Methods of safely administrating a gut-selective JAK3 inhibitor by oral administration are described. Also described are methods for providing clinically proven safe treatment of gastrointestinal inflammatory diseases, such as celiac disease, by oral administration of a gut-selective JAK3 inhibitor.

Compounds, and compositions, methods, and uses thereof, are described herein for treating neurodegenerative diseases and disorders. In particular, vasopressin receptor modulators, and compositions, methods and uses thereof, are described herein for treating neuropsychiatric aspects of neurodegenerative diseases such as Huntington's Disease, Parkinson's Disease, and Alzheimer's Disease.

Compounds, and compositions, methods, and uses thereof, are described herein for treating neurodegenerative diseases and disorders. In particular, vasopressin receptor modulators, and compositions, methods and uses thereof, are described herein for treating neuropsychiatric aspects of neurodegenerative diseases such as Huntington's Disease, Parkinson's Disease, and Alzheimer's Disease.

A RORγt inhibitor as well as a preparation method thereof and uses thereof, and a pharmaceutical composition including the compound, a method for preparing the pharmaceutical composition, and use of the compound or the pharmaceutical composition in the treatment or prevention of RORγt-mediated cancer, inflammation, or autoimmune diseases in mammals, especially humans.

A RORγt inhibitor as well as a preparation method thereof and uses thereof, and a pharmaceutical composition including the compound, a method for preparing the pharmaceutical composition, and use of the compound or the pharmaceutical composition in the treatment or prevention of RORγt-mediated cancer, inflammation, or autoimmune diseases in mammals, especially humans.

The present invention relates to a compound of formula (Ia), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X-Y is —NHSO.sub.2— or —SO.sub.2NH—; R.sub.1 is H or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H, Cl and F; R.sub.5 is selected from H, alkyl, alkynyl, alkenyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, Cl, F, SO.sub.2-alkyl, SO.sub.2NR.sub.13R.sub.14, optionally substituted heteroaryl and alkyl; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H, C.sub.1-C.sub.3-alkyl, or halo; R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an azepanyl group, wherein (a) said azepanyl group is substituted by one or more substituents, or (b) one or two carbons in said azepanyl group are replaced by a group selected from O, NH, S and CO, and said azepanyl group is optionally further substituted; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an azetidinyl, pyrrolidinyl or piperidinyl group wherein (a) said azetidinyl, pyrrolidinyl or piperidinyl group is substituted by one or more substituents, or (b) one or two carbons in said azetidinyl, pyrrolidinyl or piperidinyl group are replaced by a group selected from NH, S and CO; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an 8, 9 or 10-membered bicyclic heterocycloalkyl group, wherein one or two carbons in the bicyclic heterocycloalkyl ring are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic heterocycloalkyl group is optionally substituted; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form a 6 to 12-membered bicyclic group containing a spirocyclic carbon atom, wherein one or two carbons in the bicyclic group are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic group is optionally substituted, or said bicyclic group is optionally fused to a 5 or 6-membered aryl or heteroaryl group; R.sub.13 and R.sub.14 are each independently H or alkyl. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

##STR00001##

The present invention relates to a compound of formula (Ia), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X-Y is —NHSO.sub.2— or —SO.sub.2NH—; R.sub.1 is H or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H, Cl and F; R.sub.5 is selected from H, alkyl, alkynyl, alkenyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, Cl, F, SO.sub.2-alkyl, SO.sub.2NR.sub.13R.sub.14, optionally substituted heteroaryl and alkyl; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H, C.sub.1-C.sub.3-alkyl, or halo; R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an azepanyl group, wherein (a) said azepanyl group is substituted by one or more substituents, or (b) one or two carbons in said azepanyl group are replaced by a group selected from O, NH, S and CO, and said azepanyl group is optionally further substituted; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an azetidinyl, pyrrolidinyl or piperidinyl group wherein (a) said azetidinyl, pyrrolidinyl or piperidinyl group is substituted by one or more substituents, or (b) one or two carbons in said azetidinyl, pyrrolidinyl or piperidinyl group are replaced by a group selected from NH, S and CO; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an 8, 9 or 10-membered bicyclic heterocycloalkyl group, wherein one or two carbons in the bicyclic heterocycloalkyl ring are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic heterocycloalkyl group is optionally substituted; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form a 6 to 12-membered bicyclic group containing a spirocyclic carbon atom, wherein one or two carbons in the bicyclic group are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic group is optionally substituted, or said bicyclic group is optionally fused to a 5 or 6-membered aryl or heteroaryl group; R.sub.13 and R.sub.14 are each independently H or alkyl. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

##STR00001##

The present invention relates to the use of a farnesoid X receptor (FXR) agonist for the treatment of hepatitis D infection.

The present invention relates to the use of a farnesoid X receptor (FXR) agonist for the treatment of hepatitis D infection.

Therapeutic antibodies specific for osteopontin and methods of using them for treating osteopontin-associated disorders are provided. In particular, antibodies, or antigen-binding fragments thereof, that inhibit thrombin-cleavage of osteopontin or block the activity of thrombin cleavage fragments of osteopontin are provided. Additionally, antibody conjugates and pharmaceutical compositions or formulations comprising the antibodies or antibody conjugates as well as kits including the antibodies, conjugates, or formulations are also provided.