Every Cure's old drug new use strategy may change the landscape of rare disease treatment

Key Takeaways

• Every Cure is using artificial intelligence to find new uses for about 4,000 already-approved drugs, shortening the traditional early research timeline from up to 100 days to just 17 hours.
• The nonprofit is not focused on treating any one specific disease; instead, it follows a “disease-agnostic” R&D approach.
• Every Cure’s goal is to, by 2030, develop treatment options for 15 to 25 diseases through drug repositioning.

One of Every Cure’s founders, Dr. David Fajgenbaum

There are more than 10,000 known rare diseases worldwide, and 95% still have no cure. Developing a brand-new therapy often requires billions of dollars and more than a decade. Meanwhile, patient populations for rare diseases can sometimes be only a few thousand people—or even dozens—so pharmaceutical companies are reluctant to invest so much time and money into a drug that is unlikely to be profitable.

Drug repositioning completely overturns this model. It aims to find new indications for already-approved drugs rather than limiting them to the purposes for which they were originally developed. Today, some organizations have begun using artificial intelligence to make this process more efficient.

When Dr. David Fajgenbaum and colleagues began preparing to found the nonprofit Every Cure, which focuses on drug repositioning, they faced a key decision.

“There are two ways to do drug repositioning. One is to open the door and accept patients—so patients and disease groups come to you and ask, ‘Can you find a drug for my condition?’” Fajgenbaum said, “The other is… using AI to look across all drugs and all diseases to find the most break-throughable targets.”

Fajgenbaum and the co-founders chose the second path.

Every Cure does not look for a dedicated therapy for any one specific disease. Instead, it screens existing drugs to see whether they can show efficacy against any known diseases. The team first identifies the match-ups between drugs and diseases, and then connects with patients who could benefit from them. This is fundamentally different from the traditional rare-disease drug development model.

“Previously, the logic in research was: if you want someone to do research, you have to find them and give them money,” Fajgenbaum said. “So someone always comes to you saying, ‘We want you to research our disease, here’s the money,’ and we can only refuse… We don’t operate that way.”

He acknowledged, “To spread this idea, honestly, isn’t easy.”

So, although Fajgenbaum has been highly successful in treating rare diseases with already-approved drugs—he says his research over the past 12 years has helped save the lives of more than 1,000 patients—raising funding for the organization has remained difficult.

“In our first year, we raised not a single dollar,” Fajgenbaum said.

Charitable donations in the rare-disease space often carry strong personal emotions. Donors typically only want to fund research related to diseases connected to their own family members.

Therefore, even though in the early stages many organizations were willing to provide funding for drug repositioning research for diseases such as pancreatic cancer, Every Cure坚持disease-agnostic principles. This means Fajgenbaum had to reject all donors who only wanted to fund therapies for specific diseases.

“In the first year, we discussed deals like that dozens of times and turned down large amounts of funding. But we believe that was the right choice,” Fajgenbaum said. “I don’t want to end up in a situation where you take funding… spend five years and burn up someone else’s $5 million, and get nothing.”

However, in the end, Fajgenbaum still found partners willing to support its “disease-agnostic” model. The Chan Zuckerberg Initiative was an early supporter; the Lydia Hill Foundation, the Flagship Pioneering Innovation Fund, and the Arnold Ventures fund also joined.

Ultimately, Every Cure received a $60 million commitment from the TED Audacious program, and it also secured more than $130 million across two rounds of funding from the Advanced Research Projects Agency for Health (ARPA-H, a federally funded agency established by the Biden administration in 2022).

The initial results are encouraging. Since its founding in late 2022, Every Cure has identified 10 in-development projects in its drug repositioning pipeline.

“In our first year, we focused on fundraising and building the funding base; in the second year, we built the team; in the third year, we truly advanced the R&D pipeline,” Fajgenbaum said. “For these 10 in-development projects, we expect that most will ultimately benefit patients.”

His goal for the foundation is: by 2030, achieve accessible treatments for 15 to 25 diseases through drug repositioning, and the team already has success stories to build on. Before launching Every Cure, the core team had already successfully discovered 14 new repositioning uses for 5 diseases.

AI’s power in disease research

Fajgenbaum himself has a rare and fatal disease—Castleman disease. At the time, it was by analyzing his own blood samples, reviewing thousands of scientific papers, and personally trying the drugs that he found the already-approved drugs that could be used to treat the disease.

Over more than three years fighting this rare immune disease, he came close to death five times.

And today, Every Cure has greatly simplified that process with artificial intelligence.

Each month, the technical team scores about 4,000 already-approved drugs, assessing their potential efficacy against more than 18,000 known diseases—matching combinations total as many as about 75 million. Three years ago, generating this list required 100 days; now it takes only about 17 hours.

After that, the medical team revalidates the most promising candidates, using deep analysis to filter for the therapies most worth advancing. Every Cure will only advance options that can both effectively treat severe conditions and also be able to enter clinical trials within the organization’s funding capacity. The cost of a clinical trial for a single drug is roughly $3 million to $7 million.

Every Cure’s goal is not only to publish research results, but to drive drug development to real-world deployment end to end: laboratory validation, clinical trials, regulatory engagement, and physician education—so that the therapy truly reaches the patients who need it.

“Our unique aspect is that we cover the entire process,” Fajgenbaum said. “We don’t just find a match relationship and publish a paper—we publish outcomes, validate efficacy, and find the patients who need it.”

To illustrate the effectiveness of this model, Fajgenbaum cites Every Cure’s research on Walshman–Bupp syndrome. This is an ultra-rare neurodevelopmental disorder that was first diagnosed in 2018.

The team collaborated with the researchers who first discovered the disease and found a drug developed decades earlier to treat African sleeping sickness, which can suppress the key protein that triggers the condition.

Fajgenbaum said that currently, six patients have received the drug, five of whom are children, and all showed significant improvement: they can sit up, interact more with family members, and some children have even achieved progress that previously seemed out of reach.

“This is exactly the reason we founded Every Cure,” he said.

Drug repositioning vs brand-new drug development

Fajgenbaum does not believe that drug repositioning can replace brand-new drug development in the rare-disease field. He admits that many diseases still require brand-new therapies, and he is actively working with partners developing innovative solutions. But he firmly believes the two paths must proceed in parallel.

“I think both are indispensable,” he said. “We need someone to keep developing new drugs, and we also need an organization to systematically sort through already-approved drugs… We’re not saying all diseases can be cured with existing drugs. Instead, we believe that all diseases that can be cured with existing drugs should be cured.”

In response to the view from critics that “investing in drug repositioning will crowd out funding for new drug development,” Fajgenbaum responded with data:

“Developing a brand-new drug requires $1 billion to $2 billion and takes 10 to 15 years,” he said. “And our spending will always be only a fraction of that number.”

But when it comes to finding new uses for old drugs that no longer generate commercial profits and that pharma companies are unwilling to manufacture, Every Cure encountered a new challenge.

“Some drugs are still in patent life, but pharma companies even refuse to make them anymore, because they can’t reach even break-even and the production cost is higher than the returns,” Fajgenbaum said. “We currently have a project facing this situation, and the partner is a large pharmaceutical company. I’m working to persuade them that this is the right thing to do.”

As Fajgenbaum put it: “The healthcare system works smoothly for new drugs, but it completely fails for old drugs.” He believes that once a drug becomes a generic, “there’s no incentive to develop new uses for it.”

And that gap is precisely where Every Cure’s value lies. In the rare-disease space, where time is precious and commercial incentives are limited, running drug repositioning alongside new drug development can save lives that otherwise would not be meant to be lost.

However, turning these discoveries into real outcomes within the regulatory system is also extremely challenging.

The FDA approval process Every Cure faces is still built around the traditional sponsor model. “When we communicate with the FDA, we find that there isn’t a traditional sponsor here, because the original-drug companies aren’t interested at all,” Fajgenbaum said. “We’re just an independent nonprofit.” This seems very unusual to regulators who are accustomed to dealing with pharmaceutical companies. “They’ll ask: ‘Why are you here to do this?’ Because it can save kids!”

Therefore, educating doctors about related therapies has also become an important mission for Every Cure. Therapies from drug repositioning do not necessarily need FDA approval to be used for patients; doctors can prescribe them off-label. This is very common in the rare-disease field.

Even so, Fajgenbaum says that obtaining FDA recognition still matters: it can simplify insurance processes, strengthen doctors’ and patients’ confidence in the therapy, and improve public understanding of the drug’s efficacy.

Even with all these obstacles, Every Cure keeps expanding into new areas. Fajgenbaum believes every effort is worth it. “We do drug repositioning to save lives—that’s the only thing we care about, and it’s the only intention behind doing this… Saving and improving lives.”

For rare-disease families who have long been used to hearing that “our disease is too rare, too complex, and lacks commercial value, so it’s not worth developing a therapy,” Every Cure itself is building something equally rare: a healthcare system that will not give up under any circumstances.

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Responsible editor: Guo Mingyu