Beyond animal testing: how AI increases drug development opportunities

Quris Scientists/Quris AI

Quris team members/courtesy of Quris AI

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

Mice are terrible predictors

The artificial intelligence (AI) and pharmaceutical company has the Bio-AI Clinical Prediction Platformwhich is used to determine which drug candidates work safely in the human body and for whom they work best.

“Currently, drugs are being developed and then tested on mice to determine whether they are suitable for humans. Mice are terrible predictors,” said Dr. Isaac Bentwich, founder and CEO of Quris BioSpace† “Of all drug candidates available today in vitro and in vivo testing and then entering into clinical trials, 89% fail. That’s pretty dramatic when you 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 analyzes showed that the overall chance of approval for development candidates was only 7.9%.

Bentwich offered a creative analogy on the matter, imagining a person wanting to build a skyscraper and thus contacting the best architect and engineer available. “They’d tell you, ‘You’ve come to the right place. We’re the best in the business. Here’s what we’re going to do: We’re planning 10 skyscrapers for you. We guarantee nine will crumble. We don’t know which ones.’ ‘ As funny as this may sound, that is actually the current economics of the pharmaceutical industry.”

A doctor by training, Bentwich described his unique transition from school to industry. “I just got out of medical school and was dabbling with computerized medical records and decision support systems. It turned into a hobby. It was either that or pottery, really. And what started as a year off from continuing my medical career, ended up as a period of ten years to develop an automated medical record, which was very successful, he started three other companies in the fields of AI, computer science, biology and medicine before founding Quris.

The Quris platform

The company’s platform leverages a combination of three pillars: stem cell technology, AI, and what they call Patients-on-a-Chip. “There is a technology that is being 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.”

ChipOnChip_Quris

Quris ‘Patient-on-a-Chip Technology/Courtesy of Quris AI

The mini-organs are made 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 ​​is trained to determine which are safe and which are toxic. When a new drug is exposed to the technology, the AI ​​can discern whether it is more like the toxic drugs or the safe drugs. Bentwich stressed that “importantly, this not only gives a readout of the level of safety, but also shows who the drug is safe for. We can use this to see that drug X may be good for one person, but not the other.” Others.”

What is unique about the mini-organs is their interconnectedness. Bentwich described the first version of the platform, including the liver, brain and blood-brain barrier. This allowed the company to collect data not only about how a drug is processed in the liver, but also about what happens when it crosses the blood-brain barrier.

“When we test the drug on our system, we have it metabolized by the liver. It’s a little, little liver in a little pit, but it still metabolizes the drug. It breaks it down into different chemicals in the same way as the real liver in the human body,” he described. “Only then does it cross the blood-brain barrier, which mimics exactly how it behaves, so that only certain molecules end up in the brain. Then it interacts with the miniaturized brain.” The data collected about these interactions between the organs is used to train the AI.

The Bio-AI approach is unique in that it is not just about sorting randomized available medical data, but direct training in response to known drugs being tested on Patient-on-a-Chip. By using more specific data, the platform generates informed predictions about drug safety and individual patient suitability.

A Possible Cure for Fragile X Syndrome

The company develops its first drug for the treatment of Fragile X Syndromea 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, complicating drug development. The company combined its Bio-AI platform with a discovery by Professor Eyal Benvenisti of the Hebrew University of Jerusalem to begin developing the drug.

“The nice thing about the drug that we are developing is that if it is successful, it will be the first time a drug will try to cure the disease. Our early results show that it actually treats the root cause of the disease, not just symptomatically,” he said. The drug hopes to address the disruption of the fragile-X mental retardation protein (FMRP) production caused by a defective FMR1 gene in fragile X syndrome.

“The first studies showed that it did indeed seem to reverse the inhibition of this defective gene,” Bentwich said. “If this is successful, we may be on to something that will impact the lives of many patients.” He said clinical trials will begin within the next 12 months.

Redefining non-clinical testing

Earlier this month, the United States House of Representatives accepted an account to amend the Federal Food, Drug, and Cosmetic Act. Alternatives to animal testing are now allowed when assessing the efficacy of a drug. Such an non-clinical to test may include computer modeling, cell-based testing, organ chips, and other biology-based testing methods.

Bentwich said a revolution is underway, and Quris is at the center of it. “We believe that new combinations of patients-on-a-chip together with powerful AI can replace, or at least reduce, outdated and ineffective mouse experiments.”

He pointed out that technology can be used as a tool to accelerate the timeline for drug development. “A vaccine that usually takes 10 to 15 years to develop was developed within a year using advanced technologies like Moderna’s with its COVID vaccine, and like Quris is now using in drug development.”

Bentwich sees a future of medicines adapted to individuals rather than the masses. “We are reducing the time it takes to develop a drug. We hope it will revolutionize drug development by developing drugs much faster, much cheaper and more personalized.”

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