Swedish Orphan Biovitrum AB (Sobi)

Target group

Specify if it is a project for PhD students (1 month) or postdocs and researchers (3 months)- Preference would be for postdocs and researchers

About the company

SOBI headquarters are based in Stockholm (Solna). Today, Sobi employs approximately 1,800 people across Europe, North America, the Middle East, Asia, North Africa and we aim to expand even more geographically.

Sobi is a global biopharma company transforming the lives of people with rare and debilitating diseases.

Sobi offers the opportunity to work at an international biopharmaceutical company focused on fulfilling the high medical needs of rare disease patients and providing treatment and services to them. Our employees have their backgrounds in various fields of research, industry and the academic sphere.

The project

Interferon-γ (IFNγ) is a pleiotropic cytokine with multiple effects on the inflammatory response and on innate and adaptive immunity. Overproduction of IFNγ underlies several, potentially fatal, hyperinflammatory or immune-mediated diseases. Several data from animal models and/or from translational research in patients point to a role of IFNγ in hyperinflammatory diseases, such as primary haemophagocytic lymphohistiocytosis (pHLH), various forms of secondary haemophagocytic lymphohistiocytosis (sHLH), including macrophage activation syndrome (MAS), and cytokine release syndrome (De Benedetti et al. 2021). To improve our understanding of the role of IFNγ in human disease, IFNγ-related biomarkers that are relevant for the management of hyperinflammatory diseases are progressively being identified and studied, especially because circulating levels of IFNγ do not always reflect its overproduction in tissue. These biomarkers include STAT1 (specifically the phosphorylated form), neopterin and the chemokine CXCL9.

Chemokine ligand 9 (CXCL9), together with CXCL10 and CXCL11 are produced in response to IFN-γ and trigger inflammation with the accumulation of activated lymphocytes (Han et al. 2017), but CXCL9 is considered as the best chemokine to assess IFNγ, since it is reported to be the most specific one.

With drug targeting IFNγ, such as emapalumab, a recombinant anti- IFNγ antibody, it is important to demonstrate that such drugs are effectively reducing the levels of circulating IFNγ.

However, due to bioanalytical issues, there are no methods to quantify free IFNγ from IFNγ complexed with emapalumab. Therefore, CXCL9 is used as marker of free IFNγ (Laveille et al. 2020).

As part of the medical and scientific community, there is a strong interest to develop tests to quantify accurately CXCL9 for the treatment of patients with pHLH or sHLH with emapalumab.

Research questions:

• 1) Based on the published information, is CXCL9 really a good biomarker of IFNγ levels in the systemic circulation?
• 2) Which are the limitations of using this marker? E.g., in some conditions, can we see effects on IFNγ without seeing effects on CXCL9 or vice versa?

Of note, bioanalytical quantification of CXCL9 is challenging and comparison across different methods can lead to different results.

Based on the outcome of this initial work, evaluation of CXCL9 data from the clinical studies with emapalumab can be considered, in light of these findings.

Deliverables:  Internal presentation, possibility to write a publication .

De Benedetti, F., G. Prencipe, C. Bracaglia, E. Marasco, and A. A. Grom. 2021. 'Targeting interferon-γ in hyperinflammation: opportunities and challenges', Nat Rev Rheumatol, 17: 678-91.

Han, Jae Ho, Chang-Hee Suh, Ju-Yang Jung, Mi-Hyun Ahn, Mi Hwa Han, Ji Eun Kwon, Hyunee Yim, and Hyoun-Ah Kim. 2017. 'Elevated circulating levels of the interferon-γ–induced chemokines are associated with disease activity and cutaneous manifestations in adult-onset Still’s disease', Scientific Reports, 7: 46652.

Laveille, Christian, Philippe Jacqmin, Kathy de Graaf, and Cristina de Min. 2020. 'Population Pharmacokinetic Analysis of Emapalumab, a Fully Human, Anti-Interferon Gamma Monoclonal Antibody, in Children with Primary Hemophagocytic Lymphohistiocytosis', Blood, 136: 20.

Location: Stockholm

Time period: Start time: flexible, full time preferred.

The candidate

Please specify background and skills needed for the proposed project.

Experience in literature research  is desired, with some understanding of bioanalytical methods and translational medicine.

Contact information

Name: Erik Nordling

Email: erik.nordling@sobi.com

Telephone: +46 76 722 2401

Company website: www.sobi.com