Ngm Biopharmaceuticals, Inc.

Amgen Inc.

Other

Hui Tian

Bei Shan

Lei Ling

Joshua Schultz

Jian Luo

Darrin Anthony Lindhout

Jin-Long Chen

Raj Haldankar

Daniel David Kaplan

Jer-Yuan Hsu

Xuecai Ge

Alexander Mark Depaoli

Yasuyuki Ogawa

Ming Yu

Zice Fu

Xiaolin Hao

Leping Li

Sarah Lively

Zhaodan Cao

Mike Elias Lizarzaburu

Satoshi Shibuya

Narihiro Toda

Helen H Hobbs

Yong-Jae Kim

Robert P Barnes

Songzhu An

Ryo Okuyama

Wendy Wen Zhong

Sarah E Lively

Mike Lizarzaburu

The present disclosure provides binding agents that modulate the interaction between liver-expressed antimicrobial peptide 2 (LEAP2) and growth hormone secretagogue receptor (GHSR). Specifically, the present disclosure provides binding agents, such as LEAP2 peptides that bind GHSR and methods of their use to treat or ameliorate a neuroendocrine and/or metabolic disease or disorder such as obesity, diabetes, acromegaly, gigantism and/or Prader-Willi syndrome. The present disclosure also provides binding agents, such as antibodies, that bind LEAP2, and methods of their use to, e.g., treat or ameliorate a neuroendocrine and/or metabolic disease or disorder such as cachexia, anorexia, or other wasting syndromes, increase growth hormone levels, or increase GHSR activity.

Methods of treating a wasting syndrome, increasing growth hormone levels, and increasing GHSR activity with a LEAP2 antibody

Provided are methods of treating a FGF19-mediated cancer or tumor in a subject by administering to the subject an anti-IL-6 antibody or an anti-IL-6 receptor antibody or an inhibitor of STAT3/JAK signaling pathway, and pharmaceutical compositions relating thereto.

Methods of treating fibroblast growth factor 19-mediated cancers and tumors

Methods of treating individuals with a glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.

Compositions and methods of use for treating metabolic disorders

Provided herein are methods of modulating bile acid homeostasis or treating a bile-acid related or associated disorder, comprising using variants and fusions of fibroblast growth factor 19 (FGF19), variants and fusions of fibroblast growth factor 21 (FGF21), fusions of FGF19 and/or FGF21, and variants or fusions of FGF19 and/or FGF21 proteins and peptide sequences (and peptidomimetics), in combination with agents effective in modulating bile acid homeostasis or treating a bile-acid related or associated disorder.

Methods and uses for modulating bile acid homeostasis and treatment of bile acid disorders and diseases

Provided herein are methods of using 7&#x3b1;-hydroxy-4-cholesten-3-one (C4) in predicting the clinical sensitivity to treatment of bile acid-related and associated disorders with treatment peptides, such as variants of fibroblast growth factor 19 (FGF19) proteins and peptide sequences (and peptidomimetics) and fusions of FGF19 and/or fibroblast growth factor 21 (FGF21) proteins and peptide sequences (and peptidomimetics), and variants of fusions of FGF19 and/or FGF21 proteins and peptide sequences (and peptidomimetics).

Methods for treatment of bile acid-related disorders and prediction of clinical sensitivity to treatment of bile acid-related disorders

The present disclosure provides binding agents that modulate the interaction between LEAP2 and GHSR. Specifically, the present disclosure provides binding agents, such as LEAP2 peptides that bind GHSR and methods of their use to treat, ameliorate, or prevent a neuroendocrine and/or metabolic disease or disorder such as obesity, diabetes, acromegaly, gigantism and/or Prader-Willi syndrome. The present disclosure also provides binding agents, such as antibodies, that bind LEAP2, and methods of their use, to treat, ameliorate, or prevent a neuroendocrine and/or metabolic disease or disorder such as cachexia, anorexia, or other wasting syndromes.

LEAP2 binding agents and compositions thereof

Provided herein are variants of fibroblast growth factor 19 (FGF19) proteins and peptide sequences (and peptidomimetics) and fusions of FGF19 and/or fibroblast growth factor 21 (FGF21) proteins and peptide sequences (and peptidomimetics), and variants of fusions of FG-F19 and/or FGF21 proteins and peptide sequences (and peptidomimetics). In some embodiments, these variants and fusions modulate bile acid homeostasis, and are useful in treatment of bile acid related and associated disorders. In some embodiments, these variants and fusions have glucose lowering activity, and are useful in treatment of hyperglycemia and other disorders.

Methods of using variants of FGF19 polypeptides for the treatment of pruritus

Provided herein are methods of using 7a-hydroxy-4-cholsten-3-one (C4) in predicting the clinical sensitivity to treatment of bile acid-related and associated disorders with treatment peptides, such as variants of fibroblast growth factor 19 (FGF19) proteins and peptide sequences (and peptidomimetics) and fusions of FGF19 and/or fibroblast growth factor 21 (FGF21) proteins and peptide sequences (and peptidomimetics), and variants of fusions of FGF19 and/or FGF21 proteins and peptide sequences (and peptidomimetics).

The present invention provides nucleic acids encoding a novel ABC family cholesterol transporter, SSG. The herein-disclosed sequences can be used for any of a number of purposes, including for the diagnosis and treatment of cholesterol-associated disorders, including sitosterolemia, and for the identification of molecules that associate with and/or modulate the activity of SSG.

Screening methods using sitosterolemia susceptibility gene (SSG) polypeptides

Compounds having formula I: where A, A, L, V, W, R, R, R, Rand Rare as described herein, compositions thereof, and their use for the treatment or prevention of type 2 diabetes and type 2 diabetes-related conditions are provided herein.

N-aryl pyrazole compounds, compositions, and methods for their use

Sitosterolemia susceptibility gene (SSG): compositions and methods of use

The present invention provides polypeptides of a novel ABC family cholesterol transporter, SSG. The herein-disclosed sequences can be used for any of a number of purposes, including for the diagnosis and treatment of cholesterol-associated disorders, including sitosterolemia, and for the identification of molecules that associate with and/or modulate the activity of SSG.

Sitosterolemia susceptibility gene (SSG) polypeptides

The invention provides natural ligands of TGR183 receptors and methods of identifying modulators of various TGR183 receptors using the ligands. Methods of using the modulators to treat diseases or disorders associated with dysfunction of the TGR183 receptor are also provided.

Growing community of inventors

Foster City, CA, United States of America

Hui Tian