Acceleron Pharma Inc.

Keros Therapeutics, Inc.

Genetics Institute, Inc.

Ludwig Institute for Cancer Research Limited

Jasbir S Seehra

John L Knopf

Ravindra Kumar

Robert Scott Pearsall

Jennifer Lachey

Asya Grinberg

Matthew L Sherman

Jean E Bemis

Yibin Xiang

John C McKew

Dianne S Sako

Gray D Shaw

Frank Eldridge Lovering

Amechand Boodhoo

Neelu Kaila

Neil M Wolfman

Mark L Stahl

Lihren Chen

William Stuart Somers

Kristian Pietras

Elissa Furutani

Niels Borgstein

Alan Koncarevic

Rodney M Hewick

Naga Venkata Sai Rajasekhar Suragani

David T Rogers

Thomas E McDonagh

Guang-Yi Xu

Erik M Vogan

Erik Martinez-Hackert

Christopher R Rovaldi

Hsiang-Ai Yu

Claudia Ordonez

Jin Hong

Andrea Dessen

Ken Attie

The invention relates to methods of treating multiple osteochondroma and anemia resulting from iron imbalance using small molecule ALK2 inhibitors.

Methods of using ALK2 inhibitors

The invention features methods of treating iron overload in a subject by administering BMP or hepcidin inhibitors, such as ALK2 inhibitors. The invention also features methods of decreasing iron levels in a subject by administering BMP or hepcidin inhibitors.

Methods of treating iron overload with a BMP inhibitor

The invention features polypeptides that include an extracellular ActRIIB variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRIIB variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions containing said polypeptides and methods of using the polypeptides to treat diseases and conditions including neuromuscular diseases, osteogenesis imperfecta, myelofibrosis, thrombocytopenia, neutropenia, and metabolic disease.

Methods of using activin receptor type IIB variants

The present invention relates to compositions and methods of GDNF fusion polypeptides, wherein the GDNF fusion polypeptides include an Fc domain, an albumin-binding peptide, a fibronectin domain, or a human serum albumin, joined to a GDNF variant either directly or by the way of a linker. The GDNF fusion polypeptides may used to treat metabolic diseases, such as obesity and Type-1 and Type-2 diabetes, and neurological diseases, such as Amyotrophic lateral sclerosis (ALS) and Parkinson's disease.

GDNF fusion polypeptides and methods of use thereof

The invention features polypeptides that include an extracellular ActRIIA variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRIIA variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving low red blood cell levels, e.g., anemia or blood loss; fibrosis; or pulmonary hypertension.

Activin receptor type IIA variants and methods of use thereof

The invention features polypeptides that include an extracellular ActRIIa variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRIIa variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, e.g., Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, inclusion body myositis, amyotrophic lateral sclerosis, sarcopenia; or cancer cachexia; or metabolic diseases, e.g., obesity, Type-1 diabetes, or Type-2 diabetes.

Activin receptor type IIa variants and methods of use thereof

The invention features ALK2 antibodies and antigen binding fragments thereof (e.g., ALK2 binding fragments). The invention also features pharmaceutical compositions and methods of using the ALK2 antibodies or antigen binding fragments thereof to treat bone disease or damage, low red blood cell levels (e.g., anemia or blood loss), heterotopic ossification (e.g., heterotopic ossification resulting from fibrodysplasia ossificans progressiva), Sjogren's syndrome (e.g., dry eye associated with Sjogren's syndrome), multiple osteochondroma, diffuse intrinsic pontine glioma, posterior capsule opacification, or cardiac hypertrophy and/or cardiac fibrosis.

ALK2 antibodies and methods of use thereof

The invention features polypeptides that include an extracellular ActRIIB variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRIIB variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, bone damage, low red blood cell levels (e.g., anemia or blood loss), fibrosis, and/or pulmonary hypertension.

Activin receptor type IIB variants and methods of use thereof

In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a ligand-binding portion of the extracellular domain of activin-like kinase I (ALK1) polypeptide may be used to inhibit angiogenesis in vivo, particularly in mammals suffering angiogenesis-related disorders. The disclosure also identifies ligands for ALK1 and demonstrates that such ligands have pro-angiogenic activity, and antibodies that inhibit receptor-ligand interaction.

ALK1 receptor and ligand antagonists and uses thereof

Nucleic acid molecules encoding activin receptor type IIA variants

The invention features polypeptides that include an extracellular ActRlla variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRlla variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving bone damage, e.g., primary osteoporosis, secondary osteoporosis, osteopenia, osteopetrosis, fracture, bone cancer or cancer metastasis-related bone loss, Paget's disease, renal osteodystrophy, treatment-related bone loss, diet-related bone loss, bone loss associated with the treatment of obesity, low gravity-related bone loss, or immobility-related bone loss.

In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.

Methods for treating anemia in a subject in need thereof

Growing community of inventors

Tewskbury, MA, United States of America

Jasbir S Seehra