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Obesity is a global health concern that is associated with high blood pressure and an increased risk for developing cardiovascular disease. The purpose of this study is to find out if the investigational drug angiotensin-(1-7) can improve cardiovascular health in people with obesity and high blood pressure.

Start Date01 Dec 2024

Sponsor / Collaborator

Hershey Medical Center

[+1]

NCT06282965

/ RecruitingPhase 1/2IIT

A Randomized, Double-blind, Placebo Controlled Study of the Safety and Efficacy of Angiotensin (1-7) in Persons With Moderate to Severe Traumatic Brain Injury (TBI)

The goal of this clinical trial is to test the safety of the drug Angiotensin (1-7) and learn whether it works well as a treatment in people who have suffered a moderate to severe traumatic brain injury (TBI).
The main questions this trial aims to answer are:
* Is Angiotensin (1-7) safe?
* Does Angiotensin (1-7) improve mental functioning and reduce physical signs of brain damage in people who have suffered a moderate to severe TBI?
Participants will:
* Complete 21 days of study treatment consisting of a once-daily injection.
* Provide blood samples.
* Undergo two magnetic resonance imaging (MRI) scans of the brain.
* Complete specific tasks and questionnaires that allow researchers to evaluate the participant's brain and psychological functioning.
Researchers will compare three groups: two groups that receive different doses of Angiotensin (1-7) and one group that receives a look-alike treatment with no active drug. This will allow researchers to see if the drug has any negative effects and whether it improves mental functioning and physical signs of brain damage after a TBI.

Start Date28 May 2024

Sponsor / Collaborator

University of Arizona

RBR-3bhkdg2

/ RecruitingNot Applicable

Angiotensin formulations-(1-7) its actions on physical performance and injury repair muscular

Start Date28 Mar 2024

Sponsor / Collaborator

Universidade Federal de Ouro Preto

100 Clinical Results associated with Talfirastide

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100 Translational Medicine associated with Talfirastide

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100 Patents (Medical) associated with Talfirastide

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636

Literatures (Medical) associated with Talfirastide

05 Dec 2024·ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Intranasal liposomal angiotensin-(1-7) administration reduces inflammation and viral load in the lungs during SARS-CoV-2 infection in K18-hACE2 transgenic mice

Article

Author: Frézard, Frédéric ; Guimarães, Pedro Pires Goulart ; Guimarães, Lays Cordeiro ; Costa, Pedro Augusto Carvalho ; dos Santos, Robson Augusto Souza ; Fernandez, Clara Couto ; Teixeira, Mauro Martins ; Figueiredo, Maria Marta ; Mendes, Sabrina

ABSTRACT:

To effectively reduce the health impact of coronavirus disease (COVID-19), it is essential to adopt comprehensive strategies to protect individuals from severe acute respiratory syndrome. In that sense, much effort has been devoted to the discovery and repurposing of effective antiviral and anti-inflammatory molecules. The endogenous peptide angiotensin-(1-7) [Ang-(1-7)] has been recently proposed as a promising anti-inflammatory agent to control respiratory infections. Liposomes also emerged as a safe and effective drug carrier system for local drug delivery to the lungs. In this context, the aim of this study was to develop a liposomal formulation of Ang-(1-7) [LAng (1-7)] and investigate its impact on animal survival as well as its antiviral and anti-inflammatory efficacies after intranasal administration in transgenic K18-hACE2 mice infected with SARS-CoV-2. The liposomal formulation was prepared by the ethanol injection method, exhibiting a mean diameter of 100 nm and a polydispersity index of 0.1. Following treatment of infected mice every 12 hours for 5 days, LAng (1-7) extended animal survival compared to the control groups that received either empty liposomes, free Ang-(1-7), or phosphate-buffered saline. Furthermore, the treatment with LAng (1-7) significantly decreased the viral load, as well as IL-6 and tumor necrosis factor levels in the lungs. Conventional treatment with remdesivir by parenteral route used as a positive control promoted similar effects, leading to improved survival rates and reduced viral load in the lungs without significant effects on IL-6 level. In conclusion, liposomal Ang-(1-7) emerges as a promising formulation to improve the treatment and decrease the severity of respiratory infections, such as COVID-19.

01 Nov 2024·INFLAMMATION RESEARCH

Angiotensin-(1–7) decreases inflammation and lung damage caused by betacoronavirus infection in mice

Article

Author: Oliveira, Leonardo C ; Queiroz-Junior, Celso M ; Carvalho, Antônio Felipe S ; Santos, Felipe Rocha da Silva ; Carneiro, Fernanda S ; Santos, Robson A S ; Lara, Edvaldo S ; Resende, Filipe ; Cardoso, Camila ; Souza-Costa, Luiz Pedro ; Teixeira, Mauro M ; Zaidan, Isabella ; Monteiro, Adelson Héric A ; Tavares, Luciana P ; Sousa, Lirlândia P ; Costa, Vivian V ; Lima, Erick Bryan de Sousa ; Russo, Remo C ; Chaves, Ian de Meira

OBJECTIVE:

Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice.

METHODS:

C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1-7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated.

RESULTS:

Ang-(1-7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1-7) during MHV infection. Ang-(1-7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1-7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates.

CONCLUSION:

Ang-(1-7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance.

01 Nov 2024·EXPERIMENTAL NEUROLOGY

The angiotensin (1–7) glycopeptide PNA5 improves cognition in a chronic progressive mouse model of Parkinson's disease through modulation of neuroinflammation

Article

Author: Doyle, Kristian P ; Madhavan, Lalitha ; Polt, Robin ; Bernard, Kelsey ; Mota, Jesus A ; Hay, Meredith ; Wene, Paige ; Saez, Juben L ; Corenblum, Mandi J ; Falk, Torsten ; Heien, M Leandro ; Bartlett, Mitchell J

Cognitive decline in Parkinson's Disease (PD) is a prevalent and undertreated aspect of disease. Currently, no therapeutics adequately improve this aspect of disease. It has been previously shown that MAS receptor agonism via the glycosylated Angiotensin (1-7) peptide, PNA5, effectively reduces cognitive decline in models of vascular contributions to cognitive impairment and dementia (VCID). PNA5 has a brain/plasma ratio of 0.255 indicating good brain penetration. The goal of the present study was to determine if (1) systemic administration of PNA5 rescued cognitive decline in a mouse model of PD, and (2) if improvements in cognitive status could be correlated with changes to histopathological or blood plasma-based changes. Mice over-expressing human, wild-type α-synuclein (αSyn) under the Thy1 promoter (Thy1-αSyn mice, "line 61") were used as a model of PD with cognitive decline. Thy1-αSyn mice were treated with a systemic dose of PNA5, or saline (1 mg/kg/day) beginning at 4 months of age and underwent behavioral testing at 6 months, compared to WT. Subsequently, mice brains were analyzed for changes to brain pathology, and blood plasma was examined with a Multiplex Immunoassay for peripheral cytokine changes. Treatment with PNA5 reversed cognitive dysfunction measured by Novel Object Recognition and spontaneous alteration in a Y-maze in Thy1-αSyn mice. PNA5 treatment was specific to cognitive deficits, as fine-motor disturbances were unchanged. Enhanced cognition was associated with decreases in hippocampal inflammation and reductions in circulating levels of Macrophage Induced Protein (MIP-1β). Additionally, neuronal loss was blunted within the CA3 hippocampal region of PNA5-treated αsyn mice. These data reveal that PNA5 treatment reduces cognitive dysfunction in a mouse model of PD. These changes are associated with decreased MIP-1β levels in plasma identifying a candidate biomarker for target engagement. Thus, PNA5 treatment could potentially fill the therapeutic gap for cognitive decline in PD.

2

News (Medical) associated with Talfirastide

04 Mar 2024

·www.prnewswire.com

Constant Therapeutics Announces First Patient Dosed in Phase 2 Clinical Trial of TXA127 in Duchenne Muscular Dystrophy-Associated Cardiomyopathy

BOSTON, March 4, 2024 /PRNewswire/ -- Constant Therapeutics LLC, a biopharmaceutical company focused on the development of treatments impacting the Alternative Renin-Angiotensin System, today announced that the first patient was dosed March 3, 2024, in the Company's phase 2 clinical trial of TXA127, the Company's lead peptide product under development as a potential treatment for Duchenne Muscular Dystrophy-associated (DMD-associated) Cardiomyopathy. The phase 2 trial is an open-label, multi-center trial designed to evaluate the safety and efficacy in non-ambulatory patients with DMD-associated Cardiomyopathy who are 16 years and older and who are receiving systemic glucocorticoids. Patients will receive 6 months of treatment and have the option to enter a 12-month extension study. The study is being conducted in Israel at Sheba Medical Center and Hadassah Medical Center and is expected to enroll 10 patients. "This is a significant milestone for Constant and for the DMD community," said Rick Franklin, CEO of Constant Therapeutics. "There are few treatments for DMD patients with cardiomyopathy, and heart failure is a leading cause of death in this disease. We are excited to initiate this carefully designed trial, and we look forward to sharing the data with the DMD community upon completion of the trial." About Constant Therapeutics LLC Constant Therapeutics LLC is a private biopharmaceutical company focused on the development of treatments that effect the Alternative Renin-Angiotensin System. The lead compound, TXA127, is a pharmaceutical formulation of the naturally occurring peptide Angiotensin (1-7) and is being developed for the treatment of stroke recovery and DMD-associated Cardiomyopathy. For more information on Constant Therapeutics, please visit our website at . About TXA127 TXA127 is a pharmaceutical formulation of the naturally occurring human peptide angiotensin-(1‐7). In addition to its specific effects in cardiac dysfunction, TXA127 has shown therapeutic activity in animal models of chronic stroke, Duchenne Muscular Dystrophy (DMD), Limb‐Girdle Muscular Dystrophy (LGMD), Congenital Muscular Dystrophy (MDC1A), Marfan Syndrome and Epidermolysis Bullosa. Contact: [email protected] +1-617-245-0289 SOURCE Constant Therapeutics

Phase 2

09 Jan 2024

·www.prnewswire.com

Constant Therapeutics Announces First Patient Dosed in Phase 2 Clinical Trial of TXA127 in Ischemic Stroke Recovery

BOSTON, Jan. 9, 2024 /PRNewswire/ -- Constant Therapeutics LLC, a biopharmaceutical company focused on the development of treatments impacting the Alternative Renin-Angiotensin System, today announced that the first patient has been dosed in the Company's phase 2 clinical trial of TXA127, the Company's lead peptide product under development as a potential treatment for ischemic stroke recovery. The phase 2 trial is a randomized, placebo-controlled, double-blind, hybrid decentralized study designed to evaluate the safety and efficacy in ischemic stroke patients who are 18 to 85 years old and who are 6 to 24 months post stroke event. Patients will receive 3 months of treatment. The study is being conducted in Israel at Sheba Medical Center in collaboration with Sabar Health for the home visits, and it is expected to enroll 50 patients. "There are no drugs available to treat chronic stroke, but the design and logistics of clinical trials in these patients is particularly difficult. We are fortunate to have been able to put together the infrastructure needed, with the participation of Sabar Health and Sheba Medical Center. This unique combination will allow us to test TXA127 for this important unmet medical need," said Rick Franklin, CEO of Constant Therapeutics." About Constant Therapeutics LLC Constant Therapeutics LLC is a private biopharmaceutical company focused on the development of treatments that effect the Alternative Renin-Angiotensin System. The lead compound, TXA127, is a pharmaceutical formulation of the naturally occurring peptide Angiotensin (1-7) and is being developed for the treatment of stroke recovery and DMD-associated Cardiomyopathy. For more information on Constant Therapeutics, please visit our website at . About TXA127 TXA127 is a pharmaceutical formulation of the naturally occurring human peptide angiotensin-(1‐7). In addition to its specific effects in ischemic stroke, TXA127 has shown therapeutic activity in animal models Duchenne Muscular Dystrophy (DMD), Limb‐Girdle Muscular Dystrophy (LGMD), Congenital Muscular Dystrophy (MDC1A), Marfan Syndrome and Epidermolysis Bullosa. Contact: [email protected] +1-617-245-0289 SOURCE Constant Therapeutics

Phase 2

100 Deals associated with Talfirastide

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Ischemic stroke	Phase 2	IL	Constant Therapeutics LLC	26 Nov 2023
DMD-Associated Dilated Cardiomyopathy	Phase 2	IL	Constant Therapeutics LLC	31 Aug 2023
Muscular Dystrophy, Duchenne	Phase 2	IL	Constant Therapeutics LLC	31 Aug 2023
COVID-19	Phase 2	US	Constant Therapeutics LLC	10 Feb 2021
acute leukemia	Phase 2	US	Tarix Pharmaceuticals Ltd.	01 Dec 2013
Graft vs Host Disease	Phase 2	US	Tarix Pharmaceuticals Ltd.	01 Dec 2013
Metabolic Diseases	Phase 2	US	Tarix Pharmaceuticals Ltd.	01 Mar 2012
Hodgkin's Lymphoma	Phase 2	US	Tarix Pharmaceuticals Ltd.	01 Jun 2010
Hodgkin's Lymphoma	Phase 2	US	Constant Therapeutics LLC	01 Jun 2010
Multiple Myeloma	Phase 2	US	Constant Therapeutics LLC	01 Jun 2010

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Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04924660 (Pubmed \| JAMA)	Phase 2/3	COVID-19	-	TXA-127	rlavfdewmq(cfpuzetxfa) = zaarogajmr ptzszxtcgk (kdsmvgpopo )	-	11 Apr 2023
				TRV-027	rlavfdewmq(cfpuzetxfa) = scljefrcxf ptzszxtcgk (kdsmvgpopo )
NCT04401423 (CTgov)	Phase 2	COVID-19	22	TXA127 (TXA127)	xyejwpezbu(klxlgmgvfd) = gtnxfvuoyh gpcecvsgbf (mccikdkyyu, kubyhudtfe - ounsfqywak) View more	-	27 Jul 2022
				Placebo (Placebo)	xyejwpezbu(klxlgmgvfd) = vflxtkabjv gpcecvsgbf (mccikdkyyu, slaqcdubhf - lzzrbxefdh) View more
ASN2020	Not Applicable	Acute Kidney Injury Angiotensin 1-7	27	Angiotensin 1-7 (Angiotensin II)	ycrnwwtgha(qmohvukpwp) = vpwacwcifo xjiagiwgyv (sjirjbmkpu, 0.93 - 1.0)	Positive	19 Oct 2020
FP180 (ERA2015)	Not Applicable	Kidney Diseases	-	ANGIOTENSIN (1-7) (Unilateral Ureteral Obstructed (UUO) Rats)	nfdzhutqqf(qfklfxhzmr) = grnfqdrowq bnyicvntgj (sskwzfwlsx )	Positive	21 May 2015
				Ang (1-7) treated UUO Rats	nfdzhutqqf(qfklfxhzmr) = zsczwvxmbr bnyicvntgj (sskwzfwlsx )
ISC2014	Not Applicable	Stroke	24	dH2O	wolxoiwmag(vlzykzluwp) = solmcyekkb neagbgxtqk (ancnqpyyfu )	Positive	01 Feb 2014
				HPβCD/Ang-(1-7)	wolxoiwmag(vlzykzluwp) = fswfhvlnpj neagbgxtqk (ancnqpyyfu )
NCT01553539 (CTgov)	Phase 2	Bone Cancer \| Chondrosarcoma \| Osteosarcoma, Recurrent ... View more	20	laboratory biomarker analysis+therapeutic angiotensin-(1-7)	jkzrvgharf(dqsbjbbfmp) = ighzayofqg ryczbliaoc (udullrjkcf, dxkyxkydfk - qkejjfeuij) View more	-	30 Jan 2014
NCT00771810 (CTgov)	Phase 2	Anemia \| Thrombocytopenia \| Neutropenia ... View more	34	Placebo (Placebo)	aedjoiukoq(rvaspdawnq) = mxwfhidywa gdrluqnrdb (tmsfmxhksj, qpxfjfbhdf - ghqdpignnn) View more	-	07 Jun 2013
				TXA127 (TXA127 100 ug/kg)	aedjoiukoq(rvaspdawnq) = wrbftlimgq gdrluqnrdb (tmsfmxhksj, lgwbyovyrl - kniwpdtnmv) View more
5C.07 (ESH2010)	Not Applicable	norepinephrine	-	Angiotensin-(1-7)	dquluqdfie(svipdgiurc) = ljptkvdzps suwcjscers (dcigsdhxnw )	Positive	01 Jun 2010
NCT00471562 (Pubmed \| Clin Cancer Res)	Phase 1	Metastatic Solid Tumor \| Advanced Malignant Solid Neoplasm	18	Angiotensin-(1-7)	tkbguvimsy(drtejvmulw) = kfkegqiyys ccxcqzmluv (ixfchrthcp )	-	01 Dec 2009
ARVO2005	Not Applicable	-	-	Angiotensin (1-7)	jauofguvgj(ynosuwotkm) = xfgqkxdlkv hfrmogeohj (aohkfcwnwd )	-	01 May 2005