A revolutionary new treatment solution for coronary inflammation.

Orticumab

The next-generation solution for patients with coronary inflammation.

Our lead asset, orticumab, is a first-in-class antibody that targets oxidized LDL (oxLDL).

OxLDL Causes Coronary Inflammation And is Directly Linked to Risk of A Heart Attack

OxLDL is an inflammatory mediator with no role in health, but a well-established role in CAD. OxLDL accumulates in the the coronary arteries, activates the immune system, and leads to the formation, growth, and rupture of atherosclerotic plaques.

Orticumab: A First-in-Class Antibody Against Oxidized LDL (oxLDL), The Critical Driver Of Atherosclerotic Disease And Heart Attack

Orticumab is a fully human IgG1-type monoclonal antibody that recognizes and binds a specific oxLDL epitope, malondialdehyde (MDA)-modified apolipoproteinB-100.

Orticumab binds specifically and with high affinity to oxLDL. It does not recognize native (non-oxidized) LDL
The Orticumab-oxLDL immune complex reduces macrophage activation via FcγRII signalling, reducing plaque inflammation & vulnerability
Four clinical trials have been completed with no dose-limiting toxicities and no drug-related serious adverse events
Currently in development for secondary prevention of MACE after an Acute Coronary Syndrome

Tissue-Specific Action

Mechanism of Action

The oxidation of LDL occurs in the arterial wall, where it then triggers inflammation and can lead to progression and rupture of atherosclerotic plaque. Orticumab works directly in inflamed coronary arteries, where oxLDL is abundant.

Macrophage +- Orticumab + Plaque + HDL Efflux Graphic in Three panels

Orticumab Works Differently

A Highly Specific Approach to Coronary Inflammation.

When targeting coronary inflammation, specificity matters.

Current therapies utilize a systemic approach, affecting other physiological processes that play a vital role in health such as immune defense and healing. Due to their involvement in beneficial physiological processes, systemic therapies can come with undesirable safety risks and side effects. Additionally, increasing dosage of systemic therapies can lead to tolerability issues.

Comparison of Coronary Inflammation Targets

	oxLDL	Microtubule Polymerisation	IL-6	IL-1b
Local vs. Systemic MoA	Local	Systemic	Systemic	Systemic
Role in Health (i.e. Immune Defense)	No	Yes	Yes	Yes
Role in CAD	Yes	Yes	Yes	Yes
Class Inhibitors in CAD	Orticumab	Colchicine	Ziltivekimab	Canakinumab
Highest Development Phase in CAD	Phase 2	Marketed	Phase 3	Phase 3

By contrast, oxLDL inhibition with orticumab acts directly at the site of coronary artery inflammation. This localized and targeted approach may not only enhance treatment efficacy but also may minimize safety risks, making it an appealing therapy for patients in need. Furthermore, orticumab has demonstrated excellent tolerability in more than 300 treated patients across 4 clinical trials.

Clinical Development

Orticumab for Secondary Prevention after Acute Coronary Syndrome

Inflammation spikes in the coronary arteries during a heart attack, and so do levels of oxLDL. Our clinical development focuses on the secondary prevention of recurrent cardiovascular events in patients with prior acute coronary syndrome event, including heart attack.

Currently, there are approximately 15 million patients in the US with a prior ACS event and 700k hospitalizations per year.
1 in 5 patients will suffer from a second cardiovascular event within two years with inflammation being a key driver of risk in this population.

Orticumab Reduced Coronary Inflammation

In a pilot phase 2 study, orticumab exerted anti-inflammatory effects on the coronary arteries of patients with psoriasis and elevated coronary inflammation (A), leading to a ~50% relative reduction of the predicted risk for fatal cardiac events by the CaRi-Heart® medical device (B).

Chart A showing the results of clinical study, specifically the absolute change in FAI score between the whole population and high inflammation subgroup

Chart B showing results from clinical study, specifically the Mean CaRi-Heart Risk score in two different populations

The CaRi-Heart® medical device (offered by Caristo Diagnostics) uses AI technology to measure coronary inflammation (FAI-Score) and predict risk of a fatal attack (CaRi-Risk). For more information, please read our recently published paper in the European Society of Cardiology’s Cardiovascular Research.

Explore the Results

Our Pipeline

We are developing orticumab to decrease risk of a heart attack in patients with coronary artery disease and inflammation.

Explore Orticumab Clinical Trial

Abcentra Pipeline graphic showing the current status of two developmental applications for Orticumab in Phase 2

Orticumab in Featured Publications

Below, find some of the most recent and relevant mentions of Abcentra and Orticumab in prestigious industry publications.

FEATURED
Inhibition of oxidized low-density lipoprotein with orticumab inhibits coronary inflammation and reduces residual inflammatory risk in psoriasis: a pilot randomized, double-blind placebo-controlled trial
Farina et al, 2024, European Society of Cardiology, Cardiovascular Research March 25, 2024

Targeting oxidized LDL improves insulin sensitivity and immune cell function in obese Rhesus macaques
Li, S. et al, 2013, Molecular Metabolism Volume 2, Issue 3, August 2013, Pages 256-269
Identification of the target for therapeutic recombinant anti-apoB100 peptide antibodies in human atherosclerotic lesions
Goncalves et al, 2009, Atherosclerosis Journal Volume 205, ISSUE 1, P96-100, July 01, 2009
Inhibition of injury-induced arterial remodeling and carotid atherosclerosis by recombinant human antibodies against aldehyde-modified apoB-100
Strom et al, 2007, Atherosclerosis Journal Volume 190, ISSUE 2, P298-305, February 01, 2007
Recombinant Antibodies to an Oxidized Low-Density Lipoprotein Epitope Induce Rapid Regression of Atherosclerosis in Apobec-1-/- /Low-Density Lipoprotein Receptor-/- Mice
Schiopu et al, 2007, Journal of the American College of Cardiology Volume 50, Issue 24, December 2007
Recombinant human antibodies against aldehyde-modified apolipoprotein B-100 peptide sequences inhibit atherosclerosis
Schiopu et al, 2004, Circulation, American Heart Association Journals Vol 110, Issue 14. October 5, 2004

frequently asked questions

What is the role of oxLDL in coronary artery disease?Ben Huizinga2024-03-07T15:56:42+00:00

What is the role of oxLDL in coronary artery disease?

Oxidized LDL is highly reactive and associated with cellular toxicity. It can accumulate in the arterial wall of blood vessels, especially the coronary arteries, and not only lead to the formation and growth of atherosclerotic plaques but also induce inflammation by activating macrophages. With its dual role in plaque formation and coronary artery inflammation, oxLDL is a key driver of atherosclerosis in coronary artery disease and crucial risk factor for acute coronary syndrome, including heart attacks.

What epitope does orticumab bind on oxLDL?Ben Huizinga2024-03-07T15:55:37+00:00

What epitope does orticumab bind on oxLDL?

Orticumab recognizes and binds a specific epitope of oxLDL, malondialdehyde (MDA)-modified apolipoproteinB-100.

What kind of molecule is orticumab?Ben Huizinga2024-03-07T15:54:47+00:00

What kind of molecule is orticumab?

Orticumab is a first-in-class fully-human IgG1 type antibody directed against a specific epitope of oxidized LDL (oxLDL), a key factor in arterial inflammation, formation, and destabilization of atherosclerotic plaques.

How does orticumab ameliorate local inflammation in coronary artery disease?Ben Huizinga2024-03-07T15:58:14+00:00

How does orticumab ameliorate local inflammation in coronary artery disease?

Orticumab recognizes and specifically binds a specific epitope of oxLDL. Binding of oxLDL by orticumab not only has the potential to directly reduce cytotoxic and atherosclerotic effects of oxLDL by leading to it sequestration and increased clearance. The immune complex formed by orticumab and oxLDL has also been demonstrated to reduce inflammation by inhibiting macrophage activation in atherosclerotic plaques. Both activities of orticumab have the potential to reduce atherosclerotic plaque burden and prevent major cardiovascular events, such as acute coronary syndrome and heart attack.

How is orticumab differentiated from other anti-inflammatory therapies?Ben Huizinga2024-03-30T00:51:31+00:00

How is orticumab differentiated from other anti-inflammatory therapies?

Current anti-inflammatory drugs take a systemic approach, affecting ubiquitous molecules such as tubulin or vital immune defence factors like the pro-inflammatory cytokines IL-1β and IL-6. These non-targeted approaches not only raise safety concerns, particularly for vulnerable coronary artery disease patients, but they also do not address the root cause of coronary inflammation.

Orticumab acts directly at the site of coronary artery inflammation, binding to oxLDL and inhibiting local macrophage activation. This targeted approach may not only enhance treatment efficacy and success rates but also may minimize safety risks, making it an appealing therapy for patients in need.