Our Science

Overview

We specialize in the development of monoclonal antibodies that block inflammatory signaling from oxidized lipids.  Our lead candidate is a fully human monoclonal antibody called orticumab.

Orticumab targeting oxLDL

Orticumab

Orticumab is a fully-human monoclonal antibody against a specific epitope on malondialdehyde-modified apolipoptoteinB-100 (MDA-apoB-100), a protein contained within oxidized low-density lipoprotein (oxLDL) and lipoprotein(a).

Robust nonclinical data with orticumab are supportive of anti-inflammatory activity and favorable cardiometabolic effect. In rodent cardiovascular disease models, orticumab has demonstrated that is can reduce atherosclerosis progress, regress established atherosclerotic lesions, and stabilize plaque phenotype.  Additionally, orticumab reduced peripheral inflammatory biomarkers and improved insulin sensitivity in obese rhesus monkeys.

These findings are featured in peer-reviewed journals – see below.

Featured Publications

Mechanism of Action

Orticumab blocks inflammatory responses to oxLDL

orticumab localizes to oxLDL-rich inflammed tissue
orticumab forms an immune complex through binding densely-aggregated oxLDL
FcyR crosslinking an inhibitory signaling deactivates inflammatory activity in macrophages
Li et al (2013) Molecular Metabolism

Why target the oxLDL pathway?

Immunomodulating biologic therapies that target pathways such as IL-1b, TNF-a, and IL-17 are known to effectively treat several chronic inflammatory diseases.  However, inhibiting these immune pathways can cause immunosuppression and related safety concerns such as risk of serious infection and cancer. For this reason, immunomodulating biologic therapies are deployed as 2nd or 3rd line options for patients with acutely debilitating symptoms where the benefits of treatment outweigh the risks of possible serious side effects.

By contrast, targeting oxLDL creates the possibility of a new class of biologic therapy that can reduce damaging inflammation without interference of normal immune system functions that protect against infection and cancer, and result in therapies with a better safety profile and fewer side-effects.

Development of safer anti-inflammatory therapeutic modalities facilitates expanded use in chronic inflammatory pathologies, including cardiovascular disease, where longer-term safety is not afforded by the current therapeutic options. It is our belief that targeting the oxLDL pathway will unlock this potential for expanded use.