Abstract: The present disclosure provides methods and systems for high throughput assays for testing immune cell engager molecules and potential immune cell engager molecules. In some embodiments, multiple parameters, for example, in connection with engagement of tumor cells by immune cells such as T cells and in connection with tumor cell death, may be analyzed from the same samples in the assays, and, in some cases, may be analyzed simultaneously. In some embodiments, the methods and systems allow for determining the kinetics of various parameters.

Abstract: The invention relates generally crystalline mesylate salts, crystalline chloride salts and crystalline sulfate salts of the compound (S)-2-(3?-(hydroxymethyl)-1-methyl-5-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-6-oxo-1,6-dihydro- [3,4?-bipyridin]-2?-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one that is an inhibitor of Bruton’s tyrosine kinase. In some aspects, the crystalline salts are single polymorphs.

Abstract: Compounds of Formula (I): salts thereof and methods of making and use as Janus kinase inhibitors are described herein.

Abstract: Provided herein are high throughput methods for optimizing and manufacturing various lipid nanoparticle (LNP) compositions and uses thereof. For example, in some embodiments, the present disclosure provides a high-throughput screening method for manufacturing a LNP composition comprising, obtaining at least two intermixable solutions comprising a payload and a plurality of molecules capable of self-assembly and mixing said at least two solutions under a set of controlled conditions, by which injection sequence, speed, volume, phase ratio and mixing duration are varied. In various embodiments, the present disclosure enables optimal encapsulation efficiency, particle size distribution, purification and particle recovery rate, and formulation stability to be determined. The methods disclosed herein enable efficient optimization of manufacturing conditions for preparation of LNP-based therapeutics.

Abstract: The subject matter described herein is directed to antibody-CIDE conjugates (Ab-CIDEs) that target BRM for degradation, to pharmaceutical compositions containing them, and to their use in treating diseases and conditions where BRM degradation is beneficial.

Abstract: The invention relates to compounds and methods of using said compounds, as well as pharmaceutical compositions containing such compounds, for treating diseases and conditions mediated by TEAD, such as cancer.

Abstract: Provided herein are combination therapies comprising a KRasG12C inhibitor (e.g. GDC-6036) and an PI3K-inhibitor (e.g. inavolisib) and methods of using such combination therapies.

Abstract: The invention provides anti-Notch2 antibodies and conjugates and methods of using the same.

Abstract: The present invention relates to complement C1r subcomponent (C1R) inhibitors for use in treatment of neurological diseases. The invention in particular relates to the use of C1R inhibitors for down-regulation of C1R expression. The invention also relates to nucleic acid molecules, which are complementary to C1R and capable of reducing the level of an C1R mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment of neurological diseases.

Abstract: Provided herein are solid forms, salts, and formulations of 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropyl)azetidin-3-yl)amino)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol, processes and synthesis thereof, and methods of their use in the treatment of cancer.

Abstract: The present invention relates generally to the fields of molecular biology and growth factor regulation. More specifically, the invention relates to therapies for the treatment of pathological conditions, such as cancer.

Abstract: Provided are combination therapies comprising inavolisib (a.k.a. GDC-0077) and other HER2-targeted therapies (e.g., pertuzumab and trastuzumab) for the treatment of HER2-positive cancers; and methods of treating HER2 positive (HER2+) cancers in a patient (preferably a patient with a PIK3CA mutant breast cancer) comprising administering a therapeutically effective amount of inavolisib and a HER2-targeted therapy (e.g., trastuzumab, pertuzumab, or a combination of trastuzumab and pertuzumab).

Abstract: The present disclosure relates to methods and compositions for determining the relative distribution of glucuronidation, iduronidation, and/or galacturonidation of polypeptides, including stereoselective liquid chromatography-mass spectrometry (LC-MS) methods capable of achieving the simultaneous separation and relative quantitation of glucuronidation, iduronidation, and/or galacturonidation of polypeptides.

Abstract: The present invention relates to complement component 4 (C4) inhibitors for use in treatment of a neurological disease. The invention in particular relates to the use of C4 inhibitors for down-regulation of C4 expression. The invention also relates to nucleic acid molecules, which are complementary to C4A and/or C4B and capable of reducing the level of an C4A and/or C4B mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment of a neurological disease.

Abstract: Processes for preparing biheteroaryl compounds are provided, including the biheteroaryl compound 3-(difluoromethoxy)-5-[2-(3,3-difluoropyrrolidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridin-2-amine. Among other advantages, the processes provide for: the use of solvents that are relatively non-toxic and inexpensive; reduced usage of expensive precious metal catalysts; reaction temperature reduction in certain steps; the use of relatively non-toxic oxidation agents; the use of inexpensive transition metal catalysts; a reduction of molar ratios of certain reactants thereby improving process efficiency while reducing cost and waste; significantly higher reactant concentrations in certain steps; elimination of the need for multiple chromatographic purification steps; elimination of the need for certain extraction steps using organic solvent; and provide for higher yield and improved purity.

Abstract: Assays to analyze quality and quantity attributes of fixed dose combinations are provided. In particular, assays for fixed dose combinations of two anti-HER2 antibodies, and for subcutaneous formulations comprising pertuzumab and trastuzumab are described herein.

Abstract: A syringe (18) has a longitudinal body (28) with an interior (228) in which a pharmaceutical substance is arranged, a needle connected to one longitudinal end of the body (228) and a rigid needle shield (38) encasing the needle. The rigid needle shield (38) is essentially water vapour tight. The syringe (18) according to the invention allows for preventing needle clogging and, thus, proper provision of pharmaceuticals, particularly by subcutaneous, intramuscular or ocular injection.

Abstract: The present disclosure relates to techniques for continuous integration and continuous deployment of source code on a digital health platform. Particularly, aspects are directed to receiving source code from a software development system (the source code being validated in accordance with a first QMS), generating a profile for the source code, classifying the source code into a class of code based on the profile, retrieving a second QMS associated with the class of code, validating the source code in accordance with the second QMS, upon validation of the source code, executing a build process to generate a executable program from the source code, encapsulating the executable program in a container, and deploying the container on one or more nodes of a software platform. The first QMS is adapted from the perspective of the software development system; whereas the second QMS is adapted from the perspective of the software platform.

Abstract: The invention provides anti-Notch2 antibodies and methods of using the same.

Abstract: The invention provides compositions and methods for treating cancers. The methods comprising administering a PD-1 axis binding antagonist and an anti-GPC3 antibody. The compositions comprising a pharmaceutical composition for treating cancer which comprises a PD-1 axis binding antagonist and an anti-GPC3 antibody. Also disclosed are a pharmaceutical composition to be used in combination with a PD-1 axis binding antagonist for treating cancer which comprises an anti-GPC3 antibody as the active ingredient; and a pharmaceutical composition to be used in combination with an anti-GPC3 antibody for treating cancer which comprises as the active ingredient a PD-1 axis binding antagonist.