LEVI-04 / Levicept - LARVOL DELTA

LEVI-04 Significantly Reduces Bone Marrow Lesions and Symptoms in Knee Osteoarthritis: Results from a Phase II RCT (ACR Convergence 2025) - "A significant, dose-dependent reduction in BML presence and area across all KL grades was observed for LEVI-04 compared with placebo. Changes in BML area significantly correlated with changes in patient-reported symptoms. LEVI-04 supplements endogenous soluble p75NTR, which is present in the extracellular matrix of OA tissue including BMLs."

P2 data • Fibrosis • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology • NGFR

Pharmacology of LEVI-04, a novel treatment for OA (ACR Convergence 2025) - "LEVI-04 supplements endogenous soluble p75NTR. Like soluble p75NTR, LEVI-04 interacts with all NTs but inhibits NT-3. Of note, NGF-, BDNF- and NT-4-induced Trk receptor activity cannot be fully inhibited by LEVI-04."

Immunology • Osteoarthritis • Rheumatology • BDNF • NGFR • NTRK3

Radiologic surveillance in the Phase II RCT of LEVI-04, a novel neurotrophin-3 inhibitor, in people with knee osteoarthritis: exclusions at screening (ACR Convergence 2025) - "A significant proportion of people with OA show radiologic findings at screening. Excluding these patients is important to distinguish existing pathologies from treatment-emergent events in early trials. Rigorous radiologic surveillance supported determination of LEVI-04 joint safety; LEVI-04 was not associated with an increase in adverse joint events compared to placebo in this study1."

P2 data • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology • NGFR • NTF3

LEVI-04, a Novel Neurotrophin-3 Inhibitor, Demonstrates Clinically Meaningful Improvements in Pain and Physical Function across a Range of OA Outcomes, Including the Staircase-Evoked Pain Procedure (StEPP) (ACR Convergence 2025) - "Effect sizes at or above those reported for NSAIDs2 were observed with LEVI-04, especially with higher doses. LEVI-04 1.0 and 2.0 mg/kg resulted in significantly more patients achieving StEPP MCID, and at levels comparable or better than naproxen3.Phase 3 trials are in planning."

Clinical • Immunology • Osteoarthritis • Pain • Rheumatology • NTF3

LEVI-04-21-02: Clinical Trial to Evaluate the Efficacy and Safety of LEVI-04 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P2 | N=518 | Completed | Sponsor: Levicept | Active, not recruiting ➔ Completed

Trial completion • Immunology • Musculoskeletal Diseases • Osteoarthritis • Pain • Rheumatology

Clinical Meaningfulness of Pain Improvements and Time to Onset of Pain Relief of a Novel OA Therapy: Analyses from a Randomised Controlled Phase 2 Trial with LEVI-04, a Novel Neurotrophin-3 Inhibitor (EULAR 2025) - "Significant and clinically meaningful [3] improvement in pain, function, and other outcomes were observed with LEVI-04 vs. placebo in people with knee OA. These results suggest that LEVI-04 improves physical function and pain in people with knee OA, with a rapid onset of action, which are important treatment characteristics for people with knee OA."

Clinical • P2 data • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • NGFR • NTF3

LEVI-04, a Novel Neurotrophin-3 Inhibitor, Improves Physical Function Out of Proportion to its Pain-Relieving Effects (EULAR 2025) - "Improvement in physical function is important to patients and other stakeholders. Measurement of physical function in clinical trials is enhanced by including performance-based measures, such as the StEPP. In this study we demonstrated excellent psychometric performance of the StEPP."

Cognitive Disorders • Immunology • Osteoarthritis • Pain • Rheumatology • NTF3

A randomised controlled Phase II trial of LEVI-04, a novel neurotrophin-3 inhibitor, in knee osteoarthritis demonstrates substantially improved pain and function without deleterious effects on joint structure (BSR 2025) - "LEVI-04 demonstrated significant, clinically meaningful improvement in pain, function and other patient-reported outcomes without evidence of increased structural joint pathologies."

Clinical • P2 data • Immunology • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • Pain • Rheumatology • NGFR • NTF3

Levicept Presents Positive Phase II Data for Novel Neurotrophin-3 Inhibitor, LEVI-04, at 2025 World Congress on Osteoarthritis (GlobeNewswire) - P2 | N=518 | NCT05618782 | Sponsor: Levicept | "Levicept...is presenting key data from its positive Phase II trial of LEVI-04 at the 2025 World Congress on Osteoarthritis (OARSI) in Seoul, South Korea....LEVI-04 demonstrated significant differences to placebo for the primary endpoint for all doses: The primary endpoint was WOMACⁱ pain assessment (change from baseline at Week 17). More than 50% of the LEVI-04-treated patients reported ≥50% reduction in pain and >35% reported ≥70% reduction at week 17....'We are excited to be presenting these truly exceptional results from a robust and well-designed study at OARSI. Safe and effective pain management is of critical importance in osteoarthritis with existing treatments limited by adverse effects, addiction liabilities and poor efficacy.'"

P2 data • Immunology • Osteoarthritis

LEVI-04, a Novel neurotrophin-3 Inhibitor, Substantially Improves Pain and Function Without Deleterious Effects on Joint Structure in People with Knee Osteoarthritis: A Randomized Controlled Phase II Trial (ACR Convergence 2024) - "LEVI-04 demonstrated significant and clinically meaningful improvement in pain, function and other outcomes. LEVI-04 was well tolerated at all doses studied, supporting the concept of supplementing endogenous p75NTR as a treatment for OA and other pain conditions. Phase III trials are in planning."

Clinical • Late-breaking abstract • P2 data • Immunology • Osteoarthritis • Pain • Rheumatology • NGFR • NTF3

Levicept Announces Positive Results of Phase II Trial of novel Neurotrophin-3 Inhibitor, LEVI-04, for the Treatment of Patients with Moderate to Severe Osteoarthritis (GlobeNewswire) - P2 | N=518 | NCT05618782 | Sponsor: Levicept | "Levicept Ltd...today announces positive results from its Phase II trial of LEVI-04 a novel and first in class neurotrophin-3 (NT-3) inhibitor, showing that LEVI-04 was highly effective and well tolerated....The primary endpoint was WOMACi pain assessment (change from baseline at Week 17). The mean reduction in WOMAC pain score from baseline was greater than 50% for all three doses of LEVI-04 and all statistically different to placebo. Secondary endpoints were WOMAC subscales of function and joint stiffness, patient global assessment and daily pain scores and all statistically different to placebo."

P2 data • CNS Disorders • Osteoarthritis • Pain

Clinical Trial to Evaluate the Efficacy and Safety of LEVI-04 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P2 | N=518 | Active, not recruiting | Sponsor: Levicept | Recruiting ➔ Active, not recruiting | Phase classification: P2a ➔ P2 | Trial completion date: Dec 2023 ➔ Jul 2024 | Trial primary completion date: Sep 2023 ➔ Mar 2024

Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Immunology • Musculoskeletal Diseases • Osteoarthritis • Pain • Rheumatology

Levicept Completes Recruitment in Phase II Clinical Trial of Neurotrophin Modulator LEVI-04 (GlobeNewswire) - "Levicept Ltd...announces it has completed recruitment in its Phase II clinical trial of LEVI-04, a novel neurotrophin-modulating biological agent. Top line data are expected to be announced in late first half of 2024."

Enrollment closed • P2a data • Osteoarthritis • Pain

Clinical Trial to Evaluate the Efficacy and Safety of LEVI-04 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P2a | N=624 | Recruiting | Sponsor: Levicept

New P2a trial • Immunology • Musculoskeletal Diseases • Osteoarthritis • Pain • Rheumatology

A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of LEVI-04 in Patients with Osteoarthritis of the Knee (clinicaltrialsregister.eu) - P2 | N=416 | Ongoing | Sponsor: Levicept Ltd.

New P2 trial • Immunology • Musculoskeletal Diseases • Osteoarthritis • Pain • Rheumatology

Safety, Tolerability & Pharmacokinetics of LEVI-04 in Healthy Volunteers and Patients With Osteoarthritis Knee Pain (clinicaltrials.gov) - P1; N=56; Completed; Sponsor: Levicept; Active, not recruiting ➔ Completed

Trial completion • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Safety, Tolerability & Pharmacokinetics of LEVI-04 in Healthy Volunteers and Patients With Osteoarthritis Knee Pain (clinicaltrials.gov) - P1; N=56; Recruiting; Sponsor: Levicept; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Safety, Tolerability & Pharmacokinetics of LEVI-04 in Healthy Volunteers and Patients With Osteoarthritis Knee Pain (clinicaltrials.gov) - P1; N=56; Active, not recruiting; Sponsor: Levicept; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Safety, Tolerability & Pharmacokinetics of LEVI-04 in Healthy Volunteers and Patients With Osteoarthritis Knee Pain (clinicaltrials.gov) - P1; N=56; Recruiting; Sponsor: Levicept; Trial completion date: Oct 2019 ➔ Dec 2020; Trial primary completion date: Oct 2019 ➔ Dec 2020

Trial completion date • Trial primary completion date