Abstract: An inhaler for delivery of a medicament by inhalation includes an inhaler body for receiving a canister having a dispensing valve. A drive mechanism is provided for driving the canister from a rest position in which the valve is closed to an actuating position in which the valve is open. A resetting mechanism is provided for resetting the drive mechanism. A return mechanism is provided for returning the canister from the actuating position to the rest position, wherein the return mechanism comprises a damping system that is configured to enable the canister to automatically return from the actuating position to the rest position within a predetermined time period. A method of operation of an inhaler is also disclosed.

Abstract: Disclosed include crystalline (S)-2-amino-N-((3R,5R)-8-hydroxy-6-oxo-7-oxa-1-aza-8-boraspiro[4.7]dodecan-3-yl)-3-methylbutanamide in Form D and in Form E: (3R,5R)-8-hydroxy-3-((S)-4-isopropyl-2,2-dimethyl-5-oxoimidazolidin-1-yl)-7-oxa-1-aza-8-boraspiro[4.7]dodecan-6-one or a pharmaceutically acceptable salt thereof or the crystalline Form 1 thereof: and pharmaceutical compositions and methods of using the same.

Abstract: The specification relates to spirocyclic compounds of Formula (I) and pharmaceutically acceptable salts thereof. The specification also relates to processes and intermediates used for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.

Abstract: Methods for treating and/or preventing HFpEF and/or at least one disease, disorder, and/or condition associated therewith in patients by the use of dapagliftozin and compositions comprising the same are disclosed.

Abstract: Disclosed are compounds of formula (Ia) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of formula (Ia) and methods of using the same for treating cancer or a respiratory inflammatory disease and inhibiting arginase: wherein R1 is —NHR1a; R1a is —H or —C(O)CH(R1b)NHR1c; and R1b is selected from —H, —(C1-C4) alkyl and CH2OR1d and R1c is —H; or R1b and R1c, together with the atom to which they are attached, form a 5-membered heterocyclic ring; and R1d is H or —CH3.

Abstract: The present disclosure is directed to methods of treating patients with heart failure with reduced ejection fraction (HFrEF), with and without Type 2 diabetes, with an SGLT2 inhibitor, such as dapagliflozin. The methods disclosed herein can reduce the risk of a composite outcome of a first episode of worsening heart failure (hospitalization for heart failure or an urgent heart failure visit) or death from cardiovascular causes. Each of the three components of this composite outcome can also be reduced, as well as the total number of heart failure hospitalizations and deaths from cardiovascular causes. SGLT2 inhibitors, such as dapagliflozin, can also reduce a worsening of heart failure symptoms. The methods disclosed herein can also improve heart failure symptoms, health status, and quality of life.

Abstract: The present disclosure relates to methods for treating bronchiectasis, for example, non-cystic fibrosis bronchiectasis with compositions comprising an effective amount of certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds of Formula (I), including pharmaceutically acceptable salts thereof, that inhibit dipeptidyl peptidase 1 (DPP1) activity. Methods provided herein are useful for prophylaxis, increasing the lung function in a patient, and/or and/or decreasing the rate of pulmonary exacerbation in a patient. In one embodiment, the compound of Formula (I) is (2S)—N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide.

Abstract: The specification generally relates to compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, where R, A1, A2 and A3 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent DNA-PK mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating DNA-PK mediated disease, including cancer, using such compounds and salts.

Abstract: An inhaler 10 for delivery of a medicament by inhalation. The inhaler 10 has a drive mechanism, a canister drive 22 for receiving a canister 50 of medicament, a spring 20, and a trigger mechanism with a latch 35. The latch 35 has a locked position to prevent linear movement of the canister drive 22 and holds the spring 20 in a loaded configuration; and an unlocked position in which the latch 35 is disengaged from the canister drive 22. The trigger mechanism comprises a blocker 32. The blocker 32 has a blocking position in which it contacts the latch 35 to block movement from the locked position to the unlocked position; and a rotated position in which the blocker 32 is disengaged from the latch 35 to allow it to lock and unlock.

Abstract: The present application relates to chemical compounds of Formula (A): and pharmaceutically acceptable salts thereof, wherein X, R1, and R2 are as defined herein. The chemical compounds of Formula (A) inhibit IRAK4 and consequently have potential utility in medicine.

Abstract: An embodiment may involve obtaining a set of pre-defined features and a new document; extracting a subset of the pre-defined features from within new document; applying a natural language model to the new document, wherein the natural language model was pre-trained using scientific or medical literature and fine-tuned using a corpus of documents; applying a feature-based model to the subset of the pre-defined features extracted from the new document, wherein the feature-based model was trained with the pre-defined features and the respective labels of the documents; and applying an aggregation model to the classifications of the new document produced by the natural language model and the feature-based model, wherein the aggregation model was trained with prior classifications produced by the natural language model and the feature-based model so that the aggregation model produces a further classification of the new document representing its relevance to pharmacovigilance.

Abstract: The present disclosure provides methods of treating or preventing fatty liver disease and/or lowering cholesterol and LDL cholesterol levels in a subject. The present disclosure further provides methods of lowering expression of Pleckstrin and Sec7 Domain Containing 3 (PSD3) in a subject.

Abstract: Methods for treating and/or preventing HFpEF and/or at least one disease, disorder, and/or condition associated therewith in patients by the use of dapagliflozin and compositions comprising the same are disclosed.

Abstract: The present disclosure relates to certain (2,S)-N-[(1,S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

Abstract: The invention concerns pharmaceutical compositions containing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide and solvates, crystalline forms and amorphous forms thereof, to the use of said compositions as a medicament; and to processes for the preparation of said compositions.

Abstract: The present invention relates to azaquinolone compounds of Formula (I), and their use in medicine.

Abstract: The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

Abstract: The invention relates to a novel group of compounds of Formula (I) or salts thereof: wherein Y, Z1, Z2, R1, R4, R5 and n are as described in the specification, which may be useful in the treatment or prevention of a disease or medical condition mediated through protein kinase B (PKB) such as cancer. The invention also relates to pharmaceutical compositions comprising said compounds, methods of treatment of diseases mediated by PKB using said compounds and methods for preparing compounds of Formula (I).

Abstract: The present disclosure relates to new therapeutic uses of MPO inhibitors and methods of treatment involving the same.

Abstract: The present disclosure relates to the endothelin receptor antagonist (ERA) zibotentan in combination with the sodium-dependent glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin for use in the treatment of certain endothelin related diseases.