Piotr Zien
Director of R&D Biotechnology Operations at DEMO Pharmaceuticals S.A.
ΣΥΝΕΝΤΕΥΞΗ: KOSMAS ZAKYNTHINOS
« Now with all those super-fast genome sequencers and AI-aided screening methods, a better understanding of epigenetics, the direction towards personalized medicine is inevitable. The way how we would like to approach the molecular target – whether it is a small molecule, monoclonal antibody, RNA, enzyme or maybe something different is a different discussion. All of those approaches have their pros and cons and the choice of the active molecule really depends on the situation ».
Biotechnology changes the “game” and DEMO opens a new chapter in its history. It invests in biotechnology for the first time in Greece and joins the small league of international companies active in the development and production of biotechnological medicines. What is the goal in terms of biotechnological production and research?
DEMO as a “new kid in the block” must be careful entering this fascinating but already quite established technology for developing and producing biological drugs. The area is highly regulated and full of competitors at a global level. Therefore, we decided to start with the development and production of biosimilar antibodies, which counts for the largest chunk of biotech drugs. We hope it will let us put the cornerstone and establish this technology in the company as a kind of trampoline to the hard-to-make biotech – drugs and maybe fully innovative products in the future.
Larger pharmaceutical companies still rely on biotech’s as a source of innovation. What is DEMO’s next steps on biotech’s and what are the challenges facing in the Greek market?
It is true that biotechnology, like almost all other technologies, may be a source of innovation in the company. We can consider it at two levels. Firstly, by introducing technical innovation at drug development and manufacturing level, for example, by introducing new, more effective technologies like high-density cell cultures to increase productivity or continuous purification. Secondly, by developing new drugs and therapeutic approaches. In this area, we have had a festival of innovation in biotech in recent years. But as we know, innovation requires unique know-how and high investments, for that reason we would like to start with technical innovations which will deliver new biotech products and in the next few years and will bring us some fuel for high tech innovative products. Right now, it is hard to tell what the next step would be. Naturally, we have aspirations and we have plans, but we’re careful, taking on step at a time to achieve them.
We know that it takes many years for a medicine to walk through from a laboratory invention to an approved treatment available to patients. Given the fact that R&D procedures are now more advanced do you think they will manage to deliver more efficient and successful pipelines earlier to the industry?
Good question. Indeed, the COVID pandemic showed that it is possible to work out innovative drugs and introduce them in a super-fast pace, counted rather in months than years. But that situation was exceptional, and the registration pathway was accelerated by the regulators.
Normally, for biotech drugs, either innovative or biosimilars, the time to market is about 12-10 years or 8-10 years, respectively. Which looks quite long and, to be honest… is long.
In my opinion, the problem is not entirely on the discovery/development technologies. Now we can work quite fast in R&D by using computer-aided discovery platforms combined with high throughput methods and deliver the drug candidates within several months. The point is that new drugs should be tested in preclinical and clinical trials, which are long, risky, and expensive. On top of that, there is a registration procedure which takes 1,5-year minimum. At the moment, there is not a better way available to assess if the drug candidate is safe and effective than by conducting the trials, so I think such long timelines will stay with us for quite a long while more.
It is worth mentioning that the situation is different for orphan drugs, and here we can count on accelerated procedure and time to market.
Using pharmacogenomics, pharmaceutical companies can create medicines based on the proteins, enzymes, and RNA molecules that are associated with specific genes and diseases. These tailor-made drugs promise not only to maximize therapeutic effects. Could they also be used to decrease possible damage to nearby healthy cells?
Yes, of course, this concept of targeted drugs or personalized medicine is quite old now. And yes, the overall idea of it is to increase therapeutic efficacy and minimize overall toxicity. One of the firstly registered drugs – imatinib, is almost 20 years in use. It is true personalized medicine where genetic predisposition to the rare type of cancer triggered this innovation. It is worth mentioning that 5 years of survival for patients with CML increased from about 30% before imatinib to about 70% now. And those patients who will not develop resistance may count on the same life span as the normal population. Isn’t it great?
Now with all those super-fast genome sequencers and AI-aided screening methods, a better understanding of epigenetics, the direction towards personalized medicine is inevitable. The way how we would like to approach the molecular target – whether it is a small molecule, monoclonal antibody, RNA, enzyme or maybe something different is a different discussion. All of those approaches have their pros and cons and the choice of the active molecule really depends on the situation.
Modern biotechnology can be used to manufacture existing medicines more easily and cost effectively?
Yes, that is for sure. A good example is cell line productivity, which determines how much of a given protein (e.g. monoclonal antibody) we can get from 1L of bioreactor volume. At the beginning (30 years ago), it was around 0,05-0,2 grams per liter, and now it can be as much as 4-5 g/L for so-called fed-batch production. Even more if we use continuous process. So, it is easy to calculate that now, instead of 20.000 L bioreactor we can use 1.000 L bioreactor to produce the same amount of drug substance. Such bioreactors can be fitted in an average (in size) production facility, whereas 20.000L giant requires huge installations, which comes with a price.
All of those and other smart developments derive from step-by-step innovations. And all of those are to produce cheaper, safer, faster. I’m convinced we are just beginning in biotechnology.
Unlike most industries in these extraordinarily challenging times, biotech is experiencing significant growth. How DEMO’s investments in biotech are changing the R&D field in Greece?
Biotech already exists in Greece, and I have met a few big supporters. However, there is no company that could develop and produce biotech medicine on a high commercial scale. This is a serious obstacle for the more widespread use of biotech therapies in Greece.
DEMO has the ambition to become the first Greek biotech company which will be able to deliver biotech medicines to the patients in need. This should increase access of the Greek patients who couldn’t get innovative medication either due to the price or due to the shortages of those. Our ambition is backed by considerable investments. DEMO’s Biotech center in Agios Stefanos is under construction and will include research labs as well as pilot production dedicated to the development and manufacturing of biopharmaceuticals. Also, we are creating a scheme to be able to work in collaboration with academic departments and laboratories from Greek Universities with specialization in Biotech or related areas. We hope it will be a boost for some research institutions which will get a reliable industrial partner to collaborate with and to introduce innovative solutions either into the technology or new therapeutic approaches.
I think our investment will have a huge impact for research in Greece. Not only because we create a state-of-the-art biotech facility that will train the future generation of biotech scientists in Greece and that can be used as a platform to test innovative ideas from the academia or other researching teams in the country, but also because we are positioning DEMO and the country in the Biotech community opening up to countless possibilities.
Biotechnology is a start-up business in the Greek drug manufacturers market, that’s why DEMO is planning to invest in a bio-academy within next year. Could you please describe to us the scope of this academy as well as the scientific background of the preferred participants?
Yes, indeed industrial biotechnology is quite specific. Even though we use similar scientific instruments for development like academia, our purpose is slightly different. We are more on the applicative than the discovery side. Whatever we are developing in principle should become a drug one day. Therefore, it must be safe, effective and produced in a reliable, repetitive way. We need also to work fast but still be reliable and effective. All the data which we “produce” may be the subject of audit by regulators. This requires a slightly different set of skills which are hard to foster in academia. That’s why we decided to set up the BIO Academy. When we finalize the program, we will start to recruit. We target at ambitious people with drive for achievements, self-development and not afraid of hard work. We will recruit for different biotech sections like Upstream Process Development –here we will teach how to grow cells and operate bioreactors, Downstream Process Development– for those who will learn how to purify biomolecules and operate complex chromatography and filtration systems; Analytical Development for those who love analytical techniques spanning from bioassays to mass spectrometry.
As for the scientific background, it should be relevant to the future role. Usually, those are graduate students or scientists from the life-sciences, but if we are speaking of future operators in the production facility, those may be also with a Bachelor degree with an overall understanding the biology or technology.
While through tough times the biotech industry is expanding and investors hold high expectations for revenues, how DEMO is planning to focus on its organizational growth in order to meet these expectations?
Research and innovation are businesses of long-term ROI. Therefore, a company that invests in R&D or new technologies needs a strategic plan that will fund this period of research and will help the company get prepared for the future. At DEMO we have done exactly that.
First, we need to set up infrastructure, which are R&D laboratories, QC laboratories, and a production facility. Then we will introduce GMP into the production and QC laboratories. In the meantime, we will hire the right people and will train them to meet quality expectations –it is phase 1– investment. When we deliver the first drugs to the market, we will be able to create some revenues, which will be in about 10 years from now – it is phase 2 return from investment. Then we can talk about the growth and scaling of the business. But for now, we are focusing on establishing strong and reliable foundations because everything will be built on them.
