ActRIIB. In certain aspects, such soluble ALK4:ActRIIB complexes may be used to regulate (promote or inhibit) growth of tissues or cells including, for example, muscle, bone, cartilage, fat, neural tissue, tumors, and/or cancerous cells. In certain aspects, such ALK4:ActRIIB complexes are can be used to improve muscle formation, bone formation, metabolic parameters, and disorders associated with these tissues, cellular networks, kidney, and endocrine systems.

Abstract: In some aspects, the invention teaches pharmaceutical compositions that include a TGF-? ligand trap, and methods of using a TGF-? ligand trap to treat, prevent, or reduce the progression rate of pulmonary hypertension (PH). The invention also provides methods of using a TGF-? ligand trap to treat, prevent, or reduce the progression rate of a variety of conditions including, but not limited to, pulmonary vascular remodeling, pulmonary fibrosis, right ventricular hypertrophy, diseases associated with excessive TGF-? signaling, diseases associated with excessive GDF15 signaling, and diseases associated with excessive PAI-1 signaling. The invention further provides methods of using a TGF-? ligand trap to reduce right ventricular systolic pressure in a subject.

Abstract: In certain aspects, the present disclosure relates to polypeptides comprising a truncated, ligand-binding portion of the extracellular domain of T?RII polypeptide useful to selectively antagonize a T?RII ligand. The disclosure further provides compositions and methods for use in treating or preventing TGF? associated disorders.

Abstract: In some aspects, the invention teaches pharmaceutical compositions that include a TGF-beta ligand trap, and methods of using a TGF-beta ligand trap to treat, prevent, or reduce the progression rate of pulmonary hypertension (PH). The invention also provides methods of using a TGF-beta ligand trap to treat, prevent, or reduce the progression rate of a variety of conditions including, but not limited to, pulmonary vascular remodeling, pulmonary fibrosis, right ventricular hypertrophy, diseases associated with excessive TGF-beta signaling, diseases associated with excessive GDF15 signaling, and diseases associated with excessive PAI-1 signaling. The invention further provides methods of using a TGF-beta ligand trap to reduce right ventricular systolic pressure in a subject.

Abstract: In certain aspects, the present disclosure relates to polypeptides comprising a truncated, ligand-binding portion of the extracellular domain of T?RII polypeptide useful to selectively antagonize a T?RII ligand. The disclosure further provides compositions and methods for use in treating or preventing TGF? associated disorders.