FOR LIFE

She’s alive. All hope seemed lost, and yet she lives. A sixty-two-year-old Parisian had been diagnosed with seemingly irreversible and fatal skin cancer, but has now even started to work again. Professor Radek Špíšek, as a scientist, tends to be skeptical about miracles, but this woman’s healing makes even him gasp, “Unbelievable!”

The astonishment expressed by the head of the PPF Group biotechnology company Sotio is a pithy comment on the fate of a French lady who had been diagnosed with skin cancer the year before last and had not responded successfully to any treatment options. Surgery, radiation, chemotherapy, immunotherapy... nothing had worked. It was at this point that the patient received SOT101, a treatment being developed by Sotio that was in what is known as Phase I clinical testing. This is the initial phase of the three that a new developed therapy must go through on its way to being recognized as a medicinal product, and at this early stage, it is applied to a very small number of patients and is not expected to have a significant therapeutic effect; rather, it is a matter of investigating the proper dosing of the product so that any deleterious side effects do not outweigh the benefits. “But after the woman received SOT101, the tumor began to shrink dramatically,” explains Špíšek. “Four months down the line, it started to grow again, and that is when we combined our drug with another from Merck. Though Merck’s drug had not proved efficacious on its own in a previous stage of treatment, we believed that the two products, if combined, might work. We were right: the tumor began to shrink again, and imaging last June showed that the lady had no signs of skin cancer or metastasis in other organs. If we hadn’t done what we did, she may not have been alive now.”

Is there anything more heartwarming you could want to hear? There is surely no way you have read more terrific news today, and perhaps any time in the last few days. To be sure, Professor Špíšek is quick to quell the euphoria by noting that no conclusions can be drawn from a single case, but he also points out that, even in this initial phase of the SOT101 trials, a positive clinical response has been recorded in six out of twenty-five patients, which is a high percentage. The news may have come from Paris, but it illustrates the actions and ambitions of a company headquartered in Prague. Sotio is intent on developing and marketing an original cancer treatment. This ambition costs billions, but if the company pulls it off the returns could run high, not to mention the fact that potential profits would also sparkle with global prestige. Such fanfare is still far off, but under Špíšek’s guidance last year the company came that much closer, with the CEO himself describing 2021 as a breakthrough year.

Why do you think that?
We are successfully implementing all the plans we set ourselves at the beginning of last year. This progress is certainly not the norm in the pharmaceutical business. All three of the anticancer drug development programs we are running have entered or will soon enter various phases of clinical trials.

Let’s try to look at each program in turn, starting with the product that helped the French patient.
We consider this product to be our flagship. It’s based on a protein called interleukin-15, which we all have in our bodies, and which triggers white blood cells into attacking cancer cells. We improved this protein quite significantly, strengthened its functioning perhaps a hundredfold, and two years ago we started Phase I clinical trials with it, in which we searched for – and found – the optimal dose that can be administered to a person to kick-start the immune response without causing them harm. As we have already mentioned – and this was also discussed at expert international conferences last November – we saw clinical responses in patients as early as Phase I, when tumors shrank or the disease was stabilized. This result prompted our owner, PPF Group, to move SOT101 to Phase II.

The product helped the French woman in her battle with skin cancer, so is this the type of tumor it works on?
We will test its efficacy on liver, lung, prostate, ovarian, and kidney tumors, so we're looking at a relatively large group of solid tumors, where there is considerable room for improvement in oncology. Phase II has already begun for SOT101. On top of that, last month we struck a deal with one of the world’s largest and most successful pharmaceutical companies, Merck, which has come up with the most efficacious cancer immunotherapy product on the market to date. This is a huge and crucial agreement for us because it means that we will be testing our treatment in combination with their product.

Why is it such a big deal?
When Merck looked at our Phase I data, the product was so attractive to them that they linked their name to it and provided support for Phase II. The idea is that we will get a Merck drug worth close to $50 million to combine with our product. That alleviates the financial cost of the study considerably. But it’s not just about the money; the acclaim of the Merck-Sotio partnership is also great news for our international reputation.

Sticking to the money aspect, how much will the Phase II clinical trial cost?
Merck’s contribution covers about half the cost.

So we’re talking a hundred million dollars in total?
A little less. The study will encompass more than 300 patients meeting precise criteria that include not only the type of disease, but also the stage it is at and previous treatment.

How long will it be before the study yields results you can work with?
That’s hard to estimate, but let’s say three years.

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Away from biotechnology, Radek Špíšek loves the snow and skiing. More precisely, the CEO of Sotio is a cross-country skiing enthusiast.

He takes part in events such as the Jizerská 50 (Jizera Fifty), covering the race’s 50 km in about three and a half hours. That’s quite a trek, yet it pales into complete insignificance compared to the development of a new drug. And it is far from certain that the finish line will ever be reached. “Exactly,” agrees Špíšek. “As things stand, by entering Phase II we have moved SOT101 from an eight to ten per cent chance of success to between fifteen and twenty per cent.”

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That’s impressive progress in your line of business, isn’t it?
In terms of how the program is valued, yes, but from the investors’ point of view it remains a high-risk project. It’s always a case of will it, won’t it? A product can’t be 50% or 70% successful. It’s all or nothing.

Am I correct in assuming that investor interest grows as the hope surrounding a product in development mounts?
The issue of what type of investors are putting money into biotech is really complex. Different types are eyeing different levels of risk and different levels of potential return. You get this whole slew of investors channeling cash into early preclinical programs, even though the odds of success are minuscule, a few per cent. They tend to be investment funds looking to diversify their investments. But to answer your question: when it comes to programs with promising clinical signals, the investors are overwhelmingly big pharmaceutical companies, which buy the programs for their portfolio and take over their development and, if they reach that far, commercialization.

How difficult is it to actually get a developed product into centers where clinical trials can take place?
Starting Phase I is the most complex part, when you have something in a vial that you’re actually giving to a person for the first time in human history. You have no firm idea whether it’s doing any good. This validation will take a long time, and you have every reason to worry that it might cause harm.

Phase I is major-league medicine and a matter of great prestige because so few centers in the world are dedicated to it. There are two or three in Europe, five in America, and every pharmaceutical company that enters this phase needs to somehow “sell” its program in these centers. I would liken it to student exams: the moment we have a program ready for Phase I, we hawk it to these institutions, present it to them, and they basically put us through the wringer. They want to know as much detail as possible so that they have a solid basis for their decision.

How many fail this test?
I can’t put a figure on it, but the competition is huge. We are competing with big pharma companies, behemoths, so the fact that a more or less unknown company from Central Europe has reached Phase I is a tremendous feather in our cap.

So getting a product to the second and third phases is then easier?
It’s easier to reach Phase II. The moment Phase I confirms that we have patients who are responding positively, we can venture to more hospitals, but even at this point we’re still talking about academic, university-type facilities. By the final Phase III, in which hundreds and sometimes thousands of patients are definitively enrolled to see if the product really does help and has a chance of becoming a treatment, getting the program into hospitals and their oncology clinics is usually more straightforward. Doctors realize that investors who have decided to embark on the extremely expensive Phase III must have good reasons to do so, and as such – for the sake of their patients – they are happy to include a program like this in their activities.

Will SOT101’s Phase II also be conducted in the Czech Republic, i.e. on Czech patients?
We have been at pains all along to include Czech centers in the prestigious line-up of centers carrying out the studies. In the program we are discussing here, we have already managed to include the Masaryk Memorial Cancer Institute in Brno in Phase I, and we will continue there with Phase II. As the study expands, the plan is to involve other Czech centers.

I don’t want to jump the gun, but if the product makes it past Phase II, advances to Phase III, and everything works perfectly at that point, when will you be able to break out the bubbly and announce that you have a new treatment?
We have drawn up timelines and if we’re really, really lucky, we may well know the outcome for some cancers in 2025. Though if I were being realistic I’d push back the forecast by a year or two.

Could the treatment be on the market by then?
The way I see it, we will submit an application for the product we have developed to the drug regulatory authorities in Europe and the US, which can approve it as a medicinal product. The regulators have about a year to review an application.

It seems we got stuck on the first of the three programs that Sotio is sending for clinical trials, didn’t we?
That’s what I was just going to say. So another group of Sotio’s programs that it talks about publicly...

Hang on, you have programs that you don’t discuss publicly?
We do not publicly disclose information about early-stage programs, when the likelihood of a product reaching the clinical trial phase is very low.

Let’s move on to the second product that will now be entering the clinical phase.
It’s an antibody-drug conjugate (ADC) technology platform. Basically, it’s an antibody that you can make in the lab and you can get it to target what you want in the body. People currently know about antibodies in the context of covid, but that’s not something we’re targeting. What we have is an antibody that can find a cancer cell in the body. We bind a few molecules of an extremely toxic substance to it, which the antibody delivers directly to the cancer cells and destroys specifically those cells. We now have a program for which we submitted an application to the US Food and Drug Administration in December as we seek approval for a Phase I clinical trial on a treatment that could work against stomach and pancreatic cancer. We plan to start the first clinical trial in March. For a biotech company like Sotio, this is a big deal: three years ago, fifteen people drew a molecule on a piece of paper, which then went through complex testing in test tubes, mice, and monkeys, and now it looks so promising that it’s worth trying on patients.

In connection with this ADC, Sotio has signed an exclusive licensing and option agreement for products from the South Korean company LegoChem (LCB) at a price that could be north of a staggering $1 billion.
That would be the case if all five products for which we have purchased rights from the LCB were to reach the market.

As things stand, you have to pay LCB $29.5 million.
We like ADCs and there are multiple ways of attaching them to a molecule. At the current juncture, no one knows which way is best, so we have made arrangements with a South Korean company that has patented one of these approaches. In addition to the two products we already have, this allows us to add up to five more products based on their technology to our development portfolio.

And what is the third program you have readied for clinical trials?
In August 2020, after a two-year search, we found a program falling into the category of what are known as CAR T cells. In Czech, we have a play on words with that technical name, calling them “carts”, i.e. “tiny cars”, and there is something to that: you take white blood cells from a cancer patient, genetically modify them in the laboratory, stick a protein on their surface that is designed specifically to find the tumor cell and that – like a little car – delivers the white blood cell, a T-lymphocyte, to that tumor cell so that it can be killed. This method has proved a great success with blood tumors, but has yet to work in the solid tumors that prey on humanity the most. In Cambridge, MA, we have acquired the BOXR CAR T cell platform from Unum Therapeutics as it has very promising data specific to solid tumors. This was during the biggest of the lockdowns, so we were unable to be there in person. We had to rely on videoconferencing for everything and, despite a great deal of skepticism on my part, we managed to build a good team there. And because we have a lab in Prague where we can produce cell therapies very well, in the space of just one year – that’s a lightning fast time! – we successfully prepared everything we needed to make CAR T product as part of a clinical trial that was granted approval for liver and lung cancer patients in November. We will start enrolling them in Phase I in February or March.

How much did it cost to acquire the BOXR platform from Unum Therapeutics?
$11 million in all. If the program moves forwards successfully, there will be further payments.

In Petr Kellner, we have lost someone who lived for Sotio for ten years and did all the decision-making here.

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Throughout the interview, Radek Špíšek keeps tapping on the desk top – there may be plenty to shout about, but Radek Špíšek is touching wood and has no intention of tempting fate. In return, the head of Sotio often hears the phrase “fingers crossed” from his interviewer. This is no de rigueur expression of politeness – without a doubt, it is in everyone’s interest for this company with its “epicenter” in Prague’s Holešovice to be successful. While those of us who are not involved cross our fingers, Špíšek and his colleagues are the ones taking decisive steps and executing bold transactions in search of triumph. That means not only purchasing, but also knowing what to sell: at the end of 2020, PPF Group shed its stake in NBE-Therapeutics, a Swiss biotechnology company in which it was the main shareholder and which it had bought for a song a few years previously; this investment had been managed for PPF by Sotio.

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Your next steps are centered on a change of strategy. Sotio does not necessarily work entirely alone in developing its products from research all the way through to potential launch, but negotiates collaborations with pharmaceutical companies. Why? And does this approach work?
I think I can also speak for the owners here: we feel that a strategic partner can be very helpful when our programs reach the stage of clinical trials. The ideal is a big pharmaceutical company that would supply us not so much with money as with expertise. In Sotio’s clinical department, we have three doctors dedicated to designing clinical trials; Merck, on the other hand, has, say, 150 such doctors. We can be as optimistic as we like, dream as big as we want, but succeeding alone in the face of the competition is unthinkable. We keep to a script where, the moment we get a program into a clinical trial, we try to pitch it to potential partners and get them on board.

And that’s what happened with Merck?
Merck helps us with the study protocol and supplies us with a drug. This is our first instance of a kind of collaboration. But I could see it going much deeper and becoming more coherent.

Is any strategic partnership in the offing, then?
Searching for one takes up a lot of my time. We are making our current programs known to external partners. I can’t go into any detail, but we are discussing them all with the pharmaceutical world.

Does Sotio have what it takes to become a pharmaceutical company one day?
A surprisingly large number of us at Sotio have been here since day one. And we all remember the meetings we had with PPF’s owner, the late Petr Kellner, during the first year of Sotio – founded in 2010 – when we were driven by this naive but wonderful vision that Sotio would try to shepherd products through the entire clinical trial process and that, when they reached the market, it would turn into a business that would take care of them commercially, making us a pharmaceutical company. That idea is alive and well. It is Sotio’s ultimate vision. It is something we can indulge in because we have the backing of PPF. That fundamentally sets us apart from the classic scenario in place at conventional biotech companies, where the moment you go into clinical trials or as soon as Phase I shows promising results, you try to sell the product to a pharmaceutical corporation.

Speaking of PPF’s support, this backing was announced again in December, when another CZK 7 billion was provided to Sotio for the development of therapies.
This sends out an absolutely vital message. We feel that PPF has this tremendous support for the Sotio story and believes that there are prospects for its products.

Has anything changed in the relationship between PPF and Sotio following Petr Kellner’s tragic death?
What has changed dramatically is that we have lost a person I considered a friend; he was far from just the owner of the company. This guy who lived for Sotio for ten years, who was very often involved hands-on in internal discussions, and who of course was the person who made all the decisions because he was the owner, he’s gone. His approach made decision-making amazingly fast. But I need to stress that the human aspect of this catastrophe was the worst part of all. As for the managerial relationship between Sotio and PPF, nothing fundamental has changed. This is partly because PPF is now managed by Ladislav Bartoníček, who – as a close associate of Petr Kellner – was at Sotio from the beginning and even headed Sotio himself for several years. Mr. Bartoníček comes in several times a month and always wants to hear all the ins and outs about how Sotio is doing.

Do you discuss taking the company public?
The path of strategic partnership is Sotio’s clear priority. Having said that, we cannot turn a blind eye to alternatives and we are trying to structure Sotio so that it is ready for potential flotation. These activities are ongoing, we are coming to grips with them, and we need to work them out.

You have made headway in building a base in America – that was another thing you pulled off successfully last year.
By purchasing the CAR T cell technology, we acquired laboratories, offices, and the germ of a team of people in Cambridge... We absolutely need to be in the US, because a biotech company tucked away in Prague is invisible to the Western world. Everything that happens in the biotech and pharmaceutical industry plays out on the east and west coasts of the US, and if we are serious about strategic partnerships or bringing in more investors, our presence in America is an absolute must.

Do potential partners there still view you as – and let’s be blunt – an exotic outfit from somewhere in the East?
That’s how everyone in the US sees us, but I don’t hold it against them. It’s difficult for us to overcome that initial barrier before we can even start talking about any of our programs. We first have to convince the other side that we are not con men, that we are doing something that is respectable in the extreme, and that we have progressed very far with it. That is still the investment world’s general attitude towards this part of Europe.

In which case, how do you persuade experts to come to Sotio? What can you offer them that the big pharmaceutical companies don’t?
It’s tricky. For the longest time, there was no medical drug development in the former Eastern Europe. Sure, pharmaceutical companies had offices here, but these focused solely on promoting product sales. Nowadays, for example, companies here have, say, IT, but there is still no conventional drug development. Getting experts to come to Prague is a problem, but we have done ourselves a huge favor by opening an office in Basel, where we have managed to recruit medical experts for clinical development. And how can we lure these sorts of people away from the likes of Merck or Roche? That’s a bit of a provocative question, but it really is happening. I think a common denominator among people who join Sotio is that they are attracted to the vision. They like the fact that we have solid financial backing from an investor who has given us a mandate to build a diversified portfolio of programs. They are drawn to us because we are not a biotech company that stands or falls with one program. New people also often mention that they are looking for something different from the big corporates, where development or any kind of approval process can be quite glacial. To my surprise, they also often say that, at their old places, when new management came in the priorities and programs were completely reorganized, that they had been working on a program that they found promising, and suddenly they were dropped, and – understandably – that is frustrating for them. I think we have people coming to us who don’t want to be in big pharma, but on the other hand are looking for something less crazy than traditional biotech. We can offer them a position higher up the ladder, nimbleness, and a chance to have a say in strategy. And, we believe, a unique vision.

Source (Czech only): https://forbes.cz/o-zivot-sef-spolecnosti-sotio-popisuje-nejkuraznejsi-byznysovy-plan-v-cesku/
Author: FILIP SAIVER, PHOTO: MOJMÍR SOVA