Home Interviews Lipum and KI explore the mode of action

Lipum and KI explore the mode of action

LIpum

Lipum and KI explore the mode of action

14 October, 2024

Lipum is taking a new approach to treating chronic inflammatory diseases by targeting the protein BSSL. Through a collaboration with the Karolinska Institute, the company aims to gain deeper insights into BSSL’s role in inflammation and clarify the mechanism of action of their lead drug candidate, SOL-116. BioStock spoke with project leader Associate Professor Bence Réthi to learn more.

Lipum is developing a novel biological drug for chronic inflammatory diseases based on the discovery of Bile Salt-Stimulated Lipase (BSSL), a protein that plays a crucial role in the inflammatory process.

In the acute phase of inflammation, BSSL stimulates the recruitment of specific blood cells to the inflamed site to help combat the condition. However, in chronic inflammation, BSSL contributes to the persistent maintenance of the inflammatory process.

SOL-116 inhibits inflammatory properties of BSSL

Lipum’s drug candidate, SOL-116, is an anti-BSSL antibody designed to bind to BSSL and inhibit its properties. This mechanism has the potential to offer a safer and more effective treatment for chronic inflammatory diseases.

SOL-116 is currently being evaluated in a phase I study involving healthy subjects and patients with rheumatoid arthritis (RA). In parallel, Lipum is conducting additional research on the target molecule, BSSL, and the properties of SOL-116.

Research collaboration with KI

One year ago, Lipum entered into a collaboration with researchers at the Division of Rheumatology, Karolinska Institute (KI), to investigate the role of BSSL in the inflammation process, particularly in RA, and elucidate the mechanism of action of SOL-116.

The project focuses on three main areas: identifying the sources of BSSL in the immune system, determining which immune cells BSSL targets, and understanding how BSSL impacts those cells.

Analyses of RA samples

To investigate where BSSL is found, the research team is analyzing the presence of BSSL in synovial fluid from patients with RA and other joint diseases, as well as in synovial tissue biopsies from RA patients and healthy individuals. The aim is to analyze if BSSL is expressed in the inflamed joints during RA and whether it plays a key role in immune cell chemotaxis towards the joints.

The research group is also exploring the binding of BSSL to immune cells in both the blood and synovial fluid of RA patients, aiming to identify specific BSSL receptors on immune cells and receptor-induced signalling pathways.

Lipum hypothesizes that BSSL is involved in immune modulation and stimulates cell migration and recruitment of monocytes and other inflammatory cells towards a site of inflammation.

Project Leader shares research details

The project is expected to last two years, meaning that the final results could be published by the second half of next year. The project findings are anticipated to support both Lipum’s drug development and discussions with potential partners and investors. In the long term, the results could benefit patients suffering from chronic inflammatory diseases and contribute to advancements in the fields of rheumatology and chronic inflammation.

Bence
Bence Réthi

BioStock reached out to Bence Réthi, project leader and Associate Professor at KI, for a progress update.

To start, why is this project important for both Lipum and patients with chronic inflammatory diseases?

– Overall, these types of studies aim to move closer to the ultimate goal of eradicating life-threatening autoimmune diseases by providing cure, prevention or a more efficient and better targeted immunosuppression. It is important to mention that current therapies for life-threatening autoimmune diseases typically act via life-long immunosuppression that ameliorate symptoms but do not cure the diseases.

How is the project and collaboration with Lipum progressing so far?

– We have a good collaborative atmosphere and productive researchers working on the project. In addition to going through the questions we identified for the current period of collaboration, I think we now have many interesting ideas to study as follow-up projects.

What specific analyses are you conducting to identify the source and mechanisms of BSSL in inflammation?

– During the first year, we have analyzed BSSL expression by different immune cells obtained from rheumatoid arthritis patients or healthy controls. We have also analyzed BSSL expression in the inflamed joints. We received very important help from our clinical collaborators, as we needed patient samples, and we put a lot of emphasis on developing reliable staining protocols through flow cytometry and immunohistochemistry, and gene expression analyses. Right now, we are focusing on the target cells for BSSL and the effect of BSSL on these.

What makes SOL-116 a potentially valuable addition to the treatment of RA and other chronic inflammatory diseases, in your view?

– BSSL seems to be very important for arthritis induction in animal models, which, in combination with the relatively little knowledge on the role of BSSL in the immune system makes it an interesting subject for therapy-related studies. Targeting BSSL could lead to very different immunomodulating mechanisms as compared to other existing therapies.

The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.

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