ANX009 / Annexon Biosci - LARVOL DELTA

A Study of ANX009 in Adult Participants With Lupus Nephritis (clinicaltrials.gov) - P1 | N=7 | Completed | Sponsor: Annexon, Inc. | Recruiting ➔ Completed | Phase classification: P1b ➔ P1

Phase classification • Trial completion • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Classical Complement Activation in Lupus Nephritis Correlates with Disease Biomarkers: Results from Two Observational Studies (ACR Convergence 2023) - "In these LN patients, C4d/C4 ratios were elevated and correlated with LN biomarkers in blood and urine, supporting classical complement activity. These data support an ongoing, phase 1b study of ANX009 with the goal of assessing safety, tolerability, and pharmacodynamics of repeat doses of subcutaneous ANX009 with standard of care in adults with LN. ANX009 is an anti-C1q antigen binding fragment targeting LN patients with evidence of classical complement activity (elevated C4d/C4)."

Biomarker • Clinical • Observational data • Glomerulonephritis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Rheumatology • Systemic Lupus Erythematosus

Results of Single-Arm, Phase 1b Study of Anti-C1q Treatment (ANX009) Show That the Classical Pathway Is a Key Driver of Complement Activation and Consumption in Patients with Active Lupus Nephritis (ACR Convergence 2023) - "In this interim analysis, ANX009 administered subcutaneously was well tolerated and demonstrated C1q target engagement and complement inhibition in 5/5 patients. Normalization of all downstream activation markers and primary components, notably C3 and C5b-9, suggests the classical pathway, not the alternative pathway, is a key driver of complement activation in these LN patients. These interim results support further study of anti-C1q therapy in LN patients."

Clinical • P1 data • Dermatology • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Classical Complement Activation in Lupus Nephritis Correlates with Disease Biomarkers: Results from Two Observational Studies (KIDNEY WEEK 2023) - "In these LN patients, C4d/C4 ratios were elevated and correlated with LN biomarkers in blood and urine, supporting classical complement activity. These data support an ongoing, phase 1b study of ANX009 with the goal of assessing safety, tolerability, and pharmacodynamics of repeat-doses of subcutaneous ANX009 with standard of care in adults with LN. ANX009 is an anti-C1q antigen binding fragment targeting LN patients with evidence of classical complement activity (elevated C4d/C4)."

Biomarker • Clinical • Observational data • Glomerulonephritis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Results of Single-Arm, Phase 1b Study of Anti-C1q Treatment (ANX009) Show that the Classical Pathway Is a Key Driver of Complement Activation and Consumption in Patients with Active Lupus Nephritis (KIDNEY WEEK 2023) - "In this interim analysis, ANX009 administered subcutaneously was well tolerated and demonstrated C1q target engagement and complement inhibition in 5/5 patients. Normalization of all downstream activation markers and primary components, notably C3 and C5b-9, suggests the classical pathway, not the alternative pathway, is a key driver of complement activation in these LN patients. These interim results support further study of anti-C1q therapy in LN patients."

Clinical • P1 data • Dermatology • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

SINGLE-ARM, PHASE 1B, OPEN-LABEL STUDY ASSESSING THE SAFETY, TOLERABILITY, AND PHARMACODYNAMICS OF REPEAT-DOSE SUBCUTANEOUS ANX009 PLUS STANDARD OF CARE IN ADULT PATIENTS WITH LUPUS NEPHRITIS (ISN-WCN 2023) - "Allowed stable background standard of care for LN and SLE include mycophenolate mofetil, azathioprine, antimalarials, glucocorticoids, cyclosporin, voclosporin, tacrolimus, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Results Results for this clinical trial are anticipated in mid-2023. Conclusions n/a"

Clinical • P1 data • PK/PD data • Chronic Kidney Disease • Glomerulonephritis • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Systemic Lupus Erythematosus

A Study of ANX009 in Adult Participants With Lupus Nephritis (clinicaltrials.gov) - P1b | N=7 | Recruiting | Sponsor: Annexon, Inc.

New P1 trial • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Safety, Tolerability, and Clinical Pharmacology of ANX009, an Inhibitory Antibody Fab Fragment Against C1q, Administered Subcutaneously to Healthy Volunteers (ASH 2021) - P1 | "Ex vivo functional activity of C1q was completely inhibited in close correspondence with free C1q levels. Combined safety, tolerability, and clinical pharmacology results from this phase 1 study support advancement of ANX009 to studies in patients with complement-mediated autoimmune disorders."

Clinical • Anemia • Glomerulonephritis • Hematological Disorders • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Pathogenic Anti-C1q Antibodies Potentiate Activation of the Classical Complement Pathway in a Subset of Lupus Nephritis Patients (ACR Convergence 2022) - P1 | "Such patients would be potential candidates for anti-C1q therapy, such as ANX009 (NCT04535752). A panel of complement factors were measured using ELISA from plasma samples from a cohort of 40 patients with LN in the California Lupus Epidemiology Study and 20 healthy controls... A subset of patients with LN exhibited high C4d/C4 along with specific markers of classical pathway activation, indicative of classical complement pathway disease mediation. Reduction in this ratio appeared to correlate with treatment response, but C4d/C4 values were generally not normalized, suggesting an insufficient resolution of complement-mediated inflammation by current treatments. Our data support a clinical hypothesis that a subset of patients with LN may benefit from a precision medicine approach targeting this pathway."

Clinical • Glomerulonephritis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Rheumatology

High plasma C4d/C4 identifies lupus nephritis patients with disease mediated by activation of the classical complement pathway (EULAR 2022) - P1 | "A subset of LN patients exhibited high C4d/C4 ratio along with specific markers of classical pathway activation, indicating that the classical complement pathway may be a driving component of their disease. Reduction in this ratio appears to correlate with treatment response, but its levels are generally not normalized, suggesting an insufficient resolution of complement-mediated inflammation by currently available treatments. Our data support a clinical hypothesis that a subset of LN patients may benefit from a precision medicine approach targeting the classical complement pathway ( Figure 1 )."

Clinical • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

A Single and Multiple Ascending Dose Study of ANX009 in Normal Healthy Volunteers (NHV) (clinicaltrials.gov) - P1; N=48; Completed; Sponsor: Annexon, Inc.; Not yet recruiting ➔ Completed

Clinical • Trial completion