Every Cure’s drug repurposing strategy isn't what you think, and it could change rare disease treatment

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When Dr. David Fajgenbaum and his colleagues were looking to launch Every Cure, a non-profit focused on drug repurposing, they had a big decision to make.

"If you want to repurpose drugs, there are two ways you can go. One is you can say, we are going to open up our shop and let patients and disease groups come to us and say, 'Hey, will you find a drug for my disease?'" Fajgenbaum said. "Or you take another approach ... using AI to find basically the lowest-hanging fruit across all drugs and all diseases."

Fajgenbaum and his co-founders chose the second option.

Every Cure doesn't search for a specific treatment for a specific disease. Instead, it looks to see if there are any existing drugs that can help any existing disease. The group looks for drug-disease matches, and then connects with the patients that can benefit. This marks a big departure from the way that rare disease treatments have traditionally been developed.

"The way that research has always been done, if you want someone to do your research, you go to them, you give them money," Fajgenbaum said. "So people come to us, and they're like, we want you to work on our disease, here's money, and we're like, no, no, no, we can't … we don't do it that way."

He added, "Getting that messaging out has been a little difficult."

That's why, despite Fajgenbaum's long track record of finding existing drugs that are effective treatments for rare diseases — he estimates his work has helped save the lives of over 1,000 patients over the last 12 years — getting funding has not been easy.

"Our first year, we couldn't raise any money," Fajgenbaum said.

Rare disease philanthropy is often deeply personal. Donors usually want to support research into a disease that has touched their own family.

So while there were plenty of early offers to fund research on drug repurposing efforts for things like pancreatic cancer, Every Cure's approach was disease agnostic. Which meant Fajgenbaum had to walk away from any donors that were looking to fund specific disease treatments. 

"We had literally dozens of those conversations in year one, and we turned down a lot of money. But we felt that it was the right thing to do," Fajgenbaum said. "I just didn't want to be in a position where we were accepting funding ... and we spend five years and $5 million of someone's money, and we don't find anything."

But Fajgenbaum did find partners that were willing to fund Every Cure's disease-agnostic approach. The Chan Zuckerberg Initiative was an early backer. As were the Lydia Hill Foundation, Flagship Pioneering and Arnold Ventures.

Eventually, Every Cure was able to receive a $60 million commitment from TED's Audacious Project, and access to more than $130 million from two separate rounds of funding from the Advanced Research Projects Agency for Health, or ARPA-H, a federal funding agency established in 2022 by the Biden administration.

The early results look like they could be promising. Since its founding in late 2022, Every Cure has identified 10 active programs in its drug repurposing portfolio.

"We spent our first year fundraising and basically getting the funds in place. The second year building the team. And the third year really developing this pipeline," Fajgenbaum said.  "Of those 10 active programs, we expect the majority of them will make it to patients."

Fajgenbaum's goal for the foundation 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. Prior to starting Every Cure, the group's leadership was responsible for repurposing 14 drugs for five different diseases.

The power of AI in disease research

Fajgenbaum's success in finding a drug that could be repurposed to treat Castleman disease, the often-fatal rare condition that he suffers from, was the result of studying his own blood samples, reviewing thousands of scientific papers, and self-experimentation. 

But Every Cure is leveraging AI to streamline the process.

Each month, the group's technology team scores the roughly 4,000 drugs that exist against how effective they would be in treating the more than 18,000 known diseases — about 75 million possible matches. Three years ago, it would take 100 days to generate that list. Now it takes about 17 hours.

A medical team then reviews the most promising leads, narrowing them down through deeper analysis to identify which ones are the best treatments to pursue. Every Cure will only pursue treatments that look like they have the potential to be both effective against a devastating disease, and financially feasible for the organization to advance to the clinical trial phase, which costs somewhere between $3 to $7 million per drug.

The goal for Every Cure is not simply to publish this information, but to usher the drug through what comes next: lab work, trials, regulatory discussions, educating doctors and, ultimately, getting those treatments to the patients that can benefit from them.

"We're unusual 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, then we want to do the work to prove it, and we want to do the work to find people that need it."

To illustrate the effectiveness of this approach, Fajgenbaum pointed to Every Cure's work on Bachmann-Bupp syndrome, an ultra-rare neurodevelopmental disorder that was first diagnosed in 2018.

Working with the same researchers who first identified the condition, Every Cure found that a drug developed decades ago for African sleeping sickness appears to inhibit the protein that drives the disease.

Fajgenbaum says six people have been treated with the drug so far, including five children, and all five children showed meaningful improvement — sitting up, engaging more with loved ones, and in some cases making gains that once seemed out of reach.

"That's the kind of thing that we set Every Cure up for," he said.

Repurposing vs. novel drug development

Fajgenbaum does not see drug repurposing as a substitute for novel drug development in the rare disease space. He acknowledges that there are lots of diseases that will only benefit from new treatments, and he's actively seeking to collaborate with partners that are developing those novel approaches. But Fajgenbaum believes that both options need to move forward in parallel.

"I really believe it's both," he said. "We need people to keep coming up with new drugs, and we need to make sure that there's an entity that's looking at all the old stuff. ... We don't think that every disease can be cured with an existing medicine, it's that we think every disease that can be cured with an existing medicine should be."

To critics who say that investing in repurposing pulls money away from research to develop novel drugs, Fajgenbaum counters with data.

"It costs $1 billion or $2 billion to create one brand new drug. And that takes 10 to 15 years," he said. "We will likely always be a fraction of that."

But in finding uses for older drugs that no longer offer a strong financial incentive for pharmaceutical companies to produce, Every Cure has run into another problem. 

"In some cases, if the drug's still on patent, a drug company may not even want to manufacture anymore, because it's not even a break-even. It actually costs more to manufacture it than they're going to make," Fajgenbaum said. "We're facing this right now with one of our programs. It's a big pharmaceutical company. I'm trying to persuade them that it's the right thing to do."

As Fajgenbaum put it, "The medical system works when it's a new drug. The medical system doesn't work when it's an old drug." He argues that once a treatment is generic, "it's not profitable to find a new use for the medicine."

That gap is exactly where he believes Every Cure has a role to play. In rare diseases, where time is precious and commercial incentives are often limited, having repurposing as a second path forward alongside the search for brand new therapies can save lives that don't need to be lost.

But moving those discoveries through the regulatory system has also not been simple.

Every Cure faces an FDA approval process that is still built around a traditional sponsor model. "In our discussions with the FDA ... there is no sponsor, because the people who make the drug, they're not interested in it," Fajgenbaum said. "We're this independent non-profit," he added, describing how unusual that can sound to regulators used to dealing with drugmakers. "They're like, 'So why are you here?' Because it's gonna help kids!'"

That's why educating doctors has become such an important mission for Every Cure. FDA approval is not always required for a repurposed drug to reach patients. Doctors can prescribe medicines off-label, and in rare disease that happens often.

Still, Fajgenbaum said getting an FDA stamp of approval does help: it makes the insurance process smoother, gives doctors and patients more confidence in the treatment, and raises overall awareness of a drug's efficacy.

But despite all the hurdles Every Cure faces, the group continues to tread new ground, and Fajgenbaum says the efforts are worth it. "You want to repurpose drugs to save lives, which is all we care about. That's literally the only reason we're doing this ... to save and improve lives," he said.

For rare disease families that are used to hearing that their disease is too small, too complicated or too financially unattractive to make searching for a treatment worth it, Every Cure is building something rare in its own right: a system that looks anyway.