MeMed swiftly diagnoses if a disease is viral or bacterial

Eran Eden and Kfir Oved

The Israeli company's innovative diagnostic solutions reduce use of unnecessary antibiotics.

When his daughter is feverish and screaming incessantly, Eran Eden has a unique way of finding out what to do. He takes her to one of the few hospitals taking part in a pilot program of a device he developed with Dr. Kfir Oved, his co-founder at MeMed.

Then, with a simple blood test and the use of the diagnostic tool he and his partner created, he knows within two hours whether his daughter has come down with a bacterial or viral infection, and whether she needs antibiotics or a serving of chicken soup.

“It is not a replacement for a general check-up or a doctor’s informed opinion. But it has helped us with the consultation of the medical staff to decide whether to give her or her three-year-old sister antibiotics. And, more importantly,” says Eden with a grin, “it gives me a lot of credit with my wife and my mother-in-law. That’s one of the better benefits of the work.”

“Globes”: Your wife isn’t upset that you turn your daughters into lab rats / test subjects?

“I obviously only started trying that after receiving the regulatory approval in both Europe and Israel. But yes, on the most basic and selfish level, I use this thing on my daughters, who love to share food with the other kids in kindergarten and bring home a virus or bacteria every couple of weeks. But as to my wife, she was the first one to ask me to try it. A day before I flew abroad, when the baby hadn’t slept in two days, my wife asked ‘is it a bacteria or a virus?’ and I said I didn’t know.

“She told me, ‘lovely, the cobbler is walking barefoot, but before you leave me alone with these two, let’s go the hospital instead of giving her antibiotics for no reason.’ So we tested her, the results pointed towards a viral infection, and as expected it passed within 24 hours.”

G: You wouldn’t go to the hospital that quickly if you were any other person.

“You’re right, aside from the patients at wards or emergency rooms who are part of the trial, today that remains a privilege for MeMed employees and their families. The idea is that in the future it will be used far more widely. Not at pharmacies, because the results as of today still needed to be interpreted by a doctor, but the hope is that they would be utilized by hospitals and clinics. The second generation, which we are developing now, should be more accessible, smaller, and churn out results within a quarter hour.”

G: When will that became available?

“Within 18-24 months. We believe that, at this stage, it will be easier to receive regulatory approval.”

Viruses, Proteins, and Ice Cream

You could say Eden and Oved the MeMed founders literally spilled blood on their way to what seems like an impressive scientific breakthrough.

In June, the two founders discovered that they beat 90 other firms to a €3 million grant by the European Union’s Horizon 2020 for funding life sciences companies with innovative technology that could potentially have far-reaching effects for the EU’s economy and global healthcare.

A study published by PLOS ONE in March of a large clinical study conducted by the company led to a flood of inquiries by hospitals, investors, and healthcare groups across the world seeking to cooperate with MeMed.

Its founders, who worked under the radar for the last four and a half years, revealed to “Globes” the path they traversed from the day that “nobody wanted to invest a dime with us” to now, when they are being hailed as the great hope of the medical device industry and are being courted by global media outlets from Time to Al Jazeera.

Eden and Oved met some 15 years ago, when they were both students at Haifa’s Technion Israel’s oldest university. Together, they cracked a problem in cancer immunotherapy which received acclaim and resulted in several patents.

“Then we turned to each other,” recalls Eden, “and said ‘we had fun during this process, but it will never actually reach hospitals, partially because it would be difficult to find financial support. But we enjoy working together, so why not find another problem that had both a scientific and a financial need.’

“We need a problem that we could solve in the special language we created, me with my background in computers and biology and Kfir’s medical studies and immunology PhD.”

G: Why was it so important to have the market on your side? You aren’t businessmen, why was research not enough?

Oved: “Because we realized that if there was no financial sense behind what we were doing, it would be difficult to change the world with it. You could solve the biggest problems on a theoretical level in a research lab, where you could control conditions to cure cancer in rats. But to solve the problem on a global scale, it needs to be connected to the financial forces that would drive it.”

G: What are the financial forces in your case? It seems like the pharmaceutical companies will try to tackle you the moment you make antibiotics unnecessary in the majority of cases.

“We thought so too at the beginning. When we started MeMed, we were worried that one day one of the pharmaceutical firms would try to buy us out, only to kill the project. One of the first discussions we had with our investors was that we would under no circumstances sell ourselves to a pharmaceutical company we hadn’t done all this work for that. But as we got older, we realized that’s not how the world works, that even drug companies have an incentive to develop this technology for a number of reasons a large portion of the patents on antibiotics are about to expire, and antiviral drugs are catching on. Meaning the choice will not be between antibiotics or no treatment, but between antiviral drugs and antibiotics; the pharmaceutical companies will continue to profit in each scenario. Furthermore, you could use our technology to shorten the development of drugs and thereby save money.”

G: If there is money to be made, you must not be the first to think about offering a solution.

“Correct. When we set out, we knew were not the only smart guys on the scene, and all the big players, like Roche and Abbott, are working on it. There is a multi-billion dollar market offering solutions, starting with taking a culture which tries to develop the organism with cleverer techniques, which look for the RNA or DNA of the bug. But it takes almost two days to mature a virus, and there isn’t always access to the instigator of the infection. It’s easy for a throat infection, you use a swab, but what do you do with a lung infection or sinusitis? What about cases where it is unclear where the infection is and what should be tested? There are bugs that sit in our nose or our throat without attacking the body which set off false alarms. How do you distinguish? It was clear that it would be a major challenge, like climbing Everest.”

G: So what did you do?

“We decided to ‘cheat’ by relying on a system which does it much better than we do the immune system. It is a perfect system, which identifies bacterial and viral infections and attacks them. All it takes is to tap in to the communications network of the war taking place within and to see what units the body chooses to recruit. Is it the anti-viral delta force or the antibacterial commandos? We knew there wouldn’t be one piece of information which will tell the story in an accurate enough manner, so we decided to include a smart algorithm much like high-tech companies use to predict how the stock market will react in order to generate revenue. The algorithm connects the pieces together and gives an answer bacterial, viral, or no infection (as in the case of physical trauma or autoimmune disease), without having to seek out where the disease stems from in the body.”

G: And it worked?

“We bought equipment with our doctorate salaries. We took blood samples from ourselves and adult family members, and we infected it with bacteria or viruses. We tested and failed. We started to realize that just because the proteins which we had chosen to focus on were part of the immune process, it does not mean most of them are stable enough to function as a marker. The problem is that there are more than twenty thousand proteins in the body. Each one is a relevant applicant, which costs several thousand dollars to examine requiring seed funds of half a billion dollars and more blood than the entire population of Israel has. Impossible.

The system we developed, which was based on data banks of infectious diseases, helped us narrow the list to 600 proteins in one year. Out of them we took the top twenty and went back to the start of the blood trials. Most of the molecules showed nothing. Two or three of them were excited by the bacteria or virus. We were overjoyed and decided it was time to raise funds.”

From grandma’s kitchen to Lee Ka-shing

At that stage, it was still difficult to even call them a startup. “I was just finishing up my medical studies,” said Oved, “and we worked on our idea mostly at night. We met in my grandmother’s kitchen because we were looking for a quiet place to work. She was responsible for the blintzes, we were responsible for the work. It was what we call our garage phase, which went on for about a year and a half. It was 2009, a tough period, not exactly the time to found a company and raise funds.”

G: And yet against all odds you succeeded.

Eden: “So that’s the thing, no. No one had yet agreed to invest in us, rightly so. Everyone told us you showed a process outside the body, you infected cultured blood with viruses and bacteria, but you have no idea how it works on people who have actual infections. What about the lymphatic communication or the kidneys’ filtration? You cannot simulate these processes outside the body.

“Even those who appreciated our technology were very skeptical and said that humanity will not see this type of a solution in the next hundred years. We decided to use that skepticism and asked that same potential investor who expressed doubts to write down all the areas in which we needed to improve. We hung the list in our rooms and told ourselves that next time we fail, it will not be because of these factors and we crossed them off point by point. We also hung up pictures of quotes from people who declared that certain barriers will not be shattered and were proven wrong like Lord Kelvin, one of the great physicists of his age, who predicted that flight by machines heavier than air was impractical mere years before the Wright brothers took to the sky with the first airplane. We decided to make that the ethos of our company.”

G: With all due respect to ethos, this is the stage that requires knuckling down and starting experimental trials.

“True. We turned to a few clinicians, like Prof. Israel Potasman, the director of the infectious disease center at Bnai Zion hospital and the first to believe in us on a clinical level and we held trials with elderly patients from the hospital’s emergency room. We had no money. All the money we did have we invested in measuring devices for the experiments.

“At this stage we again tried to raise funds, and that’s when Hanina Brandes entered the picture and became our first investor. We still joke that we’re unsure whether he invested in us because he appreciated our determination or simply because he felt bad for us. Hanina said, ‘Unlike my usual habit, I want to be involved here on a personal level. One of the few companies I was involved in personally was Check Point which made billions, so don’t screw up my statistics.’ We have since tried to stick to that high bar.”

At this point, the two rented a small office in which they conducted the trials. “Something sloppy. Every dollar went towards the clinical trial. After three months we reached 200 hundred patients, and we realize that we have statistical strength and this was becoming serious. The second round of funding, in 2012, was closed quickly. It was led by a group from Silicon Valley, Social + Capital some Facebook people who were looking where to invest. After that we could finally start recruiting employees. MeMod today has 19 employees on top of 20 advisors and freelancers, and we are planning to significantly expand soon.”

Eden became the CEO, Oved the CTO. “Each one grew into his position,” said Eden, “we learned many lessons in humility from the immune system and it took us a long time to get better and improve.” Two years ago they closed another round of funding, the most substantial so far, led by Horizon Ventures Li Ka-shing’s investment fund which invested more than $7 million in the pair.

Eden: “Gilad Novik leads the fund in Israel, and we have good chemistry. They are amazing, not only in their investing and their deep pockets, but because of their connections and their ability to open doors.”

Meanwhile, they won a prize from the European Union, which granted $2 million to the company which proposes a revolutionary technology to help fight antibiotic-resistant strains.

G: How much money have you raised in total?

“MeMed has never confirmed or denied data about the sums it has raised, and that won’t change today. In terms of resources, we find ourselves in a very good situation today to continue our operations and this company far. After the last funding round, we blazed ahead with five more clinical trials with thousands of patients. The studies are double blind and the results should be in within the coming months and years. The process is nerve-wracking, like counting the votes in the Eurovision, except we go line by line and see what the actual diagnosis was and what our device told us about the nature of the infection. One of the studies which was recently wrapped up but has yet to be published was conducted by independent researchers; the results were excellent we aren’t smiling in vain. We believe a firm scientific basis will lead to commercial success.”

From the age of 3 months and up

Their first significant study ended a year and a half ago. It involved 1,002 patients and put a global spotlight on the company. Oved: “The response rate for the trial was incredible. We were surprised by how aware patients were of the need to solve the problem, especially the parents. We took patients at different stages of a disease, to deal with all the noise inherent in the real world, which a doctor must face, including cases in which the patient has already begun a course of antibiotics or received a vaccine the week before. We were able to get a 90% accuracy rating for diagnosing bacteria and viruses.”

G: How does that compare with current tests?

“The best hospitals in the world talk about an 80% accuracy in diagnosis of bacteria versus viral infections, meaning 20% of those with bacterial infections don’t receive antibiotics. At the same time, close to 40% of viral patients receive antibiotics that do not help. We are also addressing that problem. How does that work? At the end of the diagnosis there is a number on a scale from zero to 100. If the number if close to zero, the infection is viral. If it is close to 100, the probability that it is a bacterial disease if very high.”

G: What if the final number is, say, 50?

“It means our device could not decipher what is going on and is saying ‘I don’t know’. It happens in 10% of the cases and we are not sure why. People who receive such a number mostly likely have a different immune response than the rest of the population. For the meantime, we are unable to understand what characterizes them”

G: Is it possible that some viruses and bacteria like new mutations would evade the device?

“Anything is possible. The first question the board asked us was whether it would work on swine flu. It did. We sampled sixty strains of viruses and bacteria, and it turns out the immune system prepared itself evolutionarily for new infections.”

G: Let’s look at the cases in which you make a determination can you say which virus or bacteria is at fault?

“Partially. In certain segments of patients this is important, like those suffering from sepsis, and one of the products we are developing actually tries to separate between the families of bacteria. But for the hundreds of millions of patients who visit their family doctor or the emergency room each year, it doesn’t matter, because there isn’t really a different course of treatment for one bacteria as opposed to another.”

G: But you don’t give the same drug for an ear infection as a urinary tract infection.

“True. But mostly the doctor knows where to focus, because our diagnosis is being conducted alongside a physical exam. And in the case the doctor doesn’t know like with babies there are enough antibiotics that can cover multiple infections. Thus if we identify a bacterial infection, the doctor can proceed with more focused tests and begin treatment more quickly.”

G: What happens if a patient has both a viral and a bacterial infection?

“That is an important question. We assumed that both of the measures would increase, and we discovered that most likely for evolutionary reasons bacteria are far more dangerous to us than viruses; the immune system ignores the virus and musters all its resources to fight the bug. Therefore, if both are at play, the answer the doctor receives will be there is a bacterial infection, treat with antibiotics. It doesn’t matter which is the cause and which is simply riding the wave.”

G: Does this also work for infants? After all, every month-old that develops a fever comes to the emergency room.

“No, it is only for the age of three months and up. At a younger age, the immune system acts in a different manner; we are currently developing a device intended for those early months. Look, we measured 600 proteins; we discovered a lot of things that work only for parts of the population based on age, gender, or ethnicity. But we took proteins that work well for every person from the age of 3 months to 100 years, and if it doesn’t, it will be solved on an algorithmic level. We thought it was a good range of ages for a start.”

MeMed, which has received regulatory approval in Israel and Europe, runs pilot programs at Bnai Zion and Hillel Yaffe hospitals, along with hospitals in Geneva and Utrecht, and will soon add other medical centers to the picture. After the recent EU award, London is slated to join the trials. MeMed will be faced with elderly patients suffering from lung diseases for the trial in the British capital.

MeMed is also set to begin clinical trials in the US, as part of the initial effort to eventually receive FDA approval. “We are also interested in the China, a massive market with a huge problem of overusing antibiotics.”

G: You are become well-known worldwide. Have you considered moving abroad?

Eden: “We want to keep the company in Israel. We received an offer to relocate to Silicon Valley but we refused.”

Oved: “Our strategy is to build something big. We want to be the largest diagnostic company in Israel the next Teva of diagnostics and develop more tools with the capabilities we gained.”

The stage after the pilot programs is commercialization with the device being offered for sale. How much will it cost? Eden refuses to give even a ballpark figure. “We are still considering pricing models. On one hand, healthcare systems are sensitive to money and our device can save them a lot of it. On the other, we want it to be available to every patient across the world, and that a hospital could afford to purchase the device without holding a special gala to raise money for it.”

G: Somebody must be asking themselves if you are up for sale.

Eden: “If we receive an offer we can’t refuse, then we wouldn’t refuse it, right? But that’s not where we’re directing the company. We are aiming for growth, and we have the resources right now to expand it to a very large company because of the investors who are already here and those who are just now getting interested.”

G: And what about you? Are you left with symbolic shares? Have the investors taken all you had?

Eden laughs. “It’s precisely because we failed as founders to raise money for so long that we had to take much of the risk on ourselves, for a long time we worked without salary and financed a lot from our savings. When we brought investors in, we were left with relatively high worth and our situation is good. Even those who started working in the beginning for stock options are pleased with how things have developed. I mean, my smile says everything.”

The risk of resistance

The reason for the excitement over MeMed’s development stems from the global effort to curb antibiotic use. Excessive use of the drug has led to the development of antibiotic-resistant bacteria, which could, according to the head of the World Health Organization, return us to the age in which everyday sicknesses like a throat infection or a scratch on the knee could be fatal.

Approximately 50,000 people die every year in Europe and the US from antibiotic-resistant infections. This trend led President Obama to launch a national multiyear plan at a cost of $1.2 billion to streamline antibiotic use and fight the evolution of resistant strains. UK Prime Minister David Cameron appointed early in June a team to estimate the consequences to global healthcare and the economy of a world without antibiotics a world which, according to the warnings, looks a lot like the middle ages.

“The creation of resistant strains is currently defineds as one of the great threats of the 21st century,” said Eden. “But when we founded MeMed, it was not the sexiest problem in the world. No investor was willing to touch us with a stick. They told us it was a problem, but somewhere off in the future, that people weren’t really interested. Now the topic receives attention, and rightly so. Antibiotics is the base of the pyramid on which modern medicine was erected. Without antibiotics we could not treat cancer patients or keep premature babies alive, as they would die from their weak immune system. Antibiotics are the basis for many complicated procedures. The problem is that, as of now, every other antibiotic course given is unnecessary. Aside from the money being wasted, prescribing antibiotics is like dropping an atomic bomb into the stomach. Not only because of the development of resistant strains, but because it causes diarrhea in one out of ten people; in one out every hundred people it may lead to much more violent infections.”

G: How does Israel compare to the rest of the world on this?

Oved: “According to the OECD, we’re somewhere in the middle. We could learn a lot from the Netherlands, Germany, and the Nordic countries which provide minimal antibiotics, but are also much better than France, Spain, and Italy. In the US, because the nature of medicine is extremely defensive, there is excessive use of antibiotics. In developing nations China, India, and South America antibiotic use is off the charts. And anyone who thinks that it’s just their problem is sorely mistaken. We live in a global world resistant strains have no religion, race, nationality, or gender. It’s a matter of days until they spread across the globe.”

G: What about under-use, when a patient is diagnosed with a viral infection that is actually bacterial?

Eden: “That happens to a fifth of the patients that need antibiotics. Sometimes they only get it at a later stage. It’s not an issue mostly. For younger children it usually extends the duration of the disease, but in elderly patients with lung diseases it could lead to death.”

Published by Globes [online], Israel business news - www.globes-online.com - on August 19, 2015

© Copyright of Globes Publisher Itonut (1983) Ltd. 2015

Eran Eden and Kfir Oved
Eran Eden and Kfir Oved
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