Quris Team Members/Courtesy of Quris AI

Quris AI has developed an alternative to testing on animal models, and each one is smaller than the head of a pin.

Mice are Terrible Predictors

The artificial intelligence (AI) and pharma company has created the Bio-AI Clinical Prediction Platform, which is used to determine which drug candidates will work safely in the human body, and for whom theyll work best.

Currently, drugs are developed and then tested in mice in order to determine their suitability for humans. Mice are terrible predictors, Dr. Isaac Bentwich, Quris founder and CEO, told BioSpace. Out of all the drug candidates today that have in vitro and in vivo testing and then enter into clinical trials, 89% fail. Thats quite dramatic when you stop and think about it.

Biotechnology Innovation Organization (BIO) published a second report on Clinical Development Success Rates and Contributing Factors, analyzing 12,728 clinical and regulatory phase transitions from 9,704 development programs between 2011 and 2020. The analyses found the overall likelihood of approval for developmental candidates to be only 7.9%.

Bentwich offered a creative analogy on the issue, imagining a person who wanted to build a skyscraper and thus contacted the best architect and the best engineer available. They would tell you, you've come to the right place. Were the best in the trade. Here's what we'll do: we will plan 10 skyscrapers for you. We will guarantee that nine of them will crumble. We do not know which. As facetious as this may sound, that's actually the economics of the pharma industry today.

Bentwich is a medical doctor by training and described his unique transition from school into the industry. I was just out of medical school and was dabbling with computerized medical records and decision support systems. It became a hobby. It was either that or pottery, actually. And what began as a year off from continuing with my medical career ended up as a ten-year stint developing a computerized medical record which was very successful. He started three other companies related to AI, computing, biology and medicine before founding Quris.

The Quris Platform

The companys platform uses a combination of three pillars: stem cell technology, AI, and what they call Patients-on-a-Chip. There is a technology used to create miniaturized human organs, a miniaturized liver and a miniaturized brain. Each such miniaturized organ is a third of a millimeter in size, which is the size of the tip of a sewing needle.

Quris' Patients-on-a-Chip technology/courtesy of Quris AI

The mini-organs are created from the cells of an individual person. We then use precision robotics and nanosensors to test thousands of known drugs on these miniaturized patients with interconnected human miniaturized tissues. We use nano sensing to see how these miniaturized patients feel and whether they are personally affected by different drugs.

By testing thousands of drugs on Patients-on-a-Chip, the AI has been trained to determine which are safe, and which are toxic. When a new drug is exposed to the technology, the AI can discern whether its more similar to the toxic drugs or the safe drugs. Bentwich highlighted that importantly, this not only gives a readout of the level of safety, but it shows for whom the drug is safe. We can use this to see that drug X may be good for one individual but not for another.

A unique feature of the mini-organs is their interconnectivity. Bentwich described the first version of the platform, which included the liver, the brain and the blood-brain barrier. This allowed the company to collect data not only on how a drug is processed in the liver but what happens when it crosses the blood-brain barrier.

When we test the drug on our system, we actually let the liver metabolize it. It's a tiny, tiny liver in a tiny well, but it still metabolizes the drug. It breaks it down to different chemicals in the same way that the real liver in the human body does, he described. Only then, it goes through the blood-brain barrier, which mimics exactly how it behaves, allowing only certain molecules to go into the brain. Then, it interacts with the miniaturized brain. The data collected on these interactions between the organs are used to train the AI.

The Bio-AI approach is unique in that its not just sorting through randomized available medical data, but is trained directly in response to known drugs being tested on Patients-on-a-Chip. By utilizing more specific data, the platform generates informed predictions on drug safety and individualized patient suitability.

A Potential Cure for Fragile X Syndrome

The company is developing its first drug for the treatment of Fragile X syndrome, a genetic disorder that causes symptoms related to developmental delays and learning disabilities.

Bentwich said Quris chose to focus on the syndrome because it cannot be mimicked in an animal model, which makes drug development difficult. The company combined its Bio-AI platform with a discovery made by Professor Eyal Benvenisti of The Hebrew University of Jerusalem to begin developing the drug.

The cool thing about the drug that we're developing is that if its successful, it will be the first time that a drug will be attempting to cure the disease. From our initial results, it actually seems to treat the root cause of the disease, not just treat it symptomatically, he said. The drug hopes to address the disruption of fragile-X mental retardation protein(FMRP) production caused by a faulty FMR1 gene in Fragile X syndrome.

Initial studies showed that it seemed to indeed undo the inhibition of this faulty gene, Bentwich shared. If this is successful, we may be onto something that will impact the lives of many patients. He said clinical testing will begin within the next 12 months.

Redefining Nonclinical Testing

Earlier this month, the United States House of Representatives passed a bill to amend the Federal Food, Drug, and Cosmetic Act. Alternatives to animal testing are now allowed in assessing the efficacy of a drug. Such nonclinical tests can include computer modeling, cell-based assays, organ chips and other biology-based test methods.

Bentwich said that a revolution is happening, and Quris is at the center of it. We believe that using novel combinations of Patients-on-a-Chip together with powerful AI, we can replace outdated and ineffective mice experiments, or at least reduce them.

He pointed out that technology can be used as a tool to speed the drug development timeline. A vaccine which usually takes 10 to 15 years to develop was developed within a year using cutting edge technologies like Modernas with its COVID vaccine, and like Quris is now using in drug development.

Bentwich sees a future of drugs that are fitted to individuals rather than to the masses. We shrink the time that it takes to develop a drug. Were hoping that it sparks a revolution in drug development, by developing drugs much faster, much cheaper and that are more personalized.

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Beyond Animal Testing: How AI is Increasing the Odds in Drug Development - BioSpace