Data demonstrates pegtarazimod's ability to reduce inflammation and significantly increase survival rates in multiple preclinical models of aGVHD

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 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.

“These data demonstrate efficacy of pegtarazimod in both prevention and early intervention settings in mice developing acute GVHD,” commented Dr. Robert Zeiser, Professor of Medicine at the Department of Hematology, Oncology and Stem Cell Transplantation Medical Center, University of Freiburg. “Particularly noteworthy is pegtarazimod's protective effect on intestinal tissue in mice, as intestinal manifestations are a significant driver of mortality in aGVHD patients.”

The study revealed that pegtarazimod works through several mechanisms to reduce inflammation and tissue damage. Treatment with pegtarazimod significantly reduced serum levels of myeloperoxidase (MPO), a key enzyme released by activated neutrophils, by approximately 50%, and neutrophil elastase levels by approximately 50%, indicating decreased neutrophil activation and inflammation. Prior work by the Zeiser laboratory had shown the neutrophils contribute to GVHD in the mouse model (Nature Med. 2014 Jun;20(6):648-54. doi: 10.1038/nm.3517). In splenic neutrophils, pegtarazimod treatment resulted in significant reductions in multiple inflammatory markers, including TNF, IL-1β, and MCP-1/CCL2. In lab-grown intestinal tissue (organoids), pegtarazimod demonstrated significant protective effects under inflammatory conditions, improving viability by approximately 40% and reducing cell damage by 25% as measured by lactate dehydrogenase (LDH) release, a marker of cell death and tissue injury. Histological analysis revealed that pegtarazimod treatment significantly reduced GVHD scores across multiple organs in both prevention and early intervention studies, with particularly notable improvements in the colon, liver, and small intestine.

“These results highlight pegtarazimod's unique dual mechanism to simultaneously target complement and neutrophil-mediated inflammation at the earliest and most destructive points in the inflammatory cascade,” said Paolo Martini, Ph.D., Chief Research and Development Officer of ReAlta. “These data add to the comprehensive body of research supporting pegtarazimod’s therapeutic potential, as we advance our Phase 2 trial on a path towards addressing the pressing unmet need in aGVHD.”

ReAlta is currently enrolling a Phase 2, open-label clinical trial of RLS-0071 in patients with steroid-refractory aGVHD at clinical sites in the United States, Germany, and Spain. To learn more, visit: https://clinicaltrials.gov/study/NCT06343792

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.

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