Dr. David Fajgenbaum is one of the founders of Every Cure, a nonprofit organization focused on drug repurposing.
Courtesy of Every Cure
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There are over 10,000 rare diseases, 95% of which have no cure. Developing new treatments can cost billions of dollars and take more than a decade. In the field of rare diseases, where the number of patients is only a few thousand or even a few dozen, drug companies have been reluctant to invest that much time and capital into developing drugs that are unlikely to be profitable.
Drug repurposing turns that model on its head. Repurposing explores new ways to use existing drugs to treat diseases for which they were not originally intended. And now there are groups that are using AI to make that process more efficient.
When Dr. David Fajgenbaum and his colleagues were considering starting Every Cure, a nonprofit focused on drug repurposing, they faced a big decision.
“If you want to reuse medicine, there are two ways to do it. One is to open our store and have patients and disease groups come to us and say, ‘Can you find me a medicine for my disease?'” Fajenbaum said. “Or you could take a different approach…using AI to essentially find the lowest hanging fruit across all drugs and all diseases.”
Fajgenbaum and his co-founders chose the second option.
Every Cure is not a search for specific treatments for specific illnesses. Instead, we look to see if there are existing drugs that can help with the existing disease. The group looks for matches between drugs and diseases and connects patients who may benefit. This represents a major departure from the way treatments for rare diseases have traditionally been developed.
“The way research has always been done is if you want someone to do research, you go to them and give them money,” Fajenbaum said. “So people come to us and they say, ‘We want you to cure us, we have the money,’ and we say, ‘No, no, no, we can’t do that…We don’t do it that way.'”
He added: “It was a little difficult to get the message across.”
That’s why, despite Feigenbaum’s long track record of discovering existing drugs as effective treatments for rare diseases (he estimates that his research has saved the lives of more than 1,000 patients over the past 12 years), raising funds hasn’t been easy.
“We couldn’t raise the money the first year,” Fajenbaum said.
Rare disease philanthropy is often deeply personal. Donors typically want to support research into a disease that has affected their family members.
So while there were many early offers to fund research into drug repurposing efforts for things like pancreatic cancer, Every Cure’s approach was disease agnostic. This meant that Mr. Feigenbaum had to withdraw from donors seeking to fund treatments for certain diseases.
“We had literally dozens of conversations like that in our first year and turned down a lot of money, but we felt it was the right thing to do,” Fajenbaum said. “We didn’t want to be in a position where we were accepting funding… We spent five years and $5 million of someone’s money and we couldn’t find anything.”
But Feigenbaum found a partner to fund Every Cure’s disease-agnostic approach. He was an early supporter of the Chan Zuckerberg Initiative. So were the Lydia Hill Foundation, Flagship Pioneering, and Arnold Ventures.
Ultimately, Every Cure was able to secure $60 million in funding from TED’s Audacious Project and more than $130 million in two funding rounds from the Advanced Research Projects Agency for Health (ARPA-H), a federal funding agency created in 2022 by the Biden administration.
Early results look promising. Since its founding in late 2022, Every Cure has identified 10 active programs within its drug repurposing portfolio.
“We spent the first year raising money and getting the basic capital in place. The second year was spent building the team. And the third year was really developing this pipeline,” Fajenbaum said. “Of these 10 active programs, we expect the majority to be available to patients.”
Fajgenbaum’s foundation’s goal is to be able to treat 15 to 25 diseases with repurposed drugs by 2030, and he and his team have a track record of success. Before starting Every Cure, the group’s leadership was responsible for repurposing 14 drugs for five different diseases.
The power of AI in disease research
Feigenbaum’s discovery of a drug that could be repurposed to treat Castleman’s disease, a rare and deadly disease, was the result of studying his own blood samples, reviewing thousands of scientific papers, and doing some self-experimentation.
Feigenbaum nearly died five times in just over three years due to her battle with Castleman’s disease, a rare immune system disease.
Courtesy of Every Cure
But Every Cure leverages AI to streamline the process.
Each month, the group’s technology team scores the roughly 4,000 drugs in existence, comparing them to how effective they are at treating more than 18,000 known diseases, or about 75 million matches. Three years ago, it took me 100 days to create that list. Now it takes about 17 hours.
The medical team then reviews the most promising leads and narrows them down through deeper analysis to identify the best treatments to pursue. Every Cure only pursues treatments that have the potential to be effective against devastating diseases and for which it is financially viable to advance to the clinical trial stage, which can cost between $3 million and $7 million per drug.
Every Cure’s goal is not just to make this information publicly available, but to take the drug to its next steps, including laboratory studies, clinical trials, regulatory discussions, physician education, and ultimately, delivering the treatments that benefit patients.
“We’re unique because we’re end-to-end,” Fajgenbaum said. “We don’t just want to find a match and publish it. We want to publish it. And we want to do the work to prove it. And we want to do the work to find the people who need it.”
To illustrate the effectiveness of this approach, Fazigenbaum pointed to Every Cure’s work on Bachman-Bupp syndrome, an ultra-rare neurodevelopmental disorder first diagnosed in 2018.
Working with the same researchers who first identified the disease, Every Cure has discovered that a drug developed for African sleeping sickness decades ago appears to inhibit the protein that causes the disease.
Six people, including five children, have been treated with the drug so far, Fajgenbaum said, and all five have seen meaningful improvement, including sitting more, interacting with loved ones more, and in some cases achieving outcomes that once seemed out of reach.
“That’s the kind of thing we set Every Cure up to,” he said.
Reuse and new drug development
Fajgenbaum does not believe that drug repurposing can replace new drug development in the rare disease field. He acknowledges that there are many diseases that could only benefit from new treatments, and is actively seeking collaborations with partners who are developing these new approaches. But Fajenbaum believes both options need to be pursued in parallel.
Every Cure works to find new uses for existing medicines, with the goal of finding cures for previously untreatable diseases.
Photographer Jessica Kurkunis, courtesy of Every Cure
“I really believe it’s both,” he said. “We need people to continue to develop new drugs, and we need to make sure that there are organizations that are looking at all the old ones. … We don’t believe that all diseases can be cured with existing drugs. We believe that all diseases that can be cured with existing drugs should be cured.”
Fajenbaum uses data to counter criticism that investments in reuse take money away from research to develop new drugs.
“It costs $1 billion or $2 billion to make a new drug, and it takes 10 to 15 years,” he said. “We’ll probably always be a fraction of that.”
But Every Cure ran into another problem in finding uses for older drugs that no longer offered strong financial incentives for pharmaceutical companies to produce them.
“In some cases, if the drug is still on patent, the drug company may not want to make it any more because it won’t even break even. In fact, the cost to make the drug is higher than the cost they plan to make it,” Fajenbaum said. “We’re facing this problem right now with one program, and it’s a big pharmaceutical company. I’m trying to convince them that it’s the right thing to do.”
“For new drugs, the health care system works; for old drugs, the health care system doesn’t work,” Fajgenbaum said. He argues that once a treatment becomes generic, “it’s not profitable to find new uses for that drug.”
That gap is where he believes Every Cure has a role to play. For rare diseases, where time is often at a premium and commercial incentives limited, repurposing them as a second avenue alongside the search for entirely new treatments can save lives that don’t need to be lost.
However, translating these findings into the regulatory system has also not been easy.
All Cure faces an FDA approval process that is still built around the traditional sponsorship model. “In our discussions with the FDA… we don’t have a sponsor because the people who are making the drug are not interested in the drug,” Fajenbaum said. “We are an independent nonprofit organization,” he added, explaining how unusual that sounds for regulators used to dealing with drug companies. “They’re like, ‘So why are you here?’ Because it helps kids!”
That’s why physician education is such an important mission for Every Cure. FDA approval is not always required for repurposed medicines to reach patients. Doctors may prescribe drugs that are off-label or for rare conditions that occur frequently.
Still, Fajenbaum said getting the FDA’s stamp of approval certainly helps, saying it smooths the insurance process, gives doctors and patients more confidence in the treatment, and increases overall awareness of the drug’s effectiveness.
But despite all the hurdles Every Cure faces, the group continues to break new ground, and Feigenbaum says the effort is worth it. “We want to repurpose drugs to save lives. That’s all we care about. That’s literally the only reason we do this… to save and improve lives,” he said.
For rare disease families accustomed to hearing that their disease is too small, too complex, or too economically unappealing to be worth seeking a cure for, Every Cure is building something unusual in itself: a system that’s just plain pretty.
