Our very own Michael Braunagel takes us through his three-decade-long career spanning three countries, ranging from cutting edge cancer research to developing a potentially groundbreaking clinical treatment in the field of rare diseases.
Starting as an academic scientist at the University of Heidelberg, Michael transitioned to the commercial world in 1997 when he co-founded his own biotech company in Norway, Affitech, specialising in cancer therapies. He later moved to the UK in 2014 to become Managing Director of Affitech’s Cambridge-based subsidiary company, Actigen, focusing on innovative clinical trials for rare diseases.
Tell us about your career and how you got involved in the biotech industry
I’m a scientist by training, but I went on to hold almost every job in the biotech industry, before ultimately becoming a company Managing Director. I started my scientific career in molecular biology, studying molecular genetics at Heidelberg University and later completing a PhD at the German Cancer Research Centre on recombinant antibodies.
I didn’t start my career in rare diseases; my early scientific and commercial work focused on developing new cancer treatments. As part of my scientific research at the German Cancer Research Centre, my colleagues and I were developing a new form of technology related to cancer treatment. This work was pioneering at the time and involved us working in the same research field as future Nobel Laureates Greg Winter CBE FRS FMedSci from Cambridge University and George P. Smith (Distinguished Professor Emeritus of Biological Sciences) from the University of Missouri in the United States.
My work involved a specific aspect of the technology transferring aspects of antibody generation into an in vitro (bacterial) system. The practical outcome of this is that you can select and modify antibodies for your specific purposes. However, to help patients, it needed to be commercialised and not confined to laboratory benches and the research papers of academia.
In the early-90s, there was little money for biotech research commercialisation in Germany. So, I made the move to Norway, which provided a more fertile development space for our work. This ultimately resulted in me founding my first company, Affitech, with five partners.
When I started Affitech, it was supposed to be part of a temporary sabbatical from my post-doctoral research position at the German Cancer Research Centre. But, life has a way of surprising you; I planned to stay for 6 months which turned into 17 years!
We succeeded in getting several compounds into clinical trials. One has entered the market in collaboration with global pharmaceutical giant Roche, one of our biggest achievements as a company.
How did your cancer treatment work? What led to you moving into the field of rare diseases?
Our therapy worked by cutting off the blood supply for cancerous tumours. This played an important role in reducing tumour growth and potentially making them more treatable.
Cancerous tumours are typically solid, with a high metabolic rate, and they need nutrients and oxygen to continue growing. They also need to get rid of waste and CO2, which their high metabolic rate generates at significant levels. Being able to connect to the vascular system is a prerequisite for the tumour’s further growth.
Stopping and reversing the process of waste disposal means cancer stops growing and becomes intoxicated by its waste, making it more sensitive to cancer drugs. This had potentially significant benefits for cancer patients and could increase their treatment options.
This was originally meant as a cancer therapy but ended up as an ophthalmological product, where reduction in blood vessel formation was also required.
We decided to capitalise on our experience and move Actigen to the renowned biotech hub in Cambridge to concentrate on the clinical trial aspect of our work.
The treatment you have in development for MPS II has the potential to make a huge difference in the lives of patients and their families. Could you explain the effect MPS II has on patients and what the benefits of GNR-055 are likely to be?
MPS II is caused by a deficiency of the key enzyme responsible for the first step in the breakdown of glycosaminoglycans (GAGs), causing a progressive build-up in nearly all cell types, in all tissues and organs. It is a serious and highly debilitating health condition, affecting mostly young male children. For the past 30-40 years, people with the disease just didn’t get better. Few lived to 20 or even 15; most passed away as a result of heart complications between the ages of 10 and 15. Life expectancy was very short, and the patient’s quality of life was poor.
One of the main difficulties patients experience is internal organ deficiencies, especially their heart not working properly. This caused the children a great deal of physical pain and resulted in them losing their lives at a very young age.
The severity of the internal organ issues most children experience resulted in them being bedridden and requiring specialised care. The nature of MPS II meant that the children’s difficulties would become progressively worse over time, resulting in greater discomfort and putting added strain on their families and carers.
However, the development of a breakthrough enzyme replacement therapy (ERT) was able to treat these internal organ issues. While patients still don’t have a normal life expectancy; they live longer with better physical health. ERT made a big difference in addressing the physical effects of MPS II, but it was not a complete solution and left the neurological aspects of the condition untreated.
It is estimated that 1/3 of MPS II patients also have neurological problems; this includes a range of behavioural issues and learning disabilities. With physical improvements, ERT also created a new challenge. Patients were now able to hurt themselves and their carers due to their rage control issues, which they couldn’t do previously because of their poor physical strength.
The crucial innovative property of GNR-055 is its ability to cross the blood-brain barrier. This prevents GAGs from building up in the brain and the resultant neurological issues.
GNR-055 is a fusion of the missing enzyme and, importantly, an antibody fragment that it uses to access brain cells by binding to insulin receptors on capillaries and crossing the blood-brain barrier. Once in the brain, GNR-055 is expected to break down the GAGs that cause neurological issues. This treatment fulfils an unmet clinical need and could offer life-changing improvements for patients affected by MPS II and their families.
We all know that rare diseases, by their nature, affect small numbers of patients. What are the practical challenges of getting people involved in clinical trials, and how can these be overcome?
The typical way of getting into clinical trials is using an agency to look for patients, but this just doesn’t won’t work for rare diseases. The personalised medicine agenda is replacing the idea of a one-size-fits-all approach to treatment; there is not necessarily one drug and dose for all.
We have been speaking to the MPS Society in Great Britain to discuss our work and the potential opportunities for collaboration. The MPS Society has an extensive network of patients and leading scientists. It can provide valuable feedback from companies like ours that are developing potentially breakthrough treatments.
This plays an important role in assessing the patient benefits and determining the regulatory compliance issues. We are also having conversations with the regulatory authorities to convince them of the advantages of this new treatment. We aspire to bring our project to the patient and the market by building alliances and collaborations.
Rare diseases are often neglected and overlooked due to their small numbers. Why is this?
Generally, rare diseases are overlooked in the industry because the patient numbers are very low. If you have few patients, it makes the treatment expensive, which has, in turn, implications for reimbursement from the relevant authorities. You need to find the sweet spot between helping patients and being commercially viable; however, this is no mean feat in practice.
In our case, we are lucky that there is already a therapy for MPS II. We are in a relatively unusual situation as we are building on the success of an existing treatment. Therefore, developing a new treatment for MPS II comes with a twist, as it is one of the more competitive rare diseases in which to develop treatments. While orphan indications reduce the cost and speed up the clinical trial process, it doesn’t compensate if the treatment doesn’t work.
The regulators are in a tight spot; they must balance the competing demands of doing more to develop drugs for rare diseases without compromising safety. This is a complex issue, and there is no easy solution. The incentives for tackling rare diseases are not internationally harmonised across our major markets; there is a disparity in methods and requirements. The COVID-19 crisis and the rise of vaccine nationalism have further undermined international collaboration on the development of new treatment solutions. We need to rebuild the spirit of international cooperation in a post-COVID-19 world to tackle rare diseases collectively on a global scale.
What does the future hold?
At Actigen, we are establishing an exciting approach to clinical trials with GNR-055 and are working with our partner to bring products to global markets. MPS II is a very debilitating condition for those affected, and we are hopeful that the trial will establish the efficacy of the treatment.
GNR-055 is the first therapeutic in our innovative development pipeline, and we are thrilled to be working with major players in the industry to make this happen.
We have several exciting things in the pipeline, so watch this space for further developments.
