Saving sight with drugs derived from sharks

When our bodies are attacked by bacteria, fungi or viruses, our immune systems are triggered to respond and to fight back against the infection. Specialised proteins called antibodies are produced in response to these external pathogens and can identify and bind specifically to the foreign targets, allowing them to be eliminated by immune system killer cells.

But antibodies aren’t only useful inside the body. The last few decades have seen huge steps forward in researchers’ understanding of antibodies and their ability to develop these as therapeutic drugs that can target specific disease molecules. Remarkable success has been achieved both clinically and commercially, primarily in the treatment of inflammatory conditions, autoimmune diseases and cancer.

Understanding antibodies

However, this success comes with several limitations. Antibodies are large complex molecules composed of four chains that have to combine and fold correctly to be functional. Sugar molecules must also be added to specific sites on the molecule to enable the antibody-based killing of foreign cells. This results in high costs when manufacturing these molecules, making them very expensive medicines.

The large size of the antibodies also limits where they can reach within the body. Generally, antibodies target molecules that exist outside of our body’s cells or in the bloodstream and are administered either into a vein or under the skin through a needle. Given these limitations, researchers in therapeutic biologics are leading the way to find innovative alternatives to classical antibodies.

Finding a new solution

To address the challenges of these traditional antibody-based methods of treatment, a spinout company from the University of Aberdeen is developing a more effective and less invasive solution using domains known as soloMERs™. Elasmogen Ltd was founded in 2016 by Dr Caroline Barelle and Professor Andy Porter, and since then the company has developed its soloMER products which have the potential to transform the treatment of inflammatory diseases and cancer.

Variable New Antigen Receptors (VNARs) are found in sharks and form an integral part of their immune system. They are the equivalent of antibodies found in humans and respond in a similar way, protecting sharks against foreign cells, but they are much smaller, making them ideal for targeting hard-to-reach areas in the body such as tumours. Elasmogen has developed robust methods to isolate these molecules which will bind to desired disease targets, and the company has created ‘humanised’ versions of VNARs now known as soloMERs. This new technology has a number of advantages over current treatments.

“Our soloMER technology harnesses the power of antibodies when used as drugs, but in a small, stable format that is a fraction of the size of a normal antibody (1/10). This reduced size allows us to deliver the treatment directly to the affected site, and the robustness of soloMERs makes them particularly effective for use in complex and challenging environments such as the eye and gut.

Our research identified the need for a new way of administering medication that avoids invasive treatment and potential side effects. Since establishing Elasmogen, our objective has been to develop the most innovative and effective sight-saving therapies that can be administered on the surface of the eye and avoid the need for an injection. This ‘site-specific’ approach also has the potential to treat inflammatory diseases of the gut such as Inflammatory Bowel Disease (IBD), releasing the drug at the site of inflammation”.
Dr Caroline Barelle

The next generation of drug discovery

Additionally, the unique shape of soloMERs allows them to bind to different parts of the target, which potentially offers increased potency and could provide better results for patients. By creating libraries of billions of molecule clones, the team has tested the binding of soloMERs to different targets and discovered that they can also penetrate inside tumours to release a ‘warhead’ of anti-cancer drugs, specifically killing the cancer cells. This work is in collaboration with Almac Discovery and is focused on the delivery of a new class of cancer drug called a soloMER drug-conjugate or SDC.

Previously, Caroline led the development of these domains at the pharmaceutical companies, Wyeth and Pfizer, before establishing Elasmogen to commercialise soloMERS and develop a portfolio of auto-immune and oncology products. With a focus on inflammation and cancer, Elasmogen is working closely with several other biopharma partners, including Merck and Amgen, to develop and deliver a pipeline of innovative medicines. Currently in late stage pre-clinical trials, further investment and development of soloMERs will potentially allow the products to become the next generation of drugs using biological mechanisms to treat disease.