Drug discovery on a chip - and no mice

Development at Quris  credit: Quris

Dr. Isaac Bentwich reveals Quris, which aims to save pharmaceutical companies hundreds of millions of dollars and years of development.

In the early 2000s, Israel had a number of drug development companies that were ahead of their time. Compugen and Rosetta Genomics developed systems for computerized drug discovery and design, what would today be called big data and artificial intelligence. At that time, however, AI was considered science fiction, and the term "big data" hadn’t yet been invented.

Rosetta Genomics, founded by Dr. Isaac "Tzachon" Bentwich, on the basis of his father Zvi's research, was a huge scientific success when it discovered a large amount of "junk DNA", that is, DNA whose purpose was unclear at the time. It gradually became clear, however, that this DNA actually managed many physiological processes, including control over other genes. Rosetta patented all these gene sequences, but despite its tremendous scientific achievement, and despite going public on Nasdaq, it was not a commercial success, and was eventually sold for $10 million.

Now Bentwich is back with a new company, Quris, and an equally exciting and innovative vision for drug development using artificial intelligence.

"Rosetta was ahead of its time," Bentwich said in an interview with "Globes". "With Quris, our emphasis today is to do things that are ahead of their time, but also to be practical."

Quris was officially founded in early 2020 by Bentwich and Yossi Haran, raising $9 million from leading investors like Kobi Richter, Matthew Bronfman, Moshe Yanai and Rami Unger. Some very impressive names are involved in the company: Nobel Laureate Aharon Ciechanover is the scientific leader; Prof. Bob Langer of MIT, a biomedical engineering guru and a co-founder of Moderna, is on the scientific advisory board.

"This group was also with me at Rosetta Genomics; they are a highly respected group of scientists."

A $19 million funding round

Quris announced last week that it had raised $19 million, one of the biggest seed rounds for a biomed company. The round was led by Welltech Ventures, along with iAngels, GlenRock Capital and private investors.

"I'm a doctor by training, but I’ve been an entrepreneur for many years. Quris is my fourth company," says Bentwich, who approaches life sciences, information technology and artificial intelligence from several different directions. "But only now are we starting to crack one of the hardest nuts. The problem can be defined in one sentence, but it’s the key to a huge leap forward and huge financial savings in drug development: the ability to predict which molecule will be effective and safe in the human body. That's the biggest unsolved problem, and that's all that we’re dealing with."

Bentwich points out that artificial intelligence can benefit drug development in a number of ways, with each company making its contribution, and together bringing about a revolution. Over the past few years, some of have already raised hundreds of millions of dollars at very high valuations.

"All of these companies are making improvements in drug discovery, but after they quickly and efficiently discover new candidates - how do they test them? These days, in cell cultures. A drug that appears effective in culture is then tested in mice. This is not a good method. It costs lots of money, and doesn’t provide a successful prediction - maybe only two drugs that are successful in mice will also pass human trials successfully. Suppose someone told you, ‘We’re going to build ten skyscrapers. Eight will collapse and you’ll live in whatever is left standing.'"

Miniaturized human components

So, what does Quris do? "There are three components to the solution. One is a technology that’s come of age during the last two years; it’s called organ-on-a-chip (OOC). You can simulate 3-D organs that contain most of the components of a human organ, but are tiny, perhaps three millimeters in size. Tiny liver, really miniature brain. Of course, it's not a brain that thinks thoughts, but it simulates the relationships between the various cells of the brain far better than cell culture, and better than a mouse.

"We're improving this technology by producing a platform we call 'Patients-on-a-Chip', meaning we connect a number of organs-on-a-chip together. We essentially create a small-scale 'blood circulation' system that connects, let’s say, to a miniaturized kidney with a miniaturized liver. Then when we apply the drug to the organs, the liver breaks it down, and the kidney secretes it, and you can really simulate how it will function in the body, be broken down and eliminated, and from there, predict its effectiveness and its toxicity."

But creating one organ-on-a-chip, Bentwich says, is like testing a drug in a single-patient clinical trial. "It's already better than a mouse, but we want more people. So, we've formed an exclusive strategic partnership with the New York Stem Cell Foundation that allows us to produce many miniaturized organs from stem cells which represent many different types of people.

"The third component of our technology, which is where we’re really different, is the artificial intelligence component. Suppose we know a thousand drugs exist that are known to be safe, and another thousand drugs that are known to be unsafe, and we run them through our Patients-on-a-Chip, with its genetic diversity. Perhaps we could get an artificial intelligence system that begins to know what an unsafe drug looks like, and what a safe drug looks like. The artificial intelligence would differentiate between them, and understand what sets the safe ones apart in their molecular structure. That’s essentially the future we’re setting our sights on. "

Where do you obtain data about drugs that have failed or succeeded?

"At first, from previous clinical trials. For example, there is a list of 1,028 drugs that are unsafe to use due to liver toxicity. In the future, we hope to establish strategic collaborations with pharma companies which will tell us about drugs that have failed, and maybe about things that haven’t been fully reported. We’re currently in discussions about collaborations with one of the top five pharma companies, and with another that’s also in the top 20. We’re hoping the first collaboration agreement will be signed soon, and if so, it will include an $15 million option for the exclusive use of our technology to research safety only, of just one drug, for five years. So, even before we’ve really set out, one of the largest companies in the world says this technology is worth taking an option on."

A savings for pharma companies

How do you build a business model around this sort of technology? Mainly through collaboration, or your own drug development, too?

"Collaboration with pharma companies is a very clear business model. Pharma companies today lose $ 100-700 million per drug in the development process, just because of safety issues. We tell them, you’ll pay $60 million but you’ll save $700 million. We believe that $60-100 million is the appropriate price per drug, and there are a lot of drugs.

"But our real emphasis is on our own products, which we may collaborate on later. We have two development programs already started. One is for Fragile X syndrome (a genetic disorder characterized by cognitive impairment). Among rare diseases, it’s one of the most common. Giants like Novartis and Roche have tried to develop treatments for it but without success. This disease has no parallel model in mice, making drug development for it very difficult.

"We acquired the rights to develop a drug discovered by Prof. Nissim Benvenisty of the Hebrew University of Jerusalem, who is a world leader in the development of stem cell-based disease models. Our system optimizes the drug. All companies working in AI-driven drug development also develop proprietary drugs. Although it requires a very large investment and a completely different company structure, compared with being a service company only, that's where the big profit potential lies."

Will the process of all the AI companies developing drugs simultaneously lead to a revolution whose impact we, the potential patients, will feel?

"It will be an earthquake. That’s what I believe, and analysts covering this sector believe it, too. Drugs will be developed at investments of tens rather than hundreds of millions of dollars, and the development time will be much shorter. Many more products will get to market as fast as the Covid-19 vaccine did."

The company is currently located in Israel and Boston. Artificial intelligence activity takes place in Israel, while biological activity is in Boston. "To date, Israeli biomed companies have transferred only their marketing activity to the US. Apparently, that’s not enough for a relatively early-stage company to form really good relationships with people from big pharma companies, who meet up at neighborhood cafes in Boston and at scientific conferences. The price we pay is managing development in two countries, to the point where we will control a pipetting robot in the Boston lab from here, or Boston can look through a microscope located in Tel Aviv. We’re experiencing things in this area that are truly cutting edge."

Published by Globes, Israel business news - en.globes.co.il - on January 17, 2022.

© Copyright of Globes Publisher Itonut (1983) Ltd., 2022.

Development at Quris  credit: Quris
Development at Quris credit: Quris
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