• Klaus Meitinger

"If I don't do it, nobody will."

Adrenomed DSC 0759

Theragnostics. Eleven million people worldwide die with or from sepsis every year. Covid-19 also leads to septic shock in severe cases and subsequently to multiple organ failure. Nevertheless, it has not been possible to develop a therapy against it for 50 years. Andreas Bergmann has made this his life's work. As a scientist and as an entrepreneur. "Especially when the task is difficult and complex," he noted, "you can't wait for others. Then you have to become entrepreneurial yourself." That's why he founds. One after another. Now two of his companies - Adrenomed and SphingoTec - are on the verge of a breakthrough.

If everything works out the way Andreas Bergmann imagines, the entrepreneur from Henningsdorf near Berlin will produce spectacular headlines in the next few years. Because his companies have become really big. Because investors have made high profits with their shares. But above all, because he has made septic shock treatable and saved the lives of millions of people.

"Sepsis is a very serious, often fatal disease. It is an inflammatory reaction of the organism to viruses, bacteria or fungi, in the course of which failure of one or more organs often occurs. 30 to 50 percent of patients die despite maximum use of intensive medical measures," explains Konrad Reinhart, Professor at the Charité Hospital in Berlin and Chairman of the Sepsis Foundation. What few people know: Covid-19 is also so dangerous because it can lead to sepsis, which then has to be treated in intensive care.

But even though the problem has been known for decades, to this day there is little sepsis-specific therapy other than fighting the triggering infection and intensive care. "Sepsis has long been called the pharmaceutical industry's billion-dollar grave. Trial after trial has failed in the past. Today, it is almost a kind of burnt indication that the industry no longer dares to approach," explains Andreas Bergmann, a scientist and serial founder of companies conducting research around sepsis.

The difficulty: there are hundreds of pathogens and infectious diseases that can lead to sepsis. "But the studies of the past always focused on the one drug that was supposed to help all patients - one size fits all," Reinhart explains. "The result was then always the same. Some of the patients benefited. Others were harmed. And that cancelled out the result of a study. Or the positive signal wasn't as big as it needed to be to justify approval of a new drug."

"That's why we deliberately took a very different approach," Bergmann explains, "We didn't start by looking for a drug, but took a step back." In 2009, in collaboration with nearly 100 academic institutions worldwide, he launched a program to answer the question of why people actually die from sepsis. What is the exact, detectable cause of death? "Our goal was to understand the particular cause and then target only that cause. This is precision medicine - everyone talks about it, but it's hardly ever implemented. We wanted to apply this idea of therapeutics - a combination of therapy and diagnostics - consistently."

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Andreas Bergmann's fight against sepsis began almost exactly 30 years ago. Together with five colleagues, he organizes the management buyout of Henning Berlin's diagnostics division. The scientists set up a limited liability company, found financing partners, a venture capitalist, invested ten million marks in equity themselves and named the company B.R.A.H.M.S. Diagnostica. Andreas Bergmann is the "A" in the middle (private wealth has already reported on the "B", Bernd Wegener, whom Bergmann still refers to as his foster father, in the 04/2015 issue). In 1995, the company develops an innovative biomarker for the early detection of sepsis. Today, this is considered a clinical standard. In 2009, B.R.A.H.M.S. is sold to the US group ThermoFisher for 480 million US dollars. Andreas Bergmann's share is around 25 million. That is more than enough to live on for someone whom confidants describe as a "workhorse". Above all, however, it is the ticket to becoming an entrepreneur himself.

"I'm a scientist, after all, but I've realized that universities alone aren't capable of really generating value." Many resourceful minds there, Bergmann continues, have innovative ideas and then wait for someone else to pick up the ball. "But that's not the case. Experience shows that the pharmaceutical industry is busy with its own projects. And if the project is also highly risky, it becomes extremely difficult. We have to make sure ourselves that the idea gets to a stage where the industry is interested in it. And the only way to do that is by taking the risk ourselves at the beginning, becoming entrepreneurs and pushing the particular project forward."

That's exactly the Bergmann way. Working with his own capital, seeking the financial help of old companions from his B.R.A.H.M.S. days, approaching family offices - this is how the Berlin-born entrepreneur has already founded 15 companies. And invested around 20 million euros of his own assets. "The prerequisite is always to handle financial resources very prudently. If I see that an idea or a concept doesn't work properly, I don't feed it any further. Most money is lost in our industry by riding an almost dead horse for far too long. I don't want that to happen to me." That's another way Bergmann differs from many other founders. "I earn my living with my projects. And can therefore act independently and without a conflict of interest," he explains, "probably that's also why I was able to stay on the topic of sepsis for so long."

Now that seems to be paying off. The first startup - Adrenomed - is on the verge of a potential breakthrough. "Four years ago, the program to prove the exact causes of death in septic shock came to an end. Since then, we've really picked up speed."

Bergmann and his colleagues have been able to identify three major causes, sometimes occurring simultaneously. The first is renal failure. This apparently affects a quarter of patients who die in intensive care.

The second - the largest block at 70 percent - is loss of what's called endothelial function. "This sounds complicated, but it's quite simple. The endothelium is a paper-thin skin. It lines the inside of our blood vessels and keeps them sealed like a bicycle inner tube." If this endothelium is damaged by infection or inflammation, it begins to leak. Fluid then leaks out of the blood vessel where there is high pressure into the tissue where there is no pressure at all.

"Edema forms, organs become dysfunctional, water gets into the lungs. That, by the way, is the main reason why severe Covid 19 cases require ventilation. And ultimately, the organs fail."

Bergmann cites acute heart failure as the third cause of death. "It's caused by dead cells. It's called necrosis - cells break down, the contents of the cell leak out. This puts a digestive enzyme into the blood. And this eliminates a hormone that's critical to maintaining heart function. Although it may be perfectly healthy, the heart stops functioning. It just stops working."

Now Bergmann also sees exactly why previous attempts to develop a sepsis drug couldn't work at all. "A drug that improves tube function doesn't help heart failure, and vice versa. In the efficacy trials, which are, after all, conducted in all sepsis patients, the endpoint - a significant reduction in mortality - could thus not be achieved, of course." The search for a reliable diagnostic agent must therefore precede drug development. "The doctor needs to know reliably what the problem is. And he needs to know it quickly. Because in septic shock, the probability of survival decreases by seven percent every hour."

Now Andreas Bergmann and his team are back on familiar ground. In his company SphingoTec, he has been researching appropriate tests since 2010. "In the meantime, we have a diagnostic agent that immediately shows the current kidney function. This is crucial for treatment because deterioration can be very rapid in kidneys. We have a blood test that is able to quantify a person's tubular function. And we can detect the enzyme that reduces the function of the heart."

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With that, the scientist has laid the groundwork to look for therapies. "We now first considered where we could intervene to support endothelial function. Or restore it. In order to then develop an antibody. That's what we found. It's called adrecizumab."

Up to this point, the company's own capital and the support of trusted business partners are still sufficient. "But now we had to go to the patient, test safety and tolerability, rule out side effects." More than 40 million euros are needed for the necessary studies. Bergmann convinced two venture financiers - HBM from Switzerland, who were already on board for B.R.A.H.M.S., and Wellington Partners. "Andreas Bergmann's group had not only identified the trigger of septic shock, but also found an antibody that works within a few hours. I immediately saw that the impact of these discoveries on the whole of medicine could be enormous. Elucidating this connection is worthy of a Nobel Prize. And the economic prospects could be enormous," says Rainer Strohmenger, partner at Wellington Partners, explaining why he decided to get involved.

The study results are encouraging: the drug is safe, well-tolerated and has no side effects. And they fuel hope that efficacy can indeed be demonstrated. "I know the study well," says Konrad Reinhart, "what is interesting is that although Adrecizumab did not have a statistically significant positive effect on the entire collective of all patients, it did have a positive effect on the group of patients who did not have the enzyme reducing cardiac function in addition to the problem with the tube function. And that those who were treated within the first six to twelve hours after the onset of septic shock responded positively. This is important information in terms of selecting patients for the next studies. I think this approach is worth investigating and pursuing."

"The results are so positive and strong that we are now actually enthusiastically preparing a study that should eventually lead to market approval," Bergmann makes clear. Because now he knows exactly what needs to be done to optimize his drug's chances of success. "We will give the antibody very early and work exclusively with patients in whom our blood tests indicate insufficient endothelial function and rule out a heart problem."

The trial is scheduled to begin in mid-2022. If successful, market approval would be possible three years later, initially in Europe, and shortly thereafter in the U.S. and Asia. "These are fascinating prospects," judges Rainer Strohmenger.

For things to get this far, however, Strohmenger is once again in demand as an investor. "We need around 80 million euros for this study - for Europe alone. We will therefore soon conduct another capital round," informs Bergmann. In the - normally difficult - search for financiers, he could benefit today from a special mixed situation. "Covid-19 ruthlessly revealed that we have neglected infectious diseases over the last 60 years," explains Konrad Reinhart, "so the market's interest in such research is now many times greater than in the past."

In fact, Andreas Bergmann can also come up with an interesting side aspect to Covid-19. "At the University Hospital in Hamburg, so-called curative trials with Adrecizumab were carried out on eight corona patients who had no prospect of recovery. Seven survived." Of course, Bergmann immediately qualifies, such a healing trial is not real science. "But the results are quite remarkable."

In fact, doctors in Germany are now planning to conduct further trials. "They are convinced that this drug can solve a large part of the corona problem. It won't cure Covid-19, but it will address the real problem - the high mortality and the need to be treated in intensive care units. We even received a funding commitment from the German Federal Ministry of Education and Research at the end of April and are now preparing to conduct the first studies in the short term and complete them as quickly as possible."

Bergmann is also now on the trail of cardiac arrest. "We are currently developing an antibody that inhibits the enzyme responsible and immediately restores cardiac function. It's called Procizumab. I have also founded a company for this - 4TEEN4 Pharmaceuticals. Next year we will go into the first clinical trials."

On the side, Adrenomed also has a project underway to show the benefit of adrecizumab in acute heart failure. "If tube malfunction is added to heart failure and water gets into the lungs, that can also become life-threatening. So it's obvious to use adrecizumab for that problem as well."

It's breathtaking what's happening in Brandenburg. It's not just in terms of medicine that Bergmann's companies are becoming great beacons of hope. The economic prospects are also exciting.

At SphingoTec, the entrepreneur is now putting to use a testing device that works almost as simply as a Corona rapid test. "We put blood on a plastic pad that resembles a music CD. Then we put it into a reader, and within 20 minutes the doctor gets a clear result of our biomarkers on kidney, tube and heart function. And can now decide: Do I take care of the kidney, do I give adrecizumab, do I give procizumab, or both. So we could help most patients in the context of sepsis - which is where I've been wanting to go for a long time."

Each of these three markers from SphingoTec, Bergmann hopes, could develop at least a similar economic potential in the long term as the B.R.A.H.M.S. biomarker he developed at the time - "it now makes about a billion dollars in sales worldwide."

Adrenomed's earnings potential ultimately depends on the price that can be achieved for a treatment with adrecizumab and how many patients the company can supply with it. But there are only rough indications of that today. In the past, other drugs that did not work, said Bergmann, were in the 10,000-euro range per application. In Germany, at least 50,000 people suffer septic shock every year, although this figure is probably much too low due to the poor documentation in our healthcare system. Worldwide, several million are affected. Half of these people could be helped with Adrecizumab in the best case scenario. "Even if we calculate very carefully and make huge deductions, fantastic numbers still come out," Bergmann says, taking an audible breath: "The pharmaceutical world also sees it that way. Adrecizumab is a blockbuster candidate."

In order to be able to really put the horsepower on the road, Bergmann has restructured his company Adrenomed in recent months. With Wolfgang Baiker, formerly of Boehringer Ingelheim USA, the company was able to recruit a proven expert as CEO who is extremely well networked in the biopharmaceutical industry. And Mirko Scherer, the new CFO, has extensive experience with IPOs.

This suggests that an IPO in the near future or a licensing deal with Big Pharma could also play a role in Bergmann's plans. "At least we now have the management capacity that would allow us to actually conduct the market approval trial for adrecizumab ourselves. Everything else is open. But clearly - we are preparing to be ready to act."

For Bergmann himself, this would then also mean the very big financial payoff. "Oh you know, personally I'm not that interested in money," the scientist and entrepreneur waves off.

He also - probably - simply doesn't have the time to spend a fortune. "Have I told you about my new project? Alzheimer's is another hopeless story that everyone has their fingers burned on. We've found that a slowly developing disorder of the blood-brain barrier and a deficiency of a certain enzyme is responsible. It's called peptidylglycine α-amidating monooxygenase. We have already developed a blood test and are now looking for a drug. I founded PAM Theragnostics for that purpose." ®

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// How to invest in Andreas Bergmann.

There are two ways to invest in Andreas Bergmann's entrepreneurial activities - directly or through a listed vehicle.

In the course of the year, Bergmann is planning a financing round for Adrenomed, SphingoTec and 4TEEN4 Pharmaceuticals, in which primarily family offices can participate. As bridge financing until this round, the companies are currently issuing convertible bonds with a minimum investment of 50000 Euro. The conditions are interesting. The convertible bears interest at five percent per annum and allows participation in the next financing round at a discount of 20 percent.

The second option is the purchase of shares in the listed company DBI - Deutsche Biotech Innovativ AG. DBI was originally founded by Bernd Wegener, Andreas Bergmann and Metod Miklus - the BAM of B.R.A.H.M.S. - to create a broadly diversified biotech vehicle for investors in order to raise funds for the further development of the triumvirate's diverse ideas.

However, this did not really work out because interested investors preferred to invest directly in Adrenomed and some other projects did not progress either. This is why Wegener, Bergmann and Miklus still hold 97 percent of DBI today. The company itself has a 10.54 percent stake in Adrenomed. It owns 27.27 per cent of Angiomed - a company that develops antibodies to uncouple tumours from the bloodstream, 5.38 per cent of PAM Therapeutics and shares of less than one per cent in 4TEEN4 Pharmaceuticals and SphingoTec. Currently, however, DBI is highly valued with a market value of around 90 million euros.

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// "We're living in dreamland."

"It's crazy," reflects Professor Konrad Reinhart, Chairman of the Sepsis Foundation, "at every bus stop there is education about sexually transmitted diseases. Only about sepsis nobody knows. Yet probably in Germany, as in the U.S., at least 500 people per 100000 inhabitants are affected each year."

Reinhart's mission is to change this. First and foremost, that means educating people about the disease. "Sepsis can affect anyone. It is the number one preventable cause of death worldwide. In Germany, 75000 people die with or from sepsis every year. Among them are several hundred newborns, children and adolescents. Up to 75 percent of sepsis survivors suffer from long-term consequences. 15000 to 20000 deaths would be preventable just by early detection, treating it as an emergency and following hygiene rules and vaccination recommendations."

That we as a society simply accept this, Reinhart believes, is a scandal. The Sepsis Foundation therefore organizes campaigns, puts pressure on the political level and wants to achieve that - as for example in New York State - information about infectious diseases and sepsis is already provided in schools. "Only about 20 percent of infections occur in connection with hospital treatment. 80 percent already come to the hospital with sepsis. That's why the public needs to know the early symptoms so they can get them checked out quickly if they suspect an infection - confusion, shortness of breath, rapid heartbeat, fever, chills, sweating and clammy skin."

Reinhart also calls for hospitals to be required to take certain actions when sepsis is suspected - "immediately do blood cultures, give antibiotics, give fluids." That alone has reduced mortality in the U.S. from 30 to 20 percent within five years, he said. "The decades-long claim by the respective health ministers of each political hue that 'Germany has one of the best health care systems in the world' is one of the life lies of this republic. Currently, sepsis does not even appear in the annual federal health report. It was first mentioned by the Federal Centre for Health Education in 2021. We thought we had infectious diseases beat. Now they're catching up with us with a vengeance. We have to do something about that."

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Author: Klaus Meitinger

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