2021-09-02

Lipigon Pharmaceuticals stands on a solid foundation of cutting-edge research, bolstered by collaborations with leading experts in various therapeutic technology domains. The company operates four active development projects and works with traditional small molecules, gene therapy, and RNA drugs. "We choose the method or technology that best suits our target proteins, allowing us to maintain a flexible approach," says CEO and founder Stefan K. Nilsson, as he delves into the different approaches.

Stefan K. Nilsson earned his doctorate in the field of blood lipids and subsequently co-founded Lipigon with his research mentor, Gunilla Olivecrona.

Tell us how Lipigon came into being!

"When I was accepted as a doctoral student in Gunilla Olivecrona's research group, it became evident to me the formidable research foundation that Gunilla and her husband, Thomas, had built over several decades. Their names were mentioned with great respect at scientific gatherings worldwide, generating strong interest in our work on LPL – an enzyme central to breaking down fats in the blood. This made it easy for me to establish new connections and initiate collaborations.

At that time, there was no one developing drugs with a focus on LPL. We wondered why. The short answer was that it had proven to be challenging. However, our research group possessed a unique knowledge repository, and we, along with others, were gaining a deeper understanding of how LPL is regulated by the ANGPTL protein family, referred to as angiopoietin-like proteins. This became the starting point for Lipigon."

Read more about blood lipid-related diseases and the LPL enzyme.

Today, Lipigon is a project portfolio company. Was that the intention from the beginning?

"The company was formed around the idea of activating LPL, but we already had the ambition early on to develop a broad pipeline of robust drug projects.

We like to call ourselves technology-agnostic because we're not strategically tied to working with a particular drug technology. We simply choose the method or technology that best suits our target proteins, allowing us to think and work very freely.

Once we've identified a good target protein for a specific disease, part of our selection process involves matching it with the right drug technology. We seek partnerships with companies that can offer the expert competence we need. This allows us to assess the potential interest in new target proteins and efficiently develop and test new drug substances."

Lipigon has developed projects in various drug classes. What sets them apart?

"There are several classes of drug technologies. The most common and traditional technology involves small organic molecules that bind to a specific target protein, inducing a pharmacological effect. This is typically what comes to mind when you think of a tablet.

Different biological drugs, such as antibodies and proteins, have also become prevalent ways to treat and alleviate diseases. In recent years, various forms of gene therapy and RNA drugs have made advances, with several approved medications falling within these new drug classes.

In our current projects, we're working with antisense RNA, DNA Encoded Libraries (DEL), and gene therapy in collaboration with various technology partners. These are vastly different approaches with different objectives. Antisense entails preventing the production of the target protein.

DEL is used to screen small organic molecules and requires the target protein to be present for an effect, whether inhibitory or stimulatory.

Gene therapy sets itself apart from other technologies by introducing genetic material that the body's cells then read. Lipigon's collaborative gene therapy project aims to enable the body to produce the target protein on its own."

Antisense technology is used in both the flagship Lipisense^® project and the ARDS project. Could you describe this in more detail?

"Antisense RNA drugs are designed to prevent the target protein from being produced by the body's cells. The cell's DNA is transcribed into messenger RNA (mRNA), which serves as the blueprint for our proteins. By designing an RNA strand that binds to the mRNA, the protein's production is prevented.

Antisense RNA offers the advantage of preventing the production of a specific protein. This is particularly well-suited for proteins that traditional small organic molecules cannot influence.

In the Lipisense^® project, which targets significantly elevated blood lipids, we employ antisense technology to suppress the production of the target protein ANGPTL4. We do this specifically in the liver to avoid the side effects associated with a general inactivation throughout the body."

Read more about the target protein in Lipisense^®.

The ARDS project is based on the same molecules and technology as Lipisense^®. ARDS stands for Acute Respiratory Distress Syndrome, a very serious condition. It has been found that the target protein ANGPTL4 also affects lung damage in infections. By inhibiting its production in the lungs, the outlook for severe lung inflammations can be improved.

In the project for common dyslipidemia, DEL technology is used. What does DEL involve?

"Our project for common dyslipidemia aims to develop a "traditional" small molecule drug. In collaboration with HitGen, we use advanced DEL technology to identify starting molecules.

DEL, which stands for DNA Encoded Libraries, is a new type of drug screening that has gained prominence in recent years. It is a form of small organic molecule screening where hundreds of billions of substances are tested, as opposed to traditional screening, which tests at most a few million substances.

The significant difference in the number of substances tested and the streamlined screening process is that, during the library's creation, substances are marked with a unique DNA strand. This DNA is later read to identify the substances that are screened. The identified substances become starting points for the drug development we want to initiate.

By testing so many more substances and doing so in a fraction of the time traditional screening takes, we save time and increase our chances of finding excellent starting points. Small molecules are inexpensive to manufacture and are usually administered as a tablet. This makes the medication easy to administer, and it can be given preventively to many patients without substantial costs."

Lipigon is also running a gene therapy project for the rare disease lipodystrophy. Why did you choose gene therapy for that project?

"Together with CombiGene AB, we are developing a treatment for people with the rare genetic disease lipodystrophy. This disease results in the absence of fat tissue, leading to fat accumulation in the liver, which has serious consequences for metabolism. The project is based on gene therapy with the aim of stimulating fat burning in the liver.

Gene therapy is intended to replace a target protein that is missing or not produced in sufficient quantities or in the correct form. This is achieved by allowing the body's cells to produce the target protein. Different technologies are available, but most commonly, empty virus particles are designed with genetic material (blueprints) for the target protein. These particles are taken up by the body's cells, which then produce the target protein.

Gene therapy is primarily aimed at treating genetic defects that manifest through severe and rare diseases. However, as a treatment method, gene therapy has the potential to be used for broader disease areas as well if the development progresses in the right direction.

With gene therapy, we instruct the body's cells to produce more of a protein that is otherwise produced in low quantities, in the "wrong form," or perhaps not produced at all. The advantage is that we precisely stimulate the protein we want, and this occurs in a limited part of the body.

Read more about Lipigon's projects:

P1 Lipisense
P2 Lipodystrophy
P3 Dyslipidemia
P4 CAP