CAMBRIDGE, Mass., July 15, 2026
Neutrolis announced the publication of a clinical report in the New England Journal of Medicine (NEJM) demonstrating the first human clinical evidence that targeted degradation of neutrophil extracellular traps (NETs) may effectively treat severe, treatment-refractory systemic lupus erythematosus (SLE) caused by congenital DNASE1L3 deficiency. The compassionate-use case showed rapid clinical improvement following treatment with the investigational DNASE1L3 analog NTR-441, providing proof-of-concept for Neutrolis’ NET-targeting therapeutic platform.
NTR-441 Produces Rapid Clinical and Biomarker Improvements
The published report describes treatment of a 16.5-year-old patient with severe SLE and hypocomplementemic urticarial vasculitis whose disease had failed multiple immunosuppressive therapies. Following weekly intravenous administration of NTR-441, clinical symptoms improved within six hours of the first infusion. Over four weeks, vasculitic rash decreased from 76% to 20% of body surface area, while joint inflammation, episcleritis, and disease activity scores showed substantial improvement. Pharmacodynamic analyses demonstrated increased circulating DNASE1L3 activity and biomarker evidence of NET degradation, supporting the proposed mechanism of action.
First Human Proof-of-Concept for NET-Targeted Therapy
The findings represent the first clinical evidence that enzymatic degradation of NETs may directly address a fundamental driver of autoimmune disease rather than broadly suppressing immune function. Researchers reported that restoration of DNASE1L3 activity dismantled NET DNA scaffolds, with biomarker changes closely corresponding to clinical improvement. Although the patient later developed anti-drug antibodies leading to an infusion reaction and eventual treatment discontinuation after the eighth infusion, clinical benefits were maintained through dose adjustments using a desensitization protocol.
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Neutrolis Advances Next-Generation exDNASE Platform
The NEJM publication strengthens support for Neutrolis’ exDNASE™ platform and its lead clinical candidate NTR-1011, an improved DNASE1L3 fusion protein. Following favorable Phase 1a safety and tolerability results reported in April 2026, the company is initiating the Phase 1b LIBERATE-I clinical trial to evaluate NTR-1011 in patients with systemic lupus erythematosus and rheumatoid arthritis. The platform is designed to provide rapid-acting, non-immunosuppressive therapies that directly eliminate NETs, with potential applications across a broad range of autoimmune and inflammatory diseases.
Source: Neutrolis press release
