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+ [16]

Originator Organization

Tarix Orphan LLC

Active Organization

US Biotest, Inc.Constant Therapeutics LLC

Tarix Orphan LLC

Inactive Organization

Tarix Pharmaceuticals Ltd.

National Heart, Lung & Blood Institute

National Institutes of Health

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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 Aug 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 ApplicableIIT

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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1,050

Literatures (Medical) associated with Talfirastide

02 Jan 2024·The Physician and sportsmedicine

Effects of oral HPΒCD-angiotensin-(1-7) supplementation on recreational mountain bike athletes: a crossover study

Article

Author: Lima-Silva, Adriano Eduardo ; Cruz de Oliveira, Emerson ; Coelho, Daniel Barbosa ; Motta-Santos, Daisy ; de Assis Dias Martins-Júnior, Francisco ; Becker, Lenice Kappes ; Silva de Moura, Samara ; Augusto Souza Dos Santos, Robson ; Boari, Daniel

BACKGROUND:

Supplementation with Angiotensin-(1-7) [(Ang-1-7)] has received considerable attention due to its possible ergogenic effects on physical performance. The effects of a single dose of Ang-(1-7) on the performance of mountain bike (MTB) athletes during progressive load tests performed until the onset of voluntary fatigue have previously been demonstrated. This study tested the effects of Ang-(1-7) in two different exercise protocols with different metabolic demands: aerobic (time trial) and anaerobic (repeated sprint).

METHODS:

Twenty one male recreational athletes were given capsules containing an oral formulation of HPβCD-Ang-(1-7) (0.8 mg) and HPβCD-placebo (only HPβCD) over a 7-day interval; a double-blind randomized crossover design was used. Physical performance was examined using two protocols: a 20-km cycling time trial or 4 × 30-s repeated all-out sprints on a leg cycle ergometer. Data were collected before and after physical tests to assess fatigue parameters, and included lactate levels, and muscle activation during the sprint protocol as evaluated by electromyography (EMG); cardiovascular parameters: diastolic and systolic blood pressure and heart rate; and performance parameters, time to complete (time trial), maximum power and mean power (repeated sprint).

RESULTS:

Supplementation with an oral formulation of HPβCD-Ang-(1-7) reduced basal plasma lactate levels and promoted the maintenance of plasma glucose levels after repeated sprints. Supplementation with HPβCD-Ang-(1-7) also increased baseline plasma nitrite levels and reduced resting diastolic blood pressure in a time trial protocol. HPβCD-Ang-(1-7) had no effect on the time trial or repeat sprint performance, or on the EMG recordings of the vastus lateralis and vastus medialis.

CONCLUSIONS:

Supplementation with HPβCD-Ang-(1-7) did not improve physical performance in time trial or in repeated sprints; however, it promoted the maintenance of plasma glucose and lactate levels after the sprint protocol and at rest, respectively. In addition, HPβCD-Ang-(1-7) also increased resting plasma nitrite levels and reduced diastolic blood pressure in the time trial protocol.

TRIAL REGISTRATION:

RBR-2nbmpbc, registered January 6th, 2023. The study was prospectively registered.

01 Jan 2024·Cell biochemistry and function

Targeting PI3K/p‐Akt/eNOS, Nrf2/HO‐1, and NF‐κB/p53 signaling pathways by angiotensin 1–7 protects against liver injury induced by ischemia–reperfusion in rats

Article

Author: Ali, Fatma Farrag ; Hussein, Youssef ; Ibrahim, Manar Fouli Gaber ; Mohammed, Mostafa Mourad

Abstract:

The liver is an important organ, and hepatic ischemia–reperfusion (IR) injury is a frequent pathophysiological process that can cause significant morbidity and mortality. Thus, our study aimed to investigate the effect of targeting PI3K/p‐Akt/eNOS (phosphoinositide 3‐kinase/phospho‐protein kinase B/endothelial nitric oxide synthase), Nrf2/HO‐1 (nuclear factor‐erythroid 2‐related factor‐2/heme oxygenase‐1), and NF‐κB/p53 (nuclear factor‐κB/tumor protein 53) signaling pathways by using angiotensin (1–7) [ang‐(1–7)] against hepatic injury induced by IR. Thirty‐two male rats were included in sham group, ang‐(1–7)‐treated group, hepatic IR group, and hepatic IR group treated with ang‐(1–7). The levels of hepatic ang‐(1–7), angiotensin II (Ang II), angiotensin‐converting enzyme 2 (ACE2), HO‐1, malondialdehyde (MDA), PI3K, and p‐Akt were assessed. The expressions of eNOS and B‐cell leukemia/lymphoma‐2 (BCL‐2) in the liver were determined. Histological assessment and immunohistochemical expression of NF‐κB, p53, and Nrf2 were carried out. The levels of reduced glutathione (GSH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6) in serum were estimated. Results showed that administration of ang‐(1–7) to hepatic IR rats led to significant amelioration of hepatic damage through a histological evaluation that was associated with significant upregulation of the expressions of PI3K/p‐Akt/eNOS and Nrf2/HO‐1 with downregulation of NF‐κB/p53 signaling pathways. In conclusion, PI3K/p‐Akt/eNOS and Nrf2/HO‐1 signaling pathways are involved in the protective effects of ang‐(1–7) against hepatic damage induced by IR. Therefore, ang‐(1–7) can be used to prevent hepatic IR, which occurs in certain conditions such as liver transplantation, hemorrhagic shock, and severe infection.

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: Feng, Weilian ; Xu, Mingtong ; Wan, Yan ; Wang, Xiaoyun ; Chai, Jiani ; 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 Institutes of Health	15 Jul 2021
COVID-19	Phase 3	US	National Heart, Lung & Blood Institute	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
Hematologic Neoplasms	Phase 2	US	Tarix Pharmaceuticals Ltd.	01 Mar 2012
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

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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	vkpfxqldip(errjwbbhbl) = ummjwdupbj rvwleofeol (mchinrksty )	-	11 Apr 2023
				TRV-027	vkpfxqldip(errjwbbhbl) = txcwditbrz rvwleofeol (mchinrksty )
NCT04401423 (CTgov)	Phase 2	COVID-19	22	TXA127 (TXA127)	kzfaphtgpp(ktpbplaqpk) = mwxxfxrdqk fxybahyfva (wxfbrxskgn, zlbyxxqcpn - yugffwqwwk) View more	-	27 Jul 2022
				Placebo (Placebo)	kzfaphtgpp(ktpbplaqpk) = blgcvkfpvx fxybahyfva (wxfbrxskgn, ibijrnsjvc - yrnpgsizrm) View more
ASN2020	Not Applicable	Acute Kidney Injury Angiotensin 1-7	27	Angiotensin 1-7	cmxlbobbxd(joxzfyedag) = nrcyjvpsba ccmkttbkyu (ynvfieznrf, 0.93 - 1.0)	Positive	19 Oct 2020
FP180 (ERA2015)	Not Applicable	Kidney Diseases	-	ANGIOTENSIN (1-7)	hdyunsubaz(yxivlqidmp) = nynsisdnot hsoipplhfn (hllyqoobtn )	Positive	21 May 2015
				Ang (1-7) treated UUO Rats	hdyunsubaz(yxivlqidmp) = hmgbfhlxsp hsoipplhfn (hllyqoobtn )
ISC2014	Not Applicable	Stroke	24	dH2O	rnaepsufhu(tzhnbrullz) = wielmpjvzf fctfhcndcf (lpyeyganpy )	Positive	01 Feb 2014
				HPβCD/Ang-(1-7)	rnaepsufhu(tzhnbrullz) = mabjxdvckz fctfhcndcf (lpyeyganpy )
NCT01553539 (CTgov)	Phase 2	Bone Cancer \| Chondrosarcoma \| Osteosarcoma, Recurrent ... View more	20	laboratory biomarker analysis+therapeutic angiotensin-(1-7)	xgtyijnnkf(izjcdxgnge) = nvkcpmphew peaowtgaoz (npolqpjhvd, rngmhzbger - ozchuexpie) View more	-	30 Jan 2014
NCT00771810 (CTgov)	Phase 2	Anemia \| Thrombocytopenia \| Neutropenia ... View more	34	Placebo (Placebo)	hwijfwtrys(qlxeczxvyn) = afxncuzmag ikdiuukzoj (qjuhvtrrje, nnbwnncyth - cxinmoudig) View more	-	07 Jun 2013
				TXA127 (TXA127 100 ug/kg)	hwijfwtrys(qlxeczxvyn) = drhduquyxz ikdiuukzoj (qjuhvtrrje, weqpehjewl - ijycejvmxo) View more
ARVO2005	Not Applicable	-	-	Angiotensin (1-7)	buvguhhqxr(orlytxwhlj) = kukomxycam ovwykrcbke (iwdzrftrjg )	-	01 May 2005