Getting chemistry and biology to communicate

The Chemical Biology group at the University of Copenhagen has discovered an entirely new principle for the development of pharmaceuticals and has achieved a significant breakthrough in the pain-control area. This has resulted in the establishment of a new company, Avilex Pharma, which is to turn the idea into reality.

Avilex Pharma is one of the new stars on the Danish biotech sky. The research-based spin-out company is based on an entirely new principle within protein-protein interactions, which the Chemical Biology group at the Faculty of Health and Medical Sciences at the University of Copenhagen has developed. Avilex Pharma was created by the head of the group, Professor Kristian Strømgaard and Postdoc Anders Bach, who are behind the new research that may revolutionise the way in which pharmaceuticals work.

The Chemical Biology group works with pharmaceutical chemistry, biochemistry and molecular biology – fields within which you “make chemistry and biology communicate” in the words of Kristian Strømgaard.

The promising research results have meant that Kristian Strømgaard and Anders Bach in a joint effort with Novo Seeds have established a new spin-out company, Avilex Pharma. They have already hired a CEO, Robert Tansley, who has great experience in pharmaceutical development and has been headhunted from Cambridge. Kristian Strømgaard holds the position of Research Director, while Anders Bach, who is currently working as a postdoc in Italy, participates as a consultant.

Avilex Pharma is located at COBIS, Copenhagen Bio Science Park, as are a number of other biotech enterprises.

“It is extremely satisfying when academic research can be used for something that combines both worlds,” says Kristian Strømgaard.

Hardly knew what research was
When the young Kristian Strømgaard was about to choose an educational programme, he did not exactly feel called into pharmacy; he was more interested in practising athletics at elite level. However, he was inspired by a coach who was a pharmacist:

“I started studying to become a pharmacist in order to have something in addition to the athletics, and during my first study years, athletics was my primary focus. I hardly knew what research was,” he says.

However, an inflamed Achilles' tendon put an end to his elite sports, and Kristian Strømgaard transferred his drive, focus and stamina to his studies.

During the Master's programme, he became interested in medicinal chemistry and was strongly inspired by one of the great names in Danish science, Professor Povl Krogsgaard-Larsen. In connection with his thesis, he went to University College in London, where he worked with chemical research under Professor Robert Ganellin, the man who helped invent the world's first drug against gastric ulcers.

“This was the first time I got acquainted with research, and then I thought that if it was the same to do a PhD, I might as well get paid for it,” he says with a wry grin.

Research had now come to be important to the man who apparently had no idea what research was when he started his studies. “I discovered that it was exciting and enjoyable, and the ambition I had from sports started emerging in the research,” says Kristian Strømgaard.

Staking all on basic research
Following a stay at Columbia University in New York, Kristian Strømgaard returned to the then Faculty of Pharmacy as an assistant professor and later as an associate professor. In 2006, H. Lundbeck A/S offered to co-sponsor a new research area at the Faculty, and Kristian Strømgaard proposed Chemical Biology as a potentially innovative area. In 2006, he was appointed Professor:

“To me personally, it was a watershed to be appointed Professor of Chemical Biology. It means a lot that you are given a bag of money, and that people believe in you. It was generous of H. Lundbeck and the Faculty to stake so much on someone as young as me, who had not proven a lot, and I was also aware that if I failed, I would have to go looking for something else to do.”

H. Lundbeck A/S and the Faculty of Pharmacy put DKK 20 million into the sponsorship over a period of five years, and in 2010, this was extended through to 2013 by an additional eight millions.

It is this huge staking on basic research that is now beginning to pay off, and Kristian Strømgaard believes that the interdisciplinarity has been decisive for the group's success.

“It is a challenge in itself to get people to communicate between chemistry and biology. But interdisciplinary work is crucial if you want to bring the fields together and see new breakthroughs, and it is important to maintain the high level within each discipline and to raise the bar even further.”

Entirely new principle
One of the Chemical Biology group's focus areas for the development of pharmaceuticals is protein-protein actions – a promising target, i.e. the place in the body that the drug has to bind to – and Kristian Strømgaard's group has achieved a decisive breakthrough in the pain-control area. The hope is that the result will be a drug that can treat neuropathic pains, i.e. nerve pains. This is potentially great news for the millions of chronic pain patients across the world.

Drugs are often designed to bind to the receptors in the cells' membranes, which are involved in the illness, and in previous experiments, the aim has been to block these. However, the receptors are so important to the body's ordinary functions that although influencing them may have an effect on the illness, it may also have adverse effects that are so serious that the drug in question will have to be abandoned.

One example is the substance ketamine, which has an efficient pain-relieving effect. However, like other substances that affect the ‘pain’ receptor, it has unacceptable adverse effects. Following several futile experiments, Anders Bach and Kristian Strømgaard developed a substance that does not affect this receptor directly; instead it affects the interaction between the receptor and an important protein, PSD-95, inside the cell.

By doing so, in principle, it is possible to create a drug that maintains the receptor's function intact, but which stops the pains. And that is without adverse cognitive or motor effects, in contrast to what happens when patients are treated with classic receptor antagonists.

“We have shown that our substance has an equally strong pain-relieving effect, that this effect lasts surprisingly long, and that it is completely free of adverse cognitive effects,” says Kristian Strømgaard.

The work was launched in collaboration with Postdoc Anders Bach, whose PhD project was based on the development of substances that would impede specific protein-protein interactions in the brain.

Same principle against strokes
Kristian Strømgaard explains that they are also working on a platform on which the same principle can be applied to many other disease areas. They are already researching a substance that can protect the brain against cell death after a stroke.

Every year, 2,000 Danes die within a month of having a stroke. At a global level, the figure is astronomical. Those who survive often have debilitating brain damage, and for years, research has been dedicated to finding substances that could protect the brain.

Science has had upwards of a hundred potential pharmaceuticals in play, but none of them have passed the clinical tests, and a number of pharmaceutical companies have burnt their fingers badly. It is no joke when this research is called ‘biotech's cemetery’.

However, in a publication from 2012, Kristian Strømgaard, Anders Bach and their colleagues showed that their substance reduced the dead area in the brain following a brain haemorrhage by 40 per cent. This is far more efficient than a similar neuroprotective drug, which Canadian researchers are currently testing, and which has shown an effect in humans.

“However, ours is better in a number of ways; it is an entirely new substance, which works more selectively and binds 1,000 times stronger to the receptor in the brain,” says Kristian Strømgaard.

The new substance even manages to pass the blood-brain barrier, which is located in the brain's veins and makes it difficult to get medicine into the brain.

The perspectives are great: “If it turns out that the substance has no serious adverse effects, you can imagine using it immediately after a stroke, for instance, have it available in the ambulance so that it can be given to the patient straight away.”

Research into the ‘brain part’ continues along with research into the ‘pain part’, and Kristian Strømgaard hopes that it will be possible to procure soft money for the development of a neuroprotective pharmaceutical.

Without money, it hurts
The Chemical Biology group's research has caused great interest, and it has also succeeded in attracting research funds. They have received funds from the national Proof-of-Concept fund, the Exploratory Pre-seed grant from Novo Seeds and the Novo Nordisk Foundation and Copenhagen Spin-outs, as well as funds from the Novo Nordisk Foundation, the Lundbeck Foundation, the Carlsberg Foundation, and the Research Council for Health and Disease.

“At Avilex Pharma, we are looking for one or maybe two investors in the long term, so that ideally, we can take the project to the next phase of clinical testing. We are hoping to get to an Investigational New Drug Application, IND, soon. This will be a milestone, and we would like to have a co-investor at that stage,” says Kristian Strømgaard.

Currently, the researchers at Avilex Pharma are busy with a whole string of studies and tests, which are necessary in order to move on. These activities are spread across laboratories around the world, from Cambridge to China. However, the medicinal chemistry part is taking place at the Department of Drug Design and Pharmacology.

“In practical terms, we also need to produce large amounts of grams of the substance, and this is a significant challenge that is often underestimated,” Kristian Strømgaard says.

Strong Board
The newly elected Board has held its first meeting, and Kristian Strømgaard sees it as a kind of seal of approval that Avilex Pharma has been able to connect with seasoned players from the biotech industry who have extensive experience in commercialising research results.

“This is a really strong Board,” he says enthusiastically.

It is made up of Ingelise Saunders, former CEO for Action Pharma, who sold a pharmaceutical candidate to Abbot for USD 110 million in December 2012. Professor Raymond Hill who, among many other important posts, has been Executive Director at Merck, Sharp & Dohme, and who is now Chairman of the British Pharmacological Society. Also Henrijette Richter from Novo Seeds, and – naturally – Kristian Strømgaard himself.

Novo Seeds has contributed a significant amount to the maturing of the commercial project.

Knowledge and innovation hand-in-hand
The Chemical Biology group belongs under the Department of Drugs Design and Pharmacology, and being able to conduct research that has both a high scientific value and innovative class, and which can attract venture capital, naturally contributes positively to the Department's reputation.

“At the Department of Drugs Design and Pharmacology, the link between science at a high international level and innovation is very important,” says Head of Department, Professor Ole Thastrup. “We are very interested in continually exploring spin-out opportunities in our research projects. We therefore work actively to establish a research environment that integrates the innovative element. We would like to show our young PhDs and postdocs that the Department's pulsating research environment can offer a solid scientific education and academic career as well as open up for the chance of setting up a business for oneself.”

Ole Thastrup is very keen to stress that solid research and innovation are parallel events: “It's not a case of being into either basic research or innovation. The people who are scientifically strong, who publish articles of high international class, are also the ones who are innovative. These things go completely hand-in-hand,” he says.

Spin-outs have changed attitudes
“The discovery is, of course, down to our group, but we have had excellent support. We already have a number of patents, and more are in the pipeline, and in this process, the TechTrans Office and Copenhagen Spin-outs have continually been good and constructive co-players. Where formerly there was a clear focus on licensing patents to others, the university is now much more inclined to contribute to establishing spin-outs,” says Kristian Strømgaard.”

 Asked whether the sense of reaching a unique research result is similar to the rush you feel when years of sports training culminate in a winning performance, Kristian Strømgaard responds:

“In athletics, I would spend hours training mega-hard, and then there would be those 51-52 seconds in the 400-metres hurdles. Basically, it was insanely hard work – and pure euphoria once you won. So, yes.”


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