The Brigham and Women's Hospital, Inc.

The United States of America, As Represented by the Secretary, Department of Health and Human Services

The General Hospital Corporation

Acceleron Pharma Inc.

University of Houston System

Paul B Yu

Gregory D Cuny

Arthur Lee

Asaf Alimardanov

Wei Ping Zheng

John C McKew

Philip Edward Sanderson

Xiuli Huang

Agustin H Mohedas

Ravindra Kumar

Asya Grinberg

Dianne S Sako

Roselyne Castonguay

Wenwei Huang

Min Shen

Kenneth D Bloch

Rita M Steeves

Khalida Shamim

Jian-kang Jiang

Charles C Hong

Randall T Peterson

Gregory J Tawa

Junfeng Huang

Jana Bagarova

Xin Xu

Gurmit Singh Grewal

Paresma R Patel

Devaveena Dey

Lai-Ming Yung

Rita Steeves

In some aspects, the invention teaches pharmaceutical compositions that include a TGF-β ligand trap, and methods of using a TGF-β ligand trap to treat, prevent, or reduce the progression rate of pulmonary hypertension (PH). The invention also provides methods of using a TGF-β 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-β signaling, diseases associated with excessive GDF15 signaling, and diseases associated with excessive PAI-1 signaling. The invention further provides methods of using a TGF-β ligand trap to reduce right ventricular systolic pressure in a subject.

Methods for treating pulmonary hypertension with a ligand binding domain of a TGF-beta type II receptor

The present invention provides small-molecule inhibitors of BMP signaling and compositions and methods for inhibiting BMP signaling. These compounds and compositions may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds and compositions may also be used to treat subjects with Sj&#xf6;gren's syndrome, or diffuse intrinsic pontine glioma (DIPG).

ALK2 inhibitors and methods for inhibiting BMP signaling

The technology described herein is directed to methods and compositions for the treatment of hypertension, e.g. pulmonary arterial hypertension, relating to inhibition of TGF&#x3b2;1, TGF&#x3b2;3, and/or GDF-15.

Methods using GDF-15 antibodies for treatment of pulmonary arterial hypertension

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.

Methods for treating pulmonary hypertension with a TGF-beta type II receptor-FC fusion protein

Provided herein are methods and compositions for the treatment and/or prevention of abnormal bone formation in a soft tissue. In certain embodiments, the methods and compositions treat and/or prevent a disease or disorder comprising abnormal bone formation in soft tissue. Exemplary diseases or disorders that can be treated with the methods and compositions described herein include, but are not limited to, heterotopic ossification diseases such as fibrodysplasia ossificans progressive, anklyosing spondylosis, traumatic heterotopic ossification, burn- or blast-injury associated heterotopic ossification, and joint replacement surgery associated heterotopic ossification.

Methods and compositions for the treatment or prevention of abnormal bone formation in a soft tissue

The present invention provides bicyclic heteroaryl inhibitors of BMP signaling and compositions and methods for inhibiting BMP signaling. Exemplary compounds include those of Formula I:  These compounds and compositions may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds and compositions may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.

Compositions and methods for inhibiting BMP

The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.

BMP inhibitors and methods of use thereof

The present invention provides pyridinyl-substituted pyrazolyl pyrimidine small molecule inhibitors of bone morphogenetic protein (BMP) signaling having the structure of formula (I), wherein variables A, B, E, F, X, Y, Z, Ar, L, Rand Rare as defined in the specification. The compounds of the invention are useful in modulating cell growth, differentiation, proliferation, and apoptosis, and thus are useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.

Inhibitors of the BMP signaling pathway

The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.

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Boston, MA, United States of America

Paul B Yu