BiOrion Technologies was founded in 2003 on the basis of a single important discovery - a cyclic peptide that selectively binds to the PDGF-beta (platelet-derived growth factor beta) receptor, which exhibits an elevated level of expression in fibrotic tissue. Because BiOrion’s cyclic peptide can be coupled to therapeutic agents, its discovery opens up the possibility of targeted drug delivery for e.g. the treatment of chronic liver disease such as that caused by hepatitis, obesity or to a lesser extent alcohol abuse. BiOrion was set up by Professor Klaas Poelstra, who discovered the peptide, and a group of colleagues at the University of Groningen with the aim of exploiting this possibility.

 

“The aim was to develop the technology surrounding the use of this cyclic peptide to the point where the technology could be sold or licensed to a pharmaceutical company that was developing targeted therapeutic agents for liver disease,” says Dr. Herman Steen, co-founder of the company and its current CEO.

 

However, taking the technology from discovery to clinical proof-of-concept still required additional funding, and in the search for that funding the company’s narrow focus on liver fibrosis proved less than beneficial.

 

“Back in 2007, one of the difficulties in obtaining funding for research into the treatment of liver fibrosis was that the necessary clinical trials would have been very expensive and would have taken a long time to complete. Important arguments for investors not to invest in this stage of development. Luckily, however, the PDGF-beta receptor is not only expressed in fibrotic tissue. It is also present at elevated levels in fibrous stroma tissue in many tumours where it is heavily involved in angiogenesis, so we also started to focus on applications in oncology,” explains Herman.

 

That switch of emphasis not only brought in seed-capital to put the company on a firm footing, it also attracted the attention of Liesbeth de Vries, Professor and Head of the Department of Medical Oncology at the University Medical Center Groningen, who was putting together the CTMM Mammoth project. However, her interest in BiOrion’s PDGF-beta receptor targeting was not primarily related to targeted drug delivery. It was related to the molecular imaging of early stage breast cancer.

 

“In general, it is not more difficult to attach a radiolabel to our cyclic peptide than it is to attach a therapeutic agent, and although we had done some early research to see how effective these moieties would be as imaging agents, joining the Mammoth project is a great opportunity to investigate the possibilities,” says Herman. “The preliminary pharmacokinetics of the peptide show that you might get a temporary build-up in the excretion organs, the liver and kidneys, so it may not be so good at visualizing tumours in that region of the body, but its effectiveness in imaging primary and secondary tumours in other parts of the body is expected to be sufficient.”

 

While this work is being conducted in the Mammoth project, BiOrion continues to develop candidate therapeutics for the targeted treatment of fibrosis and cancer. Combining diagnostics with therapy would be a huge step forward towards personalized treatment and better therapy monitoring.

 

“One of our latest achievements was the successful coupling of interferon-gamma to the peptide in order to create a chimeric form of interferon-gamma that binds to PDGF-beta receptors rather than interferon-gamma receptors, which could provide an effective way of targeting this powerful anti-fibrotic cytokine to activated fibroblasts in tumour stroma,” says Herman. “In several animal models we have seen that almost all of the debilitating side effects of today’s systemically administered interferon-gamma treatments could be avoided whereas its anti-fibrotic and anti-angiogenic efficacy are increased.”

 

Herman believes that this dual track development process - developing candidate therapeutics in-house while testing the selectivity of its targeting molecules through imaging studies such as those in the CTMM Mammoth project - will be the quickest way to achieve the company’s objectives.

 

“Ultimately, I think that most of the companies we will target with the technology will be more interested in therapeutics than imaging, but if you want to get the most for your euro, imaging studies are a much cheaper and faster way of obtaining the required proof of concept. Taking the imaging route also allows you to go for Phase 0 clinical studies that allow you to establish whether there is homing in the target tissue. To do that you only need to pay for GMP grade manufacturing with adapted CMC, and a reduced safety and toxicology program, which means that for less than one million euros you have real clinical data that you can show to pharmaceutical companies.”

 

However, Herman is keen to point out even finding that modest level of funding for an SME is not that easy in today’s difficult economic climate.

 

“With the current changes in government policy regarding funding for the life-sciences, I think that we will definitely have to rely on additional venture capital rather than government money to move into the next phase of the translational process,” he says. “The frustrating thing is that we have the people, the knowledge and the IP to move things forward, and we even have the patients. All we lack at the moment is the money, and that is a real challenge.”

 

 

BiOrion’s PDGF-beta receptor cyclic peptides can be coupled to a therapeutic agent such as interferon-gamma (left) or a radio nucleotide for molecular imaging (right).