Phase 2 Open Label Prospective Dose-Ranging Clinical Trial With Escalation and Expansion Cohorts to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Dosing, and Efficacy of RLS-0071 for the Treatment of Hospitalized Patients With Steroid-Refractory Acute Graft-versus-Host Disease

This study is a Open Label Prospective Dose-Ranging Escalation and Expansion Trial to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Dosing, and Efficacy of RLS-0071 for the secondary treatment of acute Graft-versus-Host Disease (aGvHD) in hospitalized patients who are steroid-refractory.

Start Date01 Aug 2024

Sponsor / Collaborator

ReAlta Life Sciences, Inc.Startup

[+1]

NCT06175065 / RecruitingPhase 2

A Phase 2a Randomized, Doubled-Blind, Placebo-Controlled Trial to Evaluate Safety, Pharmacokinetics and Pharmacokinetic-Pharmacodynamic Relationships of RLS-0071 in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease

AECOPD is a major cause of hospital admission and mortality. They contribute to long-term decline in lung function, physical capacity, and quality of life (QoL). RLS-0071 is a novel peptide being developed for the treatment of AECOPD. This study is designed to evaluate the safety and tolerability of RLS-0071 in the treatment of adults with moderate exacerbations of COPD.

Start Date25 Jan 2024

Sponsor / Collaborator

ReAlta Life Sciences, Inc.Startup

NCT05778188 / RecruitingPhase 2

A Phase 2, Two-Stage, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia With Long-Term Follow-Up

Hypoxic-ischemic encephalopathy (HIE) affects approximately 4,000 to 12,000 persons annually in the United States. Mortality from HIE has been reported up to 60%, with at least 25% of survivors left with significant neurocognitive disability. Despite this vital unmet medical need, no pharmacological adjunct or alternative therapy has proven beneficial in improving outcomes in neonatal HIE.
RLS-0071 is a novel peptide being developed for the treatment of neonatal HIE. This study is designed to evaluate the safety and tolerability of RLS-0071 in the treatment of newborns with moderate or severe HIE.

Start Date27 Jul 2023

Sponsor / Collaborator

ReAlta Life Sciences, Inc.Startup

[+1]

100 Clinical Results associated with Pegtarazimod

100 Translational Medicine associated with Pegtarazimod

100 Patents (Medical) associated with Pegtarazimod

Literatures (Medical) associated with Pegtarazimod

01 Jul 2024·ERJ Open Research

RLS-0071, a novel anti-inflammatory agent, significantly reduced inflammatory biomarkers in a randomised human evaluation of mechanisms and safety study

Article

Author: Hair, Pamela ; Holz, Olaf ; Carstensen-Aurèche, Saskia ; Badorrek, Philipp ; Müller, Meike ; Hohlfeld, Jens M ; Dell, Linda ; Hohlfeld, Jens M. ; Roberson, Destrey ; Cunnion, Kenji ; Thienel, Ulrich ; Goss, Jessica ; Mϋller, Meike

Background:

This study was a randomised, double-blind, placebo-controlled study intended to establish the translatability of the RLS-0071 mechanisms of action from animal disease models to humans by inhibiting neutrophil-mediated inflammation at the tissue level and major inflammatory biomarkers. We hypothesised that RLS-0071 inhibits a temporary neutrophil-mediated inflammation in the lungs induced by inhalation of low-dose lipopolysaccharide (LPS) in healthy participants.

Methods:

Participants were randomised to one of three arms to receive inhaled LPS followed by three doses of either low-dose (10 mg·kg−1) or high-dose (120 mg·kg−1loading dose followed by two doses of 40 mg·kg−1) RLS-0071i.v.or placebo (saline) every 8 h. Biomarkers evaluating inflammatory responses, with absolute neutrophil counts in induced sputum as the primary end-point, were collected before and at 6 and 24 h after LPS challenge.

Results:

Active treatment with RLS-0071 showed a similar safety profile to participants receiving placebo. RLS-0071 significantly decreased the numbers of neutrophils in sputum at 6 h post LPS by approximately half (p=0.04). Neutrophil effectors myeloperoxidase, neutrophil elastase and interleukin-1β in sputum were also significantly decreased at 6 h for RLS-0071 compared with placebo. Several biomarkers showed trends suggesting sustained decreases for RLS-0071versusplacebo at 24 h.

Conclusion:

This clinical trial demonstrated that RLS-0071 was safe and well tolerated and modulated neutrophil-mediated inflammation in humans after inhaled LPS challenge, consistent with results from prior animal model studies.

26 May 2023·The American journal of case reports

RLS-0071 Moderated Elevated Myeloperoxidase Level and Activity in an Asymptomatic Subject in Clinical Trial RLS-0071-101.

Article

Author: Hair, Pamela ; Thienel, Ulrich ; Goss, Jessica M ; Kumar, Parvathi S ; Ellis, Alexander ; Cunnion, Kenji

BACKGROUND RLS-0071 is a dual-targeting peptide developed for the regulation of humoral and cellular inflammation via inhibition of neutrophil effectors, including myeloperoxidase and neutrophil extracellular trap formation (NETosis). The safety, pharmacokinetics, and pharmacodynamics of single and multiple doses of RLS-0071 were evaluated in a first-in-human clinical trial in healthy volunteers. Myeloperoxidase is the major peroxidase enzyme present in neutrophilic granules and contributes to cellular inflammation. Extracellular myeloperoxidase has been associated with chronic inflammation in a variety of diseases, including atherosclerosis. RLS-0071 has previously been shown to inhibit extracellular myeloperoxidase function both in vitro and in vivo in animal disease models. CASE REPORT Healthy subjects participating in the RLS-0071-101 study were screened for baseline myeloperoxidase level, leading to the identification of a 21-year-old woman with elevated baseline levels. After randomization, the subject received 9 intravenous infusions of 10 mg/kg RLS-0071. The subject tolerated the peptide infusions well with no adverse changes in vital signs, significantly abnormal clinical laboratory results, or severe adverse events. Analysis of this subject's myeloperoxidase plasma concentrations demonstrated that her myeloperoxidase levels decreased by 43% and myeloperoxidase activity levels decreased 49% after infusions of RLS-0071. The reduction in the patient's plasma myeloperoxidase levels demonstrated a partial return to baseline levels 24 hours after cessation of dosing. There were no other clinically meaningful safety observations for this subject. CONCLUSIONS This observation suggests RLS-0071 has the therapeutic potential to moderate plasma myeloperoxidase levels and activity and modulate diseases in which myeloperoxidase contributes to pathogenesis.

PloS oneQ3 · CROSS-FIELD

Peptide inhibition of acute lung injury in a novel two-hit rat model

Q3 · CROSS-FIELD

ArticleOA

Author: Krishna, Neel K ; Hair, Pamela S ; Sampson, Alana C ; Enos, Adrianne I ; Glesby, Marshall J ; Jackson, Kaitlyn G ; Vazifedan, Turaj ; Werner, Alice L ; Lassiter, Brittany P ; Lattanzio, Frank A ; Cunnion, Kenji M ; Gregory Rivera, Magdielis

Acute lung injury (ALI) often causes severe trauma that may progress to significant morbidity and mortality. ALI results from a combination of the underlying clinical condition of the patient (e.g., inflammation) with a secondary insult such as viral pneumonia or a blood transfusion. While the secondary insult may be variable, the rapidly progressive disease process leading to pulmonary failure is typically mediated by an overwhelming innate immunological or inflammatory reaction driven by excessive complement and neutrophil-mediated inflammatory responses. We recently developed a ‘two-hit’ ALI rat model mediated by lipopolysaccharide followed by transfusion of incompatible human erythrocytes resulting in complement activation, neutrophil-mediated ALI and free DNA in the blood indicative of neutrophil extracellular trap formation. The objective of this study was to evaluate the role of peptide inhibitor of complement C1 (RLS-0071), a classical complement pathway inhibitor and neutrophil modulator in this animal model. Adolescent male Wistar rats were infused with lipopolysaccharide followed by transfusion of incompatible erythrocytes in the presence or absence of RLS-0071. Blood was collected at various time points to assess complement C5a levels, free DNA and cytokines in isolated plasma. Four hours following erythrocyte transfusion, lung tissue was recovered and assayed for ALI by histology. Compared to animals not receiving RLS-0071, lungs of animals treated with a single dose of RLS-0071 showed significant reduction in ALI as well as reduced levels of C5a, free DNA and inflammatory cytokines in the blood. These results demonstrate that RLS-0071 can modulate neutrophil-mediated ALI in this novel rat model.

News (Medical) associated with Pegtarazimod

05 Nov 2024

·www.businesswire.com

ReAlta Life Sciences Announces Presentation of RLS-0071 (pegtarazimod) Data in aGVHD at American Society of Hematology Annual Meeting

NORFOLK, Va.--( BUSINESS WIRE )-- ReAlta Life Sciences, Inc. (“ReAlta” or the “Company”), a clinical-stage biopharmaceutical company dedicated to saving lives by rebalancing the inflammatory response to address rare and acute inflammatory diseases, today announced a poster presentation of its lead asset, RLS-0071 (pegtarazimod), will be presented at the 66 th American Society of Hematology (ASH) Annual Meeting & Exposition, being held December 7-10, 2024, in San Diego, California. ReAlta is developing pegtarazimod, a synthetic peptide derived from human astrovirus serotype 1, as a potential treatment for acute Graft-versus-Host Disease (aGVHD), a serious complication of allogeneic hematopoietic cell transplantation, as well as pulmonary and neurological conditions. Pegtarazimod is a dual-action anti-inflammatory agent that inhibits both the complement cascade and neutrophil-mediated inflammation. Pegtarazimod has previously demonstrated an excellent safety profile and target engagement in a Phase 1 study of healthy volunteers, with no treatment-related or serious adverse events reported. A Phase 2, open-label clinical trial of pegtarazimod for hospitalized patients with steroid-refractory aGVHD ( NCT06343792 ) is currently enrolling at clinical sites located within the United States, Germany and Spain. The data to be presented at the upcoming ASH meeting explores the underlying mechanisms of pegtarazimod in a preclinical model of aGVHD using different investigational methods. This data was generated from experiments conducted within the laboratory of Dr. Robert Zeiser at the University of Freiburg – one of the leading laboratories investigating the underlying pathogenesis and potential treatments for aGVHD. Poster presentation details: Title: Exploring a Novel Anti-Inflammatory Peptide as Potential Treatment for Acute Graft-Versus-Host Disease (aGVHD) Presenter: Verena Holzmüller, PhD candidate in the laboratory of Robert Zeiser, M.D., at the Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg Presentation: Poster #194793; Location San Diego Convention Center, Halls G-H Session: 701. Experimental Transplantation: Basic and Translational: Poster II Date/Time: Sunday, December 8, 2024, 6:00 PM - 8:00 PM The abstract can be accessed on the ASH website at https://www.hematology.org/meetings/annual-meeting/abstracts . About ReAlta Life Sciences ReAlta Life Sciences, Inc. is a clinical mid-stage biopharmaceutical company dedicated to saving lives by rebalancing the inflammatory response to address life threatening rare and acute inflammatory diseases. The Company’s EPICC peptide platform is based on discoveries related to the human astrovirus, HAstV-1, which causes a non-inflammatory, self-limiting gastroenteritis by inhibiting components of the innate immune system – a trait unique among viruses. By inhibiting activation of the complement cascade and two key neutrophil-driven mechanisms of inflammation and host tissue destruction – myeloperoxidase (MPO) and neutrophil extracellular traps (NETs), ReAlta’s therapeutic peptides leverage the dual-targeting mechanisms of this human enteric virus – and its millions of years of evolutionary adaptations – to modulate both complement and innate inflammatory pathways. The Company’s pipeline is led by RLS-0071 (pegtarazimod), which has received both Orphan Drug Designation and Fast Track Designation by the U.S. Food and Drug Administration (FDA) and Orphan Drug Designation by the European Medicines Agency, for the treatment of hypoxic ischemic encephalopathy (HIE), a devastating disease that causes brain damage in oxygen-deprived newborns and is a leading cause of cerebral palsy; Orphan Drug Designation and Fast Track Designation by the FDA for the treatment of acute graft-versus-host disease (aGVHD), a disease associated with bone marrow and stem cell transplants whereby transplanted white blood cells attack the new host in an inflammatory response; and IND clearance by the FDA for the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD), an inflammatory lung disease characterized by progressive airflow limitations and tissue destruction that makes it challenging for patients to breathe. The company launched in 2018 and is located in Norfolk, Virginia and Aguadilla, Puerto Rico. For more information, please visit www.realtalifesciences.com .

Fast TrackPhase 2Orphan DrugClinical ResultASH

23 Sep 2024

·www.businesswire.com

ReAlta Life Sciences Announces First Patient Dosed in Phase 2 Study Evaluating RLS-0071 for the Treatment of Steroid-Refractory Acute Graft-versus-Host Disease

NORFOLK, Va.--( BUSINESS WIRE )--ReAlta Life Sciences, Inc. ("ReAlta" or the “Company”), a clinical-stage biopharmaceutical company dedicated to saving lives by rebalancing the inflammatory response to address rare and acute inflammatory diseases, today announced that the first patient has been dosed in its Phase 2 study of RLS-0071, the Company’s lead therapeutic candidate, for the treatment of hospitalized patients with moderate to very severe steroid-refractory acute graft-versus-host disease (aGvHD), a serious and often fatal complication following hematopoietic stem cell transplantation. “Hematopoietic stem cell transplantation is one of the most impactful treatments available for people with cancer, autoimmune disease, sickle cell disease and other life-threatening disorders. However, the procedure can quickly turn into a severe and life-threatening condition for those who are affected by acute graft-versus-host disease in which the transplanted immune cells attack the patient, leading to severe inflammation and tissue damage,” said ReAlta Chief Medical Officer Kenji Cunnion, MD, MPH. “We believe that RLS-0071 has the potential to be a powerful new tool to improve outcomes for individuals with this serious complication of transplantation. We aim to leverage RLS-0071's unique dual mechanism-of-action (MOA) to inhibit unwanted inflammatory side-effects from the donor cells. We are committed to advancing this clinical program on behalf of patients facing steroid-refractory aGvHD.” Patients with aGvHD who do not respond to standard steroid treatments have limited therapeutic options and face severe inflammation, tissue damage and a high risk of mortality. Each year, approximately 4,000 patients develop steroid-refractory aGvHD within the U.S., EU and Japan. RLS-0071, an investigational medicine based on the Company’s novel EPICC peptide platform, seeks to address this unmet medical need by capitalizing on its unique dual-targeting MOA to modulate both the complement and innate inflammatory pathways, offering a new hope for patients with this devastating condition. RLS-0071 was recently granted Orphan Drug Designation and Fast Track Designation for the treatment of steroid-refractory aGvHD by the U.S. Food and Drug Administration (FDA). The Company is also currently conducting Phase 2 clinical trials of RLS-0071 in newborns with hypoxic ischemic encephalopathy (HIE) ( NCT05778188 ) and hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) ( NCT06175065 ). About the Study The Phase 2 study ( NCT06343792 ) is an open-label, prospective, dose-escalation trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, dosing and efficacy of RLS-0071 for the secondary treatment of acute graft-versus-host disease (aGvHD) in hospitalized patients who are steroid-refractory. Participants will receive RLS-0071 at their assigned dose level(s) for 7 or 14 days as either a monotherapy or concurrent with the standard-of-care treatment, ruxolitinib. Primary outcomes measures include safety and overall response rate. About ReAlta Life Sciences ReAlta Life Sciences, Inc. is a clinical mid-stage biopharmaceutical company dedicated to saving lives by rebalancing the inflammatory response to address life threatening rare and acute inflammatory diseases. The Company’s EPICC peptide platform is based on discoveries related to the human astrovirus, HAstV-1, which causes a non-inflammatory, self-limiting gastroenteritis by inhibiting components of the innate immune system – a trait unique among viruses. By inhibiting activation of the complement cascade and two key neutrophil-driven mechanisms of inflammation and host tissue destruction - myeloperoxidase (MPO) and neutrophil extracellular traps (NETs), ReAlta’s therapeutic peptides leverage the dual-targeting mechanisms of this human enteric virus – and its millions of years of evolutionary adaptations – to modulate both complement and innate inflammatory pathways. The Company’s pipeline is led by RLS-0071, which has received both Orphan Drug Designation and Fast Track Designation by the U.S. Food and Drug Administration (FDA) and Orphan Drug Designation by the European Medicines Agency, for the treatment of hypoxic ischemic encephalopathy (HIE), a devastating disease that causes brain damage in oxygen-deprived newborns and is a leading cause of cerebral palsy; Orphan Drug Designation and Fast Track Designation by the FDA for the treatment of acute graft-versus-host disease (aGvHD), a disease associated with bone marrow and stem cell transplants whereby transplanted white blood cells attack the new host in an inflammatory response; and IND clearance by the FDA for the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD), an inflammatory lung disease characterized by progressive airflow limitations and tissue destruction that makes it challenging for patients to breathe. The company launched in 2018 and is located in Norfolk, Virginia and Aguadilla, Puerto Rico. For more information, please visit www.realtalifesciences.com .

Orphan DrugPhase 2Fast Track

20 Aug 2024

·www.pharmaceutical-technology.com

ReAlta secures FDA orphan drug and fast track designations for GvHD therapy

Pegtarazimod is being studied as a potential treatment to aGvHD patients after haematopoietic stem cell transplant where steroid therapy is ineffective. Image: Shutterstock / Gorodenkoff. The US Food and Drug Administration (FDA) has granted an orphan drug designation and fast track designation to ReAlta Life Sciences’ lead candidate pegtarazimod (RLS-0071) to treat steroid-refractory acute graft-versus-host disease (aGvHD). These designations come as the company continues its open label Phase II AURORA trial (NCT06343792) with pegtarazimod in this indication. The FDA designations will grant ReAlta seven years of market exclusivity for pegtarazimod upon approval and expedite the review process. aGvHD is an often fatal complication following haematopoietic stem cell transplantation in which donor immune cells attack the recipient’s tissue. Standard treatment involves steroid regimens, but patients who are unresponsive to steroid therapy face limited further options and a high risk of mortality. There are an estimated 4,000 such patients in the US, EU, and Japan. Pegtarazimod is based on ReAlta’s EPICC peptide platform. The technology is based on the human astrovirus HAstV-1, which causes non-inflammatory, self-limiting gastroenteritis by inhibiting components of the immune system. Dr. Kenji Cunnion, chief medical officer at ReAlta, said the FDA decision underscored, “the significant potential of RLS-0071 and its novel dual mechanism-of-action to address critical unmet needs for patients with this life-threatening condition”. See Also: Licensing agreements for innovator GLP1R drugs weigh in with over $6.2bn in 2024 Top 20 biopharmas’ market cap up 4.3% in Q2 2024 as GLP-1 drug innovators hold top spots If successfully developed and approved, pegtarazimod is set to compete in a market inhabited by Johnson & Johnson ’s Imbruvica (ibrutinib), Novartis ’s Jakavi or Jakafi (ruxolitinib phosphate), and Bristol Myers Squibb ’s Orencia (abatacept) among others. These therapies are projected by GlobalData to generate $2.56bn, $2.25bn, and $3.44bn in annual sales by 2030, respectively. GlobalData is the parent company of Pharmaceutical Technology . The Virginia-based ReAlta is currently investigating their lead therapeutic candidate’s application in a variety of indications, fuelled in part by $20m raised in Series A financing in 2021 . Alongside the AURORA trial, the company is conducting Phase II trials to determine the efficacy of pegtarazimod in newborns with hypoxic-ischemic encephalopathy (NCT05778188) and in patients with acute exacerbations of chronic obstructive pulmonary disease (NCT06175065). ReAlta also completed a Phase I trial to investigate the therapeutic application of RLS-0071 against asthma (NCT05351671) and was conducting a Phase I trial exploring the drug’s use in Covid-19-associated acute lung injury (NCT04574869) before the trial was withdrawn due to the “low probability of enrolling patients prior to expiry of study drug”, as per ClinicalTrials.gov . Earlier this year, the company collaborated with US National Institute of Allergy and Infectious Diseases (NIAID) to evaluate the drug’s use in acute radiation syndrome.

Phase 1Fast TrackOrphan DrugPhase 2

100 Deals associated with Pegtarazimod

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Graft Versus Host Disease	Phase 2	US	ReAlta Life Sciences, Inc.Startup	01 Aug 2024
Steroid Refractory Graft Versus Host Disease	Phase 2	US	ReAlta Life Sciences, Inc.Startup	01 Aug 2024
Pulmonary Disease, Chronic Obstructive	Phase 2	US	ReAlta Life Sciences, Inc.Startup	25 Jan 2024
Hypoxia-Ischemia, Brain	Phase 2	US	ReAlta Life Sciences, Inc.Startup	27 Jul 2023
Status Asthmaticus	Phase 1	US	ReAlta Life Sciences, Inc.Startup	01 Jun 2022
Asthma	Phase 1	DE	ReAlta Life Sciences, Inc.Startup	23 May 2022
Inflammation	Phase 1	DE	ReAlta Life Sciences, Inc.Startup	23 May 2022
Acute Lung Injury	Phase 1	US	ReAlta Life Sciences, Inc.Startup	01 Jan 2021
COVID-19	Phase 1	US	ReAlta Life Sciences, Inc.Startup	01 Jan 2021

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