Marianne De Backer and Jean Stéphenne on promising treatments for COVID-19
This article was originally published on www.tijd.be and www.lecho.be on March 13, 2021:
The list of Belgian heavyweights in the cockpit of the corona battle is impressive: just think of Paul Stoffels, the number two of the American pharmaceutical giant Johnson & Johnson (J&J), Luc Debruyne, the vaccine adviser of the European Commission, or Peter Piot, the corona advisor to Commission President Ursula von der Leyen.
Jean Stéphenne, the chairman of the German biotech company CureVac, which will probably receive a European green light for his corona vaccine next month, also fits in that list. And Marianne De Backer, who is responsible for the external growth strategy at the German pharmaceutical company Bayer and previously held numerous top positions at J&J.
As Bayer's deal maker - she closed 25 deals with pharmaceutical and biotech companies last year - De Backer non-stop screens the international pharmaceutical and biotech market for the most interesting innovations and has a helicopter view of the most promising developments.
"Regardless of the corona crisis, we are in the middle of a revolution in our sector," says De Backer in a virtual double conversation with pharma veteran Jean Stéphenne, in a previous life more than 20 years CEO of the Belgian vaccine branch of GlaxoSmithKline.
"We see a lot of innovation coming onto the market for which Nobel Prizes were awarded years ago. In genetics you see the first therapies, in cell therapy spectacular things happen with stem cells, and crispr (the genetic cut and paste technology, ed.) will make a world of difference. Those innovations have the potential to tackle 45 percent of all diseases."
"There are already incredible treatments on the market, such as the CAR-T's, that make it possible to take, modify and replace individual immune cells, T cells from patients, in a way that they attack a specific tumor. Personalized medicine at its best. The big challenge is to find a way to make this affordable. As an industry, we must find a way to make these innovations widely available, as a widely applicable therapy. It is impossible to do that alone. That is why we will see more and more partnerships and networks."
How can such innovations improve the lives of patients?
Marianne De Backer: "Take Parkinson's disease, an irreversible condition affecting 8 million people worldwide and in which no progress has been made for 50 years. There is not much more we can do today than treat the symptoms. There is an enormous medical need, to which these new techniques may provide an answer."
"At Bayer, we try to do this through gene therapy, among other things, where we introduce a gene into the body, packaged in a harmless adenovirus as a means of transport. That gene leads to the production of a protein that we see in animal models can improve mobility after three to six months of production. That can make a world of difference for patients with Parkinson's, who today often fail to even hold a cup of coffee."
"Another approach is to use neurons from stem cells. With crispr/Cas you can give those cells a better functionality, effectiveness and safety, so that they are not rejected by the patient, for example. A lot will be possible."
The corona crisis also marked the breakthrough of mRNA (messenger RNA, the technology behind the vaccines from CureVac, Moderna and Pfizer-BioNTech). How big is the potential?
Jean Stéphenne: "We will initially use mRNA to combat this pandemic. It is the fastest way to act against new variants and to adapt vaccines. But mRNA also shows promise in the fight against cancer, and that remains a priority. CureVac has two clinical studies in oncology. One in skin cancer, where we inject mRNA into the tumor to make cytokines (a type of proteins that fight the tumor, ed.). We are also conducting research into lung cancer, together with the pharmaceutical company Boehringer. Collaborations like that make sense: the biotech companies have the innovations, the pharmaceutical companies have the money and scale to make clinical trials possible."
"Because mRNA is a platform technology, we also use it on rare diseases. How can we tackle a genetic defect? It has been shown to be possible in mice, but how do we do that in humans? We are working in that direction, but it could take another 20 years. You need patience and vision."
De Backer: "That costs a lot of money, but pays for itself at times like this. CureVac is lucky to have a financier (Major shareholder Dietmar Hopp, known as founder of the IT giant SAP, ed.) who has invested 1 billion euros over the years to keep the company running and stimulate innovation. We have to keep doing that. Bayer invests € 2.5 billion a year in research and development with its pharmaceutical company alone. That is very expensive and risky, but the positive impact is immense."
Bayer has not been active in vaccines so far, but has entered into an alliance with CureVac to help it develop and manufacture its corona vaccine. Why this joining of forces?
De Backer: "Before Covid-19 you had the big four in vaccines with GSK, Sanofi, Merck and Pfizer. When the pandemic broke, it quickly became clear that something special had to be done. To vaccinate the world, 12 to 14 billion doses are needed. Everyone is needed. In normal times, we would never venture into vaccine production, but CureVac can put our expertise and scale to good use. Bayer is very enthusiastic about this collaboration."
Stéphenne: "As a small biotech company, CureVac does not have the infrastructure to produce on a large scale, you need a global network for that. We cannot handle the rollout of our corona vaccine alone. That is why we recently entered into a cooperation agreement with the Swiss Novartis for the production of our vaccine."
"Size is also necessary for monitoring safety. If you vaccinate widely, you will gain more insight into possible side effects. You have to monitor them widely, which we cannot do ourselves. Bayer does have that global network."
Numerous production problems have already arisen, such as the European saga surrounding the AstraZeneca vaccines. Can you guarantee that things will not go wrong with CureVac?
Stéphenne: "A lot can go wrong. Look at the difficult discussions between AstraZeneca and Europe. Or to the attitude of the US. Based on their defense law, they block exports of both vaccines and vaccine production materials. This concerns ingredients such as the lipids needed for the production of mRNA, but also material to purify vaccines, chromatographic gels, filter material. Much of this normally comes from the US, but suppliers must deliver priority to US manufacturers before they can ship to Europe."
"Conversely, Europe would say "Europe first", with its own mechanism to block exports if necessary. To put it simply, it is not simple."
De Backer: "Bayer has to adapt its factories, purchase, install and validate new equipment, attract the right people, you name it. An incredibly complex process, not to mention producing the mRNA vaccine itself. I understand that the need is very great. But our industry is bent over backwards to do this in a fast, safe way. Maybe the companies that don't stay on the sidelines deserve a little more credit and applause."
"I understand people are impatient and concerned. My father-in-law is 87 and not yet vaccinated. That is frustrating. We all want our normal life back. But we need to make it clear to people how difficult all this is. Teaching that understanding will help more than pointing the finger at each other."
The corona crisis painfully illustrated that governments and pharmaceutical companies were not prepared for this pandemic. Are we better equipped for the next?
De Backer: "I spent a large part of my life on infectious diseases and vaccines at J&J. Even before this pandemic, infectious diseases were responsible for the largest number of deaths, but unfortunately little attention was paid to them. I think we learned a lot in the past year and that change is coming.In the United States, with BARDA (American government agency for biomedical research, ed.) You already had an organization that is fully prepared for such events."
"BARDA had a major impact during this crisis. It gave US $ 1.5 billion to Moderna to develop its vaccine and manufacturing capacity. This allowed Moderna to reserve production capacity with external companies and to progress quickly. BARDA also provided J&J with funding to develop its corona vaccine."
With the Hera Incubator, Europe is developing a kind of European BARDA to be better prepared against pandemics. What does it ideally look like?
Stéphenne: "You can compare it to the European medicines watchdog EMA, in which the 27 member states and the best experts work together. It is a great success and works just as well as the American counterpart FDA. There is a great deal of expertise in the field of infectious diseases in the Member States. Just think of the Institute of Tropical Medicine in Antwerp. You have to build a network that is coordinated at European level and that stimulates collaboration with the pharma."
De Backer: "You need a few things. A European surveillance system that raises the alarm in the event of a new pandemic. Funds for clinical research that might not otherwise receive much attention. And public-private partnerships, so you can quickly produce treatments when needed."
As vaccination campaigns slowly get under steam, many are wondering when we can resume our "normal life". How do you see the near future?
Stéphenne: "The acceptance rate of the vaccines is vital. If 30 to 40 percent of the population refuses, the virus and its dangerous variants will continue to circulate. But I am optimistic that acceptance will increase. We do not see any serious side effects in the vaccinees, which will increase confidence in the rest of the population."
"In addition, we must vaccinate the entire world. Europe has signed contracts with the COVAX vaccine coalition to make vaccines available worldwide. US President Joe Biden also announced that the US would support this. But you have to be realistic."
Meanwhile, the vaccination campaign has not even started in many developing countries. Don't pharmaceutical companies have a responsibility to speed up the pace?
De Backer: "The biotech and pharmaceutical companies behind the vaccines, such as CureVac, are already working with governments and non-profit organizations at COVAX, under the auspices of the World Health Organization. Their goal is to make 2 billion doses available to poorer countries by the end of this year. So a lot is already happening, but there is indeed more possible."
Stéphenne: "The vaccine manufacturers are now also conducting clinical research into the effect of the corona vaccines in adolescents, in order to test them in a subsequent phase in young children. That takes time. At CureVac, we make our vaccine more stable, so you don't have to store them so cold anymore. We aim to keep it at 4 degrees Celsius for three months. We think we are already there, but the regulator has yet to give its blessing. That would be important for developing countries because it would greatly facilitate distribution there."
Let's wrap up on a philosophical note. Does this pandemic have the power to change our society for the better?
De Backer: "I see a lot of positive things. The level of collaboration, with one common goal in mind, and the unprecedented speed. There is an increased awareness in the West about infectious diseases and the power of prevention. But also that we must use science to solve such problems and that governments and pharmaceutical companies must invest in it."
"When I started in pharma 30 years ago, I was hoping that I could help make a difference for patients. At Bayer, we have seen the number of spontaneous applications increase since the corona crisis. The positive thing about this crisis is that it exposes many more young people to the power of science, biotech and pharma. Beautiful, right?"
