honeycomb shape


A Monoclonal Antibody to Reduce Disease Progression in Patients with Geographic Atrophy

NGM621 is a humanized IgG1 monoclonal antibody engineered to potently inhibit complement C3, with the treatment goal of reducing disease progression in patients with geographic atrophy, and with the potential for every eight week dosing.

A Progressive Retinal Degenerative Disease,
A Significant Unmet Need

Age-related macular degeneration is a leading cause of vision loss and blindness in people over the age of 65 in the US and other industrialized countries. The two advanced stages of the disease are called neovascular (wet) age-related macular degeneration and geographic atrophy.

Geographic atrophy is a progressive retinal degenerative disease associated with irreversible loss of vision, diminished quality of life and eventual blindness. Geographic atrophy is estimated to impact about 1 million people in the US and over 5 million people worldwide.

In patients with geographic atrophy, single or multiple areas in the macular region of the retina become atrophic, forming distinct lesions that expand and coalesce over time. Enlargement of these lesions can lead to loss of vision and irreversible blindness. Geographic atrophy is often bilateral, meaning it occurs in both eyes.

1 Million
Impacted in the US
5 Million
Impacted worldwide
While there are approved treatments for wet age-related macular degeneration, there are currently no approved treatments for geographic atrophy.

Inhibition of Complement C3: A Promising Therapeutic Approach

Dysregulated activation of the complement system, a key component of the immune system, has been implicated in the onset and progression of geographic atrophy. C3 is a key component of the complement system, which helps orchestrate the body’s response to infection and maintains tissue homeostasis. The complement cascade can be activated through its three distinct pathways – classical, lectin and alternative – all of which converge to activate C3. When this cascade is dysregulated, the immune response may lead to the development and progression of geographic atrophy.

Inhibition of C3 represents a promising therapeutic approach that broadly inhibits downstream effector functions triggered by the excessive activation of C3, including inflammation, activation of the adaptive immune system, opsonization (the marking of a pathogen to be destroyed by phagocytes, a type of immune cell), phagocytosis and cell lysis (cell death)

NGM621: A Complement C3 inhibitory Antibody with a Unique profile and Best-in-Class Potential

NGM621 is a humanized IgG1 monoclonal antibody engineered to potently inhibit complement C3, with the potential for extended every eight week dosing without pegylation. In preclinical models, NGM621’s high affinity binding to C3 has demonstrated the potential for potent C3 inhibition. In addition, in well validated animal models of laser-induced choroidal neovascularization (CNV), C3 inhibition has demonstrated the ability to reduce retinal vascular leakage, suggesting the potential for NGM621 to prevent CNV development.

We are currently underway with the Phase 2 CATALINA study of NGM621 for the treatment of geographic atrophy. Designed as a Phase 3-enabling study, the Phase 2 CATALINA study will enroll 240 patients diagnosed with geographic atrophy in one or both eyes. The primary objectives of this multicenter, randomized, double-masked, sham-controlled study are to evaluate the efficacy and safety of NGM621 intravitreal injections compared to sham control.

NGM621's Potential Best-in-Class Profile

Engineered to potently inhibit complement C3
High affinity binding to C3
Potential for extended every 8 week dosing
Potential to prevent choroidal neovascularation development

Visit our Publications & Presentations page to view narrated presentations of our NGM621 preclinical data.

“The NGM621 program exemplifies our strategy to target powerful, disease-driving biology to deliver transformative medicines for patients across a range of therapeutic areas and diseases with high unmet need.”
Hsiao D. Lieu, M.D.
Chief Medical Officer - NGM Bio

i Flaxman SR, Bourne RRA, Resnikoff S, et al. Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(12): 1221-1234.

ii Friedman DS, O’Colmain BJ, Munoz B, et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122(4):564-572.

iii Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040; a systematic review and meta-analysis. Lancet 2014; 2:e106-116.