A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study to Examine the Safety, Tolerability, and Effect on Body Weight of Subcutaneous AC2307 in Obese or Overweight Subjects

A randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study to examine the safety, tolerability, and effect on body weight of subcutaneous AC2307 in obese or overweight subjects.

Start Date01 Dec 2008

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with Davalintide

100 Translational Medicine associated with Davalintide

100 Patents (Medical) associated with Davalintide

Literatures (Medical) associated with Davalintide

01 Feb 2023·Molecular Metabolism

Islet amyloid polypeptide does not suppress pancreatic cancer

Article

Author: Kopp, Janel L ; Johnson, James D ; Lynn, Francis C ; Orban, Paul C ; Taylor, Austin J ; Schaeffer, David F ; Verchere, C Bruce ; Panzhinskiy, Evgeniy

OBJECTIVESPancreatic cancer risk is elevated approximately two-fold in type 1 and type 2 diabetes. Islet amyloid polypeptide (IAPP) is an abundant beta-cell peptide hormone that declines with diabetes progression. IAPP has been reported to act as a tumour-suppressor in p53-deficient cancers capable of regressing tumour volumes. Given the decline of IAPP during diabetes development, we investigated the actions of IAPP in pancreatic ductal adenocarcinoma (PDAC; the most common form of pancreatic cancer) to determine if IAPP loss in diabetes may increase the risk of pancreatic cancer.METHODSPANC-1, MIA PaCa-2, and H1299 cells were treated with rodent IAPP, and the IAPP analogs pramlintide and davalintide, and assayed for changes in proliferation, death, and glycolysis. An IAPP-deficient mouse model of PDAC (Iapp^-/-; Kras^+/LSL-G12D; Trp53^flox/flox; Ptf1a^+/CreER) was generated for survival analysis.RESULTSIAPP did not impact glycolysis in MIA PaCa-2 cells, and did not impact cell death, proliferation, or glycolysis in PANC-1 cells or in H1299 cells, which were previously reported as IAPP-sensitive. Iapp deletion in Kras^+/LSL-G12D; Trp53^flox/flox; Ptf1a^+/CreER mice had no effect on survival time to lethal tumour burden.CONCLUSIONSIn contrast to previous reports, we find that IAPP does not function as a tumour suppressor. This suggests that loss of IAPP signalling likely does not increase the risk of pancreatic cancer in individuals with diabetes.

01 Jun 2022·European Journal of Medicinal ChemistryQ1 · MEDICINE

Design, synthesis and preclinical evaluation of bio-conjugated amylinomimetic peptides as long-acting amylin receptor agonists

Q1 · MEDICINE

Article

Author: Edwards, Wilson ; Jian, Wenying ; Zheng, Songmao ; Hornby, Pamela ; Qiu, Xi ; Rives, Marie-Laure ; Liang, Yin ; Leonard, James N ; Zhang, Rui ; Jeyaseelan, Jey ; Macielag, Mark J ; Rangwala, Shamina M ; Li, Jiali ; Edavettal, Suzanne ; Eckardt, Annette J ; Libiger, Ondrej ; Patch, Raymond J ; Hinke, Simon A

Pramlintide is an equipotent amylin analogue that reduces food intake and body weight in obese subjects and has been clinically approved as an adjunctive therapy for the treatment of adult diabetic patients. However, due to its extremely short half-life in vivo, a regimen of multiple daily administrations is required for achieving clinical effectiveness. Herein is described the development of prototypical long-acting pramlintide bioconjugates, in which pramlintide's disulfide-linked macrocycle was replaced by a cyclic thioether motif. This modification enabled stable chemical conjugation to a half-life extending antibody. In contrast to pramlintide (t_1/2 < 0.75 h), bioconjugates 35 and 38 have terminal half-lives of ∼2 days in mice and attain significant exposure levels that are maintained up to 7 days. Single dose subcutaneous administration of 35 in lean mice, given 18-20 h prior to oral acetaminophen (AAP) administration, significantly reduced gastric emptying (as determined by plasma AAP levels). In a separate study, similar administration of 35 in fasted lean mice effected a reduction in food intake for up to 48 h. These data are consistent with durable amylinomimetic responses and provide the basis for further development of such long-acting amylinomimetic conjugates for the potential treatment of obesity and associated pathologies.

01 Jan 2022·Colloids and Surfaces B: BiointerfacesQ2 · ENGINEERING & TECHNOLOGY

Amyloidogenicity of peptides targeting diabetes and obesity

Q2 · ENGINEERING & TECHNOLOGY

Review

Author: Lima, Luís Maurício T R ; Icart, Luis Peña

Since the discovery of insulin, a century ago, the repertoire of therapeutic polypeptides targeting diabetes - and now also obesity - have increased substantially. The focus on quality has shifted from impure and unstable preparations of animal insulin to highly pure, homologous recombinant insulin, along with other peptide-based hormones and analogs such as amylin analogs (pramlintide, davalintide, cagrilintide), glucagon and glucagon-like peptide-1 receptor agonists (GLP-1, liraglutide, exenatide, semaglutide). Proper formulation, storage, manipulation and usage by professionals and patients are required in order to avoid agglomeration into high molecular weight products (HMWP), either amorphous or amyloid, which could result in potential loss of biological activity and short- or long-term immune reaction and silent inactivation. In this narrative review, we present perspective of the aggregation of therapeutic polypeptides used in diabetes and other metabolic diseases, covering the nature and mechanisms, analytical techniques, physical and chemical stability, strategies aimed to hamper the formation of HMWP, and perspectives on future biopharmaceutical developments.

100 Deals associated with Davalintide

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KEGG	Wiki	ATC	Drug Bank
D09601	-	-	DB14956

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Behavioural disorders	Phase 2	US	Amylin Pharmaceuticals, Inc.	-
Obesity	Phase 2	-	Takeda Pharmaceutical Co., Ltd.	-
Obesity	Phase 2	-	Bristol Myers Squibb Co.	-
Obesity	Phase 2	-	Takeda Pharmaceutical Co., Ltd.	-
Obesity	Phase 2	US	Amylin Pharmaceuticals, Inc.	-
Obesity	Discovery	-	Bristol Myers Squibb Co.	-
Obesity	Discovery	US	Amylin Pharmaceuticals, Inc.	-

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