NTR-441 / Neutrolis - LARVOL DELTA

The Phase 1a/b study evaluated Neutrolis’s DNASE1L3 analogue therapy in both healthy volunteers and patients with high NET burden. (GlobeNewswire) - "...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."

P1 data • Systemic Lupus Erythematosus

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 (ACR Convergence 2025) - P1 | "Proof-of-concept was investigated in a 16.5-year-old male with a homozygous DNASE1L3 loss-of-function mutation (c.643del) and severe, longstanding, treatment-refractory monogenic SLE, who received weekly doses of NTR-441 (3 mg/kg) as add-on therapy to corticosteroids, antimalarials, and tofacitinib through a compassionate use protocol (Ethics Committee approval no. These combined studies validate DNASE1L3 as a therapeutic strategy to inactivate NETs. In a patient with treatment-refractory SLE with DNASE1L3-deficiency, pharmacologic degradation of NETs with NTR-441 induced rapid, sustained remission, providing the first clinical proof-of-concept for this approach. The temporal link between NET clearance and clinical benefit supports NETs as a central pathogenic driver in autoimmunity."

Late-breaking abstract • Dermatology • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Novel Coronavirus Disease • Ocular Inflammation • Ophthalmology • Rheumatology • Scleritis • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • Urticaria • Vasculitis • DNASE1L3

Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients (clinicaltrials.gov) - P1 | N=52 | Terminated | Sponsor: Neutrolis | N=92 ➔ 52 | Trial completion date: Nov 2022 ➔ Jun 2023 | Recruiting ➔ Terminated; the emergence of the omicron variant of COVID-19 lead to insufficient enrollment

Enrollment change • Trial completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease

Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients (clinicaltrials.gov) - P1 | N=92 | Recruiting | Sponsor: Neutrolis | Trial completion date: Jun 2022 ➔ Nov 2022 | Trial primary completion date: Jun 2022 ➔ Nov 2022

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients (clinicaltrials.gov) - P1; N=92; Recruiting; Sponsor: Neutrolis; Trial completion date: Nov 2021 ➔ Jun 2022; Trial primary completion date: Nov 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients (clinicaltrials.gov) - P1; N=92; Recruiting; Sponsor: Neutrolis

Clinical • New P1 trial • Infectious Disease • Novel Coronavirus Disease

Neutrolis Announces Development Of First-In-Class Treatment Targeting Neutrophil Extracellular Traps (NETs) For Patients With Severe COVID-19 (PRNewswire) - "Neutrolis...today announced the development of NTR-441, a first-in-class DNASE1L3 enzyme analog that has the potential to rapidly and systemically clear neutrophil extracellular traps (NETs) for severe cases of COVID-19....Several independent investigators have observed NETs in the lungs of autopsied COVID-19 patients, and observed that NETs biomarkers in patient blood correlate with the clinical severity of COVID-19....'We found NETs congesting blood vessels in the lungs of all patients. Clearing these NETs with NTR-441 to restore blood flow may help patients survive COVID-19...'"

Biomarker • Infectious Disease • Novel Coronavirus Disease