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10 HARTFORDBUSINESS.COM | OCTOBER 6, 2025 Bexorg CEO Zvonimir Vrselja in a lab at the company's New Haven headquarters, at 290 Congress Ave. HBJ Photos | Harriet Jones Mind Matters New Haven startup Bexorg uses donated brains to reshape drug discovery neurodegenerative diseases have an exceptionally high failure rate. For example, before 2021, the Food and Drug Administration had not approved a new Alzheimer's treat- ment in 18 years. Most experimental drugs fail early in the lab. Of those that reach human trials, the majority collapse in late- stage testing — either because they don't work or their side effects are too severe. The challenge lies in the extraor- dinary complexity of the human brain and the difficulty of predicting how a drug will actually behave in a living person. Bexorg's "brain-in-a-bucket" approach provides data that offers a clearer picture of how a drug might perform in clinical trials. "We are addressing this transla- tional gap now," Vrselja said. "That's the reason why all these drugs failed — we can't translate them from benchtop to humans. And so, that's what Bexorg is now fixing. With our approach, we are now able to be from day one in the human brain." 'A pioneer' In just three years, Bexorg has grown from five to 30 employees. The company is organized across several fronts: operations oversees the biology and perfusion technology; an AI team develops the digital platform to capture and analyze trial data; drug discovery, led by former Pfizer executive Paul Wes, drives both industry partnerships and Bexorg's own therapeutic programs; and business development focuses on revenue opportunities such as the Biohaven deal. "Bexorg is a pioneer," said Biohaven CEO Vlad Coric, who has been following the company's work for years. "I think they're going to go down in history." Biohaven has already tested two drug candidates on BrainEx — one aimed at boosting brain metabolism and function with age, and another targeting Parkinson's disease. Coric said the results gave Biohaven the confidence to advance both drugs in development, since the system showed they could reach the right concentrations and act on the correct targets in the brain. He called the technique a "fast-for- ward" that could shave years off the research timeline. Financial terms of the partnership were not disclosed. With more machines coming online, Bexorg expects to scale up to 1,000 experiments annually by next year. And although the learning curve to go from physician and academic to biotech CEO has been daunting, that scale is something Vrselja says a startup has a much better chance of achieving than an academic lab. "I would say in terms of the speed, in terms of the execution that you can achieve, it is much faster in the startup environment," he said. "You're more agile, and you can be more capital efficient." By Harriet Jones hjones@hartfordbusiness.com Z vonimir Vrselja lifted a plastic barrier to provide a better view of the tool he hopes will help cure devastating diseases including Alzheimer's and Parkinson's. "You see here in the black box, there's a human brain inside," he said. The donated brain is connected to a system of tubes that perfuses the organ with a solution designed to mimic human blood. "All of the lines that you're seeing will basically be analogous to our veins and blood vessels," Vrselja explained. "And so, we are now running artificial blood through the brain, and we are testing a drug in this particular brain." The platform, known as BrainEx, restores certain molecular functions in postmortem human brains, creating a model that closely mirrors how drugs might act in living tissue. Researchers obtain both diseased and healthy brains through established organ-do- nation networks, allowing them to compare responses side by side. That makes BrainEx valuable to pharmaceutical companies devel- oping treatments for central nervous system diseases such as Alzheimer's, Parkinson's and ALS. By testing compounds in a real human brain environment before launching costly clinical trials, companies can gather more reliable data on whether a drug is likely to succeed. "We are building this new foun- dational infrastructure for drug discovery," Vrselja said. "We are flipping drug discovery upside down." Vrselja is the CEO of Bexorg, a startup spun out of almost a decade of research at Yale University in the lab of Nenad Sestan, who is the company's co-founder. Bexorg recently came out of stealth mode to announce a partnership with fellow New Haven life sciences company Biohaven, which has been testing drug candidates on the BrainEx system for the last year. The collaboration agreement will provide Bexorg with revenue to iden- tify and decrease the risks of devel- oping therapies for brain and central nervous system disorders. Bexorg has raised $19.5 million from investors, and is imminently expected to announce another fund- raising round. It has put that capital to work by hiring across disciplines — engineers, data scientists, bioinfor- maticians, machine learning experts, as well as physicians and drug discovery specialists. The company has also been refining its technology and building capacity. It now has five fully operational BrainEx machines in its downtown New Haven lab, and a sixth in development. Brain-in-a-bucket approach Bexorg's technology first emerged under a National Institutes of Health project called the Brain Initiative, which aimed to map the human brain to understand more about its architecture. Still at Yale, Vrselja and Sestan developed their perfusion technique to help with that mapping. They began with pig brains to test their model. While the organs are not "alive" and lack the electrical activity needed for consciousness, they can, for a short time, demonstrate cellular and molecular reactions to treatments. Vrselja and Sestan realized their technology could do more than simply map the brain — it might help close a long-standing gap in brain-disease research. Potential drug candidates for Bexorg's BrainEx system running an experiment on a human brain, which sits within the black container at the center.