Abstract: The invention provides gastric residence systems with specifically tailored architectures and methods for making such systems. The components of the gastric residence systems can be manufactured by three-dimensional printing or by co-extrusion. The ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the systems.

Abstract: A gastric residence system comprises one or more retention members comprising: at least one drug eluting component; and at least one laser linker component laser welded to the at least one drug eluting component.

Abstract: Gastric residence systems for administration of risperidone are disclosed. Features which enhance gastric retention during the desired residence time and which allow for more precise control over residence time are disclosed, including circumferential filaments connecting the arms of a stellate gastric residence system; improved time-dependent and enteric disintegrating matrices (linkers); and release rate-modulating polymer coatings which are resistant to change in release rate properties during heat-assisted assembly or thermal cycling. Combinations of these features are also disclosed.

Abstract: There are disclosed certain substituted pyrazine-2-carboxamides of Formula (I), and pharmaceutically acceptable salts thereof, together with compositions containing them and their use in therapy. The compounds are inhibitors of hematopoietic progenitor kinase 1 (HPK1) and are thereby particularly useful in the treatment or prophylaxis of cancer.

Abstract: Provided are stomach simulating devices and methods for simulating a stomach. Stomach simulating devices can comprise a bag-shaped conduit, a mechanical constrictor, and a valve. The conduit can have a body portion, a first diameter at an inlet portion, and a second diameter at an outlet portion, wherein the first diameter at the inlet portion is greater than the second diameter at the outlet portion, the body portion is located between the inlet portion and the outlet portion, and at least a portion of the conduit is curved in a direction from the inlet portion the outlet portion. The mechanical constrictor can he configured to constrict at least a portion of the body portion of the conduit. The valve can be configured to at least partially close a portion of the conduit closer to the outlet portion than the inlet portion of the conduit.

Abstract: The invention provides gastric residence systems with configurations and geometrical dimensions that allow for improved shelf life during prolonged storage, and optimal residence properties when the systems are deployed in the stomach of a patient.

Abstract: The invention provides gastric residence systems with specifically tailored architectures and methods for making such systems. The components of the gastric residence systems can be manufactured by three-dimensional printing or by co-extrusion. The ability to construct precise architectures for the systems provides excellent control over drug release, in vivo stability, and residence time of the systems.

Abstract: The invention provides gastric residence systems with configurations and geometrical dimensions that allow for improved shelf life during prolonged storage, and optimal residence properties when the systems are deployed in the stomach of a patient.

Abstract: Compactable gastric residence systems comprising therapeutic agent formulations for sustained gastric release of therapeutic agents are disclosed, as well as methods and systems for encapsulating such gastric residence systems. The methods and systems for encapsulating the gastric residence systems can be automated from receiving a bulk of gastric residence systems, orienting, placing, compacting, securing, and encapsulating the gastric residence systems.

Abstract: Compactable gastric residence systems comprising therapeutic agent formulations for sustained gastric release of therapeutic agents are disclosed, as well as methods and systems for encapsulating such gastric residence systems. Hie methods and systems for encapsulating the gastric residence systems can be automated from receiving a bulk of gastric residence systems, orienting, placing, compacting, securing, and encapsulating the gastric residence systems.

Abstract: Gastric residence systems and methods of delivering a drug to an individual using a gastric residence system are described herein. The gastric residence system may include a time-dependent and/or enteric, or dual time-dependent and enteric polymeric linker. In some embodiments, the time-dependent polymeric linker includes PLGA, and optionally PLA or a carrier polymer. The enteric polymeric linker includes an enteric polymeric, and optionally a carrier polymer such as PCL or TPU. The time-dependent polymeric linker may degrade in the stomach of the individual according to a degradation (or flexural modulus loss) profile described herein, and the enteric polymeric linker may degrade in the intestine of the individual another degradation profile described herein (or flexural modulus loss).

Abstract: Gastric residence systems comprising therapeutic agent formulations for sustained gastric release of therapeutic agents are disclosed, as well as methods for using such systems. The systems are characterized by use of a dispersant in the formulations, which improves the burst release characteristics and long-term release rate characteristics of the systems. Milling of therapeutic agent can also be performed to prepare agent particles of desired size.

Abstract: Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.

Abstract: Provided are gastric residence systems comprising: a core; a plurality of arms connected to the core at a proximal end through a plurality of linker components, one linker component of the plurality of linker components corresponding to each arm of the plurality of arms, and the plurality of arms extending radially from the proximal end, and a filament circumferentially connecting each arm of the plurality of arms.

Abstract: Provided are gastric residence dosage forms comprising flexible arms that can help prevent premature passage of the gastric residence system through the pylorus of a patient. In particular, described herein are gastric residence systems comprising one or more arms extending radially, the one or more arms comprising a first segment comprising a first polymer composition and a second segment comprising a second polymer composition, wherein the first segment has a stiffness of greater than a stiffness of the second segment, as measured using a 3-point bending test per ASTM D790. The second segments of the arms of the gastric residence systems help prevent premature passage of the gastric residence system through the pylorus of a patient.

Abstract: Gastric residence systems for administration of agents, such as drugs, are disclosed. Features which enhance gastric retention during the desired residence time and which allow for more precise control over residence time are disclosed, including circumferential filaments connecting the arms of a stellate gastric residence system; flexible arms for a gastric residence system; improved time-dependent and enteric disintegrating matrices (linkers); and release rate-modulating polymer coatings which are resistant to change in release rate properties during heat-assisted assembly or thermal cycling. Combinations of these features are also disclosed.

Abstract: Certain embodiments comprise administering a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance, and, optionally, a linker. In some such embodiments, the linker may be configured to degrade.

Abstract: Provided are enrobed gastric residence dosage forms comprising: a gastric residence system in a folded configuration; and a coating enrobing the gastric residence system in the folded configuration, wherein the enrobed gastric residence dosage form is configured to release the gastric residence system in the folded configuration in a stomach of a patient, allowing the gastric residence system to assume an open configuration. The coating comprises water, a plasticizer, a gelling agent, and/or a polymer.

Abstract: Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.

Abstract: Provided are stomach simulating devices and methods for simulating a stomach. Stomach simulating devices can comprise a bag-shaped conduit, a mechanical constrictor, and a valve. The conduit can have a body portion, a first diameter at an inlet portion, and a second diameter at an outlet portion, wherein the first diameter at the inlet portion is greater than the second diameter at the outlet portion, the body portion is located between the inlet portion and the outlet portion, and at least a portion of the conduit is curved in a direction from the inlet portion the outlet portion. The mechanical constrictor can he configured to constrict at least a portion of the body portion of the conduit. The valve can be configured to at least partially close a portion of the conduit closer to the outlet portion than the inlet portion of the conduit.