Neutrolis Presented First-in-Human Proof-of-Concept Data Validating DNASE1L3-Mediated Neutrophil Extracellular Trap (NET) Clearance as a Therapeutic Approach in Autoimmunity at American College of Rheumatology Convergence 2025
- First-in-human data validating direct targeting of NETs as a novel therapeutic approach in autoimmunity and inflammatory diseases
- DNASE1L3 analogue therapy degrades NETs and results in rapid, multi-organ clinical response in treatment-refractory systemic lupus erythematosus (SLE) with DNASE1L3-Deficiency
- Building on these results, Neutrolis is advancing its next-generation DNASE1L3 analogue into Phase 2a trials in SLE and Rheumatoid Arthritis (RA) in 2026
CAMBRIDGE, Mass., Oct. 29, 2025 (GLOBE NEWSWIRE) -- Neutrolis Inc., a clinical-stage biotech company focused on targeting Neutrophil Extracellular Traps (NETs) to revolutionize the treatment of inflammatory disorders, today announced positive first-in-human clinical data demonstrating that its DNASE1L3 analogue achieved rapid, multi-organ clinical improvement and robust target engagement consistent with its mechanism of NET degradation. The results support NET clearance as a novel, disease-modifying approach in SLE and other autoimmune and inflammatory disorders. Full data was presented today at the American College of Rheumatology (ACR) Convergence 2025 8:45 AM CT in Chicago.
“SLE and RA are typically managed with immunosuppressive drugs to reduce inflammation and prevent the immune system from attacking healthy tissues, however, these treatments can increase the risk of infections and other complications,” said Daniel Wallace, M.D., Professor of Medicine, Cedars-Sinai Medical Center at the David Geffen School of Medicine at UCLA. “There is a significant unmet medical need for new non-immunosuppressive therapies such as DNASE1L3 analogues that is designed to clear NETs and has the potential to reduce disease activity without compromising the adaptive immune system's ability to fight infections.”
The early clinical development program consisted of a Phase 1a/b study (NCT04941183) and a compassionate use program. The Phase 1a/b study evaluated Neutrolis’s DNASE1L3 analogue therapy in both healthy volunteers and patients with high NET burden. The placebo-controlled, double-blind, single ascending dose study enrolled 35 healthy adults and 16 hospitalized patients with severe COVID-19, a disease characterized by elevated NET formation, across dose levels ranging from 0.01 to 10 mg/kg. In addition, the therapy was administered under compassionate use to a 16-year-old patient with severe, treatment-refractory SLE with DNASE1L3-deficiency. This patient, who presented with longstanding multi-organ involvement, received five weekly doses of 3 mg/kg alongside standard-of-care therapies. Treatment resulted in rapid (within six hours) and sustained clinical improvement across multiple organ systems, including resolution of vasculitic rash, complete resolution of active arthritis, and improvement in episcleritis.
“We are encouraged by these preliminary findings, which add to the growing body of evidence that NETs play a central role in autoimmunity,” said Andreas Reiff, M.D., Chief Medical Officer of Neutrolis. “The temporal association observed between NET reduction and clinical improvement in this patient suggests that DNASE1L3 therapy has the potential to address disease at its source. These results provide important guidance as we design future studies aimed at evaluating this mechanism across a broader patient population.”
Across all clinical data, DNASE1L3 therapy was generally well tolerated and produced robust, sustained increases in circulating DNASE1L3 levels. Infusion-related reactions were uncommon. Pharmacodynamic activity consistent with NET degradation was demonstrated by increases in MPO–DNA complexes and cell-free DNA in both the SLE and COVID-19 cohorts as early as four hours post-infusion, with no such changes observed in healthy volunteers.
Advancement of Next-Generation DNASE1L3 Analogue (NTR-1011)
Building on these findings, Neutrolis has advanced NTR-1011, an optimized DNASE1L3 analogue fused to human serum albumin designed for subcutaneous delivery with enhanced stability and pharmacokinetics. NTR-1011 represents the lead program within Neutrolis’s exDNASE™ platform, maintaining the validated mechanism of restoring NET clearance demonstrated with NTR-441. Phase 2a studies in patients with SLE and RA are planned in 2026.
Podium Presentation Details:
Title: Early Evidence of Proof-of-Concept of an Albumin-DNASE1L3 Fusion Protein (NTR-441) for the Rapid Enzymatic Inactivation of NETs in SLE with DNASE1L3-Deficiency
Presenter: Toby Fox, PhD, Co-founder and Chief Scientific Officer of Neutrolis
Abstract Number: LB22
Session Name: (LB19–LB24) Late-Breaking Abstracts
Session Date/Time: Wednesday, October 29, 8:00 AM - 9:30 AM CT
Presentation Time: 8:45 AM - 9:00 AM CT
About Neutrolis Inc.
Neutrolis is a clinical-stage biotechnology company pioneering a new class of rapid-acting, non-immunosuppressive therapies that directly target Neutrophil Extracellular Traps (NETs), a root cause of tissue damage and chronic inflammation. Unlike conventional approaches that broadly suppress immune responses, Neutrolis’s therapies harness the body’s own mechanisms to precisely degrade and inactivate NETs, offering broad potential across inflammatory disorders.
The company’s lead program, based on DNASE1L3, is the first therapeutic strategy designed to dismantle pathogenic NETs and prevent their downstream inflammatory effects, restoring immune balance. By targeting this upstream driver of disease, Neutrolis aims to deliver transformational, disease-modifying treatments for conditions such as lupus, rheumatoid arthritis and other chronic immune disorders with high unmet need where current therapies remain inadequate.
For more information, please visit www.neutrolis.com.
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