The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or in B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at least one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below: ##STR00001##

Provided herein are methods of treating graft-versus-host disease in a subject by administering pharmaceutical compositions containing bacterial strains of the Clostridia class. Also described herein are exemplary human-derived bacteria belonging to the Clostridia class, combinations of which have been shown to induce accumulation of regulatory T cells (Treg cells) in the colon and suppress immune functions, and are therefore useful for mitigating pathological immune responses. Pharmaceutical compositions containing these and/or related bacteria can be used to prevent and treat immune-mediated diseases such as graft-versus-host disease.

The present disclosure relates generally to compounds that bind to Lysophosphatidic Acid Receptor 1 (LPAR1) and act as antagonists of LPAR1. The disclosure further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of LPAR1, including fibrosis and liver diseases such as non-alcoholic steatohepatitis (NASH), interstitial lung disease (ILD), or chronic kidney disease (CKD).

The present invention relates to novel compounds as autotoxin inhibitors for treatment and prophylaxis of conditions or a disorder caused by autotaxin activation or increased concentration of lysophosphatidic acid, and also a pharmaceutical composition containing the same. The novel compounds of the present invention are autotoxin inhibitors, and by inhibiting the production of lysophosphatidic acid, they are useful for treatment or prophylaxis of cardiovascular disorder, cancer, metabolic disorder, kidney disorder, liver disorder, inflammatory disorder, nervous system disorder, respiratory system disorder, fibrotic disease, ocular disorder, cholestatic and other forms of chronic pruritus, or acute or chronic organ transplant rejection.

The present disclosure relates generally to compounds that bind to Lysophosphatidic Acid Receptor 1 (LPAR1) and act as antagonists of LPAR1. The disclosure further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of LPAR1, including fibrosis and liver diseases such as non-alcoholic steatohepatitis (NASH), interstitial lung disease (ILD), or chronic kidney disease (CKD).

The present invention is directed to a pharmaceutical composition including (e.g. for use as an adjuvant) a polymeric carrier cargo complex, comprising as a carrier a polymeric carrier formed by disulfide-crosslinked cationic components; and as a cargo at least one nucleic acid molecule, and at least one antigen that is selected from an antigen from a pathogen associated with infectious disease; an antigen associated with allergy or allergic disease; an antigen associated with autoimmune disease; or an antigen associated with a cancer or tumour disease, or in each case a fragment, variant and/or derivative of said antigen. The pharmaceutical composition allows for efficient induction of an adaptive immune response directed against said antigen. The present invention furthermore provides kits, as well as the use of the pharmaceutical composition or the kit as a vaccine, particularly in the treatment of infectious diseases, allergies, autoimmune diseases and tumour or cancer diseases.

A compound of formula (I) ##STR00001##
wherein X is 0, C=0 or S; Y is N or CH; R.sub.2 and R.sub.4 are each independently H, —(CH.sub.2).sub.pCOOH, —(CH.sub.2).sub.pCON(R.sup.5).sub.2 or —(CH.sub.2).sub.pCOOC.sub.1-6alkyl; or R.sub.2 and R.sub.4 together form a 6-membered phenyl ring fused to the five membered ring; each R.sub.1 is independently selected from H, halo (e.g. fluoro or chloro), C.sub.6-10aryl, C.sub.7-12arylalkyl, C.sub.2-12 alkenyl; OC.sub.1-12 alkyl, OC.sub.2-12 alkenyl or a C.sub.1-12 alkyl group; each R.sup.5 is H or C.sub.1-6 alkyl; each p is 0 to 3; n is 1 to 4; or a salt, ester, solvate, N-oxide, or prodrug thereof, e.g. a salt thereof.

The present invention provides bicyclic heterocyclyl kinase enzyme inhibitor compounds of formula (I), which are therapeutically useful as kinase inhibitors, particularly IRAK4 inhibitors. ##STR00001##
wherein A, Y, Z, X.sub.1, X.sub.2, X.sub.3, R.sub.1, R.sub.3, ‘m’, ‘n’ and ‘p’ have the meanings given in the specification and pharmaceutically acceptable salt or stereoisomer thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder mediated by kinase enzyme, particularly IRAK4 enzyme. The present invention also provides pharmaceutical composition comprising at least one of the compounds of compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient therefor.