Researchers have known for decades that blood, milk and other biofluids contain myriad tiny particles, a fraction of the size of cells. Generally dismissed in the past as nothing more than cell debris, they are now described as small functional vesicles that transport cargo out of certain cells.HISTORY OF EVs
Scientists studying the body’s immune response start to grasp that “extracellular vesicles” (or EVs) are far more than recycling bins. They show that immune cells release EVs loaded with specific proteins to activate the body’s T cells and stimulate an immune response, demonstrating how EVs can pass cargo from one cell to another.
This discovery pointed to EVs’ true role as key components of cell to cell communication.
EVs were eventually shown to be released and absorbed by virtually every cell type in the body.
Studies show that EVs carrying mRNA and microRNA, snippets of genetic code, can directly reprogram the behaviour of recipient cells. The potential for the development of EVs as a new class of therapeutics begins to emerge.
While examining how stem cells activate the body’s self-repair mechanisms, researchers discover that the EVs released by stem cells are responsible for the cells’ regenerative effects. Biotechnologists looking to tap EVs’ incredible regenerative power soon run into a problem: EVs prove very hard to isolate from the biological fluids that contain them.
To turn stem cell-derived EVs into regenerative medicines, researchers need a way to isolate them from the media that the cells are grown in. The current standard, ultracentrifugation, is slow and laborious. Worse, EVs are co-isolated with biological detritus which can counter the EVs’ beneficial effect. Without a consistent way to produce large quantities of EVs, they will never become medicines.THE FOUNDATION OF EXOPHARM
With a deep background in stem cells, Exopharm founder Dr Ian Dixon realises the potential of EV therapeutics and that overcoming the purification problem is the essential first step. After several years of research, Dr Dixon and his team develop LEAP. Like a nanoscopic version of Velcro, LEAP uses chemical hooks to selectively attach to the surface of EVs. Only EVs are captured; the other biological detritus in the cell culture liquid is simply washed away. Importantly the EVs can be easily released with a minor buffer change, allowing them to be isolated in a highly scalable, bioactive and inexpensive manner.
Results on the innate healing capacity of EVs derived from pro-regenerative cell types continue to pour in. In pre-human trials, researchers show that EVs can marshal the immune system, lower inflammation, reduce cell death and promote the recovery of injured tissues. EVs’ healing potential is demonstrated in conditions from stroke to heart attack to brain injury to wound healing.
With LEAP up and running, Exopharm has an efficient, scalable, proprietary method for purifying EVs from cells. Exopharm needs to grow. On the 18th of December 2018, Exopharm Ltd is listed on the ASX (EX1). With a considerable infusion of funding, the small team can be expanded and sights raised.
In January 2020, Exopharm announces that its Phase I clinical trial, PLEXOVAL I, is underway. This world-first study applies Plexaris™, a cell-free, platelet-derived exosome product manufactured with Exopharm’s LEAP Technology to wound healing.THE FUTURE OF EV MEDICINES
Exopharm has outgrown its lab space and is beginning to stage a migration of lab activities to the Baker Institute when the coronavirus begins impacting operations, with hospitals preparing to close research spaces to limit risks. The 25-person team shifts into gear, moving equipment and materials safely and effectively in record time. Today, the Baker Institute laboratory provides the key scientific facility for Exopharm’s innovation and growth.
As promising as naïve EVs are for regenerative medicine, pharmaceutical companies around the world begin to understand that by adding proteins, small molecules and nucleic acids to EVs, an entirely new class of medicine can be developed from engineered EVs (or EEVs).
Exopharm announces that it has acquired two key engineering inventions EVPS™ and LOAD™ and that it will be applying this technology to develop an anti-viral, Fortrexo™ CoV, to potentially treat coronavirus. Not only can this application have a positive effect on the ongoing COVID-19 pandemic, it will also serve as an excellent model for all of Exopharm’s EEV work.