Cliramitug (ATTR Cardiomyopathy)

Cliramitug is a first-in-class investigational human monoclonal antibody designed to deplete amyloid deposits in ATTR cardiomyopathy (ATTR-CM). Neurimmune entered into an exclusive global collaboration and license agreement for cliramitug with Alexion, AstraZeneca Rare Disease. The therapeutic antibody is being studied in the ongoing DepleTTR-CM Phase III trial to evaluate the safety and efficacy of cliratmitug in adults with ATTR-CM.

Transthyretin amyloid (ATTR)-cardiomyopathy is an age-associated disease of the heart characterized by intramyocardial deposition of misfolded and aggregated transthyretin. The accumulation of amyloid results in increased ventricular wall thickness and severely impacts heart function and survival. The disease manifests predominantly in elderly men and is diagnosed using echocardiography, scintigraphy and biopsies. The prevalence of the disease is currently unknown despite the fact that diagnosis tools are widely accessible. Despite advances in slowing disease progression, there is no approved treatment option designed to deplete ATTR from the heart to revert cardiac dysfunction.

Cliramitug induces cardiac ATTR phagocytosis. From Michalon et al., International Symposium on Amyloidosis 2024.

Cliramitug, a Cardiac Amyloid Depleter

Cliramitug is a recombinant human monoclonal IgG1 antibody that exclusively targets with high affinity the disease-associated amyloid conformation while sparing physiological TTR and its biological functions. Cliramitug targets both wild-type ATTR as well as ATTR mutants that are linked to hereditary forms of ATTR cardiomyopathy and ATTR polyneuropathy. Cliramitug induces the clearance of pathological ATTR in preclinical models.

Our joint objective with our partner Alexion, AstraZeneca Rare Disease, is to develop a potential first-in-class therapeutic to deplete cardiac amyloid in patients affected by ATTR-CM, driven by our strong commitment to improving patient long-term outcomes.

Christoph Hock, CMO

Cardiac tracer uptake on scintigraphy before and after treatment with Cliramitug. From P. Garcia-Pavia, ESC Heart Failure, 2023

Cardiac Amyloid Depletion Measured by Scintigraphy and Cardiac MRI

Primary results of Neurimmune's Phase 1 study have been published in The New England Journal of Medicine (Pablo Garcia-Pavia et al., 2023). Results indicated that the safety profile of Cliramitug (aka NI006) is favourable up to the highest dose tested. No apparent dose-limiting toxic effects or drug-related serious adverse reactions were observed. The pharmacokinetic profile was consistent with that of an IgG antibody, and no antidrug antibodies were detected. At doses of at least 10 mg per kilogram, cardiac amyloid deposition (detected by either scintigraphy or cardiac magnetic resonance imaging) was substantially reduced over a period of 12 months. Reductions were also seen in levels of biomarkers measuring cardiac stress and cardiomyocyte death, N-terminal pro-B-type natriuretic peptide and troponin T.

Collaboration with Alexion, AstraZeneca Rare Disease

In 2022, Neurimmune entered into an exclusive global collaboration and license agreement with Alexion, AstraZeneca Rare Disease for cliramitug. Neurimmune is responsible for the Phase 1 study (NI006-101) and the Phase 2 follow-on study (NI006-102, EXCEL), on behalf of Alexion. Alexion is responsible for further clinical development, manufacturing, and commercialization of cliramitug, including the ongoing DepleTTR-CM Phase III trial to evaluate the safety and efficacy of cliratmitug in adults with ATTR-CM.