March 2024 • PharmaTimes Magazine • 26-27

// PHARMA//


Exoso-what?

Working out exosomes and optimising the delivery of innovative treatments

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Treatment options for many rare and severe diseases have expanded rapidly in recent years thanks to groundbreaking research and significant technology breakthroughs.

The life sciences and pharmaceutical industry is constantly innovating to ensure that new treatments become available for patients.

One area that has seen particularly exciting progress is the genetic medicine space. Gene therapies and gene editing have opened the door to new, life-changing treatments for rare, inherited disorders that may have previously had a very inadequate standard of care.

They have offered hope of finding a cure for a range of diseases where that did not previously seem possible.

It is vital, however, to ensure that these treatments not only can be administered safely and but also can reach their intended target cells or tissues.

Fortunately, exciting progress is being made in this area.

Delivery systems

In order to fully realise the potential presented by new, potentially life-changing treatment modalities, the priority must be finding safe and more effective delivery methods to get these medicines safely inside the appropriate cells.

Gene therapies, for example, are still limited by a lack of a suitable method of delivery.

Currently, viral vectors such as adeno-associated viruses (AAV) are frequently used to deliver gene therapies for a number of primarily genetic diseases, but their wider use is limited by the high doses of AAV currently needed, which comes with significant safety concerns.

Another example is in the field of genome editing, where editors have proven to be clinically effective when delivered to hepatocytes, but the lack of non-liver delivery solutions has limited the development of genome editors in non-liver indications.

It is here that exosomes can offer a solution to both enable more effective and safe delivery of genetic medicines and to widen the number of diseases that could be addressed with these new drug modalities.

Hitting targets

Using exosomes in drug delivery can present a range of advantages for patients and medical professionals in treating rare and severe diseases.

Encapsulating AAV inside exosomes offers the possibility of shielding AAV from the immune response, providing the ability to dose all patients regardless of the presence of neutralising AAV antibodies.

A significant percentage of patients (typically 20-50%) naturally have pre-existing anti-AAV antibodies and are therefore ineligible to receive AAV gene therapy, and all patients develop them after receiving a first AAV dose, thus precluding repeat dosing.

Exosomes also have the potential to revolutionise gene-editing technology. With the ability to target cells and tissues through exosome engineering, Evox Therapeutics is developing systems that can deliver gene-editing technologies, such as CRISPR, to specific cells and tissues.

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What are exosomes?

Exosomes are nano-sized extracellular vesicles that function as transporters within the human body carrying a variety of bioactive payloads.

They are naturally secreted by cells and are easily found in biological fluids.

There is a great opportunity to harness the natural capabilities of exosomes for the transportation and delivery of a new class of drugs that can reach cells and tissues that are currently not accessible with existing drug delivery methods.

Because they are naturally occurring and ubiquitously present, exosomes have an extremely benign safety profile which differentiates them from other man-made delivery approaches such as lipid nanoparticles.

In particular, exosomes present the opportunity to make substantial advances in the development of non-viral delivery of genetic medicines, which provide so much hope to patients with a variety of rare and severe diseases.

A wide variety of genome editing payloads can be engineered inside exosomes including meganucleases, cas enzymes and base editors, all without a restriction on payload size. In this context, exosomes contain both the editing enzymes alongside the guide RNA.

Exosomes are rapidly taken up by cells, the cargo functionally delivered, and then everything is naturally degraded after a few days making it an ideal approach for delivering genome editors.

This technology has huge potential for a range of different indications and allows specialists to edit the human genome and ‘correct’ mutations or genes that are causing a particular disease.

Exosomes can be readily engineered to target specific organs and tissues. This can help overcome some of the key challenges associated with existing drug delivery methods that see insufficient penetration of target tissues.

Increased uptake of drugs and better penetration of target cells and tissues with exosomes can result in lower dosing, which leads to better tolerability for patients and, in turn, increases access to these new treatments to those who may not previously have been eligible.

A changing landscape

Thanks to the ongoing commitment and pioneering research of the life sciences industry, innovation continues to dramatically change the treatment landscape for many disease areas, particularly in rare and inherited diseases.

As new treatment modalities – including genetic medicines – emerge from this research, further innovation is required to ensure that these treatments can actually benefit from these advances.

Exosomes could have a vital role to play in ensuring that patients receive innovative treatments in a safe and effective way.


Tony De Fougerolles is Chief Executive Officer of Evox Therapeutics.
Go to evoxtherapeutics.com