In his third year at the Perelman School of Medicine, David Fajgenbaum suddenly found himself on the other side of the hospital bed. He was 25, training to be a doctor, and suddenly “completely, critically ill”—his immune system inexplicably shutting down his organs one by one. He was eventually diagnosed with Castleman disease, a rare and often fatal lymph node disorder. At the time, there was no established treatment. He received experimental chemotherapy with successful results, but he knew that wasn’t a sustainable solution.
“I almost died four more times from this disease before I eventually repurposed a drug that saved my life,” Fajgenbaum recalls. Indeed, what followed was a miracle—one of his own doing. Fajgenbaum began studying his own blood in a lab on campus, driven by the possibility that somewhere in the existing landscape of pharmaceuticals, a solution might already be available. What he found was a generic immunosuppressant typically used for transplant patients, and though it wasn’t designed for CD, it worked on him. He has now been in remission for over ten years.
Before medical school, Fajgenbaum was a student–athlete at Georgetown University, where he played football throughout his undergraduate career. During college, his mother was diagnosed with brain cancer and passed away—an experience that would shape the early direction of his work. “I wanted to become a doctor in memory of my mom,” he explains. In her memory, Fajgenbaum also launched his first nonprofit: Ailing Mothers and Fathers, which was later changed to Actively Moving Forward, a student–led support network for grieving young adults.
After Georgetown, he enrolled at Penn to study medicine. Fajgenbaum imagined a future in clinical care or research. What he didn’t anticipate was becoming a case study in his own education. “[The CD diagnosis] just changed everything,” he said. “It made me appreciate every moment of life so much more. It made me, as a researcher, have this tremendous sense of urgency and [realize] it’s all about impact, not about publications or grants and things like that. It’s just all about how much impact you can make.”
In 2012, shortly after stabilizing from a relapse in the disease, Fajgenbaum founded the Castleman Disease Collaborative Network, a nonprofit research initiative focused on accelerating treatment discoveries for CD. It was through these research efforts that Fajgenbaum discovered his own cure. “It really focused me in on drug repurposing, which is where you take existing medicine and try to find new uses for them, because that's what saved my life,” he recalls. “And I’ve learned there actually are a lot more drugs out there that could treat more patients.” That idea of drug repurposing soon became the foundation for a much larger project.
In 2022, Fajgenbaum co–founded Every Cure, a nonprofit that uses artificial intelligence to find new uses for old drugs, alongside Grant Mitchell, a fellow Penn Med graduate. The idea is centered around one critical question that arose during Fajgenbaum’s fight with CD: If repurposing an existing medication could save his life, how many other treatments might already be out there, just waiting to be matched to the right condition?
“We’d been thinking about it for about 10 years, and one of the things that led us to sort of get going on this was the realization that there’s a lot of progress being made in data science to use large data sets to try to repurpose drugs,” he says. “There were efforts being made to repurpose one drug for one disease at a time, and we thought, ‘What if we could use those same algorithms, but instead of just doing one drug and one disease at a time, we looked across all drugs and all diseases simultaneously?’”
The Every Cure system is a machine learning platform that scans the world’s medical research, from journal articles to clinical data, and flags potential connections between drugs and diseases. The Every Cure team then ranks the most promising matches based on “three main domains,” Fajgenbaum states. The first being “biological rationale,” or how likely the drug is to work. The second is “major impact,” which considers how many people the treatment could benefit. The third is “feasibility,” weighing the cost and resources required to prove the drug’s effectiveness.
A little over two years ago, the team got its first real results. They had been running the algorithm on CD, specifically for severe cases where no other treatments had worked. The top result it flagged was adalimumab, an anti–inflammatory drug more commonly used for conditions like arthritis. Around the same time, a doctor in Vancouver, B.C., was treating another patient with CD who had run out of options and was preparing to enter hospice. “Nothing was working for him, and his doctor tried adalimumab in this last–ditch effort to help him,” Fajgenbaum explains. “It worked. It saved his life. And amazingly, he didn't have to go into hospice care. That, for me, was a major turning point.”
For Fajgenbaum, the case marked more than just a success story. It was proof that Every Cure’s mission was feasible. A patient who had been out of options was now recovering because of a match made by their AI platform. It was the first time Every Cure’s technology had directly influenced a treatment decision, and it had worked. “I was like, ‘Wow, this technology is able to identify a treatment like this that hadn't been used before,’” he recalls. “That was huge, and we published that in the New England Journal of Medicine.”
Since that first success, Every Cure has expanded its scope way beyond CD. The team is now investigating drug matches for a wide range of conditions, many of which have limited or no existing treatments. One example is leucovorin, a folate–related drug typically used for certain cancers, which Fajgenbaum reveals may help a subset of children with autism.
“It turns out that a portion of kids with autism have antibodies that prevent folate from getting in their brain. Folate is a critical vitamin that you need for brain development, and if you give these kids leucovorin, which is a sort of a derivative of folate, it can get into the brain through what’s called the RFC, or the reduced folate channel,” Fajgenbaum explains. “So even though they have these antibodies against folate, they can actually get folate into their brain.” Early clinical trials have shown “improvement in verbal communication skills for these kids,” which Fajgenbaum admits the Every Cure team is “really excited about.” While they are considering other clinical trials, Fajgenbaum adds that “We’re also considering just getting the word out about it.”
Another ongoing project explores the use of lidocaine—which Fajenbaum describes as “this old, cheap numbing medicine”—in treating certain cancers. While it’s not yet clear what types of tumors are most susceptible to lidocaine, lab studies have suggested that lidocaine can kill some cancer cells. Every Cure is currently getting ready to launch similar studies to better understand which cancers might benefit. Since many of the drugs identified by the platform are already Food and Drug Administration approved and often available as low cost generics, the barrier to access these treatments is significantly lower than it would be for newly developed options.
But that also means they’re easy to overlook.
“It's really because no entity exists in our whole healthcare system that is just looking to help patients with the drugs we have in nonprofitable ways,” Fajgenbaum says. “There’s a lot of cheap drugs out there and a lot of rare diseases, but no one in our system goes after cheap drugs because you can’t make any money off of them.” The project is designed to be additive, not competitive. Every Cure is not a replacement for traditional drug development, but a way of accelerating what’s already possible.
“We had to create a solution in our system. It’s not profitable. It can just help people.”
For Fajgenbaum, the work has always been personal. The sense of urgency that drives Every Cure comes from a deep concern for people and the unshakable belief that their technology can help. And as a patient, he’s never forgotten what it feels like to be out of options.
“We are very much grounded based on the fact that we know there are millions of people suffering, and they're going to continue to suffer until we can identify drugs for them,” Fajgenbaum said. “So it’s extremely humbling and grounding to think about A, the suffering that's out there and the people who need treatments, and B, the fact that we actually already have solutions for a lot of them, but our medical system has just failed to get them to people.”
Every Cure is still growing. The team is continuing to build out its database, refine its algorithm, and pursue new clinical trials. The long–term goal is to scale the work so it can grow faster, broader, and ideally global. Still, Fajgenbaum is quick to note that progress depends on more than just technology. It takes coordination, collaboration, and people willing to challenge the existing structure of medicine, all of which he believes rely on our willingness to help others. “There’s nothing in the world that is more fulfilling than being able to help other people,” he tells me. It’s an adage that also extends toward his advice to students, especially those interested in medicine, entrepreneurship, or research that sits somewhere in between.
“I think that being in college or graduate school is the perfect time to get involved in socially impactful work,” he says. “You’re in a great place like Penn and you actually have a little bit of bandwidth. I think it’s about taking advantage of it. ”Fajgenbaum also emphasizes that making an impact doesn’t require perfection. “We often sort of wait to see if we can find the perfect thing, the greatest match for what we want to do,” he says. “And I think, sometimes, people wait too long.”
“My opinion is, find something you’re passionate about and get working on it—start trying to solve it. In the process, you might actually find something else that you’re more passionate about, and you can work on that too. But now that you’ve begun working on something, you’ve learned how to take on a challenge. You’ve learned a lot about how to solve a problem.”
For Fajgenbaum, that mindset started with AMF. It carried him through the founding of the Castleman Disease Collaborative Network. And it continues now, through Every Cure, where he’s working on a problem that in many ways still feels personal. His work is built on the idea that somewhere, hidden in plain sight, the next cure might already exist. The key is knowing where to look, and not being afraid to try.
