pegtarazimod (RLS-0071) / ReAlta - LARVOL DELTA

Anti-inflammatory drug pegtarazimod (RLS-0071) demonstrates clinical improvement in lower gastrointestinal acute graft-versus-host disease (aGvHD) and target engagement of key inflammatory marker myeloperoxidase (MPO) (ASH 2025) - P2 | "In multiplemouse models of aGvHD, pegtarazimod decreased GI tissue damage and significantly improved survival.Given these findings, pegtarazimod is currently being evaluated in a Phase 2 open-label clinical trial(AURORA; Clinical.Trials.gov ID:NCT06343792) for patients with aGvHD. In the AURORA trial, patients hospitalized with steroid-refractory aGvHD after allogeneichematopoietic stem cell transplantation received pegtarazimod simultaneously with ruxolitinib, currentlythe only authorized product for the treatment of aGvHD. Pegtarazimod was generally well tolerated and was associated with improvement in clinicalGVHD grades in patients with steroid-refractory aGvHD in only 7 days. Lower GI clinical improvementstrongly correlated with decreases in plasma MPO level linking the mechanisms of action of RLS-0071 onneutrophils with the lower GI clinical responses. These preliminary data are encouraging forpegtarazimod in the population of steroid-refractory aGvHD with..."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Inflammation • MPO

ReAlta Announces Promising Phase 2 Data Demonstrating Rapid Clinical Responses and Target Engagement in Steroid-Refractory Acute GvHD at the ASH 2025 Annual Meeting (Businesswire) - "Clinical MAGIC Stage improvement observed for 6 of 6 patients with steroid-refractory aGvHD, with 4 of 5 participants demonstrating lower GI MAGIC Stage improvement of 1, 2, or 3 stages over 7 days of treatment; Median plasma MPO levels decreased by 68% (p = 0.02), suggesting modulation of neutrophil-driven inflammatory mechanisms; Safety profile characterized by no dose-limiting toxicities or serious adverse events attributed to the study drug."

P2 data • Acute Graft versus Host Disease

AURORA: Safety, PK, PD, Dosing, and Efficacy of RLS-0071for the Treatment of Hospitalized Patients With Steroid-Refractory Acute Graft-versus-Host Disease (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: ReAlta Life Sciences, Inc. | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Oct 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Exploring a Novel Anti-Inflammatory Peptide As a Potential Treatment for Acute Graft-Versus-Host Disease (aGVHD) (ASH 2024) - P2 | "Further mechanistic studies will provide additional knowledge on the mechanism of action. Based on these promising results, RLS-0071 will be evaluated in a phase 2, open label clinical trial for hospitalized patients with acute GVHD (NCT06343792)."

Acute Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • ELANE • MPO

ReAlta Life Sciences to Present RLS-0071 (pegtarazimod) Clinical Data at 2025 American Society of Hematology Annual Meeting (Businesswire) - "The presentation will showcase data from ReAlta’s Phase 2 clinical trial, an open-label, prospective, dose-escalation study evaluating pegtarazimod in hospitalized patients with steroid-refractory aGvHD."

P2 data • Acute Graft versus Host Disease

ReAlta Life Sciences Receives EMA Orphan Drug Designation for RLS-0071 (pegtarazimod) for the Treatment of Graft-Versus-Host Disease (Businesswire) - "ReAlta is currently enrolling the Phase 2, open-label clinical trial of pegtarazimod for hospitalized patients with steroid-refractory aGvHD (NCT06343792) at clinical sites in the United States, Germany, and Spain. The Company expects to report data from additional cohorts of patients enrolled in this trial in 2026."

Orphan drug • P2 data • Acute Graft versus Host Disease

Effect of RLS-0071 on Airway Neutrophilia Following Inhaled Endotoxin Challenge Assessed by Chipcytometry (ATS 2025) - P1b | "ChipCytometry data confirm and extend previous proof-of-mechanism that RLS-0071 decreases neutrophil numbers in IS and acts on neutrophil activation and adhesion. In line to previous findings of reduced MPO and NE concentrations in sputum supernatant, we found decreased intracellular staining of MPO and NE in neutrophils. Overall, RLS-0071 demonstrates potential as a novel anti-inflammatory treatment for neutrophil-dominated lung diseases by reducing neutrophil activity and infiltration into the lungs."

Acute Lung Injury • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • CD14 • CEACAM8 • CR1 • ELANE • ITGA4 • ITGAM • MPO • PTPRC

ReAlta Life Sciences Announces New Inflammatory Biomarker Data from Acute Exacerbations of Chronic Obstructive Pulmonary Disease Program at American Thoracic Society 2025 International Conference (Businesswire) - P1b | N=30 | NCT05351671 | Sponsor: ReAlta Life Sciences, Inc | "In ReAlta’s Phase 1b study, healthy participants received inhaled LPS to induce temporary neutrophil-mediated inflammation in the lungs, followed by intravenous administration of pegtarazimod at different dose levels. Pegtarazimod demonstrated powerful inhibition of neutrophil migration into the lungs by half (~50%), with significant reductions in key inflammatory markers including MPO and NE, and pro-inflammatory cytokines IL-1β and IL-8...'We look forward to completing our Phase 2 trial in patients with AE-COPD (NCT06175065) later this year'..."

P1 data • Trial completion date • Chronic Obstructive Pulmonary Disease

The anti-inflammatory peptide RLS-0071 reduces immune cell recruitment and oxidative damage in a neonatal rat model of hypoxic ischemic encephalopathy (HIE). (PubMed, Am J Perinatol) - "Our findings suggest that RLS-0071 decreases immune cell recruitment and oxidative damage to levels comparable to therapeutic hypothermia in an animal model of HIE."

Journal • Preclinical • CNS Disorders • Inflammation • MPO

Safety, PK and PD Relationships of RLS-0071 in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: ReAlta Life Sciences, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Pharmacokinetics of RLS-0071, a Novel Anti-Inflammatory Peptide, in Newborns With Moderate or Severe Hypoxic Ischemic Encephalopathy (PAS 2025) - P1, P2 | "RLS-0071 plasma concentrations were obtained for 10 HIE neonates (8 moderate, 2 severe) and summarized in Table 1. HIE infant PK curves for RLS-0071 at the 3 mg/kg/dose were similar to adult human curves at the 2 mg/kg/dose (Figure 1) and within established safe plasma levels in adults. No drug accumulation was observed."

PK/PD data • CNS Disorders • Pediatrics • MPO

ReAlta Life Sciences to Present New Clinical Data from Hypoxic Ischemic Encephalopathy Program at Pediatric Academic Societies 2025 Meeting (Businesswire) - "The presentations will showcase important findings from ReAlta's ongoing HIE research, a serious condition that can cause brain damage in newborns, including data on inflammatory biomarkers and pharmacokinetic data from the Company’s Phase 2 STAR trial in newborns with HIE. The STAR trial (NCT05778188), currently enrolling patients at 13 NICUs across the U.S., is a two-stage, randomized, double-blind, placebo-controlled study evaluating safety, tolerability, pharmacokinetics, and preliminary efficacy of RLS-0071 (pegtarazimod), the Company’s lead candidate, in newborns with moderate or severe HIE undergoing therapeutic hypothermia."

P2 data • PK/PD data • CNS Disorders

AURORA: Safety, PK, PD, Dosing, and Efficacy of RLS-0071for the Treatment of Hospitalized Patients with Steroid-Refractory Acute Graft-versus-Host Disease (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: ReAlta Life Sciences, Inc. | Trial completion date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Apr 2025 ➔ Oct 2025

Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

ReAlta Life Sciences Announces Positive Preclinical Data for RLS-0071 (pegtarazimod) in Acute Graft-Versus-Host Disease (aGVHD) at American Society of Hematology Annual Meeting (Businesswire) - "ReAlta Life Sciences, Inc...today announced positive preclinical data for its lead asset RLS-0071 (pegtarazimod) in acute Graft-versus-Host Disease (aGVHD). These data will be presented in a poster session at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, California. The research, conducted in the laboratory of Dr. Robert Zeiser at the University of Freiburg, demonstrated that pegtarazimod significantly increased survival rates in multiple mouse models of aGVHD, showing effectiveness both when used preventively and as a treatment (Holzmüller V., et al. ASH 2024). In prevention studies using a major histocompatibility complex (MHC)-mismatch model, pegtarazimod treatment from Days 0-7 improved overall survival to Day 60 compared to vehicle control. Early intervention treatment with pegtarazimod initiated on Day 7 also significantly improved survival of mice developing aGVHD."

Preclinical • Acute Graft versus Host Disease

Safety, PK and PD Relationships of RLS-0071 in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: ReAlta Life Sciences, Inc. | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

ReAlta Life Sciences Announces Presentation of RLS-0071 (pegtarazimod) Data in aGVHD at American Society of Hematology Annual Meeting (Businesswire) - "ReAlta Life Sciences....today announced a poster presentation of its lead asset, RLS-0071 (pegtarazimod), will be presented at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition, being held December 7-10, 2024, in San Diego, California....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."

Preclinical • Acute Graft versus Host Disease

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 (Businesswire) - "ReAlta Life Sciences...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)...'We are committed to advancing this clinical program on behalf of patients facing steroid-refractory aGvHD.'"

Trial status • Acute Graft versus Host Disease

RLS-0071, a novel anti-inflammatory agent, significantly reduced inflammatory biomarkers in a randomised human evaluation of mechanisms and safety study. (PubMed, ERJ Open Res) - "Several biomarkers showed trends suggesting sustained decreases for RLS-0071 versus placebo at 24 h. 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."

Biomarker • Journal • Inflammation • ELANE • IL1B • MPO

AURORA: Safety, PK, PD, Dosing, and Efficacy of RLS-0071for the Treatment of Hospitalized Patients With Steroid-Refractory Acute Graft-versus-Host Disease (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: ReAlta Life Sciences, Inc. | Not yet recruiting ➔ Recruiting | Initiation date: May 2024 ➔ Aug 2024

Enrollment open • Trial initiation date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

ReAlta Life Sciences Granted FDA Orphan Drug Designation and Fast Track Designation for RLS-0071 for the Treatment of Steroid-Refractory Acute Graft-versus-Host Disease (Businesswire) - "ReAlta Life Sciences, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation and Fast Track Designation to RLS-0071, the Company’s lead therapeutic candidate, for the treatment of hospitalized patients with steroid-refractory acute graft-versus-host disease (aGvHD)."

Fast track • Orphan drug • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Orphan Designation: Treatment of acute graft-versus-host disease (FDA) - Date Designated: 07/31/2024

Orphan drug • Graft versus Host Disease • Immunology

STAR: A 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 (clinicaltrials.gov) - P2 | N=42 | Recruiting | Sponsor: ReAlta Life Sciences, Inc. | Trial primary completion date: Apr 2024 ➔ Apr 2026

Trial primary completion date • CNS Disorders

RLS-0071 Independently Inhibits Neutrophil Migration and Myeloperoxidase Activity and NETosis in Humans Challenged With LPS by Inhalation (ATS 2024) - P1b | "Overall, these results suggest that RLS-0071 can inhibit key drivers of neutrophil-mediated lung damage, MPO level or activity, and NETosis, independent of sputum neutrophil counts. These encouraging results support the further development of RLS-0071 for neutrophil-mediated lung diseases like acute exacerbations of COPD."

Acute Respiratory Distress Syndrome • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • MPO

AURORA: Safety, PK, PD, Dosing, and Efficacy of RLS-0071for the Treatment of Hospitalized Patients With Steroid-Refractory Acute Graft-versus-Host Disease (clinicaltrials.gov) - P2 | N=66 | Not yet recruiting | Sponsor: ReAlta Life Sciences, Inc.

New P2 trial • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

ReAlta Life Sciences Announces New Research Collaboration with the National Institute of Allergy and Infectious Diseases to Evaluate RLS-0071 as a Medical Countermeasure for Acute Radiation Syndrome (Businesswire) - "ReAlta Life Sciences, Inc...today announces that the company will be utilizing the preclinical services program offered by the National Institute of Allergy and Infectious Diseases (NIAID) to evaluate RLS-0071 as a medical countermeasure for Acute Radiation Syndrome (ARS). Under a research collaboration, scientists at the Armed Forces Radiobiology Research Institute (AFRRI), working with support from the Radiation and Nuclear Countermeasures Program (RNCP) at NIAID, will evaluate the ability RLS-0071 to mitigate the gastrointestinal effects of ARS (GI-ARS) in a preclinical mouse model."

Licensing / partnership • Infectious Disease