Neutrolis Reports Positive Phase 1a Results for First-in-Class NET-Targeting Therapy NTR-1011
核心洞察
Neutrolis (搜索) announced positive Phase 1a results for NTR-1011 (搜索), a first-in-class DNASE1L3 (搜索) fusion protein targeting neutrophil extracellular traps (搜索) (NETs) in autoimmune diseases.
The therapy demonstrated favorable safety and tolerability across all dose levels with no serious adverse events or immunogenicity in 48 healthy volunteers.
NTR-1011 (搜索) showed predictable pharmacokinetics with robust subcutaneous bioavailability, supporting development for chronic dosing in patients.
Neutrolis (搜索), Inc. announced positive topline results from the Phase 1a portion of its LIBERATE-I trial evaluating NTR-1011 (搜索), a first-in-class DNASE1L3 (搜索) fusion protein designed to target neutrophil extracellular traps (搜索) (NETs) in autoimmune diseases. The therapy demonstrated a favorable safety profile and predictable pharmacokinetics across multiple dose levels, supporting advancement into Phase 1b trials planned for mid-2026.
Novel Mechanism Targets Root Cause of Autoimmune Disease
NTR-1011 (搜索) represents a fundamentally different approach to treating systemic autoimmune diseases by directly targeting NETs, extracellular chromatin structures released by activated neutrophils that contribute to inflammation, tissue damage, and autoantigen exposure. Unlike conventional therapies that broadly suppress immune responses, NTR-1011 harnesses the body's natural mechanisms to precisely degrade and inactivate NETs.
"NTR-1011 (搜索) represents a fundamentally new approach to treating systemic autoimmune disease (搜索) by directly removing the pathogenic autoantigen that drives immune activation," said Mikael Dolsten, M.D., Ph.D., Executive Director of Neutrolis (搜索). "This approach has the potential to redefine the standard of care across chronic immune disorders with high unmet need where current therapies remain inadequate."
Phase 1a Trial Demonstrates Strong Safety Profile
The randomized, placebo-controlled, single-ascending dose study enrolled 48 healthy participants across multiple dose cohorts, evaluating both intravenous and subcutaneous administration routes. Primary endpoints included safety, tolerability, and immunogenicity, while secondary endpoints focused on pharmacokinetics.
The therapy was well tolerated across all dose levels tested, with no serious adverse events reported and no dose-limiting toxicities observed. Importantly, no clinically meaningful changes in laboratory parameters, vital signs, or electrocardiograms were detected, and no anti-drug antibodies were found at the end of the follow-up period.
Favorable Pharmacokinetics Support Chronic Dosing
NTR-1011 (搜索) displayed predictable pharmacokinetics following both intravenous and subcutaneous administration. The subcutaneous route demonstrated favorable exposure and bioavailability, supporting the development of chronic subcutaneous dosing regimens for future patient treatment.
Pharmacodynamic analyses revealed robust supraphysiologic and exposure-dependent DNASE1L3 (搜索) enzymatic activity following both administration routes, confirming the drug's biological activity at the target level.
Advancing to Patient Studies
Based on these encouraging results, Neutrolis (搜索) plans to initiate the Phase 1b portion of LIBERATE-I in mid-2026. This multi-cohort basket trial will evaluate NTR-1011 (搜索) in patients with moderate-to-severe systemic lupus erythematosus (搜索) (SLE) and rheumatoid arthritis (搜索) (RA), generating initial patient-level data to inform dose selection and guide subsequent clinical development.
"NTR-1011 (搜索) demonstrated a promising safety profile, predictable pharmacokinetics, and no immunogenicity across both intravenous and subcutaneous administration," said Anthony Aiudi, PharmD, MBA, Chief Executive Officer of Neutrolis (搜索). "These data support the advancement of NTR-1011 into a Phase 1b study and strengthen our confidence in its ability to address the unmet needs of patients with SLE and RA."
Targeting NETs as Therapeutic Strategy
The therapeutic rationale for NTR-1011 (搜索) stems from the role of DNASE1L3 (搜索), a naturally occurring nuclease responsible for degrading extracellular chromatin, the structural backbone of NETs. Genetic deficiency or impaired function of DNASE1L3 has been associated with NET accumulation and early-onset autoimmune disease (搜索), supporting DNASE1L3-based approaches as a therapeutic strategy to target this upstream driver of immune dysregulation.
Impaired clearance of NETs has been implicated in the pathogenesis of numerous autoimmune and inflammatory disorders, making this pathway an attractive target for therapeutic intervention. Neutrolis (搜索)'s exDNASE™ platform powers the development of analogs of naturally occurring enzymes that disassemble NETs, offering broad potential across inflammatory disorders.