A Phase I, Randomized, Double-blind, Parallel Group and Placebo-controlled Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Atrosimab in Response to Single Ascending Intravenous Infusion Doses.

This is a double-blind, parallel group and placebo-controlled clinical study to assess safety tolerability, pharmacokinetics and pharmacodynamics of Atrosimab in healthy volunteers

开始日期2021-07-12

申办/合作机构

Baliopharm AG

100 项与 Atrosimab 相关的临床结果

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100 项与 Atrosimab 相关的转化医学

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100 项与 Atrosimab 相关的专利（医药）

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项与 Atrosimab 相关的文献（医药）

2019-05-19·mAbs2区 · 医学

Improved monovalent TNF receptor 1-selective inhibitor with novel heterodimerizing Fc

2区 · 医学

Article

作者: Richter, Fabian ; Pfizenmaier, Klaus ; Seifert, Oliver ; Herrmann, Andreas ; Kontermann, Roland E.

The development of alternative therapeutic strategies to tumor necrosis factor (TNF)-blocking antibodies for the treatment of inflammatory diseases has generated increasing interest. In particular, selective inhibition of TNF receptor 1 (TNFR1) promises a more precise intervention, tackling only the pro-inflammatory responses mediated by TNF while leaving regenerative and pro-survival signals transduced by TNFR2 untouched. We recently generated a monovalent anti-TNFR1 antibody fragment (Fab 13.7) as an efficient inhibitor of TNFR1. To improve the pharmacokinetic properties of Fab 13.7, the variable domains of the heavy and light chains were fused to the N-termini of newly generated heterodimerizing Fc chains. This novel Fc heterodimerization technology, designated "Fc-one/kappa" (Fc1κ) is based on interspersed constant Ig domains substituting the CH3 domains of a γ1 Fc. The interspersed immunoglobulin (Ig) domains originate from the per se heterodimerizing constant CH1 and CLκ domains and contain sequence stretches of an IgG1 CH3 domain, destined to enable interaction with the neonatal Fc receptor, and thus promote extended serum half-life. The resulting monovalent Fv-Fc1κ fusion protein (Atrosimab) retained strong binding to TNFR1 as determined by enzyme-linked immunosorbent assay and quartz crystal microbalance, and potently inhibited TNF-induced activation of TNFR1. Atrosimab lacks agonistic activity for TNFR1 on its own and in the presence of anti-human IgG antibodies and displays clearly improved pharmacokinetic properties.

Scientific Reports

The TNFR1 antagonist Atrosimab reduces neuronal loss, glial activation and memory deficits in an acute mouse model of neurodegeneration

Article

作者: Chen, Tingting ; Pfizenmaier, Klaus ; Eisel, Ulrich L M ; Kontermann, Roland E ; Ortí-Casañ, Natalia ; Köpke, Karina ; Fischer, Roman ; Keijser, Jan ; Zhang, Yuequ ; Dolga, Amalia M ; Broersen, Kerensa ; Ebskamp, Amber ; Boerema, Ate S

AbstractTumor necrosis factor alpha (TNF-α) and its key role in modulating immune responses has been widely recognized as a therapeutic target for inflammatory and neurodegenerative diseases. Even though inhibition of TNF-α is beneficial for the treatment of certain inflammatory diseases, total neutralization of TNF-α largely failed in the treatment of neurodegenerative diseases. TNF-α exerts distinct functions depending on interaction with its two TNF receptors, whereby TNF receptor 1 (TNFR1) is associated with neuroinflammation and apoptosis and TNF receptor 2 (TNFR2) with neuroprotection and immune regulation. Here, we investigated the effect of administering the TNFR1-specific antagonist Atrosimab, as strategy to block TNFR1 signaling while maintaining TNFR2 signaling unaltered, in an acute mouse model for neurodegeneration. In this model, a NMDA-induced lesion that mimics various hallmarks of neurodegenerative diseases, such as memory loss and cell death, was created in the nucleus basalis magnocellularis and Atrosimab or control protein was administered centrally. We showed that Atrosimab attenuated cognitive impairments and reduced neuroinflammation and neuronal cell death. Our results demonstrate that Atrosimab is effective in ameliorating disease symptoms in an acute neurodegenerative mouse model. Altogether, our study indicates that Atrosimab may be a promising candidate for the development of a therapeutic strategy for the treatment of neurodegenerative diseases.

Frontiers in Immunology2区 · 医学

The TNFR1 Antagonist Atrosimab Is Therapeutic in Mouse Models of Acute and Chronic Inflammation

2区 · 医学

ArticleOA

作者: Fischer, Roman ; Pichi, Kira ; Richter, Fabian ; Kontermann, Roland E ; Vogel, Arndt ; Huber, Carina ; Marhenke, Silke ; Williams, Sarah K ; Bantel, Heike ; Fairless, Richard ; Pfizenmaier, Klaus ; Diem, Ricarda ; Dhaen, Marie-Ann ; Zanker, Henri ; John, Katharina ; Vaslin, Camille ; Herrmann, Andreas ; Herrmann, Stefanie

Therapeutics that block tumor necrosis factor (TNF), and thus activation of TNF receptor 1 (TNFR1) and TNFR2, are clinically used to treat inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. However, TNFR1 and TNFR2 work antithetically to balance immune responses involved in inflammatory diseases. In particular, TNFR1 promotes inflammation and tissue degeneration, whereas TNFR2 contributes to immune modulation and tissue regeneration. We, therefore, have developed the monovalent antagonistic anti-TNFR1 antibody derivative Atrosimab to selectively block TNFR1 signaling, while leaving TNFR2 signaling unaffected. Here, we describe that Atrosimab is highly stable at different storage temperatures and demonstrate its therapeutic efficacy in mouse models of acute and chronic inflammation, including experimental arthritis, non-alcoholic steatohepatitis (NASH) and experimental autoimmune encephalomyelitis (EAE). Our data support the hypothesis that it is sufficient to block TNFR1 signaling, while leaving immune modulatory and regenerative responses via TNFR2 intact, to induce therapeutic effects. Collectively, we demonstrate the therapeutic potential of the human TNFR1 antagonist Atrosimab for treatment of chronic inflammatory diseases.

100 项与 Atrosimab 相关的药物交易

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