SotioVyrocniNoviny2020EN pdf verze

Celebrates

ForeworD by rADek ŠpíŠek Dear Colleagues, Exactly 10 years ago, PPF Group decided to em- make it to the clinic. Our (perhaps naive) dream is bark on an adventure in biotechnology research. to try to overcome these negative statistics Long discussions on how to approach these acti- through careful scientific and commercial review vities led in 2010 to the decision to found SOTIO. of the investment and licensing opportunities. The The structure of the company was initially built identification of attractive and promising pro- around dendritic cell-based immunotherapy for grams is even more complicated because the re- cancer. From the beginning, the original scientific ally interesting programs attract also our team from the 2nd Medical Faculty of Charles Uni- competitors that are (yet) difficult to match: large versity in Prague and the Motol University Hospital pharmaceutical companies. The expansion of the was responsible for the scientific aspects of the portfolio of programs led to further significant de- project. The first directors Zbyněk Štěrba and sub- velopment of the company, which was managed sequently Karel Nohejl helped with the manage- (and is still supervised) by Ladislav Bartoníček. ment of the company and with legal and financial For many years, people who worked for biotech- matters. From this time, I remember very well the nology and pharmaceutical companies abroad enthusiasm and great motivation to build the have been helping us to manage programs in va- necessary infrastructure and launch a clinical rious stages of preclinical and clinical develop- program. SOTIO grew rapidly at that time and it is ment, and I am grateful for their motivation and great to see that a large number of people who the hard work they do for SOTIO. I am also grate- joined the company in the first two years since its ful that they pass their knowledge on to people in foundation are still involved in its development. In a record-breaking time, cell therapy laboratories were established, and a clinical program was laun- ched in patients with prostate, ovarian and lung cancers. We now have the results of some of these studies, and the greatest reward is to see that in a number of them, DCVAC treatment led to a significant increase in patient survival. However, from the beginning, SOTIO’s objectives have been more ambitious. The main goal remains to build a company that has a broad portfolio of programs focused on different ways of anticancer treatment. After the initial phase of building SOTIO and adjusting its structure, in the last 5 years or so the priority has Did you been to search for scientifi- know that... cally and clinically attrac- tive programs that SOTIO The production and PPF Group could of one DCVAC takes develop. Statistics show that of the substances 80 man-hours which appear promising (one person 10 working days)? in the laboratory, only less than 5 percent

their teams, leading to an increasing number of support by PPF Group, none of what we have been colleagues who understand clinical development. trying for the last ten years would have been possible to realize. The project, SOTIO as a company focused I am very proud that we launched a phase I clinical on in the clinical development of innovative medici- study with SO-C101 (RLI-15) last year. During precli- nes, is unprecedented in our region and has allowed nical and manufacturing development, we over- a large number of talented people with a background came several difficult periods. The study now runs in biology to work in the field they have studied and in the world’s four best clinical centers and SO-C101 would otherwise be able to pursue only abroad. has the potential for very extensive testing in a wide range of oncological diseases. Last year, we only Let me once again thank you all and reiterate that narrowly missed the chance for partnership for fur- I am very proud of what we have built and how ther development of this substance but it is still our motivated and friendly people at SOTIO are, priority to find a strategic partner for our ambitious striving to achieve our common vision. I wish all plans with this program. The program based on the of you and the company all the best in beating NBE-Therapeutics’ platform is also well on the way. oncology research statistics in the future, and I wish After very interesting and promising results in the that our work motivates us all to overcome new preclinical phase, the program is now moving into challenges and, above all, that it leads to improved the phase of production for clinical studies. If eve- treatment and prognosis for cancer patients. rything goes well, in 1.5-2 years this program could become another SOTIO clinical program. We planned to celebrate our 10th anniversary together. Unfortunately, given the current situ- It is not possible for me to thank everybody by name. ation, this is not possible for obvious reasons. We Nevertheless, for me personally, it is necessary to are not cancelling the celebration; we will have thank Professor Jiřina Bartůňková for her many years it at the earliest opportunity. of cooperation, sharing successes and especially her support in times when things were not going in the I wish you and your loved ones tremendous good right direction. I also have to thank Peter Kellner for health, the chance he has given us and his constant support. Without his vision and the long-term financial Radek Špíšek SoTIo Ceos over time 2010 – 2011 2011 – 2014 2014 – 2018 2018 – now Zbyněk Štěrba karel Nohejl Ladislav bartoníček radek Špíšek

SoTIo AND ITS begINNINgS An interview with Zbyněk Štěrba How long did it take from making the decision to found SOTIO to the moment of its inception? The foundation of SOTIO was a matter of an inte- resting opportunity. Scientists at Prague’s Motol Hospital were conducting research into a product but lacked the financing for it. We first met in Janu- ary 2010, but it obviously took some time to set up an operational scientific, financial and legal model. The company was founded in April 2010. How did the name SOTIO come about, and whose idea was it? My colleague Petr Havlíček, who was also a mem- ber of the company’s board for some time, came up with the name. He would write down various acronyms, ciphers, and letters, and suddenly it turned into “SOTIO”. :-) Do you remember any unusual anecdote or com- Zbyněk Šterba plication from the era of establishment? One of SOTIO’s founders; The world in 2010 was all about the anthrax trials a member of the governing bodies at the in the US and the swine flu that had swept through beginning. He managed SOTIO until the world in 2009 with vivid media coverage. That the first CEO, Karel Nohejl, joined in. was when we came to Tokovo with the idea of building superclean premises to produce medi- entists developed the medicine and the related cines. Panic burst out immediately. People sus- procedures; we never even thought of locating the pected that we wanted to explore hazardous headquarters abroad. In addition, logistics are of viruses and bacteria that could contaminate the key importance for the production and distribu- environment. It was tough explaining that there tion of autoimmune vaccines, so we were seeking was nothing to fear. Why was SOTIO formed in Prague where no similar Did you companies are active? know that... Were you worried about a lack of know-how and Our accounting experts? office processes some Not in the least. Prague 4,200 invoices is an attractive and mo- a year (350 a month, dern European capital and it attracts compe- 18 a day)? tent people. Czech sci-

a location close to an international airport right new employees, prepare the clinical trial design, from the outset. and secure the production. At the same time, we were working on establishing an international How many people worked at SOTIO in the initial holding and addressing a number of related agendas. months of its existence, and what were their Looking at SOTIO today, is it compatible with principal tasks? the ideas with which you founded the company in 2010? When I was handing the Chairman of the Board Ten years ago, I could not imagine how far SOTIO would progress over time, I guess. We position to Karel Nohejl in mid-2011, there were wished for it to become a renowned com- pany with an international reach; SOTIO has about 35 people achieved this goal and become a respected brand today. With that said, back in 2010 we working at SOTIO. Did you thought that we would know the results of several The very first know that... clinical trials in ten years’ time, and we had no employee was Ms. idea how much work, strife and effort clinical Hrabalová, who many We generate trials would take. employees remem- 210,000 liters ber as the chief ac- of municipal waste countant to this day. per year, plus Our principal tasks 73,000 l of plastic were to build clean premises, recruit and 32,000 l of paper? These are original proposals of our logo would you choose any of them instead of the current one?

AN INTerVIew wITh JIřINA bArTůňkoVá Zbyněk Štěrba stood at the birth of SOTIO mainly from the formal side - choosing a headquarter, establishing laboratories… but who was at the birth of DCVAC itself was a team of scientists from Motol University Hospital, led by Radek Špíšek and professor Jiřina Bartůňková. How she got to research of dendritic cells and when the first patient received the treatment? How and when did you encounter the topic Jiřina Bartůňková of cellular immunotherapy and dendritic cells, Head of the Department of Immunology of the and their use in combating tumors? 2nd Faculty of Medicine of Charles University, When I joined the Clinical Immunology Department Chairman of the Supervisory Board of SOTIO of the First Faculty of Medicine in 1983, known as the Faculty of General Medicine of Charles Univer- How long did it take from the first theoretical sity at the time, the topic of my postgraduate stu- idea of using active cell therapy to the actual dies was research into phagocytosis dysfunction. invention of your approach (DCVAC) and then This is how I got to study the cells whose principal to the initial tests in labs and in patients? purpose is phagocytosis, i.e., ingesting and elimina- The first idea came sometime in 1995 and we first ad- ting harmful substances. I learned how to work with ministered the treatment to a patient in 2008. That the cells in a lab environment and I examined what makes 13 years. It should be said, however, that when happens when they work incorrectly. Studying lite- I joined the Institute in Prague’s Motol hospital in 1995 rature on this topic inevitably led me to dendritic cells as the head along with my deputy, head physician because they also belong to a group known as pro- Anna Šedivá, all we had was an 8-bit Olivetti computer, fessional phagocytes. Papers on how to prepare some laboratory glassware, an old microscope, one them in large quantities in a laboratory using perip- D.Sc. and one lab technician. We had to build every- heral blood monocytes (dendritic cells themselves thing – the equipment, material and, most impor- are found rarely in blood) and the first papers on their tantly, a team of competent people who would join potential use in cancer immunotherapy were publis- the project over time. All the while, we had to cover hed in the early 1990s. The topic really thrilled me. treatment/prevention activities, routine laboratory When I became the head of the newly established work and teaching medical students. If we didn’t have Institute of Immunology of the Second Faculty to start from scratch, it would have taken significantly of Medicine in 1995 and could govern the direction less time. With a handful of enthusiastic postgradu- of its research, we focused on this field. ate students, we did experimental work on the project while preparing the paperwork and technical When did you first meet Radek Špíšek? background needed for administering dendritic cells to cancer patients. Daniela Rožková, Klára Socho- Radek joined us as a postgraduate student in 1998. Den- rová, Hana Hromádková, Vít Budinský and Luděk Sojka contributed the most to preparing all the dritic cells and their use in cancer immunotherapy that was the topic of his project. We were working with a re- search institution in Nantes, France at the time and we sent Radek there to learn the methods and develop them further. He approached the topic with a great deal of his own creativity and, having completed his PhD stu- dies, he arranged his own post- Did you doctoral study stay at the know that... most prestigious institution – the Rockefeller University Vials with DCVAC in New York City with the vaccine travelled a distance equal to later Nobel Prize winner 30 trips to the Moon Ralph Steinman. Radek has all over the world taken the dendritic cell as part of the science to a global level. SP005 trial?

documents for SÚKL (State Institute for Drug Con- Does today’s SOTIO meet the expectations that trol) and setting up the superclean premises. Michal you and your colleagues harbored when founding Podrazil was in charge of administering vaccines and it, or has it evolved in a completely different way? monitoring the patients’ clinical status. It has outgrown my expectations somewhat. At the be- ginning, none of us could imagine how complicated the Was it difficult to obtain funding for the initial drug development was – which is where cell therapy steps in scientific research and subsequent belongs to, unfortunately – or how expensive it was. testing at the university and in the teaching I don’t think even the investors at PPF had a clear idea hospital? How did it work? of what it all meant, since that was their first investment We received funds for the project from grant agen- in biotechnology. My conscience is clear in the sense cies, the Teaching Hospital in Motol and the Faculty. that, ever since the start, Radek and I would say that The Motol hospital helped us build our first superc- we were only at the beginning of the research and that lean laboratory compliant with Good Manufacturing we didn’t know if it would work, much less if it ever Practice (GMP) requirements for the production could be profitable. We just believed that this was of cellular products. The seven-year Research Plan a promising direction, and we had done a tremendous of the Ministry of Education provided a great finan- amount of experimenting and paperwork leading to cial boost. It ended in 2009, though, and there was the first administration to patients. We did not white- nothing to follow it. That meant that we would have wash anything, which we often see happening today to dismiss our laboriously built team and let go when looking for investment opportunities, in particular of all the know-how we had gained over time. So, with American biotech companies. We came out into we started looking for other sources of funding. the open and disclosed all the risks at the very begin- ning. I still have a hand-written note that I made for Did you find PPF as the financing partner for the Mr. Kellner, which was a sort of an amateurish SWOT subsequent development of DCVAC as a matter analysis, the pros and cons. We left the decision as to of chance or as a result of an elaborate strategy? whether to found and finance SOTIO entirely up to PPF Fortune favors the prepared mind, as the old pro- shareholders. Also, we have said from the beginning verb goes. Just when we were considering how to that betting everything on a single product was too fund Phase I clinical trials with dendritic cells risky, so we sought additional products that would en- (since the IGA grant that we had obtained for the hance SOTIO’s portfolio. In this respect, I believe we project would obviously not suffice), Mladá Fronta have managed to significantly expand the portfolio, wrote about our research. At the time, PPF was even though certain projects, which we hoped would monitoring research activities in the Czech Repu- be much simpler than DCVAC, were a disappointment. blic in all sectors that PPF could possibly support, And I am worried about the fact that we still continue and that’s how they got to know about us. only spending funds instead of generating them. Do you believe that DCVAC will make it to the SOTIO has grown significantly in the 10 years, market and to patients as part of standard treat- in terms of number of both employees and pro- ment one day? jects under development. Which of the projects We have always emphasized that this is a persona- is your ‘favorite’, aside from DCVAC? lized product that will never be a mass drug such I really favor the RLI (SO-C101) project by the French as Aspirin, and that it is not an omnipotent medi- company Cytune. To me, this is prime evidence that cine. It is a piece in the puzzle that is complex can- SOTIO has become a sophisticated business capable cer therapy. Of course, I would be happy if patients of developing products all the way from lab experi- were given the opportunity to use the treatment. ments to the clinical trial stage with everything that The results of the clinical trials that SOTIO has this entails. I believe that RLI will be an efficient treat- conducted so far suggest that we definitely help ment. I also favor the cooperation with NBE – the an- certain groups of patients. This gives me satisfac- tibody drug conjugate project. Here, too, I am convinced tion, knowing that our effort has not been wasted. that this will yield efficient modern treatments.

AS yeArS go by... SOTIO is celebrating the tenth anniversary of its foundation, but the roots of DCVAC as we all know it date even further back. Look at a timeline of the crucial milestones and SOTIO’s development and progress over time. 2010 2000 Scientists from University Scientist from University hospital Motol Hospital Motol joined forces developed new treatment method using with investors to build ACI based on dendritic cells biotechnology company SOTIO 2011 2012 Clean Laboratories in Prague started to work. Biggest First Phase II clinical trial with medicinal of its type in Europe! product DCVAC started for patients with prostate cancer, unique event 2013 for Czech company in this field First Phase II clinical trials SOTIO becomes part for patients with ovarian cancer, of PPF Group medicinal product DCVAC 2015 Cytune Pharma from France 2014 affiliated with PPF and cooperates on preclinical and clinical development 2016 Pivotal international Phase III clinical trial VIABLE with medicinal product DCVAC started for patients with prostate cancer Investment 2017 and later cooperation with Swiss NBE-Therapeutics License and collaboration 2018 agreement with LDC from Germany Full acquisition Investment to Cellestia Biotech of Cytune Pharma (Switzerland) 2020 2019 Final analyses Preparation of new Phase III clinical of Phase III clinical trial with DCVAC/OvCa trial VIABLE (SP005)... Start of Phase I with SO-C101 (RLI-15) Opening of SOTIO Biotech AG Investment to Autolus Therapeutics (UK) in Switzerland

SoTIo Today: Development pipeline product Indication preclinical phase I phase II phase III partner CeLL TherApy DCVAC/pCa prostate cancer DCVAC/ovCa ovarian cancer in prepa- ration DCVAC/LuCa Lung cancer IL-15 SUperAgoNIST So-C101 oncology IMMUNoCyTokINeS So-C108 oncology ANTIboDy-DrUg CoNJUgATe So-N102 oncology So-N106 oncology SMALL MoLeCULe INhIbITor So-L103 oncology Number of references to SoTIo in the media * 1.1.-14.4.2020 3212 Source: Meltwater 1885 1868 1618 1421 681 539* 2014 0 1 96 498 2015 2016 2017 2018 2019 2020 2010 2011 2012 2013

INTerVIew Libor Táborský The man who founded SoTIo in beijing How long did it take from making the decision to found SOTIO in China to the actual moment of its inception? Can you compare this to how long it takes founding businesses in other countries where SOTIO operates today? It depends on what we take as the ‘actual moment of its inception’ – if we take the legal act of esta- blishing a firm, it really was a record-breaking time for China: some five months. It took an additional year and a half from finding a suitable location for laboratories to the moment the project was completed, and the occupancy permit issued, which can also be regarded a record-breaking time. Almost nobody believed or even hoped for this ti- ming to be a reality, including those of us in charge. Libor Táborský One of SOTIO’s founders in China and its CEO Once we had signed the contract on the develop- for several years ment of the labs, nothing would happen for the Do you remember any unusual anecdote or com- plication from the era of establishment? next few months at all, although we urged the con- Early on, after Shanghai-based CEFOC was selected as the contractor for the clean rooms, our team tractor to observe the nine-month deadline for com- went to a meeting with them – Luděk Sojka as the Technology Transfer Manager, David Greco of pletion. Allegedly, they were thoroughly contem- LABOX, Tomáš Žáček of PPF in charge of project implementation and control, and myself. A prob- plating and preparing our Beijing project in the lem occurred when the contractor’s technicians, with their modest knowledge of English, could not quiet of their offices in Shanghai, perhaps following understand our requirement for the supply of a ‘washable gypsum wall’ – you know, walls made the slogan, “Never put off till tomorrow what you of plasterboard that you could actually wash. Tomáš Žáček began ‘losing it’ and started tapping can do the day after tomorrow…” The number of the office wall, repeating in “GYPSUM, GYPSUM, GYPSUUUUM!!!” with increasing volume. When workers on site only started increasing exponentially gentle tapping turned into nervous banging on the wall, another person emerged from the next shortly before the planned date of completion, their room and asked: “Can I help you with anything?” When Tomáš said emphatically, “NOTHING, only working hours eventu- a GYPSUM WALL!”, another Chinese employee got an idea and asked: “PAPER WALL?” – “YEEEEE- ally extending to about EEEES, VERY SMART GUY!” What we didn’t know at the moment was that only half the problem was 25 hours a day…!!! The building turned into a swarm of sometimes very confused wor- kers, and the deadline was actually met. Well, except for the fine-tu- ning of the programs for monitoring the super- clean room system; then again, the fine- tuning has been con- China’s highest building called ‘the bottle opener’ tinuing basically to this day...

solved. The next problem was explaining the word button if the user’s flatulence is, erm, ‘fragrant’…” Add to that the muted colored light that lit up when ‘washable’. Repeated over and over, louder and lou- you opened the door to the very pleasant private room. After that, we unfortunately didn’t get to talk der, with additions such as “WASHABLE, OH MAN… much because the team members repeatedly took turns in the restrooms, filming the LOCAL BATH- ”, the word still remained a mystery. Then Tomáš ROOMS on video using their mobile phones. started illustrating his point by actually licking the How difficult was it finding employees and training them for the highly complex production wall. When a quarter of the wall had been licked of our medicines? Surprisingly enough, finding specialist biologists for thoroughly, someone thought that this could mean the lab operation was not as difficult as it was finding literate and English-speaking operations ‘washable’ and started making gestures of washing maintenance workers. This requirement has been and remains a conundrum even for the best-known one’s hands and pointing to the wall inquisitively… and most respected international headhunter firms. BINGO!!! And so, after about three hours of discus- Did the newly recruited Chinese colleagues trust an employer from the Czech Republic at the time? sion, we finally got our ‘washable gypsum wall’ Our Chinese colleagues have always trusted a Czech employer. I think, though, that this has point across. Another story involves the Czech little to do with the renown of the Czech Republic – rather, it has to do with our noses. We Europeans members of our team and discovering new (to us look all the same to the Chinese – we’re not ‘white’ to them, but they refer to us as ‘long noses’. anyway) technologies in China. We were invited to And whatever a long nose does is always good. :D a dinner held at, I think, the 95th floor of Shanghai’s Is today’s SOTIO in China compatible with the ideas with which you founded it in 2012? tallest building at the time, also known as ‘the I’d say it certainly is in terms of technologies, exper- tise and capacity, and that’s obviously promising for bottle opener’ (see the image). The team included the future. I wish the entire SOTIO Group, including SOTIO China, a bright and promising future full of Czech engineers and medical doctors – Messrs. successful inventions and new products for patients! Táborský, Sojka, Greco, and Mrkvan. Their biggest discovery was when one of them went to the local bathroom. He came back with eyes popping out, saying: “Wow, did you see the toilet??? Self-washing, heated, with adjustable temperature of the seat… and also with adjustable temperature and inten- Did you sity of the water that know that... washes your butt, with an air drier adjustable for drying temperature and There have been intensity, a ‘privacy’ but- 145 contractual ton that plays the sound apheresis centers of either music or a to- for the SP005 study ilet flushing when the (94 in the EU and 51 in the US)? user is flatulent, and fi- nally the ‘deodorizer’ SOTIO offices in Beijing Official opening of SOTIO CN in June 2014

AN INTerVIew wITh MATT pLAUD We were also curious about our overseas office - in Boston, USA. Therefore we talked to Matt Plaud, as long-term CEO of SOTIO US. SOTIO celebrates 10 years, you are with SOTIO Matt Plaud, CEO, SOTIO US also many years. Could you imagine at the moment when you joined SOTIO how far the parking lot that covered by advertisements. The company has gone since then?  commuters leaving the train station had no idea When I joined SOTIO seven years ago it was exci- that they were within six feet of a tiger, however our ting to be a part of a new company with strong, office could see from the third floor. motivated financial backing.  The vision of grow- ing from a startup biotech into a full-fledged How difficult it is to find employees in the pharma company seemed so far away.  Yet, here US/Boston for company which originates we are seven years into my time here and I have in Central/Eastern Europe? (Czech Republic seen the company grow and expand, gaining new is often confused with Chechnya in the US…)  staffing and expertise, working on a variety of pro- Staff in the US are typically more concerned with duct lines, and making enormous strides towards the mission of the company, where the financing that vision.  I am proud to be a part of this process is coming from, and the size of the company.  The and to have contributed towards that goal. only difficulty I have seen is in trying to attract doctors who are comfortable in “big pharma” to Do you have an experience or a funny story you come to a smaller company.  will never forget? The Boston office is in a prime location in the city What would you wish to SOTIO for the next for interacting with a variety of people and seeing a variety of things. One of the most memorable mo- 10 years?  ments was when the circus came to town and was performing across the street at TD Garden.  To an- I am confident that PPF can achieve their vision of nounce their arrival they closed a major street and paraded elephants up and down the thoroughfare SOTIO becoming the Czech Republic’s first marke- to create a buzz and sell some tickets. The neigh- borhood was not told that this would happen. So ted pharma company. We have come so far in these seemingly at random one afternoon we are at our desks or in our meetings and the sound of elep- last few years that I am sure, with PPF’s support, that hants calling to one another breaks the normal sou- nds of the city. One first questions their sanity and we can bring the DCVAC platform to market in more doubts they heard what they did until it repeats or is confirmed by others. Then to look outside and than one indication as well as get see elephants on parade in the middle of the city. It was quite the site. What was even more enterta- through the regulatory process Did you ining was that the tigers were in a fenced area in the with our sister companies. I for know that... one look forward to growing Elephants in front of SOTIO in Boston. with SOTIO as we transition We administered from a company without mar- about 24,000 keted products to one with a vast portfolio of treatments injections to patients as part of all our serving a variety of needs clinical trials? in our global community.

SoTIo ThroUgh The eyeS oF CoLLeAgUeS How do your colleagues see SOTIO, what do they wish for the company for the years to come, and how do they rate Mr. Babčák’s cafeteria, which we all know so well? We got curious and asked a few of you. klára Sochorová production really started on the same day) – when the order came, the product was released and the Senior Quality Compliance Manager first dose was distributed for application… Could you imagine 10 years ago that SOTIO Everything we prepared for became real. We would become what it is now? hoped there was nothing that we might have Not at all. When we built the clean rooms and forgotten.Fortunately everything worked the way designed the batch numbering system, we did not it was supposed to, except for minor details. even think that DCVAC could have any indication other than prostate carcinoma as planned, much Will Babčák receive a Michelin star?  less that we would be the sponsor of a clinical trial If it would be granted in the ‘Cafeterias that with any drug other than DCVAC. Or in our plans serve hundreds of lunches per day’ category, the part of the second floor where Process Deve- he certainly would. Memories of an on-premises lopment laboratories are now located should not canteen in the government sector still frighten be modified too much, because it would only be me to this day. used temporarily and then vacated. We have never left thit part of the building and since that we What do you wish SOTIO for the next 10 years? extended to 3th and 4th floor. I wish SOTIO to have its own products on the Any memory associated with SOTIO which you market and to have employees who really care will never forget? about both - patients and the medicines that we It would be a sequence of memories and the provide to them. And I wish Radek and Professor atmosphere of the times rather than one specific Bartůňková to  win Nobel Prize for DCVAC. experience. I remember the first two patients (the Klára Sochorová, Daniela Rožková, Petra Dobešová and Zuzana Krátká planning in the early days of SOTIO.

SoTIo ThroUgh The eyeS oF CoLLeAgUeS Tomáš Scheiner head of Clinical project Management Could you imagine 10 years ago that SOTIO would become what it is now? Actually, the way I imagined ‘today’s’ SOTIO is completely different. When we were celebrating our first patient in SP005 in May 2014, I dreamed about beating the merciless statistics of clinical trials in oncology with Stapuldencel-T registered and on the market. When I see the results of our DCVAC, I believe this is still ahead. In fact, I dre- amed of a ‘single medicine firm’, as the case often is with small biotech businesses. But the way that we are successfully rolling out other programs – RLI, NBE, etc. – and more and more new trials – that’s like another universe to me. Any memory associated with SOTIO which you will never forget? There are a lot of intense experiences. For example, I will never forget Matt Plaud of SOTIO US telling us at the SP005 meeting that the vial with DCVAC for a patient in the US was on vacation, having fun on a beach in Brazil. Due to an error at the airport, two parcels got inter- changed so the hospital actually received aircraft components instead of DCVAC . Will Babčák receive a Michelin star? It would be a hassle if he did – just imagine having to book your table months in advance…  Anything you would like to wish for SOTIO for another ten years? Any vision? I wish for us all that there are always a lot of excited, Did you hard-working and smart know that... people who are hungry for doing great science, Our company fighting cancer and consumes approxi- helping patients! And, of course, that DCVAC mately 177 kilos (and not only it) is regis- (390 lbs.) of coffee per year? tered soon!!!

SoTIo ThroUgh The eyeS oF CoLLeAgUeS Daniela rožková Quality Control & process Development Manager Could you imagine 10 years ago that SOTIO would become what it is now? Only in a crazy dream  SOTIO has been really am- bitious in recent years and has been quite vocal about it, but early on certain things were hard to imagine, such as the Phase III clinical trial with DCVAC/PCa. Any memory associated with SOTIO which you will never forget? There are a lot of them since I have been with SOTIO for nine years. Business trips to the US were a great experience, such as an audit at PCT when we were try- ing to roll out production with them, or the blitz trip to a pre-IND meeting with the FDA (going there one day, attending the meeting next morning and going back the same day). That was incredibly tough, but I’ll never forget it indeed. On a personal level, certain team- building sessions were unforgettable – such as the last one with the QC Team where, drenched with rain and freezing on the top of Mount Říp, our nation’s mythical mountain, we had to endure the crushing truth that our nation’s mythical Forefather Czech never existed… The only thing left to do afterwards was come to terms with that with the help of many bottles of wine.  Will Babčák receive a Michelin star?  I will always stand by Babčák. For an on-premises canteen, the quality is quite good, and the stan- dard and size of the place is acceptable. Last but not least, Ms. Babčáková’s friendly and caring attitude always assures me that I’m ‘back home again’. Also, having him so close is genius. We should be more grateful for having him.  Anything you would like to wish for SOTIO for another ten years? Any vision? I wish for SOTIO to finally have some of the tested medicines registered in the next 10 years. If we move on to that stage, it will be a huge new expe- rience for everyone, and I am looking forward to it! I also wish for SOTIO to give more support to ‘primary research’, which will result in original SOTIO technologies that could pave the way for the development of more medicines.

SoTIo ThroUgh The eyeS oF CoLLeAgUeS Jitka palich Fučíková would be a dream come true for us all. I also wish for SOTIO to be able to attract new experts with the Senior Scientist ambition to achieve big goals and also to have energy and enthusiasm enough for the people who have Could you imagine 10 years ago that SOTIO been working at the company from the very beginning would become what it is now? and have helped make SOTIO what it is at this point. Ten years ago, in a lab in Motol, I could not ima- gine in the least what would be built thanks to the initial excitement among a handful of people. Scientists’ and doctors’ efforts in pushing the results of scientific work towards patient treat- ment has helped make SOTIO the contemporary biotech business it is. Any memory associated with SOTIO which you will never forget? I fondly remember the day the first DCVAC vaccine was made for the first patient. For me, it was a pivotal moment that only a small percen- tage of scientists are lucky to experience in their lifetime. I am immensely grateful for this. Anything you would like to wish for SOTIO for another ten years? Any vision? Of course, I wish that some of the medicines that SOTIO is currently developing will be registered. That Christian Frantz a lot over the last eight years. And if Babčák gets one star, then Lighthouse should get three stars. Ip Manager Anything you would like to wish for SOTIO for Could you imagine in 2013 that SOTIO would another ten years? Any vision? become what it is now? Successful phase III and market entry with DCVAC, Certainly not – back then, we were in the thick RLI, ADCs…Offices with windows that can be opened, of Phase II DCVAC/ OvCa and DCVAC/ PCa, too no more dress code and more often BBQs on the terrace far away from anything like Phase III, Cytune, (or being allowed to work from the terrace in summer). NBE and so forth... PPF’s financial generosity and involvement remains a mystery to me. Any memory associated with SOTIO which you will never forget? I signed my contract on the 10.11.12 (more like ‘easy to remember’ than ‘will never forget’). Christmas parties and Sports Days and last but not least Corona home office. Will Babčák receive a Michelin star? At least one star, it must be the most popular (or the cheapest?) restaurant in Prague based on how many people come for lunch. It actually improved

SoTIo ThroUgh The eyeS oF CoLLeAgUeS Luděk Sojka serious here, I also fondly remember the first SOTIO party! We were celebrating the birth of several children Chief Technology officer together, and the happy dads invited the entire company. A tiny pub in Prague’s Vinohrady neighbor- Could you imagine 10 years ago that SOTIO hood was big enough for the entire team back then! would become what it is now? You certainly couldn’t do it that way today. In truth, 10 years seemed like a very long time then. It passed incredibly fast! In the beginning, we were all Will Babčák receive a Michelin star?  thinking mostly about building the labs to produce I thought he had won one already?! DCVAC and getting it to as many patients as possible. SOTIO was being built as an entirely new company; it Anything you would like to wish for SOTIO needed to establish the quality systems from scratch for another ten years? Any vision? and everything else required by regulatory authorities. One product on the market with an established com- It was hardly imaginable back then that, ten years mercial production and logistics network; one pro- down the line, we would have several other and enti- duct at the market registration stage; and at least two rely different products at a pre-clinical stage and an more licensed to someone else, thus obtaining more entirely new investigational medicinal product tested experience and renown. Personally, I wish that we in Phase I clinical trials. None of our products are on also produced other cellular therapy products for the market yet, but I still see what we have built in Prague other companies. So then we could say that as well (and elsewhere) in the ten years as a huge success as spending funds, we also earn them as a business. and an even greater and totally unique experience. Any memory associated with SOTIO which you will never forget? Since I was in charge of building the production labs in Beijing for some time, I will certainly never forget the sheer excitement, drive and overall commitment of all our colleagues who were on the project with me. Some of them are still with SOTIO today and I believe they have a lot to remember too. To avoid getting too pavla Vašíčková Supply Chain Coordinator Any memory associated with SOTIO which you will never forget? I have a wealth of experiences involving SOTIO, but the greatest one would be the 2016 Christmas party when Lenny Kravitz played for us to listen and dance to :-) Will Babčák receive a Michelin star?  Yeah, sure, whatever! :D In a sci-fi novel where mankind eliminates the sense of taste through evolution, he stands a tiny little chance. Anything you would like to wish for SOTIO for another ten years? Any vision? I wish SOTIO primarily patience during clinical trials and medicine registration procedures.

SoTIo ThroUgh The eyeS oF CoLLeAgUeS gabriella Lukács Senior Clinical Data Manager Any memory associated with SOTIO which you will never forget? I cannot really highlight one specific event. There are plenty of nice memories from all the years that I spent here which made my life ‘richer’. I am grateful for my colleagues, their support and that I can be part of this team. Will Babčák receive a Michelin star?  If they would give the Michelin star based on the creative naming of the meals or based on the diverse and unexpected usage of cumin then our Babčák would definitely be awarded... Anything you would like to wish for SOTIO for another ten years? Congratulations on the 10th Anniversary. I wish it success in all the set goals. I wish for it to continue the way to grow and achieve the final aim to help patients. pavlína Čadová Will Babčák receive a Michelin star?  I’m not a great fan of Babčák but I know some col- Senior Accountant leagues who would certainly give the Michelin star to him. In the meantime, the rest of us can explore Could you imagine when you joined that SOTIO how other competitor restaurants fare. would become what it is now? When I joined in 2013, SOTIO was a small enter- Anything you would like to wish for SOTIO for prise just rolling out its first studies; a company another ten years? Any vision? full of people who were working with excitement, I wish for SOTIO, rather immodestly, to bring all but, like me, a lot of them had no idea how long the trials to a successful end and for its medicines and difficult the journey was from the initial idea to be used for treatment all over the world. to the market launch of a medicine. It is genuinely great to see how the company has progressed over the seven years and earned its place in the sun, becoming a major biotech firm with interna- tional success. Any memory associated with SOTIO which you will never forget? I cannot remember one specific experience. SOTIO is a company where I have met many great people who I love and with whom I like spending my time outside work. If I were to mention some- thing specific, it would be the Christmas parties – they are always held in special places and feature exquisite guests.

SoTIo ThroUgh The eyeS oF CoLLeAgUeS Martin Vodák from external companies that we interact with that business Development Manager our questions and our ideas are great and sensible, that I joined SOTIO in January 2012 and the company we are thinking in the right has indeed changed and moved forward in the direction and that they eight years since. When I joined, SOTIO had been in would very much like to work existence for some time already. The clean labs had with a team this knowledge- already been built, the production of a vaccine for able. That is when I fully re- the initial prostate trials was in progress and the alize that I am proud to be part of SOTIO. The clinical trials in the Czech Republic were already company has progressed incredibly over the years underway. In addition to the vaccine production thanks to its activities with DCVAC as well as through team, there was a well-established science team cooperation with companies such as Cytune and that came mostly from the university environment, NBE. Working with these companies meant our team as did DCVAC itself. DCVAC was the only techno- started to work with entirely new and unfamiliar logy in SOTIO’s portfolio at the time and understan- technologies whose technical complexity was out of ding dendritic cells with the ability to produce them our comfort zone – this was no longer our DCVAC were the company’s core asset. Other skills such as technology which we understood perfectly – and this designing complex clinical trials, more detailed pre- is precisely the reason why we have learned so many clinical development, regulatory expertise and new things from these collaborations and why the others were completely lacking at the time… teams across SOTIO have so well expanded their ca- It seems quite obvious looking back today. pabilities. It so happens that over a certain period of time the company eventually recruits people who Since then, the company has moved forward immen- are a good fit with the company, who actually do a great job instead of just talking about it, and who are sely. It has solidified and extended its scientific team a pleasure to work with. These people are building the company, step by step, and SOTIO’s abilities already and its understanding of dendritic cells and impro- now outperform many other biotech companies. ved DCVAC production so that it is currently ca- What comes next? I believe that we will continue to grow and to build our expertise in various fields of me- pable of responding flexibly and supplying the dicine development. We are a sort of ‘unicorn’ in the Czech Republic as well as in the broader geographic potential medicine for clinical trials across the globe. region. I am convinced that SOTIO will keep on se- eking, recruiting and retaining excellent new em- SOTIO of 2012 would not have managed that at all. ployees while appreciating the people who have helped it to get where it is now. Last but not least, I be- If we could travel in time and ask the people at lieve that, even though biotechnology and pharma- ceutical development are among the riskiest of SOTIO of 2012 a set of questions regarding the de- industries, we will eventually succeed through our sy- stematic and excellent work. If we don’t succeed with velopment of a new medicines, questions that SOTIO our first product, we will do so with our second, third, fifth… Importantly, SOTIO will, just like it did until now, 2020 deals with on a regular basis, most people endure, learn from the best, build skilled teams, try new things, don’t give up easily, and grow. I am happy to would not know what to answer because the people contribute with my work to this one of a kind story. with that particular expertise were simply not at SOTIO at the time and such matters used to be dealt with through consultants. We can say that when we ask an external consultant for advice now, our team is often just aiming to confirm the internal opinion that we have already arrived at Did you ourselves. It is great to see know that... how our internal opinion is aligned with that of exter- petr Šrytr from IT nal consultants who are runs on average four the best in their fields. kilometers (2.5 miles) SOTIO has succeeded in in SoTIo’s corridors recruiting and retaining many skilled people. I am in a single day? always pleased to hear

bUILDINg The LAbS AND reFUrbIShINg The CLeAN preMISeS The establishment of SOTIO involved the building of laboratories. Once a suitable site was found, preparatory work got underway. The development started at the turn of 2010/2011, and this is what it looked like at the time. Production lab (Class B Corridor in Clean Space 23 Technical corridor around clean room) – view from (Class C clean room) clean space – western part the lab towards the per- sonnel and material lock The appearance of the labs has not been modified development and growth of our company has shown that it would be useful to have two indivi- substantially since they were built in the MUZO dual, fully separated sectors of clean production rooms in the future. Such separate sectors can building. Several changes took place in the produce two different products; this would not be possible within one large sector, which is what the TOKOVO building, however – for example, QC labs production clean rooms were prior to the remodel. The completion of all the shutdown work required (PCR) got remodeled; the dispatch room was a total of 63 days of cooperation with a total of 14 external companies. In addition to the remode- formerly used as a conference room (until 2014); ling, the clean rooms as well as the related and an- cillary systems, equipment and devices underwent and the Process Development labs came into a total of 260 preventive maintenance routines, 92 calibration routines, 114 qualification routines being at the turn of 2014/2015 through the remo- and eight statutory inspections. The validation and calibration documentation that had to be deling of offices, with final touches in terms of reviewed involved 242 documents for a total of almost 10,000 pages. The remodel included, equipment taking place in 2015/2016. A scheduled among other things, the elimination of a laundry room, with laundry currently being outsourced, shutdown of the clean rooms is and many other modifications. Take a look at how the remodeling progressed. undertaken every year. The Did you most complex and exten- know that... sive shutdown so far took place in late 2018; it las- ted for a full 63 days. SOTIO generated The reason why the 16 metric tons shutdown took two of laboratory months was that the waste in 2019? clean rooms were remo- deled. Why remodel them? The constant

Refurbishment Clean rooms modifications Newly built Section 1 Newly built Section 2

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