Brisbane, Australia

Protagonist Therapeutics

www.protagonist-inc.com
Brisbane, Australia

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Patent
Protagonist Therapeutics | Date: 2017-05-03

The present invention provides novel hepcidin analogues, and related methods of using these hepcidin analogues to treat or prevent a variety of diseases and disorders, including iron overload diseases such as hereditary hemochromatosis, iron-loading anemias, and other conditions and disorders described herein.


The present invention provides novel peptide inhibitors of the interleukin-23 receptor, and related compositions and methods of using these peptide inhibitors to treat or prevent a variety of diseases and disorders, including inflammatory bowel disease. In a first aspect, the present invention provides a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of Formula (Xa). In another aspect, the present invention includes a pharmaceutical composition comprising a peptide inhibitor or a peptide dimer inhibitor of the present invention, and a pharmaceutically acceptable carrier.


Patent
Protagonist Therapeutics | Date: 2017-08-09

The invention relates to C to N cyclized (C-N cyclic) monomer and dimer peptide molecules, as well as peptide dimers which are connected by linker moieties at the N terminus and the C terminus of each peptide subunit, which inhibit binding of 47 to the mucosal addressin cell adhesion molecule (MAdCAM) in vivo, and show high selectivity against 41 binding.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 223.95K | Year: 2015

DESCRIPTION provided by applicant Inflammatory bowel disease IBD affects about of the worldandapos s population Due to its early onset and lack of adequate cure it requires lifelong treatment IBD impacts the gastrointestinal GI tract and manifests as two subtypes Crohnandapos s disease CD and ulcerative colitis UC In recent years anti TNF biological agents have revolutionized the treatment of IBD but these are not ideal drugs requiring administration by injection and in some instances hospitalization for intravenous infusion They have numerous systemically driven side effects including increased infections and anywhere from of patients either donandapos t respond or lose response Hence new therapeutic options to treat IBD are needed In this respect the recent identification of the IL pathway in chronic intestinal inflammation raises exciting new possibilities Ustekinemab targets both the IL and IL pathway and is efficacious in anti TNF resistant IBD patients However there is some concern of increased cardiovascular and cancer events as illustrated by the safety warning label on Ustekinumab and the removal of Briakinumab also targeting IL and IL These safety concerns are thought to be due to blocking the role of IL in host defense and cancer suppression whilst blocking IL signaling results in the observed efficacy IL is produced locally in the intestine and the upregulation of IL and its receptor is a primary step underpinning intestinal inflammation Since IBD represents a local inflammation of the intestinal tissue an ideal therapeutic would act from the luminal side to achieve high drug concentrations in diseased tissue enhanced efficacy whilst minimizing systemic bioavailability enhanced safety We have obtained exciting proof of concept data on the oral delivery of GI restricted drugs that are efficacious in a rodent model of disease These IL R antagonists are resistant to the proteolytic and reductive environment of the gastrointestinal tract resulting in high drug levels in diseased intestinal tissues after oral delivery and limited drug concentrations in the circulation This has the potential to transform the treatment paradigm for IBD by providing safe efficacious and durable drugs for life time treatment In this Phase I proposal we plan to Optimize the oral stability of PN a nM antagonist and optimize the potency of PN an orally stable though modestly potent nM antagonist Optimize intestinal and colonic tissue exposure of orally delivered leads and Evaluate efficacy of potent orally stable IL R antagonists in rodent models of disease This Phase I program is supported by a team that has a track record in the oral delivery of constrained peptides the proven capacity in translating early stage research to clinical outcomes a group of scientific and clinical advisors with significant experience in IBD and the appropriate research environment In addition all of the required methods are in place Phase II of the project will involve the evaluation and further optimization of lead candidates in disease models and eventual selection of Investigational New Drug candidates PUBLIC HEALTH RELEVANCE Inflammatory bowel disease which encompassed Crohnandapos s Disease and Ulcerative Colitis afflicts over million people in the United States and is estimated to cost $ billion in direct healthcare costs The disease has no cure has an onset early in life and requires life long treatment Current treatments are not effective or non durabl in many patients and have significant adverse effects This Phase I SBIR proposal describes the optimization of orally active local acting and GI restricted peptidic antagonists of IL receptor that will ultimately lead to more efficacious safe and durable treatment for IBD than current systemic approaches


Patent
Protagonist Therapeutics | Date: 2016-02-17

The invention relates to peptide dimer compounds and peptide monomer compounds that potently inhibit binding of 47 to the mucosal addressin cell adhesion molecule (MAdCAM) in vivo, possess high selectivity against 41 binding, and have high stability under gastrointestinal conditions.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 218.83K | Year: 2016

Abstract The goal of this SBIR phase I is to develop new therapeutics for treatment of various iron overload diseases that involves the use of hepcidin mimetics and to identify an Investigational New Drug IND candidate that is effica cious in the disease model of thalassemia There are two predominant diseases hemochromatosis and tha lassemia that are characterized with iron overload In both diseases low hepcidin levels increase intestinal iron absorption and increase release of recycled iron from the reticuloendothelial system which causes depletion of macrophage iron relatively lower levels of serum ferritin increase in liver iron concentration and release into the circulation of free iron that causes target organ damage Without treatment iron continues to accumulate and a considerable proportion of patients eventually reach toxic iron overload levels Patients are treated by phlebotomy blood transfusions and or iron chelators depending on the disease Chelation therapy is associated with considerable toxicity and currently existing chelators used for treating iron overload lack significant patient compliance or are associated with toxicity renal impairment hepatic impairment and gastrointestinal hemor rhage Thus there is significant need for new treatments that are safer and better tolerated Because of hepcidins complicated disulfide structure hepcidin mimetics have been proposed as a potential therapeutic To over come the physicochemical limitations of hepcidin more potent stable soluble and efficacious alternate scaffolds than hepcidin were engineered by using a purposefully built structure based drug environment Vectrix A lead compound PN was identified after optimizing and profiling engineered scaffolds identified by Vec trix In this SBIR phase I we plan to synthesize and characterize compounds with variable serum protein binding groups on a single position of PN select the best two compounds in a PD model and test the best two compounds in a PD model in diseased mice and test the best compound in a week disease model and finally undertake a PK PD study of the best compound to predict human dose A strong scientific team and consultants experienced in the field of iron overload diseases and biological drug development will lead us to select a drug development candidate that can be taken into nonclinical safety studies and then Phase I clinical trials Project Narrative Overload of toxic iron is a significant threat to the health of patients with Hemochromatosis and thalassemia Current treatments are insufficient and have other associated toxicities Therefore it is the goal of this study to develop new therapeutics for treatment of various iron overload disease and to identify an Investigational New Drug IND candidate


Patent
Protagonist Therapeutics | Date: 2015-10-01

The invention relates to peptide dimer compounds and peptide monomer compounds that potently inhibit binding of 47 to the mucosal addressin cell adhesion molecule (MAdCAM) in vivo, possess high selectivity against 41 binding, and have high stability under gastrointestinal conditions.


Patent
Protagonist Therapeutics | Date: 2016-01-19

The invention relates to disulfide-rich dimer molecules which inhibit binding of 47 to the mucosal addressin cell adhesion molecule (MAdCAM) in vivo, and show high selectivity against 41 binding.


The present invention provides novel peptide inhibitors of the interleukin-23 receptor, and related compositions and methods of using these peptide inhibitors to treat or prevent a variety of diseases and disorders, including inflammatory bowel disease.


Patent
Protagonist Therapeutics | Date: 2015-05-15

The invention relates to thioether monomer and dimer peptide molecules which inhibit binding of 47 to the mucosal addressing cell adhesion molecule (MAdCAM) in vivo.

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