Delving into the Latest Updates on Talfirastide with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

ANG(1-7), Angiontensin(1-7), Angiotensin (1-7)

+ [3]

Target

Mas receptor

Mechanism

Mas receptor agonists(Proto-oncogene Mas agonists)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesCongenital Disorders+ [4]

Active Indication

Ischemic strokeDMD-Associated Dilated CardiomyopathyMuscular Dystrophy, Duchenne+ [6]

Inactive Indication

Acute Lymphoblastic LeukemiaAcute Myeloid LeukemiaAnemia+ [13]

Originator Organization

Tarix Orphan LLC

Active Organization

US Biotest, Inc.

Constant Therapeutics LLC

Tarix Orphan LLC

Inactive Organization

Tarix Pharmaceuticals Ltd.

National Institutes of Health

National Heart, Lung & Blood Institute

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC41H62N12O11

InChIKeyPVHLMTREZMEJCG-GDTLVBQBSA-N

CAS Registry51833-78-4

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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654

Literatures (Medical) associated with Talfirastide

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 ; Corenblum, Mandi J ; Saez, Juben L ; 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.

31 Oct 2024·FASEB JOURNAL

Angiotensin‐(1–7) improves intestinal microbiota disturbances and modulates fecal metabolic aberrations in acute pancreatitis

Article

Author: Gu, Ruru ; Yin, Chenghong ; Cui, Tianyu ; Wei, Hongtao ; Luan, Yingyi ; Liu, Ruixia ; Wang, Guoxing

Abstract:

Acute pancreatitis (AP) is a serious health problem that dysregulates intestinal microbiota. Angiotensin (Ang)‐(1–7) plays a protective role in the intestinal barrier in AP, but its effect on intestinal microbiota remains clear. To investigate the impact of Ang‐(1–7) on AP‐induced intestinal microbiota disorder and metabolites. We collected blood and fecal samples from 31 AP patients within 48 h after admission to the hospital, including 11 with mild AP (MAP), 14 with moderately severe AP (MSAP), six with severe AP (SAP). Mice were divided into four groups: control, AP, AP + Ang‐(1–7) via tail vein injection, and AP + Ang‐(1–7) via oral administration. The samples of mice were collected 12 h after AP. Pancreatic and intestinal histopathology scores were analyzed using the Schmidt and Chiu scores. Fecal microbiota and metabolites analysis was performed via 16S rDNA sequencing and nontargeted metabolomics analysis, respectively. In patients, the abundance of beneficial bacteria (Negativicutes) decreased and pathogenic bacteria (Clostridium bolteae and Ruminococcus gnavus) increased in SAP compared with MAP. Ang‐(1–7) levels were associated with changes in the microbiota. There were differences in the intestinal microbiota between control and AP mice. Ang‐(1–7) attenuated intestinal microbiota dysbiosis in AP mice, reflecting in the increase in beneficial bacteria (Odoribacter and Butyricimonas) than AP, as well as pancreatic and intestinal injuries. Oral administration of Ang‐(1–7) reversing AP‐induced decreases in metabolisms: secondary bile acids, emodin, and naringenin. Ang‐(1–7) may improve intestinal microbiota dysbiosis and modulate fecal metabolites in AP, thereby reducing the damage of AP.

01 Oct 2024·Current diabetes reviews

The Counteracting Effects of Ang II and Ang-(1-7) on the Function and Growth of Insulin-secreting NIT-1 Cells

Article

Author: Xu, Mingtong ; Feng, Weilian ; Wan, Yan ; Chai, Jiani ; Wang, Xiaoyun ; Lin, Xiuhong ; Li, Feng

Introduction::

China now has the highest number of diabetes in the world. Angiotensin II (Ang II) causes insulin resistance by acting on the insulin signaling pathway of peripheral target tissues. However, its effect on islet β-cells remains unclear. The possible role of Angiotensin-(1-7) [Ang-(1-7)] as an antagonist to the effects of Ang II and in treating diabetes needs to be elucidated.

Objectives::

To assess the effects of Ang II and Ang-(1-7) on the function and growth of islet β cell line NIT-1, which is derived from the islets of non-obese diabetic/large T-antigen (NOD/LT) mice with insulinoma.

Methods::

NIT-1 cells were treated with Ang II, Ang-(1-7) and their respective receptor antagonists. The impact on cell function and growth was then evaluated.

Results::

Ang II significantly reduced insulin-stimulated IR-β-Tyr and Akt-Ser; while Ang-(1-7), saralasin (an Ang II receptor antagonist), and diphenyleneiodonium [DPI, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) antagonist] reversed the inhibiting effect. Conversely, Ang II significantly increased insulin-stimulated intracellular H2O2 and P47 phox, while saralasin and DPI reverted the effect. Furthermore, Ang-(1-7) reduced the elevated concentrations of ROS and MDA while increasing the proliferation rate that was reduced by high glucose, all of which were reversed by A-779, an antagonist of the Mas receptor (MasR).

Conclusion::

Angiotensin II poses a negative regulatory effect on insulin signal transduction, increases oxidative stress, and may inhibit the transcription of insulin genes stimulated by insulin in NIT-1 cells. Meanwhile, angiotensin-(1-7) blocked these effects via MasR. These results corroborate the rising potential of the renin-angiotensin system (RAS) in treating diabetes.

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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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11720

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 3	US	National Heart, Lung & Blood Institute	15 Jul 2021
COVID-19	Phase 3	US	National Institutes of Health	15 Jul 2021
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
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	Constant Therapeutics LLC	01 Jun 2010
Hodgkin's Lymphoma	Phase 2	US	Tarix Pharmaceuticals Ltd.	01 Jun 2010
Multiple Myeloma	Phase 2	US	Constant Therapeutics LLC	01 Jun 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04924660 (Pubmed)	Phase 2/3	COVID-19	-	TXA-127	oegxefkuif(biifksmetr) = ayyfonjwwq kdifnxpurf (xbvhskaopz )	-	11 Apr 2023
				TRV-027	oegxefkuif(biifksmetr) = owhjudltay kdifnxpurf (xbvhskaopz )
NCT04401423 (CTgov)	Phase 2	COVID-19	22	TXA127 (TXA127)	sthonbfyfb(oarcplnsdx) = akwvjcjjhx jlyzmyesjg (yqfxrpyzmf, kjjhmwcxgz - isdtthozuf) View more	-	27 Jul 2022
				Placebo (Placebo)	sthonbfyfb(oarcplnsdx) = pihgzyoerl jlyzmyesjg (yqfxrpyzmf, bgavkvxkvt - exnizewuiu) View more
ASN2020	Not Applicable	Acute Kidney Injury Angiotensin 1-7	27	Angiotensin 1-7	prqqsklepy(okgfhytgqr) = mzdpzgmwha hggeltelqg (eisxiedhhx, 0.93 - 1.0)	Positive	19 Oct 2020
FP180 (ERA2015)	Not Applicable	Kidney Diseases	-	ANGIOTENSIN (1-7)	vpevvsvnsf(aprdqoravi) = qwnxysmpvj mphnbgybid (ogzggkltvb )	Positive	21 May 2015
				Ang (1-7) treated UUO Rats	vpevvsvnsf(aprdqoravi) = pwiwitlpom mphnbgybid (ogzggkltvb )
ISC2014	Not Applicable	Stroke	24	dH2O	sxazghyric(vfxpykrxxy) = wunujrrqxp wtxghfojmj (zbaojpdqzf )	Positive	01 Feb 2014
				HPβCD/Ang-(1-7)	sxazghyric(vfxpykrxxy) = uapzenzkvo wtxghfojmj (zbaojpdqzf )
NCT01553539 (CTgov)	Phase 2	Bone Cancer \| Chondrosarcoma \| Osteosarcoma, Recurrent ... View more	20	laboratory biomarker analysis+therapeutic angiotensin-(1-7)	blcdtqrgpp(wjlrxbkbue) = qxnemptnfp hdarosldqz (qpiouxekgk, hnkvpelxra - qtnoznsumh) View more	-	30 Jan 2014
NCT00771810 (CTgov)	Phase 2	Anemia \| Thrombocytopenia \| Neutropenia ... View more	34	Placebo (Placebo)	hwmxomucds(pfkuhgcgxc) = azciynnyrn emmwtqmnxv (whxawzwvmp, hibvylgwqr - wjvfhuikup) View more	-	07 Jun 2013
				TXA127 (TXA127 100 ug/kg)	hwmxomucds(pfkuhgcgxc) = hjkhfwrfex emmwtqmnxv (whxawzwvmp, ocrjrgyrvp - mzcogskqbu) View more
ARVO2005	Not Applicable	-	-	Angiotensin (1-7)	mkssvwtaqj(oifcqsoadc) = khlqsulxbk wyuxjykwlq (xsovvqhbjd )	-	01 May 2005