Ardelyx, Inc.

Pfizer Corporation

Threshold Pharmaceuticals, Inc.

Lycia Therapeutics, Inc.

Jason Gustaf Lewis

Jeffrey William Jacobs

Tao Chen

Michael Robert Leadbetter

Christopher Carreras

Noah Bell

Dominique Charmot

Eric Labonte

Dean R Dragoli

Rakesh K Jain

Han-Ting Chang

Marc Navre

Nicholas Reich

Jeremy Caldwell

Helene Baribault

Irina Dotsenko

Jianhua Chao

Lily Hu

Matthew John Siegel

Patricia Finn

Mikhail Fedorovich Gordeev

Gary Luehr

Liansheng Li

Mark D Matteucci

Eric Douglas Turtle

Justin T Ernst

Garrick Kenneth Packard

Brett Bradley Busch

Hailong Jiao

Sampath Kumar Anandan

Charles Francavilla

Matthew Siegel

Ingrid Langsetmo

Andrew King

Hardwin O'Dowd

Ying He

Xunxiang Du

Johan Oslob

The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

Compounds useful for treating gastrointestinal tract disorders

The present disclosure provides a class of compounds including a ligand moiety that specifically binds to a cell surface asialoglycoprotein receptor (ASGPR). The cell surface ASGPR binding compounds can trigger the receptor to internalize into the cell a bound compound. The ligand moieties of this disclosure can be linked to a variety of moieties of interest without impacting the specific binding to, and function of, the cell surface receptor ASGPR. Also provided are compounds that are conjugates of the ligand moieties linked to a biomolecule, such as an antibody, which conjugates can harness cellular pathways to remove specific proteins of interest from the cell surface or from the extracellular milieu. Also provided herein methods of using the conjugates to target a polypeptide of interest for sequestration and/or lysosomal degradation.

ASGPR cell surface receptor binding compounds and conjugates

The invention relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): wherein L, A, X, X, R, R, and Rare described herein.

Hormone receptor modulators for treating metabolic conditions and disorders

The invention relates to non-systemic TGR5 agonist useful in the treatment of chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition especially during short bowel syndrome, and irritable bowel syndrome (IBS), and other TGR5 associated diseases and disorders, having the Formula:

Substituted 4-phenyl pyridine compounds as non-systemic TGR5 agonists

The present invention provides a compound of formula (I) or a salt thereof: (Formula (I)) wherein X, L, V, R; R, Rand R, are as defined herein. The claimed compounds inhibit the enzyme 11-hydroxysteroid dehydrogenase type 2 (11-HSD2) and as a result are useful in the treatment of hyperkalemia by preventing cortisol from being oxidised to cortisone and thus allowing it to occupy the mineralocorticoid receptor, thus stimulating potassium excretion.

Glycyrrhetinic acid derivatives for use in treating hyperkalemia

Provided are non-NHE3-binding agents having activity as phosphate transport/uptake inhibitors in the gastrointestinal tract, including in the small intestine, methods for their use as therapeutic or prophylactic agents, and related methods of drug discovery.

Compounds and methods for inhibiting phosphate transport

The present invention provides a compound of formula (I) or a salt thereof: (I) wherein X, L, V, R, R, Rand R, are as defined herein. These compounds are inhibitors of 11-hydroxysteroid dehydrogenase type 2 (11-HSD-2) and are used to treat hyperkalemia.

Glycyrrhetinic acid derivatives for treating hyperkalemia

The disclosure relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): wherein L, L, A, B, R, R, R, and Rare described herein.

Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators

The present disclosure is directed to compounds (I') and to their use in methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds (I&#x2032;) and their use in methods for the treatment of hypertension. The present disclosure is also directed to compounds (I&#x2032;) and to their use in methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders. 

Inhibitors of NHE-mediated antiport

The disclosure relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): wherein L, L, A, B, R, R, R, and Rare described herein. 

The invention relates to non-systemic TGR5 agonist useful in the treatment of chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition especially during short bowel syndrome, and irritable bowel syndrome (IBS), and other TGR5 associated diseases and disorders, having the Formula: where R, R, R, R, R, X, X, X, X, Q, and n are described herein.

Provided are NHE3-binding and/or NHE3-modulating agents having activity as phosphate transport inhibitors, including inhibitors of phosphate transport in the gastrointestinal tract and the kidneys, and methods for their use as therapeutic or prophylactic agent.

NHE3-binding compounds and methods for inhibiting phosphate transport

The invention relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): (I), wherein L, A, X, X, R, R, and Rare described herein. 

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Castro Valley, CA, United States of America

Jason Gustaf Lewis