TXA-127 / Constant Therap - LARVOL DELTA

Angiotensin-(1-7) Provides Potent Long-Term Neurorepair/Neuroregeneration in a Rodent White Matter Stroke Model: Nonarteritic Ischemic Optic Neuropathy (rNAION). (PubMed, Cells) - "Ang-(1-7) is the first agent effective ≥1 day after rNAION induction. Ang-(1-7) type agonists may be useful in improving long-term function and neuronal survival in clinical NAION and other forms of white matter ischemia."

Journal • Preclinical • Cardiovascular • Inflammation • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

The Association of Circulating Renin Angiotensin System Components With Clinical Outcomes and Treatment Responses in COVID-19: A Mechanistic Substudy of the ACTIV-4 Host Tissue Trials (ATS 2024) - "In this nested, multicenter, mechanistic study within the ACTIV-4 Host Tissue Platform trial, we evaluated the association of the circulating RAS with clinical outcomes and treatment responses to the RAS modulators TXA-127 [Angiotensin-(1-7)], TRV-027 (a biased AT1R agonist) or placebo. 60)]. Conclusions Baseline levels of key RAS peptides and enzymes may be useful for outcome risk prediction or RAS-directed treatment responsiveness in COVID-19 or other pathologies."

Clinical • Clinical data • Late-breaking abstract • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

NECTAR: Novel Experimental COVID-19 Therapies Affecting Host Response (clinicaltrials.gov) - P2/3 | N=871 | Completed | Sponsor: Sean Collins | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Hematological Disorders • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

Phase 2 Study of TXA127 in Post-ischemic Stroke Patients (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Constant Therapeutics LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Ischemic stroke • BDNF • NEFL

Phase 2 Study to Evaluate the Safety and Efficacy of Daily SC Injection of TXA127 in Post-ischemic Stroke Patients (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Constant Therapeutics LLC

New P2 trial • Cardiovascular • Ischemic stroke • BDNF • NEFL

NECTAR: Novel Experimental COVID-19 Therapies Affecting Host Response (clinicaltrials.gov) - P2/3 | N=871 | Active, not recruiting | Sponsor: Sean Collins | Recruiting ➔ Active, not recruiting | N=1600 ➔ 871

Enrollment change • Enrollment closed • Cardiovascular • Hematological Disorders • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

TXA127 in Non-Ambulant Patients With DMD Cardiomyopathy (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Constant Therapeutics LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

TXA127 in Non-Ambulant Patients With DMD Cardiomyopathy (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: Constant Therapeutics LLC

New P2 trial • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials. (PubMed, JAMA) - P2/3 | "To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19. ClinicalTrials.gov Identifier: NCT04924660."

Clinical • Journal • Allergy • Hypotension • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

NECTAR: Novel Experimental COVID-19 Therapies Affecting Host Response (clinicaltrials.gov) - P2/3 | N=1600 | Recruiting | Sponsor: Sean Collins | Trial completion date: Apr 2023 ➔ Oct 2023 | Trial primary completion date: Feb 2023 ➔ Aug 2023

Trial completion date • Trial primary completion date • Cardiovascular • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

LP2, a stable lanthipeptide derived from cAng-(1-7), exerts myeloprotective action in mice. (PubMed, Eur J Haematol) - "LP2 exerts myeloprotective action with perspectives for continuation of its clinical development."

Journal • Preclinical • Hematological Disorders • Oncology

NECTAR: Novel Experimental COVID-19 Therapies Affecting Host Response (clinicaltrials.gov) - P2/3 | N=1600 | Recruiting | Sponsor: Vanderbilt University Medical Center | Trial completion date: Dec 2023 ➔ Apr 2023 | Trial primary completion date: May 2023 ➔ Feb 2023

Trial completion date • Trial primary completion date • Cardiovascular • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

A randomized, placebo-controlled, double-blinded pilot study of angiotensin 1-7 (TXA-127) for the treatment of severe COVID-19. (PubMed, Crit Care) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

NECTAR: Novel Experimental COVID-19 Therapies Affecting Host Response (clinicaltrials.gov) - P2/3; N=1600; Recruiting; Sponsor: Vanderbilt University Medical Center; Trial completion date: Dec 2022 ➔ Dec 2023; Trial primary completion date: May 2022 ➔ May 2023

Clinical • Trial completion date • Trial primary completion date • Cardiovascular • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

[VIRTUAL] The Mas Receptor Agonist TXA127 Blocks Neurovascular Inflammation Associated with Sars-CoV-2 Infection (ANA 2021) - "After exposure to live Sars-CoV-2 virus, TXA127 can effectively inhibit C3 expression and reduce complement activation in conditioned media and endothelial exosomes in monolayer and 3D models endothelialized with human brain microvascular endothelial cells. Identification of the neurovascular inflammatory cascades activated by Sars-CoV-2 can play a critical role in developing therapeutic approaches to reduce the burden of cerebrovascular disease in COVID-19."

Cerebral Hemorrhage • CNS Disorders • Vascular Neurology

NECTAR: Novel Experimental COVID-19 Therapies Affecting Host Response (clinicaltrials.gov) - P2/3; N=1600; Recruiting; Sponsor: Vanderbilt University Medical Center; Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

TXA127 for the Treatment of Severe COVID-19 (clinicaltrials.gov) - P2; N=22; Completed; Sponsor: Columbia University; Recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • PCR

NECTAR: Novel Experimental COVID-19 Therapies Affecting Host Response (clinicaltrials.gov) - P2/3; N=1600; Not yet recruiting; Sponsor: Vanderbilt University Medical Center

New P2/3 trial • Cardiovascular • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

Constant Therapeutics TXA127 For COVID-19 To Enter NIH-Funded Clinical Trial At 60 Sites Around The U.S. (PRNewswire) - "...U.S. researchers, funded by the NIH, are undertaking a large new clinical trial...'This trial will help us understand how TXA127 hastens recovery in patients with COVID-19 and will contribute to our understanding of how restoring balance to the Renin Angiotensin Aldosterone System (RAAS) impacts patient outcome' said Sean Collins, MD, MSci, Principal Investigator of the ACTIV-4d trial....The trial will test several compounds, each against a placebo group. The TXA127 segment will involve 300 patients treated with the peptide and will be conducted at some 60 sites nationwide."

Trial status • Infectious Disease • Novel Coronavirus Disease

TXA127 for the Treatment of Severe COVID-19 (clinicaltrials.gov) - P2; N=100; Recruiting; Sponsor: Columbia University; Initiation date: Aug 2020 ➔ Feb 2021

Clinical • Trial initiation date • Infectious Disease • Novel Coronavirus Disease • PCR

Promising Treatment for Covid-19 Enters Clinical Trials in Israeli Medical Centers (PRNewswire) - "Researchers at two major medical centers in Israel...have initiated a Phase 2 clinical trial of a promising new treatment for COVID-19....As of this date 21 patients have been enrolled in a double-blind placebo-controlled 120-patient Phase 2 trial...The FDA has allowed an IND for a second Phase 2 trial being conducted at Columbia University Irving Medical Center and New York-Presbyterian Allen Hospital. This double-blind placebo-controlled trial will enroll 100 patients....'We have been contacted by medical centers and scientists in the US, UK, Belgium, Italy, Spain and Australia suggesting the use of TXA127 for the treatment of COVID-19 and requesting drug for trials'....Israeli trial will be completed within four months....Constant is currently investigating the potential to use TXA127 for the treatment of more severely ill patients in the ICU and for outpatient treatment of newly infected patients to be treated with an oral formulation of TXA127."

IND • Trial status • Infectious Disease • Novel Coronavirus Disease

Angiotensin 1-7 as a Therapy in the Treatment of COVID-19 (clinicaltrials.gov) - P2; N=120; Recruiting; Sponsor: Rambam Health Care Campus; Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

USBTXA127CBT: TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation (clinicaltrials.gov) - P1; N=20; Terminated; Sponsor: Tarix Pharmaceuticals; Trial completion date: Mar 2022 ➔ Dec 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Dec 2021 ➔ Dec 2020

Clinical • Trial completion date • Trial primary completion date • Trial termination • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukaemia • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Myelodysplastic Syndrome • Myelofibrosis • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • FLT3

Acceleration of Platelet Recovery Following Autologous Peripheral Blood Stem Cell Transplant (PBSC) in Hodgkin, Non-Hodgkin Lymphoma or Multiple Myeloma Patients (clinicaltrials.gov) - P2; N=75; Terminated; Sponsor: Tarix Pharmaceuticals; Trial completion date: Mar 2022 ➔ Dec 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Dec 2021 ➔ Dec 2020

Clinical • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD34

Acceleration of Platelet Recovery Following Autologous Peripheral Blood Stem Cell Transplant (PBSC) in Hodgkin, Non-Hodgkin Lymphoma or Multiple Myeloma Patients (clinicaltrials.gov) - P2; N=75; Active, not recruiting; Sponsor: Tarix Pharmaceuticals; Trial completion date: Sep 2020 ➔ Mar 2022; Trial primary completion date: Jun 2020 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD34