Abstract: The present invention provides co-formulations of anti-PD-1 antibodies and anti-LAG3 antibodies, and their use in treating various disorders.

Abstract: The present invention is directed to substituted certain 1-pyrazolyl, 5-, 6-disubstituted indazole derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, and ring A are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of diseases, such as Parkinson's disease, in which LRRK-2 kinase is involved.

Abstract: In its many embodiments, the invention provides compounds of structural Formula (I): (I), and pharmaceutically acceptable salts thereof, wherein, ring A, R1, R2 and R3 are as defined herein, and pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents). The invention further provides methods for the preparation and use of the compounds of the invention, or a pharmaceutically acceptable salt thereof, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.

Abstract: The present invention relates to Compounds of Formula I: and pharmaceutically acceptable salts or prodrug thereof. The present invention also relates to compositions comprising at least one compound of Formula I, and methods of using the compounds of Formula I for treatment or prophylaxis of lysosomal storage diseases, neurodegenerative disease, cystic disease, cancer, or a diseases or disorders associated with elevated levels of glucosylceramide (GlcCer), glucosylsphingosine (GlcSph) and/or other glucosylceramide-based glycosphingolipids (GSLs).

Abstract: The application relates to a pharmaceutical combination or combinational therapy comprising a therapeutically effective amount of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, and at least one second agent, or a pharmaceutically acceptable salt thereof, for use in the treatment of a BTK-mediated disease or disorder.

Abstract: The present disclosure is directed to cyclohexylglycine derivatives of Formula I and their use as HIV-infected cell kill agents which accelerate the death of HIV GAG-POL expressing cells without concomitant cytotoxicity to HIV naïve cells.

Abstract: The present disclosure provides methods for the acute treatment of migraine with or without aura, comprising the administration of ubrogepant. In particular, the present disclosure provides methods for the acute treatment of migraine in patients having hepatic impairment; in patients with renal impairment; and in patients concurrently taking CYP3A4 modulators or BCRP and/or P-gp only inhibitors.

Abstract: The present invention is directed to heteroaryl pyrrolidine and piperidine compounds which are agonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.

Abstract: The invention provides compositions and methods for the treatment of diseases associated with amyloid deposits of A? in the brain of a patient, such as Alzheimer's Disease. Such methods entail administering a pharmaceutical composition comprising an immunogenic fragment of A? capable of inducing a beneficial immune response in the form of antibodies to A?. The immunogenic fragments comprise linear or multivalent peptides of A?. Pharmaceutical compositions comprise the immunogenic fragment chemically linked to a carrier molecule which may be administered with an adjuvant.

Abstract: Provided are compounds of the Formula (I), or their pharmaceutically acceptable salts, wherein X1, X2, X3, R1-R9, RA, RB, RD, A1, A2, and subscripts t and w are as herein described. The compounds and their pharmaceutically acceptable salts can trap IL-1? and are expected to have utility as therapeutic agents, for example, for treating cardiovascular disease and inflammatory disorders. The disclosure also provides pharmaceutical compositions which comprise the compounds disclosed herein or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cardiovascular disease and inflammatory disorders and for preparing pharmaceuticals for this purpose.

Abstract: Described herein are compounds of Formula I or a pharmaceutically acceptable salt thereof. The compounds of Formula I act as RIPK1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for RIPK1-related diseases.

Abstract: The present invention provides immunogenic compositions having one or more polysaccharide-protein conjugates in which one or more polysaccharides from Streptococcus pneumoniae bacterial capsules are conjugated to a carrier protein in an aprotic solvent such as dimethylsulfoxide (DMSO). The present invention also provides methods for providing an enhanced immune response to a pneumococcal polysaccharide protein conjugate vaccine comprising administering to a human subject an immunogenic composition comprising polysaccharide-protein conjugates prepared in DMSO conditions.

Abstract: The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W1, W2, Y, Z, M, L, Cy, Cz, R1, R2, R3, R4, R2a, Ry, Rz, and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

Abstract: An adaptive risk management application retrieves data corresponding to an asset. The asset is a computing device or software application of an enterprise system. The adaptive risk management system identifies a set of vulnerabilities of the asset. For each vulnerability in the set of vulnerabilities, the adaptive risk management application generates a recommendation for mitigating the vulnerability. The adaptive risk management application generates a user interface for the asset. The user interface comprises a list of the recommendations. The adaptive risk management system provides the user interface for display.

Abstract: A method of treating metastatic pancreatic adenocarcinoma in a subject in need thereof is provided. The method comprising administering to the subject a therapeutically effective amount of each of a peptide set forth in SEQ ID NO: 1, an anti PD-1 and a chemotherapy, thereby treating the metastatic pancreatic adenocarcinoma.

Abstract: The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W1, W2, Y, Z, M, L, Cy, Cz, R1, R2, R3, R4, R2a, Ry, Rz, and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

Abstract: In some embodiments, devices for use as blood-brain barrier models are disclosed. The devices may include either a hydrogel component that surrounds a channel formed between a first opening and a second opening of the hydrogel component, or a hydrogel component that forms a groove. The devices may further include pericytes disposed in the channel or the groove, and endothelial cells may be disposed in the channel or the groove. The hydrogel component may include astrocytes (e.g., printed into the hydrogel component via projection stereolithography). Also disclosed are various methods of making and using these devices.

Abstract: The present invention relates to Compounds of Formula I: and pharmaceutically acceptable salts or prodrug thereof, wherein R1, R2, R3, A and B are as defined herein. The present invention also relates to compositions comprising at least one compound of Formula I, and methods of using the compounds of Formula I for treating or preventing cancer, inflammation, neurodegeneration disease and/or diabetes in a subject.

Abstract: The present invention provides pneumococcal conjugate vaccine formulations comprising surfactant systems incorporating polysorbate 20 or a combination of a poloxamer and a polyol.

Abstract: Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof (I). Also disclosed herein are uses of the compounds disclosed herein in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising a compound disclosed herein. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.